Oxford Handbook of Clinical and Laboratory Investigation pdf

Oxford Handbook of Clinical and Laboratory InvestigationDrew Provan Senior Lecturer in Haematology, St Bartholomew’s and The Royal London Hospital School of Medicine & Dentistry, London,

Drew Provan Andrew Krentz

OXFORD UNIVERSITY PRESS

OXFORD MEDICAL PUBLICATIONS

Oxford Handbook of Clinical and Laboratory Investigation

Oxford University Press makes no representation, express or implied, thatthe drug dosages in this book are correct Readers must therefore alwayscheck the product information and clinical procedures with the most up-to-date published product information and data sheets provided by themanufacturers and the most recent codes of conduct and safety regula-tions The authors and the publishers do not accept responsibility or legalliability for any errors in the text or for the misuse or misapplication ofmaterial in this work.

iExcept where otherwise stated, drug doses and recommendationsare for the non-pregnant adult who is not breast-feeding

Oxford Handbook of Clinical and Laboratory Investigation

Drew Provan

Senior Lecturer in Haematology,

St Bartholomew’s and The Royal London Hospital School of Medicine & Dentistry, London, UK

Andrew Krentz

Honorary Senior Lecturer in Medicine, Southampton University Hospitals NHSTrust, Southampton, UK

1

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© Oxford University Press 2002

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First published 2002

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ISBN 0 19 263283 3

Typeset by Drew Provan and EXPO Holdings, Malaysia

Printed in Great Britain on acid free paper by The Bath Press, Avon, UK

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99 165 241 257 303 325 355 383 423 459 487 495 539 583

Contributors vi

Foreword by Professor Sir George Alberti viii

Preface ix

Acknowledgements x

Symbols & abbreviations xi

Introduction: Approach to investigations xix

Part 1 The patient

1 Symptoms and signs

Contributors

John Axford

Reader in Medicine, Academic

Unit for Musculoskeletal Disease,

Department of Neurology, The

Queen Elizabeth Hospital,

Birmingham B15 2TH

Neurology

Joanna Brown

Clinical Research Fellow,

University of Southampton, School

Southampton University Hospitals

NHS Trust, Southampton SO16

6YD

Radiology

Keith Dawkins

Consultant Cardiologist, Wessex

Cardiology Unit, Southampton

University Hospitals NHS Trust,

Southampton SO16 6YD

Cardiology

Colin Dayan

Consultant Senior Lecturer in

Medicine, Division of Medicine

Laboratories, Bristol Royal

Respiratory medicine

Stephen T Green

Consultant Physician andHonorary Senior Clinical Lecturer,Department of Infection & TropicalMedicine, Royal HallamshireHospital, Sheffield S10 2JF

Infectious & tropical diseases

Alison Jones

Consultant Physician and ClinicalToxicologist, Medical ToxicologyUnit, Guy’s & St Thomas’ Hospital,London SE14 5ER

Poisoning & overdose

Andrew Krentz

Consultant in Diabetes &Endocrinology and HonorarySenior Lecturer in Medicine,Department of Medicine,Southampton University HospitalsNHS Trust, Southampton SO166YD

Endocrinology & metabolism

Val Lewington

Consultant in Nuclear Medicine,Department of Nuclear Medicine,Southampton University HospitalsNHS Trust, Southampton SO166YD

Nuclear medicine

Praful Patel

Consultant Gastroenterologist,

Department of Gastroenterology,

Southampton University Hospitals

NHS Trust, Southampton SO16

6YD

Gastroenterology

Drew Provan

Senior Lecturer, Department of

Haematology, St Bartholomew’s &

The Royal London School of

Medicine & Dentistry, London E1

1BB

Haematology, transfusion &

cyto-genetics

Rommel Ravanan

Specialist Registrar, The Richard

Bright Renal Unit, Southmead

Hospital, Westbury-on-Trym,

Bristol BS10 5NB

Renal medicine

Charlie Tomson

Consultant Nephrologist, The

Richard Bright Renal Unit,

Southmead Hospital,

Southampton University Hospitals

NHS Trust, Southampton SO16

6YD

Radiology

Adrian Williams

Professor of Neurology,Department of Neurology, TheQueen Elizabeth Hospital,Birmingham B15 2TH

Neurology

Lorraine Wilson

Senior Registrar, Department ofNuclear Medicine, SouthamptonUniversity Hospitals NHS Trust,Southampton SO16 6YD

Nuclear medicine

Dr Tanay Sheth

Specialist Registrar inGastroenterology, SouthamptonUniversity Hospitals NHS Trust,UK

Our registrars

We are indebted to our juniorsfor writing and checking varioussections, in particular Symptoms & signs.

