Diagnostic Medlab

Diagnostic Handbook
The Interpretation of Laboratory Tests
Diagnostic Medlab
Auckland
August 2000
Mike Gill
Paul Ockelford
Arthur Morris
Tony Bierre
Cam Kyle
First edition 1992
Second edition 1994
Third edition 2000
 Copyright 2000 by
Diagnostic Medlab Limited
No part of this publication may be reproduced by any process without written permission from
Diagnostic Laboratory Holdings Ltd.
PO Box 5728, Auckland 1,
New Zealand.
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by accessing this handbook:
Use of Information
We have developed this handbook to provide you with information relating to our services. The information in this
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advice on any specific problem or a replacement for individual professional medical advice, opinions or therapies
advised to you by your medical practitioner. We endeavour to keep the information in this handbook up to date
however, we make no warranty as to the accuracy, reliability, suitability or currency of information in this handbook.
All information in this handbook is subject to change at any time. Always seek the advice of a qualified medical
professional before acting on the information in this handbook.
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PREFACE TO THE FIRST EDITION
The starting-point for this Handbook, which has been written for doctors, midwives, practice
nurses, receptionists, laboratory staff, students, and other health care workers, was a file of
questions phoned through to Diagnostic Medlab over the past decade or so. Often the question
has been about a relatively minor abnormality: What does it mean? Can it be ignored? Should
the test be repeated? When will follow-up be necessary? This may help to explain what might
otherwise appear to be an unusually capricious selection of information. Once upon a time
someone asked about it.
Along with the enormous increase in types of laboratory tests over the past 30 years there has
been an increase in the sophistication we apply to interpretation of results. Age, sex, biological
variation, posture, diurnal rhythm, pregnancy all have major effects quite apart from those of
disease. Medications, singly or in combination, add a further set of variables; and any serious or
even trivial illness can have non-specific effects on a wide range of laboratory values.
As well as presenting factual information, we have attempted, with some tests, to give an opinion
on their value, particularly where their usefulness is limited or even non-existent. There will
undoubtedly be errors and omissions; we apologise for these and for opinions which turn out to
be wrong.
PREFACE TO THE THIRD EDTION
Comments received about the Handbook since the last edition was published in 1994 suggest that
we have provided a useful resource for practitioners in primary health care, always our target
audience. The more one works in the primary sector, the more one realises it is a different entity
from secondary and tertiary healthcare where either the diagnosis is known before the patient
reaches hospital or at least they have been recognised as being seriously ill. In primary
healthcare the problems are often more nebulous. The serious acute problems are small in
number beside those with vague symptoms which might be due to early disease, resolving
disease, transient disease or sometimes no disease at all.
One of the roles of laboratory medicine is to look at the possibility of early disease and provide
evidence for or against, before the classical picture has had time to develop. Many of the
laboratory abnormalities themselves will be equivocal and a goal of the Handbook has been to
help practitioners when deciding what to do next — treat, refer, investigate further, watch and
repeat in weeks or months, ring and discuss with a pathologist — or no action at all.
When we first embarked on this edition we thought revision would be a simple process, an extra
sentence here, a revised reference range there but laboratory medicine has, in the event, moved a
long way, even in five years, and the text has grown by a third.
For this edition the contributors have been:
biochemistry Mike Gill

Cam Kyle
cytology/histology Tony Bierre
haematology Paul Ockelford
immunology Mike Gill

David Haines
microbiology Arthur Morris

Selwyn Lang
Rod Ellis-Pegler
The other contributors are all those general practitioners, practice nurses, midwives, and others,
who have rung us at the laboratory to talk over a problem, ask for information, make a
suggestion. Having entered the new millennium, the role of the laboratory is not just to provide a
result but to help practitioner and patient understand what that result means. The Handbook will
help, we believe, and beyond that we suggest a phone call to the pathologist - one of the quickest,
simplest and most under-utilised of all consultations.
The last and most important acknowledgement is to Annie Curran for her painstaking care as she
typed draft after draft after draft.
Mike Gill
Editor
August 2000
How To Use This CD ROM
To find a Handbook entry, e.g. “CK (creatine kinase) total”, expand the “C' file by clicking on
the plus sign (+) beside the C in the left-hand “Bookmarks” window. All the C items are now
displayed. Use the scroll bar in the Bookmarks window to take you to “CK (creatine kinase)
total”. Click the words “CK (creatine kinase) total”. Use the scroll bar in the right-hand window
to take you through the pages of the CK entry.
At the end of the CK entry are two lines in blue indicating hyperlinks. Clicking on the 2nd line
for example takes you to "Myocardial Markers for Infarction". Clicking the - box beside “C”
shrinks the C entries back to a single line.
Specimen Collection
More detail than the minimum information provided can be obtained by ringing the lab or asking
for our detailed Collection Manual.
Reference Ranges
For the common analytes, reference ranges are roughly the same throughout New Zealand or,
indeed internationally, but for hormones and other tests where methodology can vary from one
lab to another, the reference ranges can differ quite markedly. Even within the same lab, ranges
may change from time to time as new methods are introduced.
Reference ranges are at best only a guide and results which are found unexpectedly to lie outside
their stated range should be treated with circumspection.
see also — Reference ranges and the concept of normality
Units
S.I. units are used throughout.
Enzymes and some other tests, including some hormones and antibodies, are expressed in
International Units (IU)/litre (L), or Units/litre or simply Units. IU/L are particularly misleading,
implying as they do that the reference range given is applicable world-wide. The reality is that
International Units for the same test can vary widely depending on the method used whilst still
calling themselves IU/L.
Interfering Drugs
The lists are not meant to be complete but will cover the most common interferences. Additional
queries about a specific drug/test combination should be directed to a pathologist.
Notes on Interpretation
These are not claimed to be comprehensive. Again, additional queries should be directed to a
pathologist. Brief clinical details (usually one line only) help immeasurably with interpretation
e.g. routine, wt-loss 1/12, pale and tired 3/12, on T4, on phenytoin,
? hepatitis and so on.
A
Abiotrophia
Abiotrophia defectiva and A. adjacens
Nutritionally variant streptococci which need growth factors to support growth. An

uncommon cause of endocarditis.
ABO type
see Blood grouping
ABS
see Antibacterial substance (ABS)
© 2000 Diagnostic Medlab View Terms of Use Page 7

Accidental inoculation of infected blood
see Needlestick injuries
ACE (angiotensin converting enzyme)
specimen: serum
Although ACE levels can be used in the diagnosis of sarcoidosis (two thirds of
patients with active disease have elevated ACE), elevations are also found in other
chronic inflammatory disorders, giving the test poor specificity.
Acetaminophen
see Paracetamol (acetaminophen)
Acetone
see Ketones
Acid-base investigations
see Blood gases & pH

Bicarbonate

Acid-fast bacilli/infections
see Tuberculosis (TB)

Tuberculin test (Mantoux test)
Acid phosphatase, prostatic (PAP)
specimen: serum
ref. range: males 0.1 – 0.6 U/L
Acid phosphatase is an obselete test and no longer available, PSA being a superior
prostatic tumour marker. PAP is not usually elevated until a tumour has spread
outside the prostatic capsule whereas PSA is usually elevated while the tumour is still
localised to the gland.
Non-prostatic acid phosphatase is found in bone marrow, platelets, red cells and liver
and can be elevated in diseases affecting these tissues.
Acinetobacter
A gram-negative bacillus commonly present in soil and water. In the hospital

environment it is found in moist situations, tap water, hand basins and ventilator
equipment. Acinetobacter species are opportunistic pathogens in the urinary tract,
respiratory tract and on skin surfaces. They are occasionally associated with invasive
processes. They have caused hospital epidemics. Infections are uncommon in the
community. Acinetobacter is usually resistant to most antimicrobial agents but many
strains are susceptible to trimethoprim/sulphamethoxazole. For serious hospital-
acquired infection, imipenem is the drug of choice.

ACTH (adreno-corticotrophic hormone)
specimen: plasma (EDTA) Collect 0700 – 1000 hr along with simultaneous cortisol
level.
ref. range: 2 – 11 pmol/L at 0700 – 1000 hrs
ACTH is elevated in primary adrenal insufficiency (Addison's disease).
It is not used in the early investigation of Cushing's syndrome (qv) but may help in
evaluating proven hypercortisolism where a high ACTH suggests pituitary adenoma
or, uncommonly, ectopic ACTH production, e.g. by small cell carcinoma of lung.
Actinomyces
An anaerobic gram-positive filamentous bacillus found as a normal commensal in the

mouth and gut. The most commonly encountered species is A.israelii. Actinomyces
species are susceptible to penicillin and doxycycline. Most isolates are resistant to
metronidazole.
The most common form of infection is cervicofacial infection characteristically

occurring in association with poor oral hygiene and tooth abscesses or decay.
Thoracic and gastrointestinal infections also occur. All these deep seated infections
may declare themselves by developing draining sinuses.
Actinomyces species also grow in association with IUCDs (intrauterine contraceptive

devices). They may be detected in a cervical smear or by culture of a removed IUCD.
Opinions vary as to what should be done when they are detected on a cervical smear
in an asymptomatic woman. Although pelvic actinomycosis is well reported in
association with IUCD use, the individual risk of infection with a colonised IUCD is
small. There is no indication for antibiotic treatment in response to a positive smear
alone. If the IUCD is left in place the woman should have the symptoms of infection

explained and follow-up must include enquiries about symptoms and a bimanual
examination. If the IUCD is close to being replaced it may be prudent to remove it.
One recommendation has been to remove the device, repeat the smear in 6 weeks - 6
months and reinsert if the smear is negative. There are, however, no data to show this
approach prevents the development of pelvic actinomycosis and there is the risk of
unwanted pregnancy while the IUCD is out.
Activated partial thromboplastin time
see APTT (activated partial thromboplastin time)
Activated protein C resistance (APCr)

specimen: plasma (citrate)
ref. range: 2.4 - 4.0
Activated protein C resistance occurs in patients with the Factor V mutation known as
Factor V Leiden (FVQ506). This mutation is present in 5% of a normal Caucasian
population. It is the commonest of the recognised thrombophilia markers. It is
detected in 16-20% of consecutive patients presenting with thromboembolism but the
frequency is higher in selected patient groups. Although it increases the thrombotic
risk 5-10 fold, it is generally regarded as a relatively weak risk factor.
APCr is measured using an APTT ratio with and without activated protein C. The
normal ratio is 2.4 - 4.0. Heterozygous positive patients with the Factor V mutation
have ratios of 1.6 or less. Homozygosity, which is much less common, is associated
with a higher thrombotic risk and a lower APCr.
see also Factor V Leiden (FVQ506)

Acute leukaemias
The diagnosis is usually obvious because of blast cells in the blood film, raised total
white count, anaemia, thrombocytopenia and neutropenia, but one or more of these
features can be absent at the time of diagnosis.
Acute lymphoblastic leukaemias (ALL)
The more common childhood leukaemia. Prognosis is relatively good in children

with 80-90% remission rates and 50% cure. Remission rates are lower in adults.
Acute myeloid leukaemia (AML)
The more common leukaemia in adults. AML may arise de novo or through
transformation of chronic myeloid leukaemia or myelodysplastic syndromes.
Transformed AML responds poorly to treatment.
In de novo AML, first remission is achieved in 70-80% of patients with 30-40% long
term survivors when treated with chemotherapy alone. With allogeneic bone marrow
transplantation for patients aged less than 55 years there is a 50-60% five year
survival.
The M3 subtype, acute promyelocytic leukaemia (APML), is treated with ATRA (a

retinoic acid derivative) initially, to promote cell differentiation, followed by
chemotherapy. This gives 85-90% remission rate with 80% 12-month disease free
survival.

