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Beschreibung

Clinical Biochemistry Lecture Notes presents the fundamental science behind common biochemical investigations used in clinical practice. Taking a system-based approach, it explores the underlying physiological rationale for tests, with each test explained within the context of disruption by disease. It also explores the value and limitations of biochemical investigations, while helping readers to quickly develop the knowledge and skills required to select the appropriate investigations for diagnosis and management, and to correctly interpret test results. Case studies throughout chapters place the information within a clinical context to further assist readers in the development of test-selection and interpretation skills.

Key features include:

  • A comprehensive, yet concise overview of the science behind common biochemical investigations
  • Helps readers rapidly acquire a fully integrated, practical understanding of biochemical diagnostics
  • Full-colour flowcharts and algorithms detailing the rationale for tests, the biochemical processes involved, and test procedures, for quick comprehension and reference
  • More clinical cases demonstrating application to practice

Now in its tenth edition, this classic introductory, reference, and revision text is indispensable to medical students, and all those who want to quickly acquire a practical understanding of the scientific principles underpinning biochemical tests and a working knowledge of test selection, test procedures, and the interpretation of results within a clinical context. 

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Clinical Biochemistry

Lecture Notes

Peter Rae

BA, PhD, MBChB, FRCPE, FRCPathConsultant Clinical BiochemistRoyal Infirmary of EdinburghHonorary Senior Lecturer in Clinical BiochemistryUniversity of Edinburgh

Mike Crane

BSc, PhD, MSc, FRCPathConsultant Clinical BiochemistRoyal Hospital for Sick Children & Royal Infirmary of EdinburghHonorary Lecturer in Clinical BiochemistryUniversity of Edinburgh

Rebecca Pattenden

BSc, MSc, FRCPathConsultant Clinical BiochemistWestern General Hospital, Edinburgh

Tenth Edition

This edition first published 2018 © 2018 by John Wiley & Sons Ltd

Edition HistoryJohn Wiley & Sons Ltd (9e, 2013)

All rights reserved. No part of this publication may be reproduced, stored in a retrieval system, or transmitted, in any form or by any means, electronic, mechanical, photocopying, recording or otherwise, except as permitted by law. Advice on how to obtain permission to reuse material from this title is available at http://www.wiley.com/go/permissions.

The right of Peter Rae, Mike Crane, Rebecca Pattenden to be identified as the authors of the editorial material in this work has been asserted in accordance with law.

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Library of Congress Cataloging‐in‐Publication Data

Names: Rae, Peter, 1953– author. | Crane, Mike, 1979– author. | Pattenden, Rebecca, 1974– author.Title: Lecture notes. Clinical biochemistry/Peter Rae, Mike Crane, Rebecca Pattenden.Other titles: Clinical biochemistryDescription: Tenth edition. | Hoboken, NJ : Wiley, 2018. | Preceded by Lecture notes. Clinical biochemistry. 9th ed./Geoffrey Beckett … [et al.]. 2013. | Includes bibliographical references and index.Identifiers: LCCN 2017013974 (print) | LCCN 2017014660 (ebook) | ISBN 9781119248699 (pdf) | ISBN 9781119248637 (epub) | ISBN 9781119248682Subjects: | MESH: Biochemical Phenomena | Clinical Laboratory Techniques | Clinical Chemistry Tests | Pathology, Clinical–methodsClassification: LCC RB40 (ebook) | LCC RB40 (print) | NLM QU 34 | DDC 616.07/56–dc23LC record available at https://lccn.loc.gov/2017013974

Cover design by WileyCover image: © Miguel Malo/gettyimages

Preface

This is the tenth edition of the book originally written by Professor Gordon Whitby, Dr Alistair Smith and Professor Iain Percy‐Robb in 1975. It remains an Edinburgh‐based book, but both the content and the authorship continue to evolve.

Ever since the first edition this book has been primarily aimed at medical students and junior doctors, but we also believe that it will be of value to specialist registrars, clinical scientists and biomedical scientists pursuing a career in clinical biochemistry and metabolic medicine, and studying for higher qualifications. It has continued to develop in line with changes that have both reshaped the undergraduate curriculum and taken place in medical practice.