Southampton University Hospitals:

Martin Taylor, Michael Masding, Mayank Patel, Ruth Poole and Catherine Talbot.

St Bartholomew’s & The RoyalLondon School of Medicine &Dentistry: Simon Stanworth, Jude Gaffan, Leon Clark and Nikki Curry.

Contributors

This book fills an obvious gap in the Handbook series and indeed a majorlacuna in the medical literature Too often investigations of a particularcondition are lost in the welter of other text Alternatively, they appear asspecialist books in pathology and radiology One unique feature of thisbook is the inclusion of all clinical investigative techniques, i.e both trulyclinical tests in the shape of symptoms and signs and then laboratory-based investigations This stops what is often an artificial separation Eachsection is clearly put together with the intent of easing rapid reference.This is essential if the book is to have (and I believe it does have) real use-fulness for bedside medicine There are many other useful aspects of thetext These include a comprehensive list of abbreviations—the bugbear ofmedicine, as well as reference ranges which some laboratories still do notappend to results Overall, the Handbook should be of benefit to not justclinical students and junior doctors in training, but all who have patientcontact With this in one pocket, and Longmore in the other, there should

be little excuse for errors in diagnosis and investigation, with the addedbenefit that the balance between the two will allow the upright posture to

Such knowledge takes many years to acquire and it is a fact of life thatsenior doctors (who have attained such knowledge) are not usually thosewho request the investigations In this small volume, we have attempted

to distil all that is known about modern tests, from blood, urine and otherbody fluids, along with imaging and molecular tests The book is divided

into two principal parts: the first deals with symptoms and signs in The patient section, because that is how patients present We have tried to

cover as many topics as possible, discussing these in some detail and haveprovided differential diagnoses where possible We also try to suggesttests that might be of value in determining the cause of the patient’s

symptom or sign The second part of the book, Investigations, is

spe-cialty-specific, and is more relevant once you know roughly what type ofdisease the patient might have For example, if the symptom section sug-gests a likely respiratory cause for the patient’s symptoms, then the reader

should look to the Respiratory investigations chapter in order to determine

which tests to carry out, or how to interpret the results

The entire book is written by active clinicians, rather than scientists, since

we wanted to provide a strong clinical approach to investigation We have

tried, wherever possible, to cross-refer to the Oxford Handbook of Clinical Medicine, 5th edition, Oxford University Press, which provides the clinical

detail omitted from this handbook The symbol is used to highlight across-reference to OHCM, in addition to cross-referencing within this book

We would value feedback from readers since there will doubtless betests omitted, errors in the text and many other improvements we could,and will, make in future editions All contributors will be acknowledgedindividually in the next edition We would suggest you e-mail us directly:

a.provan@virgin.net.

Drew ProvanAndrew Krentz2002

Even small books such as this rely on the input of many people, besidesthe main editors and we are indebted to many of our colleagues for pro-viding helpful suggestions and for proofreading the text Dr Barbara Bain,

St Mary’s Hospital, London, kindly allowed us to peruse the proofs of

Practical Haematology, 9th edition (Churchill Livingstone) to help make

sure the haematology section was up to date Dr Debbie Lillington,Department of Cytogenetics, Barts & The London NHS Trust, London,provided invaluable cytogenetic advice Our registrars have had input intomany sections and we thank the London registrars: Simon Stanworth, JudeGaffan, Leon Clark and Nikki Curry, and the Southampton registrars:Fiona Clark, Michael Masding, Mayank Patel, Ruth Poole and CatherineTalbot