Acute phase proteins (reactants)
Following inflammation or tissue destruction there is an increase in the so-called

acute phase proteins with the development of a typical pattern on serum protein
electrophoresis.
analyte rise response time adult ref range

CRP up to 1000x 6-10 h <5 mg/L
a- 1 antitrypsin 2-4x 24-48 h 0.9-2.0 g/L
orosomucoid 2-4x 24-48 h 0.5-1.5 g/L
haptoglobin 2-4x 24-48 h 0.3-2.0 g/L
fibrinogen 2-4x 24-48 h 1.4-4.5 g/L
ceruloplasmin 1.5-2x 48-72 h 0.15-0.45 g/L
C3 1.5-2x 48-72 h 0.55-1.2 g/L
C4 1.5-2x 48-72 h 0.2-0.4 g/L
Plasma analytes which decrease with inflammation include albumin, transferrin, iron,
total cholesterol and HDL cholesterol.
see also separate entries for each acute phase protein
Addison's disease
see Adrenocortical insufficiency

ADH (antidiuretic hormone, vasopressin)
ADH measurements are not easily available.
In suspected SIADH (syndrome of inappropriate ADH), urine osmolality, which

correlates strongly with ADH, is a simpler and cheaper alternative.
Where there is difficulty separating pituitary-hypothalamic diabetes insipidus from

that of renal origin, the response to exogenous ADH usually makes the diagnosis.
see also Osmolality, SIADH (syndrome of inappropriate ADH), Diabetes mellitus

(DM)
Adrenal antibodies
specimen: serum
Adrenal antibodies are present in 80% of autoimmune Addison's disease.
Adrenal medullary hormones
see Catecholamines
HMMA (hydroxy methyl mandelic acid)
Metanephrines

Adrenocortical hormones
Hypofunction - see
Addison's disease
Synacthen stimulation test
Hyperfunction - see
Cortisol, serum, Cortisol, urine free
Cushing's syndrome
Dexamethasone suppression test
Conn's syndrome
Hirsutism/virilism
Congenital adrenal hyperplasia (CAH)
Adrenocortical insufficiency
Addison's disease (primary insufficiency)
Usually autoimmune (70%), less often due to TB, haemorrhage, iron overload, HIV,
infiltration.
Tests: • 0900 hrs cortisol (but 20-30% of Addison's have

an 0900 cortisol within the reference range).
• Synacthen test (qv) — an excellent test
• ACTH (elevated)
• plasma renin (elevated)
• s. potassium (may be elevated)
• s. sodium (may be decreased)
• adrenal antibodies
Secondary insufficiency: • hypopituitarism

• suppression by long term steroid therapy

Adrenocortical hyperfunction
see Cushing's syndrome

Conn's syndrome
Adrenocorticotrophic hormone
(adrenocorticotropin)
see ACTH (adreno-corticotrophic hormone)
Aeromonas
Aeromonads are widely distributed in stagnant or flowing fresh water and in soil.
Human infections include:

• cellulitis or wounds contaminated with soil or water
• acute diarrhoeal disease – worldwide, affecting any age
• septicaemia
• other infections, including the urinary tract
Aeromonads are mostly resistant to the penicillins but are often susceptible to
trimethoprim/sulphamethoxazole and quinolones, e.g. ciprofloxacin. Nalidixic acid
or nitrofurantoin may be used for urinary tract infection. Although there are no data

on the benefits of treating Aeromonas associated diarrhoea, there may be benefit for
those with severe disease. Options include cotrimoxazole or norfloxacin for three
days.
AFP (alpha foetoprotein)

specimen: serum
ref. range: adult non-pregnant <10 µg/L
AFP has two uses:
tumour marker – large elevations (>100) can be found in hepatomas and testicular
tumours and are used for monitoring treatment and in diagnosis.
Smaller non-diagnostic elevations are found in many forms of liver disease and
malignancy.
screening for neural tube defects and Down's syndrome – serum AFP is measured
in conjunction with hCG and oestriol to give a risk estimate. Definitive diagnosis
requires measurement of AFP in amniotic fluid.
see Maternal serum testing for foetal Down's syndrome and neural tube defects
(NTD)
AGA (antigliadin antibodies)
see Gliadin (gluten) antibodies (AGA)

AHT (antihyaluronidase titre)
A streptococcal antibody test that is no longer used.
AIDS
see HIV (human immunodeficiency virus)
Alanine aminotransferase
see ALT (alaninine transaminase or amino transferase)
Albumin
specimen: serum
ref. range: 35 – 45 g/L
Decreases
• acute or chronic inflammatory illnesses
• urinary protein loss
• advanced liver disease
• gastrointestinal loss
• severe malnutrition
Increases are usually due to dehydration.

Alcaligenes
A gram-negative bacillus, part of the normal human flora. In hospitals it can be

found in moist environments including respirators and haemodialysis systems. It is
occasionally isolated from the urinary tract, ear discharges, wounds or sputa.
Treatment is according to susceptibility testing, but on the basis of in vitro results,
imipenem is likely to replace cotrimoxazole as the agent of first choice for serious
Alcaligenes infection.
Alcohol, ethyl (ethanol)
specimen: serum / plasma (heparin) / whole blood

conversion factor 1mmol/L = 4.6 mg/100ml
17.4 mmol/L in whole blood corresponds to 20 mmol/L in serum or
plasma.
ranges: legal limit while driving 17.4 mmol/L whole blood
fatal above 80 - 100 mmol/L
Alcohol is metabolised by the liver at a rate independent of blood alcohol

concentration. Although there is wide individual variation, 10g alcohol/hour is an
indicative figure. A 750 ml bottle of wine with an alcohol content of 12%
(12g/100ml) contains 90g alcohol. For an individual metabolising at the indicative
rate of 10g/hr, it would take 9 hours to clear the blood stream of alcohol - and 18
hours to clear two bottles.
A "standard unit" of drink contains 10g alcohol.
Identifying alcoholism

When considering the possibility of excessive alcohol intake, the two most useful
markers are:
• GGT 50 - 200 U/L, occasionally up to 1000
After a heavy weekend's drinking, levels rise about 50%, peaking on about the
third day.
An elevated GGT due to alcohol should fall by about half after two weeks
abstinence and reach baseline by about six weeks.
• red cell MCV in the range 95 - 115 (ref. range 80 - 98)
Other tests affected by alcohol include:
• other liver enzymes: alk. phos, AST, ALT, ratio AST/ALT >1.5
• triglyceride elevated – fatty liver
• urate elevated
• ferritin elevated – alcoholic hepatitis
• CK elevated – alcoholic myopathy
• thrombocytopenia

Aldosterone and renin, plasma
specimens: plasma (EDTA), 2 tubes at room temp (must not be refrigerated).
The patient should have a normal sodium intake and have been
ambulant at least 1-2 hours.
ref. ranges: aldosterone 100-850 pmol/L (standing)

50-450 pmol/L (recumbent)
renin 5-75 mU/L (ambulatory)
aldosterone/renin ratio <20 hyperaldosteronism unlikely

>20 hyperaldosteronism possible
Effect of drugs:
Spironolactone, which inhibits aldosterone formation, must be stopped six weeks

before testing.
The test is fairly robust with other drugs but the aldosterone/renin ratio may
sometimes be altered by:
loop diuretics, calcium antagonists — false high ratio

ß-blockers, NSAIDs, methyl dopa — false low ratio
ACE inhibitors lower the aldosterone/renin ratio in normals, but in those with Conn's
syndrome, the ratio usually remains high.
Primary hyperaldosteronism (Conn's syndrome)

The basic pathology is an adrenal adenoma (2/3) or adrenal hyperplasia (1/3) causing:
• hypertension
• hypokalaemia, with s. potassium classically <3.5 mmol/L but often in the range
3.5-3.9 mmol/L.
• elevated aldosterone/renin ratio. This is the most sensitive test.
A positive screening test is an aldosterone/renin ratio >20 (usually >40). Typically

the renin is suppressed to <15 mU/L and the plasma aldosterone is >600 pmol/L.
Renin suppression by beta-blockers or NSAIDs may give a false positive screening
test.
A negative screening test is a ratio <20, especially if the renin is >25 mU/L. A
negative test is valid in patients who continue taking diuretics, ACE inhibitors or
calcium-channel blockers.
Secondary hyperaldosteronism
This is found in oedematous and hypertensive states where the plasma aldosterone
increase is secondary to an increased renin, e.g. diuretic therapy, renal artery stenosis.
Alkaline phosphatase (ALP)

specimen: serum
ref. range:
Age male U/L female U/L

up to 10 y 30-350 30-350
11-15 y 30-400 30-300
16-20 y 30-200 30-250
21-49 y 25-110 25-100
50-60 y 25-120 25-120
>60 y 25-130 25-130

The bone isoenzyme comes from active osteoblasts, hence high levels during
childhood, pubertal growth spurt, healing fractures.
In the liver, ALP is found in biliary canaliculi, increased production being stimulated
by biliary obstruction and to a lesser extent other liver pathology.
Causes of hyperphosphatasaemia can be grouped under three main headings:
Liver disease
ALP of liver origin is usually identified by an accompanying rise in GGT which is

also an "obstructive" enzyme. AST and ALT are usually also elevated to varying
extents in liver disease. For further discussion see liver enzymes.
Bone and other non-liver disease

• Paget's diseases of bone
• malignant disease, secondary or primary
• hyperparathyroidism
• rickets/osteomalacia
• chronic renal failure
• healing fractures
• thyrotoxicosis
• rheumatoid arthritis
• intestinal disease, e.g. Crohn's, ulcerative colitis
Benign isolated elevations of ALP
• Growth in childhood, particularly the pubertal growth spurt when levels can
go up to 650 U/L.

• Third trimester of pregnancy, up to 400 U/L.
• Isolated elevations of ALP are common in the elderly and usually attributed to
foci of subclinical Paget's disease provided there is no evidence of
malignancy. Another possibility is osteomalacia due to vitamin D deficiency.
• In transient hyperphosphatasaemia of infancy and early childhood, ALP can
go up to 3000 U/L for up to 3 months. Other liver enzymes remain
unaffected. Aetiology remains obscure but viral infection is a possibility.
• Familial benign hyperphosphatasaemia shows as a raised ALP throughout life.
Alkaline phosphatase isoenzymes

specimen: serum
Assessment of other laboratory tests and the clinical picture will usually explain
elevations of ALP without resorting to isoenzyme fractionation – which usually
provides a clear-cut answer only when the answer is already obvious.
A useful generalisation is that where both ALP and GGT are raised, liver is the
source. When GGT is normal, the raised ALP is probably from bone.
Occasionally, however, the answer is not obvious. Heat stability is a method of

isoenzyme analysis, the ALP being measured before and after 10 mins incubation at
56ºC.
% ALP remaining likely origin of raised ALP

after incubation
<20% mainly bone
25-55% mainly liver and/or intestine
>90% placenta

Allergy
These are all tests for Type I immediate hypersensitivity reactions mediated by IgE
antibodies as seen in allergic rhinitis, anaphylaxis, allergic skin reactions, food
allergies, drug allergies.
see Skin tests for allergy, RAST (Radioallergosorbent test)

IgE total, Bee and wasp venom allergy, Food allergy
Penicillin allergy, Anaesthetic allergy
Alopecia
The common age and gender related variant does not warrant laboratory investigation
but specific aetiologies to be considered include:
• hypothyroidism
• hyperthyroidism
• drugs : cytotoxics, lithium
• dermatological pathology
• any severe illness
• zinc deficiency
• warfarin hypersensitivity (rare)
• polycystic ovary syndrome
When associated with a severe but correctable illness, the alopecia is likely to be
transient.

