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Guidelines for the training of medical graduates in clinical chemistry
Clinica Cbimica Acru, 177 (1988) S13-S22 6 1988, Elsevier Science Publishers B.V. (Biomedical Division)
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INTERNATIONAL FEDERATION OF CLINICAL CHEMISTRY (IFCC) ’ EDUCATION COMMITTEE 2 AND INTERNATIONAL UNION OF PURE AND APPLIED CHEMISTRY (IUPAC) CLINICAL CHEMISTRY DIVISION COMMISSION ON TEACHING OF CLINICAL CHEMISTRY 3
Guidelines for the training of medical graduates in clinical chemistry Preparedfor pdlicotion for the Education Committee by P.R. Pannall ‘, P.M. Dennis j, I. Farrance ’ and P. Garcia- Web6 ’
1. Introduction
The richness of clinical chemistry as a scientific discipline is largely due to the variety of shills it attracts. It provides a core of common knowledge from which expertise in many directions may be developed. Medical graduates entering clinical chemistry will have some experience of the selection of tests and their interpretation as well as a basic knowledge of pathology, but in addition, medical graduates must acquire an appreciation of analytical techniques, laboratory practice and scientific thinking in order to function usefully in the laboratory. The purpose of this document is to detail the training of medical graduates wishing to make a career in clinical chemistry (chemical pathology). Trainees in
’ The exclusive 0 for all languages and countries is vested in the International Federation of Clinical Chemistry. * Education Committee Members: 0. Zinder (IL), Chairman; H.G.J. Worth (GB), Secretary; N. de Cediel (CO); A. Deom (CH); C.G. Fraser (GB); L. Josephson (DK), representative of the International Union of Biochemistry. ’ Membership of the Teaching Commission during the period (1985-1986) in which these Guidelines were prepared: 0. Zinder (IL), Chairman; H.G.J. Worth (GB), Secretary; Titular member: C.G. Fraser (GB); Associate members: M.A:Drosdowsky (FR); P. Garcia Webb (AU), N. Montalbetti (IT); C.J. Porter (CA), B. Straus (YU); V.N. Titov (SU); R. Vihko (FI); W.H.C. Walker (CA); National Representatives: M.M. Abdel Kader (EG); J. Agneray (FR); K. Bergstrom (SE); B. Chrlstophersen (NO); A.F. Delbruck (DE); H.A. Fritsche, Jr. (US); A. Gomall (CA); A.G. Hadjivassiliou (GR); T. Kanno (JP); M. Nemeth Csoka (HU); P. Strom (IT). 4 The Queen Elizabeth Hospital, Woodville, South Australia 5011, Australia. ’ Prince Henry’s Hospital, Melbourne, Victoria 3004, Australia. 6 Geelong Hospital, Geelong, Victoria 3220, Australia. ’ The Queen Elizabeth II Medical Centre, Nedlands, Western Australia 6009, Australia.
s14
clinical briefly.
pathology,
of which clinical
chemistry
is only one aspect:
will be considered
2. Objectives of training At the end of a defined period of training the medical graduate should: _ have a sound knowledge of physiology and the pathophysiology of disease, and of the biochemical changes that may occur (chemical pathology); _ have a comprehensive understanding of the application and interpretation of biochemical tests in clinical medicine; _ be familiar with current analytical methods and instrumentation and be aware of new- developments; _ be competent in laboratory management; _ possess basic skills for the performance of research and development. 2. I. Physiology and pathophysiologv Medical graduates enter training with a basic knowledge of the pathology and clinical manifestations of disease and some experience in diagnosis and treatment. This knowledge must be expanded with particular emphasis being placed on pathophysiological mechanisms of disease and how changes in laboratory tests relate to such processes; this philosophy is implied in the use of the term ‘chemical pathology’. A sound knowledge of biochemistry and physiology is essential, although the former may be more selective and confined to an understanding of general principles with detailed study only of relevant areas. A suggested list of topics to be covered appears in Appendix A. This is offered as a guide only as it will be modified by changes in clinical practice. The medical clinical chemist should be aware of, and anticipate, such changes. In addition to the defined systems and disorders in Appendix A the trainee must learn to recognise and understand clinical chemical changes associated with disorders that may complicate or accompany other diseases. These include: sepsis and trauma (including burns); cardiac failure; shock; neoplasia; malnutrition; alcohol and other drug abuse; ageing. As the boundaries between laboratory disciplines are becoming increasingly blurred it is desirable that the trainee become familiar with current practice in other disciplines such as: haematology; immunology: genetics; toxicology; pharmacology. 2.2. Application of biochemical tests The medical clinical chemist will spend much of his or her time in consultation with clinicians on the selection and interpretation of clinical chemical tests and advising on optimal therapy of relevant conditions. Most practicing clinicians would consider themselves competent in selecting and interpreting laboratory data, particularly in their own speciality, and therefore the chemical pathologist must bring a different perspective to this activity, one in which clinical chemical results are fully evaluated. The trainee must become conversant with: - correct patient preparation and specimen collection, and the recognition of artefactual results:
S15
- physiological variation and other factors affecting reference values; - effects and interferences (both physiological and analytical of drugs or metabolites on test results; - the performance characteristics of the test, e.g. imprecision, inaccuracy and likely sources of error. 2.3. Interpretation of results The trainee must become familiar with the tests performed in a modern clinical chemistry laboratory. Results should be considered in the relevant clinical context and evaluated in terms of: _ the pathophysiological mechanisms that may produce such a result in that particular patient; _ the disease processes most commonly associated with the result; _ other causes, such as associated disease or the effects of drugs and metabolites; _ associated findings (patterns) that may help in assessing the result. 2.4. Selection of tests The trainee must learn the best test or tests, and their relative usefulness in a particular disorder or clinical problem. In general, he or she must consider: - the likely significance of a result in the context of the patient’s condition (predictive value); _ other factors present that may influence test results and in consequence the choice of tests; _ the most cost-effective way of investigating the problem. The trainee must become familiar with other tests not performed in the clinical chemistry laboratory, but which are relevant to the diagnosis. He or she must be aware of the basis of such tests in order to be able to advise on the appropriate role of clinical chemistry. In addition, the medical clinical chemist should be able to advise on patient management and to select (and reduce) tests suitable for monitoring the progress of the disease and the effects of treatment. The knowledge required to function efficiently as a consultant is acquired, as it is in all medical specialties, by constant exposure to clinical problems. The trainee medical clinical chemist should attend ward rounds and clinical meetings and should discuss results with clinicians in order to learn how to interpret them in the context of particular patients. Clinical involvement should include advising on, or performing, dynamic clinical chemical tests such as stimulation or suppression tests of endocrine systems. Training is essentially an apprentice system, and the trainee should therefore be able to discuss results and clinical problems with an experienced and qualified supervisor on a regular basis. As with other specialties, the degree of consultant supervision will depend on the stage of training. 2.5 Analytical aspects The trainee must acquire
a sound knowledge
of the principles
and applications
of
S16
currently used analytical techniques. These are listed in Appendix B. Much of this knowledge will be obtained by reading standard texts, attending courses and practical experience. The list does not deal with specific assays but, in addition to understanding the principles of analysis, the trainee must become familiar with those used in his or her laboratory. This should be done by actually performing the tests at the bench and learning and understanding the basis for each technique and the purpose of each reagent. He or she should be actively involved in trouble-shooting and quality assurance in order to learn the problems that may be encountered with each assay and instrument. It is likely that time will have to be spent in different laboratories to gain experience in all the necessary techniques. This is also important in order to realise that different laboratories have different approaches to solving similar problems. 2.6. Laboratory management The trainee must become familiar with all aspects of laboratory practice and management. This should include: _ the theory of reference values; - external and internal quality assurance procedures; - work flow and reporting systems; _ the appropriate provision of cost-effective services (equipment and methods) for different needs, e.g. emergency laboratories, neonatal services; _ laboratory safety _ awareness of hazards (physical, chemical and infectious); - means of minimising hazards. - selection and evaluation of instruments and reagent kit sets; - assessment of efficiency and workload: _ laboratory design; - use of computer and statistics in the laboratory; - staff management, including: _ selection; - training; _ work satisfaction; - appropriate delegation of responsibilities; - knowledge of local and national legal requirements. This knowledge is also acquired by discussion and experience. A trainee should become progressively involved in decision-making processes. 2.7. Research and development Whether a trainee is research-oriented or not, he or she will be involved in research or development projects. A basic knowledge of how research and development are carried out should be acquired during training. This includes: - planning of projects _ definition of problem or hypothesis; - experimental design;