Dr Murray Longmore, the undisputed Oxford Handbook king, has vided invaluable wisdom and has very kindly allowed us to use his speciallydesigned OHCMtypeface (OUP) for many of the symbols in our text.Murray also provided page proofs of the OHCM,5th edition, which wasinvaluable for cross-referencing this handbook

pro-Warm thanks are also extended to Oxford University Press, and in ticular Esther (Browning) who first commissioned the book Very specialthanks must go to Catherine (Barnes), commissioning editor for medicine,who has stuck with the project, and most likely has aged 10 years as aresult of it! She has provided constant encouragement and helped keep ussane throughout the entire process (well, almost sane) Katherine Suggand Victoria Oddie relentlessly chased up missing artwork, text and gen-erally kept the project moving

par-x

Acknowledgements

A&E accident & emergency

AAFB acid and alcohol fast bacilli

ABGs arterial blood gases

ACD anaemia of chronic disease

ACE angiotensin converting enzyme

ACL anticardiolipin antibody

ACR acetylcholine receptor

ADA American Diabetes Association

AF atrial fibrillation

AIDS acquired immunodeficiency syndrome

AIHA autoimmune haemolytic anaemia

AKA alcoholic ketoacidosis

ALL acute lymphoblastic leukaemia

ALT alanine aminotransferase

AMI acute myocardial infarction

antinuclear antibodies

ANF antinuclear factor

APCR activated protein C resistance

APL antiphospholipid antibody

APML acute promyelocytic leukaemia

APS antiphospholipid syndrome

APTR activated partial thromboplastin time ratioAPTT activated partial thromboplastin time

ARF acute renal failure

AT(ATIII) antithrombin III

ATLL adult T cell leukaemia/lymphoma

ATP adenosine triphosphate

B-CLL B-cell chronic lymphocytic leukaemia

bd bis die (twice daily)

BMJ British Medical Journal

BMT bone marrow transplant(ation)

C1 INH C1 esterase inhibitor

C3Nef complement C3 nephritic factor

C&S culture & sensitivity

CABG coronary artery bypass graft

CAH congenital adrenal hyperplasia

cALL common acute lymphoblastic leukaemiaCBC complete blood count (American term for FBC)CCF congestive cardiac failure

CEA carcinoembryonic antigen

CF cystic fibrosis or complement fixation

CGL chronic granulocytic leukaemia

cold haemagglutinin disease

xii

Symbols & abbreviations

xiii

CHD coronary heart disease

CJD Creutzfeldt-Jacob disease (v = new variant)

CLL chronic lymphocytic (‘lymphatic’) leukaemia

CLOtest Campylobacter-like organism

CML chronic myeloid leukaemia

CMML chronic myelomonocytic leukaemia

CNS central nervous system

COPD chronic obstructive pulmonary disease

CPAP continuous positive airways pressure

CREST calcinosis, Raynaud’s syndrome, (o)esophageal motility

dysfunction, sclerodactyly and telangiectasiaCRF chronic renal failure

CSF cerebrospinal fluid

CTLp cytotoxic T lymphocyte precursor assay

CVA cerebrovascular accident (stroke)

CVD cardiovascular disease

CVS cardiovascular system or chorionic villus sampling

DAT direct antiglobulin test

DCCT Diabetes Control and Complications Trial

DDAVP desamino D-arginyl vasopressin

DIC disseminated intravascular coagulation

DIDMOAD diabetes insipidus, diabetes mellitus, optic atrophy and

deafnessDKA diabetic ketoacidosis

DVT deep vein thrombosis

EDTA ethylenediamine tetraacetic acid

FACS fluorescence-activated cell sorter

FBC full blood count (aka complete blood count, CBC)

FDPs fibrin degradation products

FeSO4 ferrous sulphate

FISH fluorescence in situ hybridisation

FOB faecal occult blood

FPG fasting plasma glucose

FUO fever of unknown origin (like PUO)

FVIII factor VIII

G&S group & save serum

GAD glutamic acid decarboxylase

GT -glutamyl transpeptidase

GIT gastrointestinal tract

GPC gastric parietal cell

Symbols & abbreviations

HNA heparin neutralising activity

HONK hyperosmolar non-ketotic syndrome

HPA human platelet antigen

HPFH hereditary persistence of fetal haemoglobin

HPLC high-performance liquid chromatography

HPOA hypertrophic pulmonary osteoarthropathy

HPP hereditary pyropoikilocytosis

HTLV human T-lymphotropic virus

IAGTor IAT indirect antiglobulin test

IBS irritable bowel syndrome

ICA islet cell antibodies

ICH intracranial haemorrhage

IDA iron deficiency anaemia

IDDM insulin dependent (type 1) diabetes mellitus

IEF isoelectric focusing

IFG impaired fasting glucose

IFN- interferon alpha

IGT impaired glucose tolerance

ischaemic heart disease

INR international normalized ratio

ITP idiopathic thrombocytopenic purpura

ITU intensive therapy unit

iu/IU international units

JCA juvenile chronic arthritis

JVP jugular venous pressure

LA lupus anticoagulant or lactic acidosis or local anaesthetic

LAP leucocyte alkaline phosphatase (score)