Over the course of the book’s existence changes in medical education have tended to reduce or abolish courses exclusively covering laboratory medicine disciplines, with their content being integrated into the relevant parts of a systems‐based curriculum. This clearly places the laboratory disciplines at the heart of medical teaching in the diagnosis and management of patients, but risks losing the opportunity to take a closer view of the principles behind the use of diagnostic investigations. This book aims to focus on the choice and interpretation of investigations in the diagnosis and management of conditions where biochemical testing plays a key role, with a view to understanding not only their uses but also developing an appreciation of their limitations. This is underpinned by brief summaries of the relevant pathophysiology. There is an emphasis on commonly requested tests and commonly occurring pathology, but less common tests and disorders are also described.

We have reviewed and updated all chapters to ensure that they reflect current clinical practice, the availability of new tests, and where relevant the latest versions of national guidelines, with an emphasis on those published in the UK. Planning this new edition benefited from helpful feedback from a number of sources, including groups of both students and their teachers, commissioned by Wiley, and in response to this we have among other changes increased the numbers of diagrams and tables where these help to summarise useful information. We have also increased the numbers of clinical cases, as these remain a popular feature. Multiple choice questions with an explanation of the answers, and key learning points for each chapter are available as an on‐line resource for revision.

Since the last edition, Geoff Beckett, Simon Walker and Peter Ashby have all retired. They were authors since the fourth, fifth and seventh editions, respectively, and have had an enormous effect on the development and success of this book. Their places have been ably taken by Mike Crane and Rebecca Pattenden, who have brought a fresh perspective to many of the topics covered. As ever, we are also indebted to a number of colleagues who read various chapters and provided valuable comment and advice, in particular Catriona Clarke and Jonathan Malo. We remain grateful for the continued interest and support provided by the staff at Wiley towards this title since its first appearance over forty years ago.