s17
- use of library facilities and evaluation of literature;
_ statistical evaluation of results; - logical presentation and discussion of results; - ethics of research. These are best acquired by carrying out a research project and its subsequent publication and/or presentation at a meeting of a professional body. 3. Implementation It is recommended that a medical graduate should have at least two years clinical experience before entering a training programme in laboratory medicine. In order to acquire the necessary skills, the training programme should be structured in a logical and progressive way. While different licencing bodies will have different requirements, it is unlikely that the time spent will be less than 5 years. 3.1. Chemical pathology A suggested scheme is as follows. Years 1 to 2: an apprenticeship in analytical techniques and methodology by performing tests as part of the routine service. This achieves an understanding of laboratory functions, (1) revision of basic physiology and .pathophysiology, (2) regular discussions and interpretation of results with supervisor, (3) limited consultative responsibilities. Towards the end of this time it is likely that the trainee will have developed a special interest. This should be encouraged. Years 3 to 5: (1) increasing consultative responsibilities, (2) experience in specialised techniques, (3) time spent in other laboratories, (4) increasing involvement in laboratory management, (5) research project. 3.2. Clinical pathology Training in clinical pathology may differ in depth but not scope from that outlined above. A training programme must include aspects common to all disciplines: (1) laboratory management, (2) research experience, (3) clinical contact. The clinical chemistry component should stress: (1) selection and interpretation of tests in particular clinical situations; this implies an understanding of pathophysiology, (2) principles of analysis and performance of routine tests; some practical experience is essential to aquire an appreciation of the analytical factors involved in a test result, (3) quality assurance. 4. Bibliographic sources There are many textbooks dealing with methodological and interpretative aspects and the trainee should selectively read from these. Review articles will form a major source of study material. Access to a good medical library is essential as these reviews appear in a wide range of specialist
journals, reflecting the diversity of clinical chemistry. In general, useful reviews are likely to be found in the following: Clinical Chemistry; Annals of Clinical Biochemistry; Clinical Biochemistry; New England Journal of Medicine; Clinical Science; Clinical Endocrinology; The Clinical Biochemist Reviews (Australia ACB); The ‘Clinics’ series (W.B. Saunders Company), i.e. The Medical Clinics of North America, Clinics in Endocrinology and Metabolism, Clinics in Laboratory Medicine, Advances in Clinical Chemistry (Academic Press), Recent Advances in Clinical Biochemistry (Churchill Livingstone). Appendix A. Core topics in physiology, pathophysiology
and use of tests.
1. Fluid, electrolyte and hydrogen ion homeostasis - Normal control: renal factors; renin, angiotensin, aldosterone; arginine vasopressin; atria1 peptides; sympathetic nervous system. - Causes and investigation of; hypo- and hypernatraemia; hypo- and hyperkalaemia; acidaemia and alkalaemia; hypertension; oedema. 2. Calcium (II), phosphate and magnesium (II) metabolism - Normal control: parathyroid hormone; vitamin D; renal factors. - Causes and investigation of: hypo- and hypercalcaemia; hypo- and hyperphosphataemia; hypo- and hypermagnesaemia; _ Metabolic bone disease. 3. Renal function _ Factors affecting glomerular filtration and tubular function. - Renal failure; detection and diagnosis; investigation of causes; assessment and monitoring of consequences; principles and biochemical complications of treatment (including dialysis). - Consequences of tubular damage. _ Investigation of polyuria and oliguria. - Investigation of proteinuria. - Investigation of renal stone disease. 4. Hepatic function _ Normal liver function. - Bilirubin metabolism and hyperbilirubinaemia. _ Clinical chemical manifestations of liver disease. _ Detection, investigation and monitoring of acute and chronic liver disease. - Drugs affecting the liver. - Bile salt metabolism; gallstones. 5. Lipids _ Structure, synthesis and metabolism of lipoproteins. - Factors affecting plasma lipid and lipoprotein levels. - Metabolic basis of primary and secondary hyperlipidaemia. _ Principles of therapy of hyperlipidaemia. - Other disorders of lipid metabolism. 6. Proteins - Interpretation of protein electrophoretic patterns.