LBBB left bundle branch block

LFTs liver function tests

LIF left iliac fossa

LKM liver/kidney microsomal

LVF left ventricular failure

LVH left ventricular hypertrophy

MAG myelin-associated glycoprotein

MAIPA monoclonal antibody immobilisation of platelet antigensMAOI monoamine oxidase inhibitor

MC&S microscopy, culture & sensitivity

MCHC mean corpuscular haemoglobin concentration

mean cell volume

xvi

Symbols & abbreviations

MODY maturity onset diabetes of the young

MPD myeloproliferative disease

MRI magnetic resonance imaging

mRNA messenger ribonucleic acid

MS multiple sclerosis or mass spectroscopy

MUD matched unrelated donor (transplant)

NADP nicotinamide adenine diphosphate

NADPH nicotinamide adenine diphosphate (reduced)

NAP neutrophil alkaline phosphatase

NEJM New England Journal of Medicine

NRBC nucleated red blood cells

NSAIDs non-steroidal anti-inflammatory drugs

NSTEMI non-ST-elevation myocardial infarction

OCP oral contraceptive pill

OGTT oral glucose tolerance test

OHCH Oxford Handbook of Clinical Haematology

OHCM Oxford Handbook of Clinical Medicine

PA posteroanterior or pernicious anaemia or pulmonary

artery

PAN polyarteritis nodosa

PaO2 partial pressure of O2in arterial blood

PAS periodic acid-Schiff

PBC primary biliary cirrhosis

PC protein C or provocation concentration

PCH paroxysmal cold haemoglobinuria

PCI percutaneous coronary intervention

PCL plasma cell leukaemia

PCP Pneumocystis carinii pneumonia

PCR polymerase chain reaction

PCT proximal convoluted tubule

PDA patent ductus arteriosus

PEFR peak expiratory flow rate

PET positron emission tomography

PRV polycythaemia rubra vera

PS protein S or Parkinson’s syndrome

PSA prostate-specific antigen

qds quater die sumendus (to be taken 4 times a day)

RA refractory anaemia or rheumatoid arthritis

RAS renal angiotensin system or renal artery stenosis

RBBB right bundle branch block

RBCs red blood cells

RDW red cell distribution width

Symbols & abbreviations

xix

RIF right iliac fossa

RIPA ristocetin-induced platelet aggregation

RPGN rapidly progressive glomerulonephritis

RT-PCR reverse transcriptase polymerase chain reaction

SCA sickle cell anaemia

SCD sickle cell disease

SHBG sex-hormone-binding globulin

SLE systemic lupus erythematosus

SmIg surface membrane immunoglobulin

SOL space-occupying lesion

SPECT single photon emission computed tomography

stat statim (immediate; as initial dose)

STEMI ST-elevation myocardial infarction

sTfR soluble transferrin receptor assay

SVCO superior vena caval obstruction

tds ter die sumendum (to be taken 3 times a day)

TdT terminal deoxynucleotidyl transferase

TENS transcutaneous nerve stimulation

TFT thyroid function test(s)

TIAs transient ischaemic attacks

TIBC total iron binding capacity

tumour necrosis factor

TPO thyroid peroxidase

TRAB thyrotropin receptor antibodies

TRALI transfusion-associated lung injury

TRAP tartrate-resistant acid phosphatase

TSH thyroid-stimulating hormone

TTE transthoracic echocardiography

TTP thrombotic thrombocytopenic purpura

U&E urea and electrolytes

UKPDS United Kingdom Prospective Diabetes StudyURTI upper respiratory tract infection