Peter RaeMike CraneRebecca Pattenden

List of abbreviations

α‐MSH

α‐melanocyte stimulating hormone

AAT

α

1

‐antitrypsin

ABP

androgen‐binding protein

A&E

accident and emergency

ACE

angiotensin‐converting enzyme

ACTH

adrenocorticotrophic hormone

ADH

antidiuretic hormone

AFP

α‐foetoprotein

AI

angiotensin I

AII

angiotensin II

AIII

angiotensin III

AIP

acute intermittent porphyria

AIS

androgen insensitivity syndrome

ALA

aminolaevulinic acid

ALP

alkaline phosphatase

ALT

alanine aminotransferase

AMA

anti‐mitochondrial antibodies

AMH

anti‐Mullerian hormone

AMP

adenosine 5‐monophosphate

ANP

atrial natriuretic peptide

AST

aspartate aminotransferase

ATP

adenosine triphosphate

AT

Pase adenosine triphosphatase

β‐LPH

β‐lipotrophin

BChE

butylcholinesterase

BMI

body mass index

BMR

basal metabolic rate

BNP

B‐type natriuretic peptide

CABG

coronary artery bypass grafting

CAH

congenital adrenal hyperplasia

cAMP

cyclic adenosine monophosphate

CBG

cortisol‐binding globulin

CCK

cholecystokinin

CCK‐PZ

cholecystokinin‐pancreozymin

CDT

carbohydrate‐deficient transferrin

CEA

carcinoembryonic antigen

CFT

calculated free testosterone

ChE

cholinesterase

CK

creatine kinase

CKD

chronic kidney disease

CNS

central nervous system

CoA

coenzyme A

COC

combined oral contraceptive

COHb

carboxyhaemoglobin

CRH

corticotrophin‐releasing hormone

CRP

C‐reactive protein

CSF

cerebrospinal fl uid

CT

computed tomography

CV

coefficient of variation

DDAVP

1‐deamino,8‐D‐arginine vasopressin

DHEA

dehydroepiandrosterone

DHEAS

dehydroepiandrosterone sulphate

DHCC

dihydrocholecalciferol

DHT

dihydrotestosterone

DIT

di‐iodotyrosine

DKA

diabetic ketoacidosis

DPP

4 dipeptidyl peptidase‐4

DSD

disorder of sexual differentiation

DVT

deep venous thrombosis

ECF

extracellular fluid

ECG

electrocardiogram/electrocardiography

ED

erectile dysfunction

EDTA

ethylenediamine tetraacetic acid

eGFR

estimated glomerular filtration rate

EPH

electrophoresis

EPP

erythropoietic protoporphyria

ERCP

endoscopic retrograde cholangiopancreatography

ESR

erythrocyte sedimentation rate

FAD

flavin adenine dinucleotide

FAI

free androgen index

FBHH

familial benign hypocalciuric hypercalcaemia

FIT

faecal immunochemical test

FMN

flavin mononucleotide

FOB

faecal occult blood

FPP

free protoporphyrin

FSH

follicle‐stimulating hormone

FT3

free tri‐iodothyronine

FT4

free thyroxine

GAD

glutamic acid decarboxylase

Gal‐1‐PUT

galactose‐1‐phosphate uridylyl‐transferase

GDM

gestational diabetes mellitus

GFR

glomerular filtration rate

GGT

γ‐glutamyltransferase

GH

growth hormone

GHD

growth hormone deficiency

GHRH

growth hormone‐releasing hormone

GI

gastrointestinal

GIP

glucose‐dependent insulinotrophic peptide/gastric inhibitory polypeptide

GLP‐1

glucagon‐like polypeptide‐1

GnRH

gonadotrophin‐releasing hormone

GP

general practitioner

GSH

glucocorticoid‐suppressible hyperaldosteronism

GTT

glucose tolerance test

Hb

haemoglobin

HC

hereditary coproporphyria

HCC

hydroxycholecalciferol

hCG

human chorionic gonadotrophin

HDL

high‐density lipoprotein

HGPRT

hypoxanthine‐guanine phosphoribosyltransferase

HHS

hyperosmolar hyperglycaemic state

5‐HIAA

5‐hydroxyindoleacetic acid

HIV

human immunodeficiency virus

HLA

human leucocyte antigen

HMG‐CoA

β‐hydroxy‐β‐methylglutaryl‐coenzyme A

HMMA

4‐hydroxy‐3‐methoxymandelic acid

HNF

hepatic nuclear factor

HPA

hypothalamic–pituitary–adrenal

HPLC

high‐performance liquid chromatography

HRT

hormone replacement therapy

hsCRP

highly sensitive C‐reactive protein

5‐HT

5‐hydroxytryptamine

5‐HTP

5‐hydroxytryptophan

IBS

irritable bowel syndrome

ICF

intracellular fluid

ICU

intensive care unit

IDL

intermediate‐density lipoprotein

IFCC

International Federation for Clinical Chemistry

IFG

impaired fasting glucose

Ig

immunoglobulin

IGF

insulin‐like growth factor

IGFBP

insulin‐like growth factor‐binding protein

IGT

impaired glucose tolerance

IM

intramuscular

INR

international normalised ratio

IV

intravenous

LCAT

lecithin cholesterol acyltransferase

LDH

lactate dehydrogenase

LDL

low‐density lipoprotein

LH

luteinising hormone

Lp(a)

lipoprotein (a)