ALP
see Alkaline phosphatase isoenzymes
alpha-1-antitrypsin
see Antitrypsin (alpha-1-antitrypsin - AAT)
alpha-foetoprotein
see AFP (alpha foetoprotein)
17 alpha-hydroxy progesterone (17-OHP)
see 17 alpha-hydroxy progesterone (17-OHP)
ALT (alaninine transaminase or amino

transferase)
specimen: serum
ref. range:

Age (yrs) U/L
female male
0-20 35 40
21-60 40 45
>60 35 40
Also called SGPT or GPT.
ALT elevations, which are common and usually accompanied by other enzyme
elevations, are found in:
• liver disease, other system diseases, drugs

see Liver enzymes
• AST/ALT ratio — in healthy persons the average ratio is about 1.3. In
chronic liver disease (including alcoholic hepatitis) the ratio tends to rise
whereas in acute viral hepatitis, the ratio tends to fall.
• obesity – up to 50% higher in moderately obese and up to 300% in the
extremely obese male.
• skeletal muscle damage – see CK-MB in myocardial infarction (MI) for a
list of conditions to be considered. ALT elevations are much smaller than
those of CK but if only the ALT has been tested, a myopathy or myocarditis
can be missed.
• idiopathic — where no cause has yet been found.
Aluminium
specimen: blood in trace metal tube (navy blue stopper)
ref. ranges: <2.2 µmol/ acceptable

>3.7 µmol/L at risk
>7.4 µmol/L dangerous

Used to monitor dialysis patients using aluminium hydroxide. In the past, aluminium
accumulation sometimes led to dementia and osteomalacia but with monitoring this
no longer occurs.
Aluminium-containing antacids in non-dialysis patients, aluminium kitchenware, or

working with aluminium, do not cause measurable increases in serum aluminium.
Some patients with Alzheimer's disease have increased aluminium deposits in the
CNS but serum tests will not detect this.
Amenorrhoea
Consider:
• pregnancy – an hCG is the first test in the investigation of amenorrhoea

• hyperprolactinaemia
• thyroid disease
• premature ovarian failure: FSH and LH elevated
• adrenal disease
• drugs – oestrogens and/or progestagens
– post-oral contraceptives
– anabolic and other steroids
• stress, including chronic disease
• eating disorders
• intense athletic training
American units for cholesterol and glucose
see SI (systeme internationale) units

Amikacin
see Antibiotics, serum levels
Amino acids
specimen: serum
or urine, fresh random specimen for screen test
For specific amino acids, e.g. phenylalanine monitoring in phenylketonuria (qv), a

dried blood spot on a Guthrie card is often adequate.
Aminoglycoside, serum levels
Aminophylline
see Theophylline (Nuelin)
Amiodarone
specimen: serum
therapeutic range: 1.5 – 3.9 µmol/L (trough level)

Amiodarone, which is rich in iodine (1/3 by weight), blocks conversion of thyroxine
(T4) to tri-iodo thyronine (T3) causing high free T4 (up to 50 pmol/L) and low free
T3 in many patients. TSH often rises early up to 10-15 mU/L but should return to
normal within 3-4 months except in the small percentage of patients where hyper- or
hypo-function develop.
Amitriptyline
see Antidepressant drugs, tricyclic
Ammonia
specimen: whole blood (heparin) collected without haemolysis, transported on ice

and analysed promptly.
ref. ranges: macro-collect <70µmol/L
micro-collect <115 µmol/L
A specialist test sometimes used in hepatic failure, Reye's syndrome and some inborn
errors of metabolism.
Amoeba
see Entamoeba coli

Amphetamine
see Drug screen – pre-employment screen and drugs of abuse
Amylase, serum
specimen: serum
ref.range: 25 - 135 U/L
Amylase, found mainly in pancreas and salivary glands, is used in the differentiation
of acute pancreatitis from other causes of the acute abdomen.
In acute pancreatitis, amylase typically rises above 400 U/L, returning to normal in
about 4 days.
The enzyme pattern is inconsistent, however, and failure to detect an elevation does
not preclude the diagnosis even when there is severe infarction.
Acute peritonitis, causing inflammation of the serosal surfaces of the pancreas and
other organs, can elevate amylase but usually not above 400 U/L.
Other causes of hyperamylasaemia include mumps, diabetic ketoacidosis, biliary tract
disease, renal insufficiency, shock, some drugs (particularly narcotics), hypoxia,
pelvic infection, macroamylasaemia.
Chronic pancreatitis does not raise amylase except sometimes during acute
exacerbations.
In macroamylasaemia, as in other macromolecular enzyme variants, a consistently

elevated enzyme level is found in a well person. A definitive diagnosis can be made
using the amylase/creatinine clearance ratio, ACCR.
ur . amylase s . creatinine
ACCR(%) = x x 100
s . amylase ur . creatinine

In macroamylasaemia, the ACCR is <2%. The usual reference range is 2-5%.
Amylase, urine
specimen: random or 24-hr urine without preservative
ref. range: <650 U/L or U/day
Urine amylase is elevated in all conditions where serum amylase is raised except
renal failure and macroamylasaemia. It is not often used except perhaps in the
diagnosis of macroamylasaemia where the ACCR is calculated.
see Amylase, serum
ANA (antinuclear antibodies)

specimen: serum
Interpretation:
<1:40 negative
1:40 or 1:80 borderline
>1:160 consistent with auto-immune disease
but not diagnostic
In SLE (systemic lupus erythematosus)
The main indication for ANA is as a screen test in suspected SLE where it will be
positive in 95% of cases. A negative ANA makes SLE unlikely. A positive ANA
requires follow up by anti-DNA, which has a much higher specificity for SLE, and
ENA to check specificity of the antibody.
see SLE (systemic lupus erythematosus)

DNA, paternity
ENA (extractable nuclear antigen) antibodies
ANA in healthy people
The exact incidence of positive ANAs in healthy populations depends on gender

(commoner in women) age-group (rises with age) test methodology, ethnicity etc. and
for this reason precise figures are not available.
A commonly quoted overall incidence is 5%.
A recent study narrowed this to 5% in women age 40 - 50.
Another quotes 20% in women over the age of 60 rising to 30% over age 80.
The only certain statement is that positive ANAs are fairly common in healthy people
and should never, as an isolated finding, be represented as possibly indicating SLE
which requires additional laboratory and clinical features before the diagnosis can be
made.
ANA in other autoimmune disorders
Incidence of positive ANA in other conditions:
rheumatoid arthritis 30%

Sjogren's syndrome 60%
limited scleroderma (CREST) 50%
diffuse scleroderma (systemic 80%
sclerosis)
mixed connective tissue disease 80%
(MCTD)

polymyositis 30%
autoimmune liver disease <10%
Drugs causing positive ANA and sometimes a lupus-like illness
• procainamide – responsible for most drug-related SLE

• anticonvulsants
• isoniazid
• hydralazine
• chlorpromazine
• methyldopa
The clinical manifestations of drug-related SLE are mild and subside within six
weeks of drug withdrawal.
ANA patterns
ANA is detected by adding patient serum to a layer of cells on a slide, then adding a
fluorescent detection system. If ANA is present it shows up as a fluorescent pattern
illuminating various nuclear structures. Usually the pattern is not specific for a
particular disorder but associations have been suggested:
nucleolar pattern — diffuse scleroderma
centromere — limited scleroderma, CREST
speckled — MCTD, Sjogren's, polymyositis, RA
peripheral, diffuse — SLE
(homogeneous)

Anaemia
Anaemia is a reduction of the Hb concentration below the 95% reference range
selected for age and sex.
see Blood count for Hb reference ranges.
A full classification of anaemia encompasses the whole discipline of haematology but

there needs to be a starting point and a simple one is the morphological classification
based on MCV (mean red cell volume), measured in femtolitres. The usual MCV
reference range is 80-98 fl. There are, of course, big overlaps between the three
divisions – acquired microcytic or macrocytic conditions will have started in the
normocytic range before moving in the direction of an MCV outside the reference
range.
Investigating an anaemia
Anaemia is probably the commonest of all laboratory abnormalities and

investigations should proceed logically, starting with the most probable causes of
anaemia for that person's age, sex and clinical findings, proceeding through the less
common abnormalities, and ending with a phone-call to the haematologist if the cause

is not apparent after the first couple or so rounds of investigation. Here are some
early questions/tests to consider:
• are there any other diagnostic haematological abnormalities in blood film,

white cells or platelets?
• does the patient have a history or clinical findings of an illness that can cause
anaemia?
• drug history
• ferritin – iron deficiency is the commonest cause of anaemia. Ferritin should
be a routine test in all menstruating women and in anaemias in other patient
groups where the aetiology is not yet known.
• vitamin B12 and folate – though deficiencies are much less common than iron
deficiency
• creatinine – renal impairment is typically silent and is almost invariably
accompanied by anaemia
• ESR and/or CRP looking for inflammatory disease
• serum protein electrophoresis and immunoglobulins
• TSH for hypo- and occasionally hyper-thyroidism
• liver enzymes
• reticulocytes and haptoglobulins as a screen for haemolysis
• thalassaemia screen for the disproportionately microcytic film
• hCG if pregnancy is a possibility
Anaemias of chronic disease
These are typically normocytic, normochromic anaemias but there may be mild
microcytosis and hypochromia.

They are often multi-factorial. For example in the anaemia associated with
rheumatoid arthritis, iron uptake into erythroblasts is inhibited and the anaemia will
be unresponsive to iron therapy - except when there is iron deficiency due to chronic
blood loss secondary to analgesic use. And the anaemia of renal insufficiency is due
to a combination of reduced erythropoietin, shortened red cell survival and
sometimes GI or gynaecologic bleeding.
Common causes of anaemia of chronic disease:
• renal insufficiency – there is a rough correlation between

elevation of s. creatinine and anaemia.
• rheumatoid arthritis
• other connective tissue diseases
• chronic infections
• malignancy
• chronic liver disease
• endocrine deficiencies – hypothyroidism (occasionally hyperthyroidism)
– hypopituitarism
– hypoadrenalism
– hypogonadism
Anaerobic infections
Anaerobic organisms, which are widely distributed in soil and as part of the normal
flora of mouth, gut, and vagina, grow readily in deeply-placed abscesses in the
abdomen, wounds, pleural cavities, brain, oropharynx and in peritonitis or
endometritis. Foul-smelling discharge indicates anaerobic infection.
Routine cultures do not grow anaerobes which require special media and an oxygen-
reduced environment. Anaerobic cultures are set up only on specific request or when
clinical details indicate the need for them. Swabs are not the ideal specimen, tissue
obtained at debridement being the ideal. Aspirated pus or fluid is best collected and
transported in a syringe which should not be refrigerated. IUCDs (intrauterine
contraceptive devices) are routinely cultured for Actinomyces.