s19
_ _ _ _ -
Uses and interpretation of specific protein assays. Uses and interpretation of immunoelectrophoretic techniques. Causes and investigation of paraproteinaemia. Causes and investigation of immunoglobulin deficiencies. Complement system and abnormalities. 7. Intermediary metabolism _ Interrelationship of carbohydrate, lipid and protein metabolism; factors controlling plasma glucose levels. - Insulin, glucagon and C-peptide. _ Nature, diagnosis and monitoring of diabetes mellitus. _ Acute metabolic complications of diabetes mellitus. _ Causes and investigation of hypoglycaemia. _ Ketosis. 8. Endocrine systems _ General principles of hormone secretion, control and mechanisms of cellular action. _ Dynamic testing of endocrine function; stimulation and suppression tests. _ Normal hypothalamic and anterior pituitary interrelationship; effects of drugs. _ Diagnosis and assessment of hypopituitarism, acromegaly, pituitary tumours. _ Normal thyroid hormone secretion and metabolism. _ Diagnosis of hyper- and hypo-thyroidism. _ Thyroid hormone changes due to drugs and non-specific illness. _ Principles and monitoring of therapy of thyroid disorders. -’ Normal adrenocortical steroid synthesis and control. - Causes, effects and diagnosis of Cushing’s syndrome. - Causes, effects and diagnosis of adrenocortical insufficiency. _ Congenital adrenal hyperplasia. _ Normal pituitary-gonadal function. _ Investigation of amenorrhoea and infertility. - Investigation of precocious puberty and intersex. 9. Nutrition - Principles of enteral and parenteral nutrition. _ Role of vitamins and trace elements. _ Role of biochemical analyses in assessing nutritional state. 10. Haemopoietic system _ Iron (II), vitamin B,, (cyanocobalamin) and folate metabolism. .- Changes in hematological disease. _ Investigation of iron deficiency and iron overload. 11. Clinical enzymology _ Factors affecting plasma enzyme activities. _ Causes of unusually high or low plasma enzyme activities. _ Use of isoenzyme and isoform analyses in diagnosis. _ Drugs and plasma enzymes (e.g. suxamethonium and cholinesterase; gammaglutamyltransferase).
12. Purine metabolism _ Synthesis and metabolism of urate. - Causes and consequences of hyperuricaemia. _ Causes of hypouricaemia. 13. Porphyrins - Metabolism of porphyrins. - Diagnosis of porphyria. 14. Gastrointestinal and pancreatic function _ Normal digestion and absorption. - Assessment of malabsorption. - Clinical chemical tests in acute and chronic pancreatitis. - Syndromes associated with pancreatic islet cell tumours. - Nature and function of GIT hormones. 15. Drug monitoring - Principles of pharmacokinetics. - Therapeutic drug monitoring. 16.. Toxicology - Effects of and use of clinical chemical tests in toxicity of: lead; toxic trace metals; acetaminophen (paracetamol); salicylate; lithium; antidepressants; barbiturates; digoxin; drugs of abuse. 17. Clinical chemical changes associated with neoplasia including - Hormonal syndromes. - Tumour markers. - Non-specific changes. 18. Clinical chemistry of special groups of patients - Infancy, childhood and puberty (including principles of diagnosis of inborn errors of metabolism). - Pregnancy (including fetoplacental monitoring and diagnosis of fetal abnormality). - Old age. Appendix B. Core topics in instrumentation
and methodology
1. Specimen collection, transport, handling and preservation. 2. Quantities and units in clinical chemistry, including use of SI. 3. Use and calibration of equipment such as thermometers, pipettes, dilutors, balances. 4. Principles of reagent preparation; quality and sources of reagents, water, etc. 5. Principles and practice of - Colorimetry and spectrometry. - Fluorimetry. - Nephelometry and tubidimetry. - Luminescence. 6. Principles and practice of - Flame spectroscopy.
s21
- Atomic absorption
spectroscopy. - Osmometry. 7. Ion-selective electrodes 8. Enzyme activity analysis - Factors affecting analysis of enzyme activity in body fluids. - Use of enzymes as analytical reagents. 9. Separation techniques - Electrophoresis: use of cellulose acetate and gels. - Chromatography; thin layer chromatography, gas-liquid chromatography, high performance liquid chromatography. - Isoelectric focussing. 10. Principles of immunological reactions and their use in identification and quantitation, e.g. - immunodiffusion, - immunofixation, - immunonephelometric and immunoturbidimetric analysis. 11. Principles and application of ligand assays - Radioimmunoassay and immunoradiometric assay. _ Alternative binders. - Alternative labels: chemiluminescent, enzyme, fluorescent. 12. Use of radioisotopes in analytical systems - Principles and precautions. 13. Principles and application of automated analytical systems - Random access. - Continuous flow. - Dry chemistry. - Parallel fast (centrifugal) analysers. 14. Principles and uses of ‘bedside’ analyses and in vivo monitoring 15. Principles and uses of new techniques such as _ Mass spectrometry. - Magnetic resonance. - DNA technology.
