Competencies in clinical biochemistry and analytical toxicology

Details

Title

Competencies in clinical biochemistry and analytical toxicology

Type

Stage Two

Module code

HLS116

Requirement

Compulsory

Module objective

By the end of the training period trainees will, in respect of relating an understanding of normal human biochemistry and physiology to the clinical biochemistry/analytical toxicology of screening, diagnosis, monitoring and prevention of poisoning/adverse drug reactions be able to

• analyse, synthesise, evaluate and apply knowledge
• perform, adapt and master a range of technical and clinical skills and procedures
• demonstrate the attitudes and behaviours necessary for professional practice as a consultant clinical scientist dealing with the complexities, uncertainties and tensions of professional practice at this level.

Knowledge and understanding

By the end of the training period the trainee will be able to demonstrate the ability to analyse, evaluate and synthesise relevant knowledge and its application to their professional practice in relation to:

Generic aspects

• biochemical, haematological and radiological techniques required for the differential diagnosis of poisoning.
• analytical toxicological techniques used in the differential diagnosis of poisoning and in therapeutics
• knowledge of the clinical pharmacology of therapeutic agents
• role of molecular biology in identifying genetic variability in response to poisons

Biological variability

• reference values and population statistics:
  • common reference values/target ranges
  • inter- and intra-individual variation
  • assessment and application of biological variance data in setting analytical goals
  • assessing utility of target ranges
  • effects of age upon target ranges
  • significance of changes in serial results.

Basic biochemistry

• metabolic functions including xenobiotic metabolism

Functions of the liver Diseases of the liver

• drug metabolism, plasma proteins, coagulation factors, glycogen
• hepatitis
• cirrhosis
• Wilson’s disease
• drug hepatotoxicity
• Reye’s syndrome

Distribution of water and electrolytes

• homeostasis of body fluids
• water depletion and excess
• sodium depletion and excess: hypo- and hyper-natraemia
• hypo- and hyper-kalaemia
• principles of intravenous fluid therapy

Biochemical assessment of hepatic function/integrity

• bilirubin
• plasma enzymes
• prothrombin time

Properties and functions of some plasma proteins

• albumin
• α1-acid glycoprotein
• caeruloplasmin
• 2-microglobulin
• ferritin/transferrin
• others (e.g. retinol, c-reactive protein)

Haemoglobin and porphyrins

• biosynthesis and catabolism of haem
• anaemia and its investigation
• methaemoglobinaemia

Diabetes mellitus and hypoglycaemia

• glucose metabolism
• classification of diabetes
• principles of treatment of diabetes and monitoring of diabetic control
• use of insulin and other pharmacological agents
• causes and laboratory investigation of hypoglycaemia/diabetic ketoacidosis
• uses of insulin, insulin c peptide, and glucagons assays

Metabolic response to insult

• trauma
• burns
• water and electrolyte balance
• laboratory investigation of thyroid disease and monitoring of thyroid replacement therapy
• inflammatory and immune responses
• the effects and investigation of vitamin deficiency or excess

Toxicology/ Therapeutics Drug metabolism

• phase 1 and phase 2 metabolism
• activation/detoxification
• pharmacogenetics including TPMT and nucleotide metabolism
• cytochrome P450 phenotypes
• perinatal enzyme development

Basic pharmacokinetics

• routes of drug administration
• drug absorption [preparation/disease] and distribution
• enterohepatic recirculation
• half-life (t½), clearance, t_max, c_max, auc
• dose response relationships
• compartmental and non-compartmental models
• bioavailability
• volume of distribution (v)
• plasma protein binding
• the blood-brain barrier
• impact of age/sex/disease/nutrition/dose, etc.
• enzyme induction and inhibition
• dose prediction

Physiology and toxicology of organ systems

• brain
• endocrine
• heart and circulation
• blood
• liver
• gastrointestinal tract
• lung
• kidney
• role of plasma enzyme assays and other indicators of tissue/organ damage in diagnosis and management

Therapeutic drug monitoring

• principles of therapeutics – pharmacodynamics
• plasma drug concentration and therapeutic/toxic effects
• ‘target’ or normally-expected ranges and dose prediction
• inter- and intra-individual variation
• significance of changes in serial results
• quality control/quality assessment

Diagnosis and management of poisoning

• principles of diagnosis and treatment
• poisons information services and TOXBASE
• antidotes
• active elimination therapies

Diagnosis of poisoning – role of the laboratory

• role of biochemical/haematological testing
• drug/poison ‘screening’ – the unconscious patient
• influence of analyses on treatment (paracetamol, lithium, ethylene glycol/methanol, etc.)
• non-accidental poisoning
• brain-stem death
• assay calibration and quality assurance [IQC and EQA]

Substance abuse

• heroin/morphine and other opioids
• cocaine
• barbiturates
• amphetamines including MDMA
• cannabis
• LSD, phencyclidine, etc.
• ‘legal highs’ including synthetic cannabinoids
• GHG/GBL
• volatiles·
• physiology/pharmacology/economics of addiction
• treatment – harm reduction strategies including substitution therapy
• other abused substances (benzodiazepines, buprenorphine, methadone)