Common anaerobic species are Bacteroides, Fusobacterium, Actinomyces and
Clostridium.
Most of the anerobes we isolate will be susceptible to amoxycillin - clavulanate,

clindamycin and metronidazole.
Anaesthetic allergy
Allergy to local anaesthetic is rare but often suspected by patients who may request
skin tests in a specialist allergy laboratory to exclude the possibility – before dental
anaesthesia for example.
Reactions to other allergens can occur under general anaesthesia, particularly to

muscle relaxants and the latex of surgical gloves.
Analytical variation or error
see Variation
Errors
ANCA
see Antineutrophil cytoplasmic antibodies (ANCA)
Ancylostoma duodenale

see Hookworm
Androgens
see Testosterone
DHEAS (dehydroepiandrosterone sulphate)
Androstenedione
Androstenedione
specimen: serum
ref. range: adult female 3.5 - 9.0 nmol/L
adult male 3.0 - 8.5 nmol/L
Androstenedione is secreted by the adrenal cortex, testis and ovary and is a precursor
of testosterone and oestrone. In pre-menopausal women, the adrenal cortex and
ovaries contribute equally but after the menopause androstenedione is almost entirely
of adrenal origin.
In hirsutism and polycystic ovary syndrome it can be elevated but testosterone is the
preferred test.
Androstenedione can be markedly elevated in adrenal hyperplasia and is used in the

investigation of virilism.
ANF (antinuclear factor)

see ANA (antinuclear antibodies)
Angioedema
see Complement, C1 inhibitor (C1 INH)
Angiotensin converting enzyme
see ACE (angiotensin converting enzyme)
Anion gap
specimen: serum
ref. range: 8 – 16 mmol/L
The anion gap is a simple calculation which, if increased above 16 mmol/L, gives a
crude (very crude) indication of metabolic acidosis as in salicylate or methanol
poisoning, ketoacidosis, lactic acidosis, renal acidosis.
The calculation and its derivation are as follows:
In serum, total anions = total cations

C1- + HCO3- + acid anions (the anion gap) = Na+ (the major cation)
anion gap = Na+- (C1- + HCO3-)
For example a patient with salicylate poisoning might have

Na+ = 146, C1- = 100, HCO3- = 16
The anion gap, at 30 mmol/L is increased, with acidic salicylate anions being the
cause of the increased gap.
Ankylosing spondylitis
A seronegative spondyloarthropathy causing low back pain and reduced spinal
mobility due to sacroileitis and spondylitis. Typically it occurs in younger males with
95% positivity for HLA B27 (qv).
Anorexia nervosa and bulimia

Laboratory abnormalities include:
• hypokalaemia is common in both conditions and can be profound (<2.0) in

bulimia due to the combination of vomiting and use of laxatives. In this
situation there may be a metabolic alkalosis with raised serum bicarbonate.
• anaemia (normocytic)
• low FSH/LH accompanying the amenorrhoea which is almost invariable in
anorexia.
• hypoalbuminaemia, particularly when there is oedema.
• hypocalcaemia is uncommon but is found occasionally.
• cortisol may be elevated
Other wasting disorders need to be excluded:
– glucose to exclude diabetes

– TSH/T4 to exclude hyperthyroidism

– Addison's disease causes wasting but is rare in young women under the age of 25
which is the common age group for eating disorders.
Antenatal group, first visit

specimen: 1 tube serum + 2 tubes EDTA whole blood
tests: • CBC
• ABO and Rh group
• red cell antibodies
• hepatitis Bs antigen
• rubella antibodies
• syphilis antibodies
Antenatal group, follow-up visit

specimen: 1 tube serum + 1 tube EDTA whole blood
tests: • CBC
• red cell antibodies
Antiarrhythmic drugs
specimen: serum
therapeutic ranges:

Drug umol/L
amiodarone 1.5-3.9
disopyramide 6-15
flecainide 630-2100
lignocaine 6-21
procainamide 15-37
quinidine 7-15
mexiletine - therapeutic 3-11
toxic >16
propranolol 200-390
Antibacterial substance (ABS)

Finding ABS in a urine usually indicates antibiotic therapy and provides an
explanation for sterile pyuria (qv), if present.
see also Urinalysis (routine biochemistry and microbiology) and UTIs (urinary tract
infections).
Antibiotics, serum levels

specimen: serum
collection times: trough = just before dose
peak = IV bolus 15 mins after dose
IV infusion 1 hr after dose
IM or oral 1 hr after dose
Aminoglycosides
Therapeutic ranges for aminoglycosides when given 8-hourly:

Drug mg/L
peak trough
amikacin 20-30 <10
gentamicin 5-10 <2
netilmicin 5-10 <2
tobramycin 5-10 <2
If gentamicin is given as a single daily dose (4-5 mg/kg/day) the trough level should
be <0.5 mg/L. Peak levels are not necessary for single daily dosing.
Vancomycin
Trough levels should be <15 mg/L. It is seldom necessary to do peak levels.
Antibody screen in pregnancy
see Red cell antibodies
Anticardiolipin
see Cardiolipin antibodies (aCL)
Anticholinesterase insecticides
see Cholinesterase

Anticoagulant therapy using warfarin
see INR (international normalised ratio)
Anticoagulant therapy
see Heparin therapy
INR (international normalised ratio) for warfarin therapy
Anticonvulsants
specimen: serum
time of collection: quoted therapeutic ranges refer to trough levels.

Specimens must be collected at least 8 hours after last dose,
preferably just before next dose e.g. delay morning dose until after
morning blood collect.
Drug Therapeutic Half-life

range (µmol/L) (hours)
carbamazepine (Tegretol) 16-40 20
clobazam (Frisium) 800-1600
clonazepam (Rivotril) 70-230 40
ethososuximide (Zarontin) 300-700 30
phenobarbitone 65-170 100
phenytoin (Dilantin) 40-80 30
primidone (Mysoline) measured as phenobarbitone
valproic acid (Epilim) 350-700 13
Indications for monitoring anticonvulsants vary between the different drugs.

Suggested guide-lines:
• monitoring initial stabilisation or change of dose – phenytoin, carbamazepine,

phenobarbitone
• suspected toxicity – all drugs
• suspected non-compliance – all drugs
• failure to control seizures – all drugs
• ongoing routine monitoring – phenytoin only, and even this may not be
essential.
The therapeutic range is a guide only. Levels below the range may control seizures;
levels above the range may not be toxic and may be necessary for control. When
changing doses, retesting should be delayed a week or so till a new equilibrium
develops.
Phenytoin, carbamazepine and phenobarbitone are potent inducers of hepatic

enzymes thereby raising serum levels of GGT and ALP. The raised enzymes are
regarded as an acceptable side-effect.
Primidone (qv) is measured as phenobarbitone which is the active metabolite.
For more details, see under separate drug entries.
Antidepressant drugs, tricyclic

specimen: serum
Overdose screen
Detects overdose of amitriptyline, nortriptyline, imipramine, desipramine,
trimipramine, protriptyline, doxepin or dothiepin, but is nonspecific.

Therapeutic monitoring These drugs are not monitored routinely but estimations may
be useful where there is lack of therapeutic response or uncertain compliance.
Therapeutic ranges:
Drug nmol/L
amitriptyline 550-1290
clomipramine 830-2000
desipramine 470-1130
doxepin 550-1300
imipramine 610-1670
nortriptyline 280-570
protriptyline 430-1430
trimipramine 400-1000
The method is generic for all tricyclics so cannot distinguish one drug from another.
Knowing which drug has been given is essential when assessing whether a level is in
the therapeutic range.
Antidiuretic hormone
see ADH (antidiuretic hormone, vasopressin)
AntiDNA
see DNA antibodies (anti-double-stranded DNA)

AntiDNAse
see Streptococcal antibodies (ASK, ASOT, ADNAse)Streptococcal antibodies (ASK,

ASOT, ADNAse)
Antiendomysial antibodies (EMA)
see Endomysial antibodies (EMA)

Antigliadin antibodies (AGA)
see Gliadin (gluten) antibodies (AGA)
Antihyaluronidase titre (AHT)
see Streptococcal antibodies (ASK, ASOT, ADNAse)
Antimicrobials
Antimitochondrial antibodies
see Mitochondrial antibodies
Antineutrophil cytoplasmic antibodies (ANCA)

specimen: serum
ref. ranges: not present in unaffected people
>1:160 is significantly positive

As their name indicates, these autoantibodies are directed against the cytoplasm of
neutrophils.
Their presence indicates vasculitis including:
– Wegener's necrotising granulomatous vasculitis

– systemic vasculitis
– focal necrotising glomerulonephritis with vasculitis
An initial ANCA screen test has 95% sensitivity for these conditions and is followed
by the more specific antiproteinase 3 (PR3) and myeloperoxidase (MPO) tests.
Antinuclear antibodies
see ANA (antinuclear antibodies)
Antiphospholipid antibody syndrome (APS)
A syndrome characterised by widespread, recurrent arterial and venous thromboses

causing ischaemia in the affected organs. Clinical presentations include:
– recurrent foetal loss, frequently mid-trimester with placental infarcts
– recurrent arterial or venous thrombosis
– stroke at a young age

– other neurological and cardiological presentations
APS is found frequently in SLE. When it occurs independently it is known as the

primary antiphospholipid syndrome.
Markers used in the diagnosis of APS are autoantibodies directed against

phospholipids, the main ones being:
· cardiolipin (qv) antibodies which are used as the initial test when APS is suspected
· lupus anticoagulant (qv)
· biological false positive RPR/VDRL
The aetiology of these antibodies, which may be transient, is unknown but the
presence of elevated titres of anticardiolipin antibodies and/or the lupus
anticoagulants, six months after an episode of venous thromboembolism is a predictor
for an increased risk of recurrence with probable benefit from long-term oral
anticoagulation therapy.
see Cardiolipin antibodies (aCL)

Lupus anticoagulant (LAC)
Hypercoagulability
Antistreptokinase
Antistreptolysin-O-titre (ASOT)

Antithrombin III (ATIII, antithrombin)

ref. range: functional assay 80-120%
immunological assay 70-140%
Antithrombin III is a non-vitamin K dependent physiological inhibitor of coagulation.

It is essential for the anticoagulant effect of heparin.
Deficiency of ATIII, transmitted as an autosomal dominant, is associated with venous

thrombosis. It is a strong but uncommon risk factor which accounts for <5% of
patients with thrombophilia. The approximate incidence of the deficiency state is
1:5,000. Thrombosis occurs in 50% of patients before age 40. It is usually an
indication for life long anticoagulant therapy after a thrombotic event.
ATIII can be spuriously reduced in the presence of heparin and after a thrombotic
event, as well as in nephrotic syndrome, liver disease and pregnancy. Elevated levels
are of no clinical significance.
Antitrypsin (alpha-1-antitrypsin - AAT)

specimen: serum
ref. range: 0.9 - 2.0 g/L
AAT deficiency in its severe forms predisposes to early onset emphysema and
juvenile cirrhosis and should be sought in these situations.