LSD

lysergic acid diethylamide

MCAD

medium chain acyl‐CoA dehydrogenase

MCV

mean cell volume

MDRD

Modification of Diet in Renal Disease

MEGX

monoethylglycinexylidide

MEN

multiple endocrine neoplasia

MGUS

monoclonal gammopathy of unknown significance

MI

myocardial infarction

MIT

mono‐iodotyrosine

MODY

maturity onset diabetes of the young

MOM

multiples of the median

MRCP

magnetic resonance cholangiopancreatography

MRI

magnetic resonance imaging

MTC

medullary thyroid cancer

MUST

Malnutrition Universal Screening Tool

NABQI

N

‐acetyl‐

p

‐benzoquinoneimine

NAC

N

‐acetylcysteine

NAD

nicotinamide–adenine dinucleotide

NADP

NAD phosphate

NAFLD

nonalcoholic fatty liver disase

NASH

nonalcoholic steatohepatitis

NICE

National Institute for Health and Clinical Excellence

NIPT

noninvasive prenatal testing

NSAID

nonsteroidal anti‐inflammatory agent

NTD

neural tube defect

NTI

nonthyroidal illness

OCP

oral contraceptive pill

OGTT

oral glucose tolerance test

PAPP‐A

pregnancy‐associated plasma protein A

PBG

porphobilinogen

PCI

percutaneous coronary intervention

PCOS

polycystic ovarian syndrome

PCSK9

proprotein convertase subtilisin/kexin type 9

PCT

porphyria cutanea tarda

PE

pulmonary embolism

PEG

percutaneous endoscopic gastrostomy

PEM

protein‐energy malnutrition

PIIINP

pro‐collagen type III

PKU

phenylketonuria

PLP

pyridoxal 5′‐phosphate

POCT

point of care testing

POP

progestogen‐only pill

PRPP

5‐phosphoribosyl‐1‐pyrophosphate

PSA

prostate‐specific antigen

PT

prothrombin time

PTH

parathyroid hormone

PTHrP

PTH‐related protein

RBP

retinol‐binding protein

RDA

recommended dietary allowance

RF

rheumatoid factor

RMI

risk of malignancy index

ROC

receiver operating characteristic

SAAG

serum‐ascites albumin gradient

SAH

subarachnoid haemorrhage

SD

standard deviation

SHBG

sex hormone‐binding globulin

SIADH

inappropriate secretion of ADH

SGLT

sodium‐glucose cotransporter

SUR

sulphonylurea receptor

T3

tri‐iodothyronine

T4

thyroxine

TBG

thyroxine‐binding globulin

TDM

therapeutic drug monitoring

TDP

thiamin diphosphate

TGN

6‐thioguanine nucleotide

THR

thyroid hormone resistance

TIBC

total iron‐binding capacity

TNF

tumour necrosis factor

TPMT

thiopurine

S

‐methyltransferase

TPN

total parenteral nutrition

TPOAb

thyroid peroxidase antibody

TPP

thiamin pyrophosphate

TRAb

thyrotrophin receptor antibody

TRH

thyrotrophin‐releasing hormone

TSH

thyroid‐stimulating hormone

TSI

thyroid‐stimulating immunoglobulin

tTG

tissue transglutaminase

U&Es

urea and electrolytes

UFC

urinary free cortisol

UV

ultraviolet

VIP

vasoactive intestinal peptide

VLDL

very low density lipoprotein

VMA

vanillylmandelic acid

VP

variegate porphyria

WHO

World Health Organization

XO

xanthine oxidase

ZPP

zinc protoporphyrin

About the companion website

This book is accompanied by a companion website:

 www.lecturenoteseries.com/clinicalbiochemistry

The website includes:

Interactive multiple‐choice questions

Key revision points for each chapter

1Requesting and interpreting tests

Learning objectives

To understand:

how sample handling, analytical and biological factors can affect test results in health and disease and how these relate to the concept of a test reference range;

the concepts of accuracy, precision, test sensitivity, test specificity in the quantitative assessment of test performance.

Introduction

Biochemical tests are crucial to modern medicine. Most biochemical tests are carried out on blood using plasma or serum, but urine, cerebrospinal fluid (CSF), faeces, kidney stones, pleural fluid, etc. are sometimes required. Plasma is obtained by collecting blood into an anticoagulant and separating the fluid, plasma phase from the blood cells by centrifugation. Serum is the corresponding fluid phase when blood is allowed to clot. For many (but not all) biochemical tests on blood, it makes little difference whether plasma or serum is used.

There are many hundreds of tests available in clinical biochemistry but a core of common tests makes up the majority of tests requested. These core tests are typically available from most clinical laboratories throughout the 24‐h period. Tests are sometimes brought together in profiles, especially when a group of tests provides better understanding of a problem than a single test (e.g. the liver function test profile). More specialist tests may be restricted to larger laboratories or specialist centres offering a national or regional service.

In dealing with the large number of routine test requests, the modern clinical biochemistry laboratory depends heavily on automated instrumentation linked to a laboratory computing system. Test results are assigned to electronic patient files that allow maintenance of a cumulative patient record. Increasingly, test requests can be electronically booked at the ward, clinic or in General Practice via a terminal linked to the main laboratory computer. Equally, the test results can be displayed on computer screens at distant locations, removing the need to issue printed reports.

In this first chapter, we set out some of the principles of requesting tests and of the interpretation of results. The effects of analytical errors and of physiological factors, as well as of disease, on test results are stressed. Biochemical testing in differential diagnosis and in screening is discussed.

Collection of specimens

Test requests require unambiguous identification of the patient (patient’s name, sex, date of birth and, increasingly, a unique patient identification number), together with the location, the name of the requesting doctor and the date and time of sampling. Each test request must specify the analyses requested and provide details of the nature of the specimen itself and relevant clinical diagnostic information. This may be through a traditional request form and labelled specimen or be provided electronically in which case only the sample itself need be sent to the laboratory with its own unique identifier (typically a bar code which links it to the electronic request).

Clinical laboratories have multiple procedures at every step of sample processing to avoid errors. Regrettably, errors do occur and these arise at different stages between the sample being taken and the result being received:

Pre‐analytical. These arise prior to the actual test measurement and can happen at the clinical or laboratory end. Most errors fall into this category (see

Table 1.1

).

Analytical. Laboratory based analytical errors are rare but may occur, e.g. reagent contamination, pipetting errors related to small sample volumes, computing errors.