Substance abuse – analytical issues

• drug ‘screening’/confirmation
  • clinical
  • workplace (UKWDT and SAMHSA guidelines)
  • matrices (blood, urine, saliva, sweat, breath, hair, nail, etc.)
• alcohol
• volatile substances
• diuretics/laxatives
• anticoagulants

Forensic toxicology – operational issues

• the post-mortem examination and examination of death scene
• role of the coroner/procurator fiscal
• specimen collection post-mortem – role of pathologist
• documentation/chain of custody
• storage/disposal of post-mortem specimens
• documentation of case work
• death in custody including excited delirium
• criminal cases and police liaison
• drug-facilitated crime
• forensic reports
• preparation for court – giving evidence
• quality assurance
• audit of cases and procedures

Forensic toxicology – interpretation of results

• post-mortem diffusion and redistribution, degradation/putrefaction
• pharmacokinetics of alcohol and calculation of consumption
• drugs and driving deaths
• substance abuse-related deaths
• scope of post-mortem toxicological investigations

Trace elements/heavy metals

• essential trace elements and their role in health and disease
• toxic metal salts
• non-essential trace elements and their associated pathology – overview
• specimen collection/sources of contamination
• analytical methods – overview:
  • zinc
  • chromium
  • cobalt
  • copper
  • selenium and tellurium
  • lead
  • aluminium
  • cadmium
  • arsenic
  • mercury
  • lanthanum

Clinical pharmacology/ toxicology/analysis of specific analytes/ groups of analytes

• paracetamol
• salicylates
• ethanol
• ethylene glycol, 2-propanol, methanol
• paraquat
• antidepressants
• iron salts
• organophosphorus compounds and carbamates (cholinesterase inhibitors)
• barbiturates
• amphetamines including MDMA and related compounds
• cocaine
• opioids including methadone
• benzodiazepines and other hypnosedatives
• other abused substances (anabolic steroids, GHB, ketamine, volatiles, etc.)
• anticonvulsants
• insulin and oral hypoglycaemics
• lithium
• antipsychotics including clozapine
• theophylline and other xanthines
• digoxin and other digitalis glycosides
• cardioactive drugs other than digoxin
• carbon monoxide
• other toxic gases (hydrogen sulfide, etc.)
• antimalarials (quinine, chloroquine, etc.)
• antibiotics
• anaesthetics (local/topical/regional/general)
• methotrexate
• ciclosporin and other immunosuppressive drugs
• antiretrovirals
• azole antifungals
• tyrosine kinase inhibitors
• warfarin and other anticoagulants

Analytical methods:

Spectrometry

• UV-visible spectrometry
• infra-red spectrometry
• nuclear magnetic resonance spectrometry
• flame emission spectrophotometry
• atomic absorption spectrophotometry
• flame
• furnace

Automated instrumentation

• random access analysers
• immunoassay analysers
• continuous flow
• pipetting work stations
• elementary robotics and modular systems

Electrometric methods

• Ion selective electrodes Na⁺, K⁺, Cl^– , F^–, Li⁺, Ca²⁺, Mg²⁺, NH ₄⁺ pH/H⁺, pCO² , pO²
• polarographic oxygen electrodes e.g. glucose
• hydrogen peroxide electrodes
• field effect transistor technology

Osmometry

Enzymology

• fixed interval assays
• kinetic assays
• isoenzyme fractionation/quantitation
• tissue enzymes
• use of enzymes as reagents

Radioisotope counting

• β-counting systems
• γ-counting systems

Immunochemical techniques

• immunoelectrophoresis
• immunofixation
• immunodiffusion
• electroimmunoassay
• competitive radioimmunoassay
• immunoradiometric assay
• preparation of radioisotopic and non-radioisotopic labels
• antibody preparation – polyclonal
• antibody preparation – monoclonal
• enzyme labels
• fluorimetric labels
• chemiluminescent labels

Electrophoresis chromatography

• capillary electrophoresis
• automated electrophoresis systems
• TLC/HPTLC
• column (ion exchange, affinity, etc.)
• GC
• HPLC
• sample preparation methods (e.g. salting-out, liquid-liquid extraction, derivatisation)

Mass spectrometry

• GC-MS
• ICP-MS
• Use of stable isotope internal standards/internal calibrators
• dipstick Technology
• immobilised EnzymesHPLC-MS
• thin Film Technology.

Solid/dry phase chemistry

Point-of-care testing/emergency systems

Technical and clinical skills

By the end of the training period the trainee will be able to demonstrate a critical understanding of current relevant research, theory and knowledge and its application to the performance, adaptation and mastery of the following technical procedures and laboratory skills:

• advising on the appropriate use and interpretation of the results of the laboratory investigations in differential diagnosis of poisoning, in monitoring progress, and in guiding treatment
• liaise and communicate clearly with colleagues and other clinical teams in primary and secondary care both verbally and via secure email/clinic letters
• the effect of genetic, environmental and other influences such as age, sex, nutrition, time of day, stress, posture, hospitalisation and therapeutic agents on biochemical and toxicological results.

By the end of the training period the trainee will be able to apply knowledge of competencies in clinical biochemistry and analytical toxicology to perform, adapt and master the clinical skills necessary to manage to:

• liaise with clinical and forensic colleagues.

Specialty code	Specialty title	Action
Specialty code HLS1-5-20	Specialty title Analytical Toxicology [V1]	Action View