Sometimes the deficiency is detected as an absent or markedly reduced alpha-1 band
on routine serum protein electrophoresis.
Genetically there is one normal gene, M, and two abnormals, S and Z.
Genotype Prevalence Reduction AAT

% level (%)
MM 88 0
MS 7 20
MZ 4 40
SS 1 40
SZ 0.1 70
ZZ 0.03 90
ZZ, and to a lesser extent SZ are associated with emphysema and cirrhosis, and both
smoking and alcohol should be strongly discouraged. The importance of MS, MZ
and SS is uncertain but avoiding smoking is a wise precaution.
Tests for AAT deficiency:

Protein electrophoresis – a crude screen test but an absent or reduced alpha-1 band,
or a band of slow mobility, is often the first clue to AAT deficiency.
AAT quantitation – a result of <1.0 g/L is suspicious and requires pheno-typing which
gives the best measure of risk.
APCr
see Activated protein C resistance (APCr)e

Apolipoproteins
specimen: serum
Cholesterol and triglyceride particles in serum are coated with apoproteins to render
them soluble. Quantitation of the various apoproteins provides a more sophisticated
basis for classifying the hyperlipoproteinaemias but in Auckland at present they are
not used routinely, classification being based on the simpler (and cheaper)
measurements of total and HDL cholesterol and fasting triglyceride. As a
generalisation, Apo-B is associated with LDL cholesterol and apo-A with HDL.
APTT (activated partial thromboplastin time)
The APTT is a basic test used to detect abnormalities of coagulation involving the
intrinsic pathway. It is used to screen for deficiencies of plasma coagulation factors
(except Factors VII and XIII) or for the presence of an acquired inhibitor. The '1+1'
test is performed to distinguish between a deficiency and an inhibitor.
The APTT is usually sensitive to factor deficiencies <40% normal. It is most

commonly prolonged by deficiencies of contact factor FXII, FVIII (reduced in
classical haemophilia and von Willebrand's disease) and Factor IX (haemophilia B or
Christmas disease).
Marked prolongation of the APTT (>80 secs) is usually due to haemophilia if the
patient presents with bleeding, or due to Factor XII deficiency if the patient is
asymptomatic.
The lupus anticoagulant, found in the antiphospholipid antibody syndrome (qv), can
prolong the APTT markedly. It is usually associated with an increased thrombotic
tendency rather than bleeding.
Heparin therapy

The APTT is used to monitor standard or unfractionated heparin but not low
molecular weight heparin (LMWH) therapy.
Arcanobacterium haemolyticum
Previously called Corynebacterium haemolyticum. It is a gram-positive bacillus

which causes pharyngitis and cutaneous infections. Acute pharyngitis due to A.
haemolyticum is indistinguishable from that caused by S. pyogenes (Group A
streptococci). In nearly half of all reported cases a maculopapular exanthem is
present which resembles the rash of scarlet fever. Pharyngitis occurs mainly in
adolescents and young adults. No prospective trials have been performed to see if
therapy offers any benefit. A. haemolyticum is susceptible in vitro to erythromycin,
clindamycin and tetracycline; penicillin susceptibility is variable. Cotrimoxazole
resistance is common. Pencillin treatment failures have responded to erythromycin.
Arsenic
Acute poisoning
specimens: random urine
and whole blood (heparin)
Chronic exposure
specimen: 24 hr-urine with 10 ml HCl in plastic container
or early morning urine collected at end of working week
ref. range: normal <0.7 µmol/L

toxic >1.3 µmol/L
Arsenic is the 20th most common element in the earth's crust and is found in most
living organisms and in low concentration in water. Because a high urine level can be

due to non-toxic organic arsenic found in relatively high concentrations in fish and
shellfish, a high result should be repeated 2-3 weeks after abstaining from seafood.
Industrial exposure to toxic inorganic arsenic occurs in users of arsenical pesticides
and in the metal and marine paint industries.
Arthritis
Some of the diagnoses and tests to be considered include:
- septic arthritis – immediate joint aspiration (see Synovial aspirate) will give
definitive diagnosis of septic arthritis and differentiate it from gout
- gout and pseudogout – see Synovial aspirate and Uric acid
- rheumatoid arthritis, SLE and other connective tissue diseases. see under
disease heading
- reactive arthritis – see Arthritis, reactive
Arthritis, reactive
Reactive arthritis is an aseptic arthritis that develops after an infection elsewhere in

the body.
• post-enteric – Yersinia
– Chlamydia
– Campylobacter
– Salmonella
– Brucella
• post-venereal – Chlamydia
– Ureaplasma
Reiter's disease, which includes arthritis, conjunctivitis, and urethritis, is an example

of a reactive arthritis. 60 - 90% of affected patients are positive for HLA B27 antigen
(qv).

Ascorbic acid (Vitamin C)
specimen: whole blood (EDTA or heparin)
ref. range: 20 – 80 µmol/L
This test for suspected vitamin C deficiency is rarely indicated.
ASOT (antistreptolysin O titre)
Aspartate transaminase
see AST (aspartate transaminase)
Aspergillus
A fungus common in soil and decaying material and the cause of an invasive disease
in immuno-compromised patients. Diagnosis is by demonstration of hyphae in tissue
biopsy, sputum or culture.
We often recover A. fumigatus and occasionally other Aspergillus species from ear
swabs taken from patients with otitis externa. There is no easily applied antifungal
agent for this situation. Management requires thorough debridement and keeping the
ear dry. Adequate ear toilet is often possible only at an ENT clinic.

Allergic pulmonary aspergillosis is characterised by asthma and eosinophilia. The
total IgE level is often above 1000 IU/L. Aspergillus precipitins should be tested for
and skin prick testing arranged.
Aspirated fluids, synovial, pleural, ascitic etc
Culture and microscopy
Collect the specimen into two vacutainer tubes:
– plain tube (no additive)

– citrate tube – the citrate acts as an anticoagulant and makes microscopy easier.
If the volume of specimen is small, (<1ml) collect it all into the plain tube.
Cytology
There are two methods of preservation:
– add up to 25ml aspirate or fluid to 3ml 3.8% sodium citrate or 20ml EDTA.
Submit to lab as soon as possible, storing in fridge meanwhile; or
– add 50-75ml fluid to an equal volume of ethyl or methyl alcohol and add 3 units
of heparin/ml body fluid. Submit to lab as soon as possible, storing in fridge
meanwhile.
see also Synovial aspirate
AST (aspartate transaminase)

specimen: serum
ref. range:

Age (yrs) U/L
0-1 30-100
2-10 20-80
11-18 10-60
>18 5-45
AST is found in high concentrations in liver, skeletal muscle and cardiac muscle. It is
also found in red cells and small increases (up to 100 U/L) are found in haemolysed
specimens or those left standing for more than 6 hours after collection. Small
increases may be seen in the last trimester of pregnancy.
for more detail see Liver enzymes

Myocardial enzymes
ALT (alaninine transaminase or amino
transferase)
ATIII
see Antithrombin III (ATIII, antithrombin)
Atypical pneumonia
see Pneumonia
Mycoplasma pneumoniae
Legionella
Psittacosis (Chlamydia psittaci)
Chlamydia pneumoniae

Autoantibodies
specimen: serum
The list of autoantibodies used in the diagnosis of autoimmune disorders continues to

lengthen.
Specificities for particular diseases are seldom absolute and low titre auto-antibodies
can be found in apparently disease-free people. Observation over months or years
may show regression, no change or progression to clinical disease.
Each autoantibody is described in more detail under its own alphabetic entry.
For more detail see table below

Tissue disease autoantibody
adrenal cortex Addison's disease adrenal
islet cells Type I diabetes GAD
IA2
islet cell (ICA)
insulin (IAA)
thyroid hypothyroidism microsomal
thyroglobulin
Grave's disease TSH receptor
gastric pernicious anaemia intrinsic factor
parietal cell
small intestine coeliac disease gliadin (AGA)
endomysial (EMA)
reticulin
liver autoimmune hepatitis smooth muscle (SMA)
1° biliary cirrhosis liver kidney microsomal (LKM)
mitochondrial (AMA)
neuromuscular myasthenia gravis acetylcholine receptor
kidney Goodpasture's syndrome glomerular basement membrane
crescentric glomerulonephritis
testis seminal infertility sperm
skin pemphigus pemphigus
haematological ITP platelet antibodies
post-transfusion red cell
lymphocyte
antiphospholipid (APS) cardiolipin
connective tissue disease rheumatoid arthritis rheumatoid factor
SLE ANA
polydermatomyositis ds DNA
scleroderma ENA
© 2000 Diagnostic Medlab mixedView

CTD Terms of Use neutrophil cytoplasm
Page 61(ANCA)
Sjogren's syndrome
B
see beta
B12
see Vitamin B12
Bacterial swabs
Bacterial specimens are collected for identification of microorganisms and for

antibiotic susceptibility testing. The quality of the specimen is all-important and will
determine whether a pathogen is successfully isolated or whether a false negative
culture occurs.

Human pathogenic bacteria like a moist environment, close to body temperature
(37°C) with no exposure to toxic chemicals. Conversely they are killed by:
• drying • sunlight
• high temperatures • antiseptics
• low temperatures • antibiotics
To provide an optimum environment for swabs, we place them in transport medium

which should be stored at room temperature rather than at 4°C in the fridge.
Gonococci, for example, survive 24 hours in transport medium at room temperature
but only 2 hours at 4°C.
An exception is urines which should be stored in the fridge to prevent overgrowth of

contaminants.
Details about collecting swabs from specific sites will be found under their own
alphabetic headings.
• cervical • skin
• ear • sputum
• eye • throat
• nasal • urethral
• rectal • vaginal
Bacterial vaginosis
see Vaginal discharge
Bacteroides

An important group of anaerobic gram-negative bacilli. B. fragilis, which is part of
the normal flora of the bowel, has the ability to form abscesses when released into the
peritoneal cavity. Specimens from intra-abdominal sites must always be cultured
anaerobically as well as aerobically. Septicaemia and puerperal or post-abortion
sepsis often include B. fragilis as a major pathogen.
Bacteroides fragilis produces beta-lactamase which inactivates pencillin and

amoxycillin. Amoxycillin-clavulanate, metronidazole and clindamycin are the most
effective agents.
Bacteroides other than B. fragilis are grouped as Bacteroides species. Some may be
sensitive to penicillin. Antibiotic susceptibility testing should be discussed with a
clinical microbiologist.
Some species in the genus have recently been reclassified as Prevotella and
Porphyromonas species.
Barbiturates
see Phenobarbitone (anticonvulsant monitoring)

Drug screen – pre-employment screen and drugs of abuse
Bartonella henselae
see Cat scratch disease
Base excess

Basophils
specimen: whole blood (EDTA)
ref. range: 0-0.20 x 109/L
The basophil count is part of a routine blood count (qv).
Basophilia is rare as an isolated abnormality. Increases occur in chronic myeloid

leukaemia and other myeloproliferative disorders including polycythaemia rubra vera.
Bee and wasp venom allergy
These tests are generally done in a specialist rather than general laboratory setting.
The tests are of two sorts:
• skin prick testing

• specific IgE antibodies (RAST tests)
Tests are done for:
– honey bee
– paper wasp (polistes)
– German or common wasp (vespula)
Of the two, skin tests are the more sensitive and are preferred when performed by an
experienced allergist. A negative result using allergen at a concentration of 7µg/ml

makes it unlikely that there is important allergy or that immuno-therapy will be
required.
RAST tests are graded on a scale 0 to 4+ with a crude correlation between the result
and the severity of the patient's response.
Clinically the allergic response varies from local pain and inflammation at the site of
the sting, through an extended local reaction over a larger area, to a generalised
anaphylactic response with urticaria, flushing, angio-edema, and sometimes severe
bronchospasm and cardiovascular collapse. Any generalised response requires
referral to a specialist allergy physician for consideration of immunotherapy
(desensitisation) which can be highly effective.
Bence Jones protein (BJP)
specimen: random urine

or 24-hr urine for quantitation when monitoring myeloma
ref. range: not present in normal urine
In 1848, Bence-Jones described a protein in the urine of myeloma patients that

precipitated at 50°C and redissolved on boiling. It consists of free light chain
fragments (kappa or lambda) derived from IgG and IgA paraproteins found in serum
in myeloma and occasionally from an IgM lymphoma-associated paraprotein.
Because free light chains are small molecules they pass through the glomerular filter
whereas the larger paraprotein molecules are usually retained in serum.
Presence of BJP in urine is an indication that a paraprotein is malignant rather than

benign. In Bence Jones (light chain) myeloma there is no paraprotein in serum but a
heavy band of free light chains in urine which means that testing for myeloma must
include urine as well as serum electrophoresis.