UTI urinary tract infection

VIII:C factor VIII clotting activity

VIP vasoactive intestinal peptide

VSD ventricular septal defect

vWD von Willebrand’s disease

vWF von Willebrand factor

vWFAg von Willebrand factor antigen

WBC white blood count or white blood cells

WM Waldenström’s macroglobulinaemia

XDPs cross-linked fibrin degradation products

xx

of very useful and sophisticated tests that help us to confirm our nostic suspicions.

diag-By ‘test’ we mean the measurement of a component of blood, marrow

or other body fluid or physiological parameter to determine whether thepatient’s value falls within or outside the normal range, either suggestingthe diagnosis or, in some cases, actually making the diagnosis for us

Factors affecting variable parameters in health

Many measurable body constituents vary throughout life For example, anewborn baby has an extremely high haemoglobin concentration whichfalls after delivery; this is completely normal and is physiologicalrather thanpathological A haemoglobin level this high in an adult would be patholog-ical since it is far outside the normal range for the adult population

Reference ranges (normal values)

These are published for most measurable components of blood and othertissue and we have included the normal ranges for most blood and CSFanalytes at the end of the book

Factors affecting measurable variables

2 Physiological conditions (e.g at rest, after exercise, standing, lying).

2 Sampling methods (e.g with or without using tourniquet).

2 Storage and age of sample.

2 Container used, e.g for blood sample, as well as anticoagulant.

2 Method of analysis.

of very useful and sophisticated tests that help us to confirm our nostic suspicions.

diag-By ‘test’ we mean the measurement of a component of blood, marrow

or other body fluid or physiological parameter to determine whether thepatient’s value falls within or outside the normal range, either suggestingthe diagnosis or, in some cases, actually making the diagnosis for us

Factors affecting variable parameters in health

Many measurable body constituents vary throughout life For example, anewborn baby has an extremely high haemoglobin concentration whichfalls after delivery; this is completely normal and is physiologicalrather thanpathological A haemoglobin level this high in an adult would be patholog-ical since it is far outside the normal range for the adult population

Reference ranges (normal values)

These are published for most measurable components of blood and othertissue and we have included the normal ranges for most blood and CSFanalytes at the end of the book

Factors affecting measurable variables

2 Physiological conditions (e.g at rest, after exercise, standing, lying).

2 Sampling methods (e.g with or without using tourniquet).

2 Storage and age of sample.

2 Container used, e.g for blood sample, as well as anticoagulant.

2 Method of analysis.

What makes a test useful?

A really good test, and one which would make us appear to be

out-standing doctors, would be one which would always be positive in the presence of a disease and would be totally specific for that disease alone;

such a test would never be positive in patients who did not have the order What we mean is that what we are looking for are sensitiveteststhat are specificfor a given disease Sadly, most tests are neither 100% sen-sitive nor 100% specific but some do come very close

dis-How to use tests and the laboratory

Rather than request tests in a shotgun or knee-jerk fashion, where everybox on a request form is ticked, it is far better to use the laboratory selec-tively Even with the major advances in automation where tests arebatched and are cheaper, the hospital budget is finite and sloppyrequesting should be discouraged

Outline your differential diagnoses: what are the likeliest diseases given

the patient’s history, examination findings and population the patientcomes from?

Decide which test(s) will help you make the diagnosis: request these and

review the diagnosis in the light of the test results Review the patientand arrange further investigations as necessary

The downside of tests

It is important to remember that tests may often give ‘normal’ results even

in the presence of disease For example, a normal ECGin the presence of

chest pain does not exclude the occurrence of myocardial infarction with

100% certainty Conversely, the presence of an abnormality does not essarily imply that a disease is present This, of course, is where clinicalexperience comes into its own—the more experienced clinician will beable to balance the likelihood of disease with the results available even ifsome of the test results give unexpected answers

nec-Quick-fix clinical experience

This simply does not exist Talking to patients and examining them forphysical signs and assimilating knowledge gained in medical school areabsolute requirements for attainment of sound clinical judgement Thosestudents and doctors who work from books alone do not survive effec-tively at the coal face! It is a constant source of irritation to medical stu-dents and junior doctors, when a senior doctor asks for the results of aninvestigation on the ward round and you find this test is the one that