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INTERNATIONAL FEDERATION OF CLINICAL CHEMISTRY (IFCC) ’ EDUCATION COMMITTEE 2 AND INTERNATIONAL UNION OF PURE AND APPLIED CHEMISTRY (IUPAC) CLINICAL CHEMISTRY DIVISION COMMISSION ON TEACHING OF CLINICAL CHEMISTRY 3
Guidelines for the training of medical graduates in clinical chemistry Preparedfor pdlicotion for the Education Committee by P.R. Pannall ‘, P.M. Dennis j, I. Farrance ’ and P. Garcia- Web6 ’
1. Introduction
The richness of clinical chemistry as a scientific discipline is largely due to the variety of shills it attracts. It provides a core of common knowledge from which expertise in many directions may be developed. Medical graduates entering clinical chemistry will have some experience of the selection of tests and their interpretation as well as a basic knowledge of pathology, but in addition, medical graduates must acquire an appreciation of analytical techniques, laboratory practice and scientific thinking in order to function usefully in the laboratory. The purpose of this document is to detail the training of medical graduates wishing to make a career in clinical chemistry (chemical pathology). Trainees in
’ The exclusive 0 for all languages and countries is vested in the International Federation of Clinical Chemistry. * Education Committee Members: 0. Zinder (IL), Chairman; H.G.J. Worth (GB), Secretary; N. de Cediel (CO); A. Deom (CH); C.G. Fraser (GB); L. Josephson (DK), representative of the International Union of Biochemistry. ’ Membership of the Teaching Commission during the period (1985-1986) in which these Guidelines were prepared: 0. Zinder (IL), Chairman; H.G.J. Worth (GB), Secretary; Titular member: C.G. Fraser (GB); Associate members: M.A:Drosdowsky (FR); P. Garcia Webb (AU), N. Montalbetti (IT); C.J. Porter (CA), B. Straus (YU); V.N. Titov (SU); R. Vihko (FI); W.H.C. Walker (CA); National Representatives: M.M. Abdel Kader (EG); J. Agneray (FR); K. Bergstrom (SE); B. Chrlstophersen (NO); A.F. Delbruck (DE); H.A. Fritsche, Jr. (US); A. Gomall (CA); A.G. Hadjivassiliou (GR); T. Kanno (JP); M. Nemeth Csoka (HU); P. Strom (IT). 4 The Queen Elizabeth Hospital, Woodville, South Australia 5011, Australia. ’ Prince Henry’s Hospital, Melbourne, Victoria 3004, Australia. 6 Geelong Hospital, Geelong, Victoria 3220, Australia. ’ The Queen Elizabeth II Medical Centre, Nedlands, Western Australia 6009, Australia.
s14
clinical briefly.
pathology,
of which clinical
chemistry
is only one aspect:
will be considered
2. Objectives of training At the end of a defined period of training the medical graduate should: _ have a sound knowledge of physiology and the pathophysiology of disease, and of the biochemical changes that may occur (chemical pathology); _ have a comprehensive understanding of the application and interpretation of biochemical tests in clinical medicine; _ be familiar with current analytical methods and instrumentation and be aware of new- developments; _ be competent in laboratory management; _ possess basic skills for the performance of research and development. 2. I. Physiology and pathophysiologv Medical graduates enter training with a basic knowledge of the pathology and clinical manifestations of disease and some experience in diagnosis and treatment. This knowledge must be expanded with particular emphasis being placed on pathophysiological mechanisms of disease and how changes in laboratory tests relate to such processes; this philosophy is implied in the use of the term ‘chemical pathology’. A sound knowledge of biochemistry and physiology is essential, although the former may be more selective and confined to an understanding of general principles with detailed study only of relevant areas. A suggested list of topics to be covered appears in Appendix A. This is offered as a guide only as it will be modified by changes in clinical practice. The medical clinical chemist should be aware of, and anticipate, such changes. In addition to the defined systems and disorders in Appendix A the trainee must learn to recognise and understand clinical chemical changes associated with disorders that may complicate or accompany other diseases. These include: sepsis and trauma (including burns); cardiac failure; shock; neoplasia; malnutrition; alcohol and other drug abuse; ageing. As the boundaries between laboratory disciplines are becoming increasingly blurred it is desirable that the trainee become familiar with current practice in other disciplines such as: haematology; immunology: genetics; toxicology; pharmacology. 2.2. Application of biochemical tests The medical clinical chemist will spend much of his or her time in consultation with clinicians on the selection and interpretation of clinical chemical tests and advising on optimal therapy of relevant conditions. Most practicing clinicians would consider themselves competent in selecting and interpreting laboratory data, particularly in their own speciality, and therefore the chemical pathologist must bring a different perspective to this activity, one in which clinical chemical results are fully evaluated. The trainee must become conversant with: - correct patient preparation and specimen collection, and the recognition of artefactual results:
S15
- physiological variation and other factors affecting reference values; - effects and interferences (both physiological and analytical of drugs or metabolites on test results; - the performance characteristics of the test, e.g. imprecision, inaccuracy and likely sources of error. 2.3. Interpretation of results The trainee must become familiar with the tests performed in a modern clinical chemistry laboratory. Results should be considered in the relevant clinical context and evaluated in terms of: _ the pathophysiological mechanisms that may produce such a result in that particular patient; _ the disease processes most commonly associated with the result; _ other causes, such as associated disease or the effects of drugs and metabolites; _ associated findings (patterns) that may help in assessing the result. 2.4. Selection of tests The trainee must learn the best test or tests, and their relative usefulness in a particular disorder or clinical problem. In general, he or she must consider: - the likely significance of a result in the context of the patient’s condition (predictive value); _ other factors present that may influence test results and in consequence the choice of tests; _ the most cost-effective way of investigating the problem. The trainee must become familiar with other tests not performed in the clinical chemistry laboratory, but which are relevant to the diagnosis. He or she must be aware of the basis of such tests in order to be able to advise on the appropriate role of clinical chemistry. In addition, the medical clinical chemist should be able to advise on patient management and to select (and reduce) tests suitable for monitoring the progress of the disease and the effects of treatment. The knowledge required to function efficiently as a consultant is acquired, as it is in all medical specialties, by constant exposure to clinical problems. The trainee medical clinical chemist should attend ward rounds and clinical meetings and should discuss results with clinicians in order to learn how to interpret them in the context of particular patients. Clinical involvement should include advising on, or performing, dynamic clinical chemical tests such as stimulation or suppression tests of endocrine systems. Training is essentially an apprentice system, and the trainee should therefore be able to discuss results and clinical problems with an experienced and qualified supervisor on a regular basis. As with other specialties, the degree of consultant supervision will depend on the stage of training. 2.5 Analytical aspects The trainee must acquire
a sound knowledge
of the principles
and applications
of
S16
currently used analytical techniques. These are listed in Appendix B. Much of this knowledge will be obtained by reading standard texts, attending courses and practical experience. The list does not deal with specific assays but, in addition to understanding the principles of analysis, the trainee must become familiar with those used in his or her laboratory. This should be done by actually performing the tests at the bench and learning and understanding the basis for each technique and the purpose of each reagent. He or she should be actively involved in trouble-shooting and quality assurance in order to learn the problems that may be encountered with each assay and instrument. It is likely that time will have to be spent in different laboratories to gain experience in all the necessary techniques. This is also important in order to realise that different laboratories have different approaches to solving similar problems. 2.6. Laboratory management The trainee must become familiar with all aspects of laboratory practice and management. This should include: _ the theory of reference values; - external and internal quality assurance procedures; - work flow and reporting systems; _ the appropriate provision of cost-effective services (equipment and methods) for different needs, e.g. emergency laboratories, neonatal services; _ laboratory safety _ awareness of hazards (physical, chemical and infectious); - means of minimising hazards. - selection and evaluation of instruments and reagent kit sets; - assessment of efficiency and workload: _ laboratory design; - use of computer and statistics in the laboratory; - staff management, including: _ selection; - training; _ work satisfaction; - appropriate delegation of responsibilities; - knowledge of local and national legal requirements. This knowledge is also acquired by discussion and experience. A trainee should become progressively involved in decision-making processes. 2.7. Research and development Whether a trainee is research-oriented or not, he or she will be involved in research or development projects. A basic knowledge of how research and development are carried out should be acquired during training. This includes: - planning of projects _ definition of problem or hypothesis; - experimental design;