BJP is detected in two ways:
• as an abnormal band found on EPP (electrophoresis) of concentrated urine
• as a kappa or lambda arc on IMF (immuno-fixation) of concentrated urine
Benign paraprotein
see Immunoglobulins, IgA, IgG, IgM
Beta carotene
see Carotene
Beta hCG
see hCG (human chorionic gonadotrophin)
Beta-hydroxybutyrate
specimen: serum
ref. range: 0 - 200 µmol/L
Beta-hydroxybutyrate is the test of choice when looking for ketosis in Type I

diabetics because of its greater sensitivity than the more commonly (and easily)
performed tests for "ketones", including dipsticks, which detect mainly aceto-acetic
acid.

Beta 2 microglobulin
specimen: serum
ref. range: <2.4 mg/L
ß2 microglobulin is elevated in autoimmune conditions where there is lymphocyte

activation or destruction.
• multiple myeloma — used for monitoring and prognosis

• HIV — levels above 4.0 g/L are more likely to progress to AIDS
• autoimmune disease
• viral infections
• lymphoid neoplasms
• renal impairment
Bicarbonate
specimen: serum
ref. range: <2 yrs 18 – 28 mmol/L
>2 yrs 22 - 32 "
Also known as total CO2, this is a crude acid-base measure. In metabolic acidosis,
bicarbonate is reduced, e.g. in diabetic ketoacidosis. In metabolic alkalosis, it is
increased – as in pyloric stenosis or the compensated respiratory acidosis of chronic
obstructive airways disease.

Bile pigments in urine
This old test was used in the diagnosis of liver disorders in the first half of this
century before liver enzyme assays were developed. Bilirubin is found in the dark
urine of obstructive jaundice and later in the course of hepatitis. Urobilinogen is
found in early hepatitis. It is colourless but darkens on standing. Bile pigments are
included in the routine strip used in urinalysis. Positive results are an indication for
measuring s. bilirubin and liver enzymes.
Bilharzia
see Schistosomiasis
Biliary calculi
see Gallstones

Bilirubin, conjugated (direct) and unconjugated
(indirect) fractions
total bilirubin = conjugated + unconjugated
specimen: serum
ref. range: conjugated bilirubin is about 10% of total but precision is not good
below a total of 50 µmol/L and at low levels 20% conjugated or even
30% may be normal.
Bilirubin fractions are used in two main situations:
• Persistent neonatal jaundice

A conjugated bilirubin above 20-30 µmol/L at age 3 weeks requires
consideration of biliary atresia/neonatal hepatitis.
see Bilirubin, total
• Isolated hyperbilirubinaemia
In Gilbert's syndrome (qv) and haemolysis, unconjugated bilirubin is the

predominant fraction.
Dubin-Johnson and Rotor's Syndromes are benign, inherited, conjugated

hyperbilirubinaemias.
see also Gilbert's syndrome

Bilirubin, total
specimen: serum
A. Hyperbilirubinaemia in children and adults
ref. range: children and adults 5-20 µmol/L
1. Hyperbilirubinaemia with raised enzymes
see Liver enzymes
2. Hyperbiliruinaemia with normal enzymes
• Disorders of hepatic excretion

– Gilbert's syndrome (qv), a common incidental finding,
is an unconjugated hyperbilirubinaemia
– Dubin Johnson and Rotor syndromes, much less
common but also found incidentally, are conjugated
hyperbilirubinaemias
– Crigler-Najjar syndrome is a rare severe unconjugated
hyperbilirubinaemia.
• Haemolytic anaemias
– uncommon but important. Check blood count, film,
reticulocytes, haptoglobins
• Other
– thyroid disease, iron overload, drug reaction, resolving
hepatitis
B. Hyperbilirubinaemia in neonates – neonatal jaundice
specimen: serum, usually micro-collects which give more variable results

than a venous specimen
ref. ranges:

Age µmol/L
cord blood 15-50
1-2 days 30-150
3-7 days 50-200
1-2 wks 10-100
3-4 wks 5-50
>1 mth 5-20
These are a rough guide to indicate levels that are likely to be comfortably
within healthy limits for most neonates. Acceptable limits are lower for
premature babies.
The problem with neonatal bilirubins is that many healthy, thriving babies
have levels higher than the above because of two common benign conditions;
physiological jaundice and the jaundice of breast-feeding.
Diagnosis of these benign conditions relies on exclusion of serious

pathologies.

1. Benign Jaundice
Physiological jaundice
This is due to breakdown of foetal red cells, "immaturity" of the

liver's glucuronyl transferase system and increased bilirubin resorption
from bowel meconium in infants as maturation is completed during the
first days and weeks of life.
The bilirubin reaches a peak in 5 days (sometimes as high as 300

µmol/L) and in bottle-fed infants disappears in 2 weeks.
Jaundice of breast-feeding
This condition, an extension of and inseparable from physiological

jaundice, is due to the presence of maternal hormone in breast milk
inhibiting the maturation of glucuronyl transferase.
Bilirubins can stay high for a long time. In about 2-5%, levels reach
250-350 µmol/L by the 3rd week, remain high for 3-4 weeks, falling
to normal over another 1-3 months.
Despite being yellow, the infant thrives, feeds and grows. Changing to
bottle-feeding results in a prompt and sustained fall in bilirubin levels
and cessation of breast-feeding for 24-48 hours, with bilirubins before
and after, can be used as a diagnostic test whilst maintaining lactation
by manual expression.
2. Pathological jaundice
• Haemolytic disease of the newborn – Rhesus or ABO

incompatibility
Rhesus incompatibility
The most severe forms of this previously dreaded disease were due
to rhesus incompatibility between mother, (Rh -ve and with anti-Rh
antibodies) and baby (Rh +ve). The Rhesus system was first
described in 1940. Before that time, and until modern methods of
prevention and treatment were developed, these babies were born

dead or anaemic with jaundice at birth increasing rapidly in the first
days of life to cause long-term brain damage in the form of
kernicterus. In the late 20th century, kernicterus has almost
entirely disappeared but the fear of it lingers on.
Haemolytic disease is caused by anti -Rh antibodies in an Rh -ve

mother who has been sensitised during a previous pregnancy with
an Rh +ve baby whose red cells have spilled into the maternal
circulation at the time of placental separation.
Over the past 40 years this sensitisation process has been prevented
by injecting the mother at delivery with enough anti-Rh immune
globulin to render the foetal cells non-antigenic.
Sensitisation of the mother by an incompatible blood transfusion,

unavoidable before 1940, is now an exceptionally rare event.
Despite the success of preventive measures in most patients,

haemolytic disease will still occasionally be found.
The at-risk mother is Rh-ve and will have red cell autoantibodies
when screened ante-natally,
Haemolytic disease in the at-risk infant, is diagnosed by examining

cord blood at birth looking for:
— Rh+ve infant
— +ve Coombs test
— hyperbilirubinaemia using this table as a guide:
µmol/L
full term premature
normal <50 <25

uncertain 50-125 25-80
affected >125 >80
ABO incompatibility and other blood groups

This is more common but rarely severe enough to require exchange
transfusion. The at-risk situation is found in 20% of pregnancies. Usually
the mother is Group O and the infant Group A or B. Prior sensitisation is not
required and haemolysis can occur in the first pregnancy.
Maternal antibody tests are of no use and often the direct Coombs test on cord
blood is negative.
Other blood groups include Kell (K), Duffy (Fya, Fyb) and Kidd (Jka, Jkb). For
these incompatibilities, maternal antibodies will be present and the direct
Coombs on cord blood positive.
• Neonatal bacterial infections

Septicaemia is life-threatening and the
infant is obviously unwell. Urinary tract
infections are more easily overlooked,
the infant being less obviously unwell to
begin with.
• Hypothyroidism, cystic fibrosis and galactosaemia

Tested on all neonates by way of the Guthrie Card blood spots – see
Neonatal screening
• G-6-PD deficiency (qv)

The vitamin K given routinely to neonates elevates bilirubin in G-6-PD
hetero- and homozygotes. On rare occasions homozygous infants
(usually males of SE Asian or Mediterranean origin) develop a severe
haemolytic process in the neonatal period, especially if exposed to
certain drugs.
• Biliary atresia and neonatal hepatitis

The infant is often clinically well during the first few weeks but
thereafter there is an increasing obstructive jaundice shown by rising

total bilirubin, a raised level of conjugated bilirubin, pale faeces and
dark urine.
When and how often should bilirubins be measured?
As always, clinical judgement and experience are more important than rigid guide-
lines.
A healthy term baby, growing and feeding well, without visible jaundice, does not
need to have its bilirubin measured.
Premature babies need to be watched more carefully than full-term babies,

particularly during the first 3-5 days.
Jaundice in the first 24 hours of life is not benign.
If the jaundiced baby is unwell, the underlying cause must be identified urgently.
If bilirubin levels continue rising after the first week or so, a cause should be sought.
How accurate is the test?
The short answer to this is "not very". At a level of 325, repeated tests on the same
baby will show results varying between 300 and 350 which is the difference between
referring to hospital for treatment under lights or leaving at home. Reasons for this
variance are:
• problems with specimen collection. An experienced blood-collector obtaining

a free flow of blood will get better results than an inexperienced person
obtaining a scanty, haemolysed specimen. Haemolysis may give a result
which is falsely low by up to 30-50 µmol/L.

• different laboratories use different methods
• even at best, methods have a variance of ± 7%
• the baby's bilirubin level varies throughout the day, depending on when it was
last given water or milk and other variables.
What levels require treatment?
The treatment of pathological jaundice will depend on the underlying cause.
Once it has been decided the jaundice is benign, the baby is treated under lights if the
bilirubin exceeds cut-off limits, usually 350 µmol/L in a full-term baby more than 3
days old. The threshold may be lower in premature babies and where the bilirubin is
rising rapidly e.g. >250 @ 48 hrs.
For reasons given above, a baby with a result of 350 will sometimes be referred to
hospital only to be sent back home because its in-hospital result is 320.
Levels above 400, sometimes found in infants who have escaped observation, always
require urgent and immediate referral.
Biological variation
see Variation
Biopsy specimens for culture
Send in sterile container with sterile saline and label clearly "for culture".

BJP
see Bence Jones protein (BJP)
Blastocystis hominis
A protozoan parasite whose status as a cause of diarrhoea is still unresolved. It can

be observed in the stool of asymptomatic people. Metronidazole, 400-800mg 8-
hourly for 10 days, may be effective treatment.
Bleeding disorders
see Coagulation screen
Bleeding time
ref. range: up to 8 minutes
The test is performed as part of the standard coagulation screen.