Post‐analytical. These are increasingly rare because of electronic download of results from the analyser but include, for example, transcription errors when entering results from another laboratory into the computer manually; results misheard when these are telephoned to the clinician.

Table 1.1Some more common causes of pre‐analytical errors arising from use of the laboratory.

Error

Consequence

Crossover of addressograph labels between patients

This can lead to two patients each with the other’s set of results. Where the patient is assigned a completely wrong set of results, it is important to investigate the problem in case there is a second patient with a corresponding wrong set of results.

Timing error

There are many examples where timing is important but not considered. Sending in a blood sample too early after the administration of a drug can lead to misleadingly high values in therapeutic monitoring. Interpretation of some tests (e.g. cortisol) is critically dependent on the time of day when the blood was sampled.

Sample collection tube error

For some tests the nature of the collection tube is critical, which is why the Biochemistry Laboratory specifies this detail. For example, using a plasma tube with lithium–heparin as the anti‐coagulant is not appropriate for measurement of a therapeutic lithium level. Electrophoresis requires a serum sample rather than plasma so that fibrinogen does not interfere with the detection of any monoclonal bands. Topping up a biochemistry tube with a haematology (potassium ethylenediamine tetraacetic acid [EDTA]) sample will lead to high potassium and low calcium values in the biochemistry sample.

Sample taken from close to the site of an intravenous (IV) infusion

The blood sample will be diluted so that all the tests will be correspondingly low with the exception of those tests that might reflect the composition of the infusion fluid itself. For example, using normal saline as the infusing fluid would lead to a lowering of all test results, but with sodium and chloride results that are likely to be raised.

Despite the scale of requesting of biochemical tests, errors are fortunately very rare. However, occasional blunders do arise and, if very unexpected results are obtained, it is important that the requesting doctor contacts the laboratory immediately to check whether the results are indeed correct or whether some problem may have arisen. Occasionally this reveals that more than one problem has occurred, for example two samples were labelled with each other’s details on the ward, so querying the results can have wider benefits.

The use of clinical biochemistry tests

Biochemical tests are most often discretionary, meaning that the test is requested for defined diagnostic purposes. The justification for discretionary testing is well summarised by Asher (1954):

Why do I request this test?

What will I look for in the result?

If I find what I am looking for, will it affect my diagnosis?

How will this investigation affect my management of the patient?

Will this investigation ultimately benefit the patient?

The main reasons for this type of testing are summarised in Table 1.2. Tests may also be used to help evaluate the future risk of disease (e.g. total cholesterol and HDL‐cholesterol levels contribute to assessment of an individual’s risk of cardiovascular disease), or in disease prognosis (e.g. biochemical tests to assess prognosis in acute pancreatitis or liver failure), or to screen for a disease, without there being any specific indication of its presence in the individual (e.g. maternal screening for foetal neural tube defects).

Table 1.2Test selection for the purposes of discretionary testing.

Category

Example

To confirm a diagnosis

Serum free T4 and thyroid‐stimulating hormone (TSH) in suspected hyperthyroidism

To aid differential diagnosis

To distinguish between different forms of jaundice

To refine a diagnosis

Use of adrenocorticotrophic hormone (ACTH) to localise Cushing’s syndrome

To assess the severity of disease

Serum creatinine or urea in renal disease

To monitor progress

Plasma glucose and serum K

+

to follow treatment of patients with diabetic ketoacidosis (DKA)

To detect complications or side effects

Alanine aminotransferase (ALT) measurements in patients treated with hepatotoxic drugs

To monitor therapy

Serum drug concentrations in patients treated with anti‐epileptic drugs

Screening may take several forms:

In well‐population screening a spectrum of tests is carried out on individuals from an apparently healthy population in an attempt to detect pre‐symptomatic or early disease. It is easy to miss significant abnormalities in the large amount of data provided by the laboratory, even when the abnormalities are highlighted in some way. For these and other reasons, the value of well‐population screening has been called into question and certainly should only be initiated under certain specific circumstances (

Table 1.3

).

In case‐finding screening programmes appropriate tests are carried out on a population sample known to be at high risk of a particular disease. These are inherently more selective and yield a higher proportion of useful results (

Table 1.4

).

Table 1.3Requirements for well‐population screening.

The disease is common or life‐threatening

The tests are sensitive and specific

The tests are readily applied and acceptable to the population to be screened

Clinical, laboratory and other facilities are available for follow‐up

Economics of screening have been clarified and the implications accepted

Table 1.4Examples of tests used in case‐finding programmes.