s17
- use of library facilities and evaluation of literature;
_ statistical evaluation of results; - logical presentation and discussion of results; - ethics of research. These are best acquired by carrying out a research project and its subsequent publication and/or presentation at a meeting of a professional body. 3. Implementation It is recommended that a medical graduate should have at least two years clinical experience before entering a training programme in laboratory medicine. In order to acquire the necessary skills, the training programme should be structured in a logical and progressive way. While different licencing bodies will have different requirements, it is unlikely that the time spent will be less than 5 years. 3.1. Chemical pathology A suggested scheme is as follows. Years 1 to 2: an apprenticeship in analytical techniques and methodology by performing tests as part of the routine service. This achieves an understanding of laboratory functions, (1) revision of basic physiology and .pathophysiology, (2) regular discussions and interpretation of results with supervisor, (3) limited consultative responsibilities. Towards the end of this time it is likely that the trainee will have developed a special interest. This should be encouraged. Years 3 to 5: (1) increasing consultative responsibilities, (2) experience in specialised techniques, (3) time spent in other laboratories, (4) increasing involvement in laboratory management, (5) research project. 3.2. Clinical pathology Training in clinical pathology may differ in depth but not scope from that outlined above. A training programme must include aspects common to all disciplines: (1) laboratory management, (2) research experience, (3) clinical contact. The clinical chemistry component should stress: (1) selection and interpretation of tests in particular clinical situations; this implies an understanding of pathophysiology, (2) principles of analysis and performance of routine tests; some practical experience is essential to aquire an appreciation of the analytical factors involved in a test result, (3) quality assurance. 4. Bibliographic sources There are many textbooks dealing with methodological and interpretative aspects and the trainee should selectively read from these. Review articles will form a major source of study material. Access to a good medical library is essential as these reviews appear in a wide range of specialist
journals, reflecting the diversity of clinical chemistry. In general, useful reviews are likely to be found in the following: Clinical Chemistry; Annals of Clinical Biochemistry; Clinical Biochemistry; New England Journal of Medicine; Clinical Science; Clinical Endocrinology; The Clinical Biochemist Reviews (Australia ACB); The ‘Clinics’ series (W.B. Saunders Company), i.e. The Medical Clinics of North America, Clinics in Endocrinology and Metabolism, Clinics in Laboratory Medicine, Advances in Clinical Chemistry (Academic Press), Recent Advances in Clinical Biochemistry (Churchill Livingstone). Appendix A. Core topics in physiology, pathophysiology
and use of tests.
1. Fluid, electrolyte and hydrogen ion homeostasis - Normal control: renal factors; renin, angiotensin, aldosterone; arginine vasopressin; atria1 peptides; sympathetic nervous system. - Causes and investigation of; hypo- and hypernatraemia; hypo- and hyperkalaemia; acidaemia and alkalaemia; hypertension; oedema. 2. Calcium (II), phosphate and magnesium (II) metabolism - Normal control: parathyroid hormone; vitamin D; renal factors. - Causes and investigation of: hypo- and hypercalcaemia; hypo- and hyperphosphataemia; hypo- and hypermagnesaemia; _ Metabolic bone disease. 3. Renal function _ Factors affecting glomerular filtration and tubular function. - Renal failure; detection and diagnosis; investigation of causes; assessment and monitoring of consequences; principles and biochemical complications of treatment (including dialysis). - Consequences of tubular damage. _ Investigation of polyuria and oliguria. - Investigation of proteinuria. - Investigation of renal stone disease. 4. Hepatic function _ Normal liver function. - Bilirubin metabolism and hyperbilirubinaemia. _ Clinical chemical manifestations of liver disease. _ Detection, investigation and monitoring of acute and chronic liver disease. - Drugs affecting the liver. - Bile salt metabolism; gallstones. 5. Lipids _ Structure, synthesis and metabolism of lipoproteins. - Factors affecting plasma lipid and lipoprotein levels. - Metabolic basis of primary and secondary hyperlipidaemia. _ Principles of therapy of hyperlipidaemia. - Other disorders of lipid metabolism. 6. Proteins - Interpretation of protein electrophoretic patterns.