clinches the diagnosis How do they do it? Like appreciating good wine—

they develop a nose for it You can learn a great deal by watching your

Sensitivity & specificity

Sensitivity % of patients with the disease and in whom the test is

positive

Specificity % of people without the disease in whom the test is

negative

Minimising spurious results using blood samples

2Use correct bottle

2Fill to line (if anticoagulant used) This is less of a worry when vacuumsample bottles are used since these should take in exactly the correctamount of blood, ensuring the correct blood : anticoagulant ratio This

is critical for coagulation tests

2Try to get the sample to the lab as quickly as possible Blood samplesleft lying around on warm windowsills, or even overnight at room tem-perature, will produce bizarre results, e.g crenated RBCs and

abnormal-looking WBCs in old EDTAsamples

2Try to avoid rupturing red cells when taking the sample (e.g using

narrow gauge needle, prolonged time to collect whole sample) wise a ‘haemolysed’ sample will be received by the lab This may causespurious results for some parameters (e.g [K+])

other-2Remember to mix (not shake) samples containing anticoagulant

Variations in normal ranges in health

As discussed earlier, most of the normal ranges for blood parameters cussed in this book are for non-pregnant adults The reason for this is thatblood values, e.g Hb, RCCare high in the newborn and manyFBC, coagu-lation and other parameters undergo changes in pregnancy

dis-This page intentionally left blank

Part 1

The patient

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Dizziness & blackouts 29

Dysarthria & dysphasia 31

Abdominal distension

Patients may describe generalised abdominal swelling or localised fullness

in a specific area of the abdomen In the history enquire specifically about

2 change in bowel habit 2weight loss 2associated pain

Ascites: fluid in the peritoneal cavity Look for shifting dullness and fluid

thrill on percussion, stigmata of chronic liver disease, lymphadenopathy,oedema and assess JVP

Causes

2Intraluminal: faecal impaction, gallstone ileus.

2Luminal: inflammatory stricture (e.g Crohn’s), tumour, abscess.

2Extraluminal: herniae, adhesions, pelvic mass, lymphadenopathy,

volvulus, intussusception

2Paralytic ileus: drug induced, electrolyte disturbances

2Age-related causes of obstruction

2Neonatal: congenital atresia, imperforate anus, volvulus,

Hirschsprung’s, meconium ileus

2Infants: intussusception, Hirschsprung’s, herniae, Meckel’s diverticulum.

2Young/middle age adults: herniae, adhesions, Crohn’s.

2Elderly: herniae, carcinoma, diverticulitis, faecal impaction.

Investigations

2 FBC

4

2 AXR(erect and supine).

2Consider barium enema, barium follow-through, sigmoidoscopy, gical intervention for complete acute obstruction

sur-Localised swelling/masses: common causes according to site RUQ

LIF

Faecal loading Colonic mass

— cyst

— pseudotumour

— carcinoma Aortic aneurysm (is it pulsatile?) Lymphadenopathy

Urinary retention or tumour Uterine mass

Fig 1.1

Investigate according to site

2Consider USSabdomen and pelvis

Abdominal pain may be acute or chronic Severe, acute pain may indicate a

surgical emergency including perforation, peritonitis or obstruction.Assess nature and radiation of pain, clinical status of patient includingfever, tachycardia and hypotension

Common causes of abdominal pain according to site

Epigastric pain

Peptic ulcer disease, gastritis or duodenal erosions, cholecystitis, atitis

pancre-5

Metabolic causes—e.g diabetic ketoacidosis, hypercalcaemia, Addison’s

disease, porphyria, lead poisoning

Atypical referred pain—e.g myocardial infarction, pneumonia Investigations

2 FBC

2 U&E,e.g deranged electrolytes following vomiting, diarrhoea or bowelobstruction

2Plasma glucose

2Serum amylase (4 in pancreatitis and bowel obstruction)

2Urinanalysis and MSU,e.g haematuria, proteinuria, glucose

2 LFTs (consider obstructive vs hepatitic picture).

2Plain AXR(erect and supine to assess for perforation and bowelobstruction)

2 KUBfor renal tract calculi

2 USSabdomen, particularly for biliary tract, gallbladder and renal tract

2 IVUto assess for renal tract calculi/pathology

OHCMpp50, 462

Alteration of behaviour

This is usually reported by a relative or friend rather than by the patient.Often the patient will have little or no insight into the disease and taking ahistory can be difficult In addition to a full general and neurological phys-ical examination a mental state examination is required

6

Find out if this is the first episode of altered behaviour or if the episodesare recurrent Is there a gradual change in behaviour (and personality)over time?