In practice it is a measure of platelet function though when the platelet count is less
than
30-50 x 109/L the bleeding time may be prolonged due to the reduced numbers of
platelets.
The test is performed using a template to make a standard incision in the forearm.
The time taken for bleeding to stop is a measure of platelet plug formation. The test
is operator dependent and sensitive to technical variables.
It is a useful test in the diagnosis of inherited minimal bleeding disorders associated

with a platelet function defect such as von Willebrand's disease. Other congenital
causes of a long bleeding time include rare platelet aggregation abnormalities
(Glanzmann's thrombasthenia) or storage pool defects. It is often prolonged in
patients on aspirin therapy and in chronic renal failure. Acquired platelet dysfunction
also occurs in immune thrombocytopenia (ITP) where the bleeding time is prolonged
more than predicted for the reduced platelet count, in myeloproliferative disorders
(essential thrombocythaemia), in paraproteinaemias (MGUS, myeloma) and
sometimes in association with viral illness. The bleeding time is a poor predictor of
the risk of surgical bleeding.
Blood collection tubes
see Tubes for blood collects
Blood count
ref. range:
• red cells

Age Hb g/L PCV MCV fl MCH pg
Cord Blood 136 - 196 0.40 - 0.60 100 - 120 33 - 41
1—4 days 165 - 215 0.50 - 0.70 107 - 128 33 - 41
5—14 days 150 - 200 0.41 - 0.65 93 - 130 32 - 40
2—5 weeks 110 - 185 0.31 - 0.54 93 - 130 31 - 40
5—7 weeks 105 - 135 0.30 - 0.43 92 - 120 30 - 39
7—12 weeks 100 - 125 0.28 - 0.37 80 - 105 28 - 35
3—12 months 110 - 140 0.30 - 0.40 66 - 90 23 - 31
1—3 years 110 - 143 0.30 - 0.44 66 - 90 23 - 31
3—5 years 110 - 143 0.30 - 0.44 74 - 90 23 - 31
5—12 years 115 - 152 0.33 - 0.47 74 - 90 23 - 31
Females 13—15 115 - 160 0.35 - 0.47 78 - 94 25 - 34

Males 13—15 yrs 116 - 165 0.37 - 0.48 78 - 92 25 - 34
Females >15 yrs 115 - 160 0.35 - 0.47 80 - 98 25 - 34
Males >15 yrs 130 - 175 0.38 - 0.52 80 - 98 25 - 34
Antenatals 100 - 150 0.31 - 0.47 80 - 98 25 - 34
• white cells
Age WBC b/L Band. Neut. Seg. Neut. Lymphs Baso. Eos. Mono.
0—7 days 10.0-25.0 0-0.6 2.0-13.0 2.0-8.5 0-0.2 0-2.0 0.3-2.5
1 wk—2yrs 5.0-17.0 0-0.6 0.5-7.0 2.5-12.0 0-0.2 0-1.0 0-1.0
2—12 yrs 4.5-14.0 0-0.6 1.2-8.3 1.5-7.3 0-0.2 0-0.5 0-0.9
>12 yrs 4.0-11.0 0-0.6 2.2-7.5 1.0-3.9 0-0.2 0-0.5 0-0.9
Antenatal 4.0-15.0 0-0.6 3.4-10.5 1.4-3.2 0-0.2 0-0.5 0-1.0
All cell counts are x 109/L.

Absolute counts for individual white cells give more information than the %
differential counts.
Excess or deficiency of each cell type is described under individual alphabetic entries.

• platelets
Age yrs Range
0 - 12 150 − 500 x 10 9 / L
>12 female 150 − 450 x 10 9 / L
male 150 − 400 x 10 9 / L
see also Thrombocytopenia

Thrombocytosis
Blood culture
Bacteraemia is usually found in life-threatening illnesses which need investigation in

hospital rather than at home. Nevertheless there are a few patients with low-grade
febrile illnesses due to infections that shed bacteria into the blood stream but without
causing overwhelming sepsis. These are found particularly in patients with cardiac
valvular disease or prostheses in the heart or elsewhere. We have at times grown
pneumococci, Listeria, Salmonella typhi. Almost any organism can cause
bacteraemia given the right circumstances.
Blood cultures should always be considered before starting antimicrobial therapy for
an undifferentiated febrile illness in a patient with a prosthetic heart valve.
Blood culture collection protocols vary from one laboratory to another. For adults
two sets of adequately filled bottles, depending on clinical situation, will isolate the
organism in >95% of bacteraemias. In this laboratory two sets are drawn with each
collect, an aerobic and an anaerobic bottle from each arm. Standard aseptic technique
must be rigidly adhered to if contamination by skin flora is to be avoided.

We use an automated detection system which allows prompt reporting of positive
cultures: 60% and 90% of all positives have growth detected within 24 and 48 hours
respectively. Slow-growing or antibiotic-damaged bacteria may take up to 7 days.
Blood film examination
Blood films are not routinely examined unless one or more of the blood count
parameters is shown to be abnormal by the electronic cell counting analyser. In
practice this means that films from 20% of blood counts are checked. The film report
describes the morphological appearance of red cells, white cells and platelets. Where
appropriate, the film comment will suggest a diagnosis and recommend follow-up. A
blood film examination will always be performed if specifically requested even if the
CBC (complete blood count) parameters are normal.
Blood gases & pH

specimen: 3ml arterial blood in heparinised syringe transported on ice.
ref. ranges: In Auckland and world wide, two sets of units are in use, traditional
(mm Hg) and SI (kPa).
Conversion factor, 1 kPa = 7.6 mm Hg

Traditional units SI units
pH 7.36-7.44 35-45 nmol/L
pCO2 35-45mm Hg 4.6-6.0 kPa
pO 2
80-100mm Hg 10.6-13.3 kPa
HCO3- 20-28 mmol/L 20-28 mmol/L
base excess -2 to +2 meq/L -2 to +2 mmol/L
O2 saturation 95-100% 0.95-1.00
metabolic alkalosis = base excess >2 mmol/L

metabolic acidosis = base excess <-2 mmol/L
Blood grouping
specimen: 1 EDTA (preferred) or 1 plain tube
ABO and Rh (D) phenotype are done routinely. The frequencies of the four main
groups in the ABO system and their naturally occurring antibodies are:
ABO Group Genotype Frequency Naturally occurring

(%) antibodies
O OO 46 anti A,anti B
A AA/AO 40 anti B
B BB/BO 9 anti A
AB AB 5 none
see also Crossmatch

Cord blood testing
Blood in faeces

see Faeces for occult blood: occult blood
Blood in urine
see Haematuria
Blood volume
Blood volume = plasma volume + red cell mass
Blood volume is measured when investigating polycythaemia (raised Hb

concentration) which may be:
• relative, due to reduced plasma volume

• absolute, due to increased red cell mass
see Polycythaemia
BMI, (body mass index)
weight in kg
BMI =
( height in metres ) 2

ref. ranges: 20-26 healthy weight range
(kg/m²) 26-30 overweight
>30 obese
18-20 underweight
<18 very underweight
The BMI, by adjusting weight according to height, provides a useful assessment of

nutritional status.
Body mass index
see BMI, (body mass index)
Bone marrow
By consultation with a haematologist.
Bone marrow trephine is performed routinely together with bone marrow cytology
(aspirate) and clot section. Chromosomes and cell marker analysis will be performed
whenever appropriate.
Bone marrow chromosome analysis
Chromosome analysis is commonly done in the leukaemias, myelodysplastic

disorders, and some lymphomas to help with classification, treatment and prognosis.

Bone marrow transplantation (BMT)
Bone marrow transplantation is being used more often. Allogeneic BMT from a
matched sibling donor is still a risky procedure with mortality up to 30% primarily
from graft versus host disease and infection. Autologous BMT, where the patients
are their own donor, has a much lower mortality risk. Stem cells, collected from
peripheral blood, are increasingly used in place of conventional autologous
transplantation. They are associated with rapid engraftment and reduced hospital stay
and cost. Autologous transplantation is also used in the treatment of solid tumours.
Longer term complications of BMT include infertility, secondary neoplasms and
endocrine dysfunction.
Bone turnover markers
When bone is resorbed, collagen cross-links are released as part of the break-down
process and excreted in urine where they provide a measure of bone turnover rate in
conditions such as Paget's disease, thyrotoxicosis, bone cancer, renal bone disease
and hyperparathyroidism. Tests include:
– N-Telopeptide
– deoxypyridinoline (DPD, Pyrilinks D)
– hydroxyproline — no longer used
Serum alkaline phosphatase (ALP) and urine calcium excretion, though less specific,
may also give a useful measure of bone turnover and the effectiveness of therapy.
see also N-telopeptide
Bordetella pertussis

This organism is the cause of whooping cough. Despite vaccination, the disease
remains endemic in New Zealand with outbreaks at about 4-yearly intervals.
Diagnosis is by growth of the organism from a swab. A fine wire nasopharyngeal

swab is passed through a nostril to reach the nasopharynx and left in place there for a
few seconds. If one nostril is blocked by a turbinate or deviated septum, use the
other. The swab is placed in routine transport medium for delivery to the laboratory.
Delay in transport of the specimen will decrease the chances of isolation.
Adults with a chronic cough may have chronic pertussis infection which can be
detected by measuring serum antibodies.
Erythromycin may reduce the duration of the disease if administered early and will
reduce infectivity. A fourteen day course of erythromycin is also recommended for
household and other close contacts.
Borrelia
Borrelia recurrentis, a spirochete transmitted by ticks or lice, causes relapsing fever.

B. burgdorferi causes Lyme disease. Neither disease is endemic in New Zealand but
they may occasionally be found in travellers. Tests for antibodies against B.
burgdorferi are available locally.
Branhamella catarrhalis
see Moraxella catarrhalis

Breast aspirate cytology
see Fine needle aspirate (FNA)
Breast tumour hormone receptors

specimen: breast tissue fixed in formalin as for histology.
More than half of all breast cancers have oestrogen receptors indicating the need for
endocrine therapy. They have a better prognosis than receptor negative tumours. The
test uses an immunoperoxidase labelled antibody applied directly to tissue sections.
Breath test
see Helicobacter pylori
Bromsulphthalein (BSP) test
no longer done
Bronchial brushings or washings
Cytology Smears are made from brushes and fixed in Cytofix immediately.
Washings are submitted to the laboratory as soon as possible for
cytocentrifugation.

Microbiology Collect washings into sterile containers. Please indicate special
requests such as culture for TB or fungi.
Bronchitis, acute or chronic
Acute bronchitis is often a viral disease and sputum evaluation is seldom useful.
In chronic bronchitis the important pathogens are Strep. pneumoniae and

Haemophilus influenzae, both usually susceptible to doxycycline, cotrimoxazole,
amoxycillin-clavulanate and cefaclor. 10% of H. influenzae are resistant to
amoxycillin.
Brucella antibodies
specimen: serum
Brucellae are gram-negative bacilli infecting domestic animals, particularly cattle and
pigs. Human infection occurs in farmers and meat-workers as an occupational hazard
or by ingestion of contaminated milk products.
Over the past 30 years, brucellosis has been virtually eliminated from New Zealand
cattle and human brucellosis, when found here, will almost invariably have been
contracted abroad, including the Pacific Islands.
Agglutination and Coombs antibody tests detect both IgM and IgG antibodies.
Results may be negative in the early stages of acute disease and sometimes antibodies
are not detected at any stage. Seroconversion, however, or a >4-fold increase in
antibody titre, strongly suggests active infection.

Distinguishing previous resolved infection from chronic continuing infection is
impossible using antibody tests alone.
BSP (bromsulphthalein test)
no longer done
Buccal smears
This test for sex chromatin (the 2nd X chromosome in females) has been replaced by
karyotype analysis.
see Cytogenetics
Bulimia
see Anorexia nervosa and bulimia
Butyrate
see Beta-hydroxybutyrate

C
C1 (esterase) inhibitor
see Complement, C1 inhibitor (C1 INH)
C3
see Complement fractions C3 and C4
C4
see Complement fractions C3 and C4
CA 15-3
specimen: serum
ref. range: <30 U/ml
Sometimes used for monitoring established breast malignancy.

Elevations are found in other benign and malignant conditions.
CA 19-9
specimen: serum
70 - 80% sensitive in late stage pancreatic carcinoma. May be elevated in other

gastrointestinal malignancies.
CA 72-4
specimen: serum
ref. range: <4.6 u/ml
Used for monitoring gastrointestinal (especially stomach) malignancies, and

mucinous ovarian malignancies where it is more often elevated than Ca 125.
CA 125
specimen: serum
Mainly used for monitoring treatment and progress in established ovarian cancer.
Values >65 are consistent with ovarian malignancy in a patient with an ovarian mass.
Elevated levels may be found in other malignancies, or occasionally other non-

malignant conditions including endometriosis, PID (pelvic inflammatory disease),
cirrhosis, renal failure and pregnancy.