Programmes to detect diseases in

Chemical investigations

Neonates

Phenylketonuria (PKU)

Serum phenylalanine

Hypothyroidism

Serum TSH

Adolescents and young adults

Substance abuse

Drug screen

Pregnancy

Diabetes mellitus in the mother

Plasma glucose

Open neural tube defect (NTD) in the foetus

Maternal serum α‐foetoprotein

Industry

Industrial exposure to lead

Blood lead

Industrial exposure to pesticides

Serum cholinesterase activity

Elderly

Malnutrition

Serum vitamin D levels

Thyroid dysfunction

Serum TSH and thyroxine

Point of care testing (POCT)

These are tests conducted close to the patient, for example in the emergency department, an outpatient clinic, or a general practitioner’s surgery. The instrumentation used is typically small and fits on a desk or may even be handheld. This approach can be helpful where there is a need to obtain a result quickly (e.g. blood gas results in the emergency department in a breathless patient), or where a result can be used to make a real‐time clinical management decision (e.g. whether to adjust someone’s statin dose on the basis of a cholesterol result). A further attraction is the immediate feedback of clinical information to the patient. POCT can be used to monitor illness by the individual patient and help identify if a change in treatment is needed (e.g. blood glucose monitoring in a diabetic patient). There is also an increasing number of urine test sticks that are sold for home use (e.g. pregnancy and ovulation testing by measuring human chorionic gonadotrophin (hCG) and luteinising hormone (LH), respectively). Table 1.5 shows examples of POCT tests in common use.

Table 1.5Examples of POCT that are in common use.

Common POCT in blood

Common POCT in urine

Blood gases

Glucose

Glucose

Ketones

Urea and creatinine

Red cells/haemoglobin

Na, K and Ca

Bilirubin

Bilirubin

Protein

Alcohol

hCG

The introduction of POCT methodology requires attention to cost, ease of use, staff training, quality, health and safety as well as need. The advantages and disadvantages of POCT are summarised in Table 1.6.

Table 1.6Advantages and disadvantages of point‐of‐care testing (POCT).

Advantages

Disadvantages

Rapid results on acutely ill patients

More expensive than centralised tests

Allows more frequent monitoring

Wide staff training may be needed

Immediate patient feedback

Nontrained users may have access, with potential for errors

Available 24 h if required

Calibration and quality control may be less robust

Health and Safety may be less well monitored

Results less often integrated into patient electronic record

Interpretation of clinical biochemistry tests

Most reports issued by clinical biochemistry laboratories contain numerical measures of concentration or activity, expressed in the appropriate units. Typically, the result is interpreted in relation to a reference range (see Chapter 1: Reference ranges) for the analyte in question. Results within and outside the reference range may be subject to variation caused by a number of factors. These include analytical variation, normal biological variation, and the influence of pathological processes.

Sources of variation in test results

Analytical sources of variation

Analytical results are subject to error, no matter how good the laboratory and no matter how skilled the analyst. The words “accuracy” and “precision” have carefully defined meanings in this context.

An accurate method will, on average, yield results close to the true value of what is being measured. It has no systematic bias. Lack of accuracy means that results will always tend to be either high or low.

A precise method yields results that are close to one another (but not necessarily close to the true value) on repeated analysis. If multiple measurements are made on one specimen, the spread of results will be small for a precise method and large for an imprecise one. Lack of precision means that results may be scattered, and unpredictably high or low.

A ‘dartboard’ analogy is often used to illustrate the different meanings of the terms accuracy and precision, and this is illustrated in Figure 1.1.

Figure 1.1 The ‘dartboard’ analogy can be used to illustrate accuracy and precision.

The standard deviation (SD) is the usual measure of scatter around a mean value. If the spread of results is wide, the SD is large, whereas if the spread is narrow, the SD is small. For data that have a Gaussian distribution, as is nearly always the case for analytical errors, the shape of the curve (Figure 1.2) is completely defined by the mean and the SD, and these characteristics are such that:

About 67% of results lie in the range mean ± 1 SD.

About 95% of results lie in the range mean ± 2 SD.

Over 99% of results lie in the range mean ± 3 SD.

Figure 1.2 Diagram of a Gaussian (normal or symmetrical) distribution curve. The span (A) of the curve, the distance between the mean ± 2 SD, includes about 95% of the ‘population’. The narrower span (B), the distance between the mean ± 1 SD, includes about 67% of the ‘population’.

Blunders