s19
_ _ _ _ -
Uses and interpretation of specific protein assays. Uses and interpretation of immunoelectrophoretic techniques. Causes and investigation of paraproteinaemia. Causes and investigation of immunoglobulin deficiencies. Complement system and abnormalities. 7. Intermediary metabolism _ Interrelationship of carbohydrate, lipid and protein metabolism; factors controlling plasma glucose levels. - Insulin, glucagon and C-peptide. _ Nature, diagnosis and monitoring of diabetes mellitus. _ Acute metabolic complications of diabetes mellitus. _ Causes and investigation of hypoglycaemia. _ Ketosis. 8. Endocrine systems _ General principles of hormone secretion, control and mechanisms of cellular action. _ Dynamic testing of endocrine function; stimulation and suppression tests. _ Normal hypothalamic and anterior pituitary interrelationship; effects of drugs. _ Diagnosis and assessment of hypopituitarism, acromegaly, pituitary tumours. _ Normal thyroid hormone secretion and metabolism. _ Diagnosis of hyper- and hypo-thyroidism. _ Thyroid hormone changes due to drugs and non-specific illness. _ Principles and monitoring of therapy of thyroid disorders. -’ Normal adrenocortical steroid synthesis and control. - Causes, effects and diagnosis of Cushing’s syndrome. - Causes, effects and diagnosis of adrenocortical insufficiency. _ Congenital adrenal hyperplasia. _ Normal pituitary-gonadal function. _ Investigation of amenorrhoea and infertility. - Investigation of precocious puberty and intersex. 9. Nutrition - Principles of enteral and parenteral nutrition. _ Role of vitamins and trace elements. _ Role of biochemical analyses in assessing nutritional state. 10. Haemopoietic system _ Iron (II), vitamin B,, (cyanocobalamin) and folate metabolism. .- Changes in hematological disease. _ Investigation of iron deficiency and iron overload. 11. Clinical enzymology _ Factors affecting plasma enzyme activities. _ Causes of unusually high or low plasma enzyme activities. _ Use of isoenzyme and isoform analyses in diagnosis. _ Drugs and plasma enzymes (e.g. suxamethonium and cholinesterase; gammaglutamyltransferase).
12. Purine metabolism _ Synthesis and metabolism of urate. - Causes and consequences of hyperuricaemia. _ Causes of hypouricaemia. 13. Porphyrins - Metabolism of porphyrins. - Diagnosis of porphyria. 14. Gastrointestinal and pancreatic function _ Normal digestion and absorption. - Assessment of malabsorption. - Clinical chemical tests in acute and chronic pancreatitis. - Syndromes associated with pancreatic islet cell tumours. - Nature and function of GIT hormones. 15. Drug monitoring - Principles of pharmacokinetics. - Therapeutic drug monitoring. 16.. Toxicology - Effects of and use of clinical chemical tests in toxicity of: lead; toxic trace metals; acetaminophen (paracetamol); salicylate; lithium; antidepressants; barbiturates; digoxin; drugs of abuse. 17. Clinical chemical changes associated with neoplasia including - Hormonal syndromes. - Tumour markers. - Non-specific changes. 18. Clinical chemistry of special groups of patients - Infancy, childhood and puberty (including principles of diagnosis of inborn errors of metabolism). - Pregnancy (including fetoplacental monitoring and diagnosis of fetal abnormality). - Old age. Appendix B. Core topics in instrumentation
and methodology
1. Specimen collection, transport, handling and preservation. 2. Quantities and units in clinical chemistry, including use of SI. 3. Use and calibration of equipment such as thermometers, pipettes, dilutors, balances. 4. Principles of reagent preparation; quality and sources of reagents, water, etc. 5. Principles and practice of - Colorimetry and spectrometry. - Fluorimetry. - Nephelometry and tubidimetry. - Luminescence. 6. Principles and practice of - Flame spectroscopy.
s21
- Atomic absorption
spectroscopy. - Osmometry. 7. Ion-selective electrodes 8. Enzyme activity analysis - Factors affecting analysis of enzyme activity in body fluids. - Use of enzymes as analytical reagents. 9. Separation techniques - Electrophoresis: use of cellulose acetate and gels. - Chromatography; thin layer chromatography, gas-liquid chromatography, high performance liquid chromatography. - Isoelectric focussing. 10. Principles of immunological reactions and their use in identification and quantitation, e.g. - immunodiffusion, - immunofixation, - immunonephelometric and immunoturbidimetric analysis. 11. Principles and application of ligand assays - Radioimmunoassay and immunoradiometric assay. _ Alternative binders. - Alternative labels: chemiluminescent, enzyme, fluorescent. 12. Use of radioisotopes in analytical systems - Principles and precautions. 13. Principles and application of automated analytical systems - Random access. - Continuous flow. - Dry chemistry. - Parallel fast (centrifugal) analysers. 14. Principles and uses of ‘bedside’ analyses and in vivo monitoring 15. Principles and uses of new techniques such as _ Mass spectrometry. - Magnetic resonance. - DNA technology.