Acute delirium

Causes

2Sepsis (common)

2Acute intracranial event, e.g haemorrhage

2Metabolic disturbance, e.g uraemia, hypercalcaemia (common)

2Intracerebral tumour (including meningioma)

2Drugs—especially interactions in elderly

2Alcohol (and withdrawal syndrome)

2Hypoxia (common)

2Hypoglycaemia (iatrogenic in diabetic patients receiving insulin ment or oral insulin secretagogues or insulinoma and other causes, pxx)

treat-Dementia

2Alzheimer’s (common), Pick’s (rare)

2Vascular, e.g multi-infarct

2Normal pressure hydrocephalus

Note: ‘Frontal lobe syndrome’ from SOL, e.g meningioma Presents withdisinhibition, impaired social functioning, primitive reflexes, e.g graspreflex

Anxiety states

Usually psychogenic but consider organic possibilities such as

2Phaeochromocytoma (rare)

2Hyperthyroidism (common)

2Paroxysmal atrial tachycardia (fairly common)

2Alcohol withdrawal (usually history of excessive alcohol intake)

– Thyrotoxicosis (‘apathetic’ thyrotoxicosis in the elderly)

Temporal lobe epilepsy

2Temporary disturbance of content of consciousness

Investigations: guided by history and examination

2Glucose (in non-diabetics take fasting venous plasma in fluoride oxalatetube with simultaneous serum or plasma for insulin concentration— pxx for details of investigating suspected insulinomas and othercauses of spontaneous hypoglycaemia).

2Urine drug screen ( Chapter 11)

2Blood ethanol level (may be low in withdrawal state)

2 EEG

224h ECG

2Sleep study

Alteration in bowel habit

A change in bowel habit in an adult should always alert you to the bility of bowel cancer Ask about associated features—PR bleeding,tenesmus, weight loss, mucus, abdominal pain or bloating

possi-Has the patient started any new medications, including ‘over the counter’?Look for signs of systemic disease

Consider

2Carcinoma of the colon

2Diverticular disease

2Irritable bowel syndrome (IBS)

2Constipation with overflow diarrhoea

2All of the above may present with alternating diarrhoea and tion

Anaemia

Reduced Hb, no specific cause implied (and not a diagnosis, so don’t becomplacent): 9 <13.5g/dL, 3 <11.5g/dL Often associated with non-spe-cific symptoms such as fatigue, poor concentration, shortness of breathand dizziness Older patients may experience palpitations and exacerba-tion of angina, congestive cardiac failure or claudication

Signs

Pallor of conjunctivae and skin creases, nail pallor and koilonychia(spoon-shaped nails, rare finding in severe chronic iron deficiency),angular cheilitis and glossitis Difficult to gauge anaemia from skin signs

alone.

Causes

Two common approaches to assess anaemia

1 Red cell dynamics

24RBCloss/breakdown, e.g haemolysis (congenital or acquired) orbleeding

25 red cell production, e.g vitamin/mineral deficiency, marrow sion/infiltration, myelodysplasia, haemoglobin disorders (e.g thalas-saemia), chronic disease, renal failure

suppres-2 Red cell indices

Normocytic, normochromic 6MCV& MCHC

Anaemia of chronic disease (e.g chronic infection, inflammatory disease

or malignancy), acute blood loss, renalfailure, myeloma

Investigations

FBC and film

Assessment of RBCindices helps direct investigation as above

Microcytic

2Check iron stores (ferritin or soluble transferrin receptor assay) Note:

ferritin is 4 in acute inflammation and may be misleading Iron/TIBCnolonger used for assessment of iron deficiency ( p176)

Consider thalassaemia screening if not iron deficient

2If iron deficient assess dietary history (vegetarians) and look for riskfactors for blood loss and increased demands.

2Premenopausal women—assess menstrual losses

2Pregnancy/infants/adolescence consider physiological (4 requirements)

2All others: look for source of blood loss GItract is most commonsource Consider OGDand/or colonoscopy guided by symptoms andbarium studies

Macrocytic

2Reticulocyte count

2Serum B12and red cell folate levels

2If folate deficient: assess dietary history and physiological requirements

2If B12deficient: rarely dietary cause alone, usually an associated

pathology Pernicious anaemia is the most common cause: check etal cell antibodies (90% patients with PAare +ve, but seen in other

pari-causes of gastric atrophy, especially in older individuals) and/or intrinsic factor antibodies (+ve in only 50% with PAbut specific) Consider ilealdisease and malabsorption

2Bilirubin and serum LDH

2Haptoglobins (absent in haemolysis)

2 DAT(old term is direct Coombs’ test)

Causes of unilateral ankle oedema

2Chronic venous insufficiency (especially post-DVT)

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2Milroy’s disease ( OHCMsection 19).

Causes of bilateral ankle oedema

2Right ventricular failure—2° to chronic lung disease

2Congestive cardiac failure (CCF)—cardiomyopathy, constrictive carditis, etc

peri-2Hypoalbuminaemia—nephrotic syndrome, hepatic cirrhosis, losing enteropathy, malnutrition (starvation or malabsorption),

protein-(gravity)

2Dependent oedema (immobility)

2Drugs—Ca2+channel blockers, NSAIDS

2Idiopathic/cyclical oedema syndrome

2Urine dipstick for proteinuria

2Urine protein/creatinine ratio or 24h urine protein excretion

2Filariasis serology/blood film

2Xylose breath test

2 OGDwith small bowel biopsy

iAll the causes of unilateral ankle oedema may also cause bilateraloedema

Anorexia

This describes a loss of appetite for food, and is associated with a widerange of disorders In fact, anorexia is a fairly common consequence ofunderlying disease, and represents a general undernourishment Anorexia

per se is associated with increased morbidity especially when present in

patients undergoing surgery; post-operative infection is commoner, as isprolongation of the hospital stay.

The extent to which it will be investigated depends on the general status

of the patient, presence and duration of any symptoms or signs Clinicaljudgement will help!

2Full history and examination

2 FBC—looking for anaemia or non-specific changes seen in underlyingdisease

2 ESR—may be elevated in inflammatory disorders

2 U&E

2 LFTs

2Serum Ca2+

2 CXR(e.g lung cancer, TB, etc.)

2Cultures of blood, sputum, urine, stool if pyrexial and/or localisingsymptoms or signs

Anuria

Anuria denotes absent urine production Oliguria (<400mL urine/24h) ismore common than anuria A catheter must be passed to confirm anempty bladder

Causes

2Urinary retention—prostatic hypertrophy, pelvic mass, drugs, e.g cyclic antidepressants, spinal cord lesions

tri-2Blocked indwelling urinary catheter

2Obstruction of the ureters—tumour, stone, sloughed papillae eral)

(bilat-2Intrinsic renal failure—acute glomerulonephritis, acute interstitialnephritis, acute tubular necrosis, rhabdomyolysis

2Pre-renal failure—dehydration, septic shock, cardiogenic shock

An urgent ultrasound of the renal tract must be performed and any ical obstruction relieved as quickly as possible, directly (urethral catheter)

phys-or indirectly (nephrostomy) iiRenal function and serum electrolytes must

be measured without delay.

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2Urine microscopy (for casts).

2Urine osmolality, sodium, creatinine, urea concentrations

Ataxia is an impaired ability to coordinate limb movements There must

be no motor paresis (e.g monoparesis) or involuntary movements (e.g

the characteristic cog-wheel tremor in Parkinson’s disease is not ataxia).

2Genetic analysis (discuss with regional genetics laboratory—counsellingmay be required).

2Venous plasma glucose (diabetic neuropathy)

2Serum vitamin B12(subacute combined degeneration of the cord—rare, but serious)

2 LFTs

2Cryoglobulins

Cerebellar ataxia

2Demyelinating diseases, e.g multiple sclerosis (MS)

2Cerebellar infarct or haemorrhage

2Alcoholic cerebellar degeneration

2Cerebellar tumour—primary in children, metastases in adults Note:

Von Hippel Lindau disease ( OHCMsection 19)

2Arnold Chiari malformation

2Dandy Walker syndrome

2Paget’s disease of skull

2Wilson’s disease (hepatolenticular degeneration)

2Hypothyroidism

2Creutzfeldt-Jacob disease and other chronic infections

2Miller Fisher syndrome

2Normal pressure hydrocephalus

Ataxia should be distinguished from movement disorders, e.g.