Cadmium
ref. range:
nmol/L
non-smokers < 36
smokers < 90
potentially lethal > 270
Used where toxicity is a possibility in workers involved with cadmium in industry.
Eating contaminated shellfish may raise levels. If in doubt, repeat after two weeks
abstention from seafood.
Caeruloplasmin
see Ceruloplasmin (copper oxidase)
Calciferol
see Vitamin D
Calcitonin
specimen: plasma (EDTA)
ref. ranges: female <17 pg/ml
male <26 pg/ml

Calcitonin is a hypocalcaemic hormone produced naturally by the thyroid. There are
no clinical excess or deficiency states.
Calcitonin's clinical use is as a marker for medullary thyroid carcinoma either as an

isolated tumour or as part of MEN (qv) multiple endocrine neoplasia, type II, along
with phaeochromocytoma and parathyroid tumours.
Calcium (total)
specimen: serum
ref. range:
0 - 1 mth 1.90 - 2.85

1 mth - 12 yrs 2.20 - 2.70
>12 yrs 2.10 - 2.55
A protein correction is routinely applied:

adjusted Ca + + = observed Ca + + + 0 .02 (40 - albumin)
Hypercalcaemia
The two most important causes are:
• Hyperparathyroidism due to parathyroid adenoma
The parathyroid hormone (PTH) level is increased.

Severe 1° hyperparathyroidism with calcium levels above 3.00 mmol/L will
require surgical removal of the parathyroid adenoma.

Minor asymptomatic degrees are common, however, and are generally
managed with observation rather than surgery, particularly when s. calcium
<2.75. These "benign" hypercalcaemias are much more common in the
elderly.
• Malignant disease, particularly metastatic tumour in bone, multiple myeloma

or cancer of lung, breast or urinary tract, producing an ectopic PTH-like
hormone, PTHrP (PTH related Peptide).
Other causes of hypercalcaemia include:
• drugs – vitamin D
thiazides
lithium
antacids
• thyrotoxicosis
• sarcoidosis
• familial hypocalciuric hypercalcaemia
• renal transplantation
• Paget's disease with immobilisation
Hypocalcaemia
• chronic renal failure
• vitamin D deficiency
• hypoparathyroidism (usually post-thyroidectomy)
• drugs — anticonvulsants
— frusemide
— biphosphonates
— oral phosphate
• malabsorption
• pancreatitis
• hypomagnesaemia

Calcium (ionised)
specimen: serum
ref. range: 1.15–1.35 mmol/L
About half of total serum calcium is bound to albumin and inactive. The other,
ionised half is the physiologically active fraction. Ionised calcium levels are raised in
sera with an acid pH and lowered when alkaline.
For most clinical purposes, adjusted total calcium is adequate but in severe protein
abnormalities, including malignant paraproteinaemias and chronic renal failure,
ionised calcium may be more useful.
Calcium, urine
specimen: 24-hr urine collected into HCl
ref. range: 2.5–7.5 mmol/day
Some patients with recurrent renal calculi have a high urinary calcium output –
idiopathic hypercalciuria. Serum calcium must be checked to exclude
hypercalcaemia.
Calculi, biliary
see Gallstones
Calculi, renal

see Renal calculi
Campylobacter jejuni/coli
Infections with Campylobacter jejuni or Campylobacter coli cause 60% of bacterial

diarrhoea in the community. These organisms cause an acute enterocolitis which can
be associated with intense abdominal pain. The average incubation period is 3 days;
most patients recover within a week. Antibiotic treatment is usually not required but
for severe infections erythromycin is effective. Treatment with quinolones is not
recommended because resistance to them emerges commonly and rapidly. Untreated
patients may excrete Campylobacter in their faeces for 2–3 weeks but
transmissability is low and it is not usual to put restrictions on otherwise healthy food
handlers who are excreting the organism.
Campylobacter pylori
see Helicobacter pylori
Candida
Candida albicans, the principal pathogenic yeast in humans, is a member of the

normal flora of the gut, respiratory tract and vagina. It can gain dominance under
certain conditions such as diabetes, antibiotic use and suppression of the immune
system. Other species of Candida which are occasionally isolated cause the same
type of infection as C. albicans. For most, the treatment is the same as for C.
albicans.
The main sites and types of infection are:

Vulvo-vaginitis Predisposing factors are antibiotics, diabetes, pregnancy and
progestagens. Some individuals suffer from recurrent thrush for no detectable reason.
A random glucose should be checked to exclude diabetes.
specimen: vaginal swab in transport medium
Skin Infection occurs in warm moist areas such as the groin, perianal region, axillae,
the breasts or in interdigital webs. It is often seen in those who frequently immerse
their hands in warm water, such as dishwashers.
specimen: skin swab in transport medium
Nails Candida can cause a painful red swelling of the nail fold resembling pyogenic
paronychia, This may progress to nail involvement (onychomycosis).
specimen: skin swab in transport medium

nail scrapings for mycology will grow Candida if present
Mouth Infections are found mainly in infants and show up as white adherent patches.
Laboratory identification is not usually necessary but a swab will grow the yeast.
Systemic candidiasis Found in immunocompromised patients or in association with

prostheses.
Cannabinoids
specimen: random urine (no preservative)

Cannabis is rapidly absorbed into fat depots with cannabinoids remaining detectable
in the urine for up to 1 - 2 weeks after a single exposure. In chronic users,
cannabinoids remain detectable for up to 6 weeks after cessation.
Cannabis
see Cannabinoids
Carbamates
Carbamates are insecticides similar in their mode of action to organophosphates (qv)

but with a shorter duration of effect and lower order of toxicity.
see Cholinesterase
Carbamazepine (Tegretol)
see Anticonvulsants
Carbon dioxide (CO2)

Bicarbonate

Carbon monoxide
see Carboxyhaemoglobin
Carboxyhaemoglobin
specimen: whole blood (heparin)

ref. range:
COHb as % of total Hb
non-smokers 0.5 - 1.5
smokers 2.0 - 9.0
toxic levels:
mild symptoms 15 - 20
moderate symptoms 20 - 40
severe symptoms 40 - 60
often fatal >60
The affinity of CO for Hb is 200 x that of oxygen.
CO toxicity is mainly due to deliberate or accidental exposure to car exhaust fumes.
Levels fall about 15% per hour in air after removal of the CO source. Oxygen
treatment, particularly hyperbaric, accelerates clearance of CO.

Carcinoembryonic antigen (CEA)
specimen: serum
ref. range: <3.0 µg/L non-smokers
<5.0 µg/L smokers
CEA is elevated in some malignancies, particularly of the bowel. It is used for

monitoring treatment of tumours and for detecting recurrence but because of its low
specificity it is not used diagnostically in patients without known malignancy. Non-
malignant elevations occur particularly in disorders of liver, blood and lungs but are
usually below 20 µg/L.
see also Tumour markers
Carcinoid syndrome
see HIAA (5-hydroxy indole acetic acid)
Cardiac enzymes
see Myocardial enzymes

Cardiolipin antibodies (aCL)
specimen: serum
ref. range: IgG aCL <5 GPL
IgM aCL <5 MPL
High levels of the IgG antibody are found in:-
• antiphospholipid syndrome (qv)

• SLE
• other autoimmune disorders
• in some healthy people
A first indication of aCL may be a "false positive" VDRL or RPR test during routine
antenatal screening.
Low titre antibodies may be transient and are of uncertain significance.
see also Antiphospholipid antibody syndrome (APS)
Cardiovascular disease (CVD) risk assessment

In cardiovascular disease until relatively recently, each risk factor (e.g. serum
cholesterol) has been treated in isolation but the preferred option now is to present all
risk factors integrated into a single figure – the 5-year absolute cardiovascular risk –
and select treatment options according to the level of risk.
A CVD event is any of the following:
• Myocardial infarct (MI), angina, cardiac death, congestive heart failure (CHF)

• stroke, transient ischaemic attack (TIA)
• claudication
A 5-year absolute risk of say 10% means that of 100 patients with a similar risk
profile, 10 will have a CVD event in the next 5 years.
Or, put another way, a patient with a 10% absolute risk has a 1 in 10 chance of a
CVD event within 5 years.
Absolute risk is automatically assessed as very high (>20%) if the patient has any of
the following:
– known CVD (MI, angina, CHF, stroke, TIA)

– diabetic nephropathy
– known familial dyslipidaemia (see lipid disorders)
Otherwise risk is calculated using the tables overleaf; or using the appropriate
programme in your computer; or by having the laboratory add it your patient's lipid
profile in which case you will have to add information on the laboratory request form
– diabetes yes/no
– systolic BP
– smoker yes/no
– personal history CVD (automatically >20%)
Age is a potent risk factor and above 70, risk is always high.
If total cholesterol is >8 mmol/L or total/HDL ratio is >8, the patient is always
classified as at least high risk (i.e. >15%).

see also Cholesterol
Lipid disorders
MEN
No diabetes Diabetes
nonsmoker smoker nonsmoker smoker
ratio of total cholesterol:HDL ratio of total cholesterol:HDL
4 5 6 7 8 4 5 6 7 8 4 5 6 7 8 4 5 6 7 8
180/105 180/105
160/95 AGE 160/95
140/85 70 140/85
120/75 120/75
180/105 180/105
AGE
Blood Pressure
160/95 160/95
Blood Pressure
140/85 60 140/85
120/75 120/75
180/105 180/105
160/95 AGE 160/95
140/85 50 140/85
120/75 120/75
180/105 180/105
160/95 AGE 160/95
140/85 40 140/85
120/75 120/75
4 5 6 7 8 4 5 6 7 8 4 5 6 7 8 4 5 6 7 8
To use tables:
— identify table relating to person's gender, diabetic status, smoking status, age.
— within the selected table, find the cell nearest to the person's blood pressure
and ratio of total cholesterol : HDL.
— use cell shading from key on opposite page to identify risk level.

WOMEN
No diabetes Diabetes
nonsmoker smoker nonsmoker smoker
4 5 6 7 8 4 5 6 7 8 4 5 6 7 8 4 5 6 7 8
180/105 180/105
160/95 AGE 160/95
140/85 70 140/85
120/75 120/75
180/105 180/105
160/95 AGE 160/95
Blood Pressure
Blood Pressure
140/85 60 140/85
120/75 120/75
180/105 180/105
160/95 AGE 160/95
140/85 50 140/85
120/75 120/75
180/105 180/105
160/95 AGE 160/95
140/85 40 140/85
120/75 120/75
4 5 6 7 8 4 5 6 7 8 4 5 6 7 8 4 5 6 7 8
high >30%
25-30%
20-25% Risk Level:

Percent chance of
15-20%
a cardiovascular
10-15% event in 5 years
5-10%
2.5-5%
low <2.5%

Carotene
specimen: serum, protected from light to prevent photo-decomposition.
ref. range: 0.2–1.5 µmol/L
Carotene levels are used in the diagnosis of carotenaemia, an orange-yellow

coloration of the skin (but not conjunctivae) that can look like jaundice. The usual
cause is a high intake of vitamin A precursors in carrot or other coloured fruit or
vegetable juice but some systemic illnesses, including hypothyroidism, diabetes, liver
and renal disease, can cause carotenaemia. Because carotene is lipid-soluble,
hyperlipidaemias can give elevated levels. Low values have been used as an indicator
of malabsorption but specificity and sensitivity are poor.
Casts in urine
see Urinalysis (routine biochemistry and microbiology) and UTIs (urinary tract
infections)
Catecholamines
specimen: 24–hr urine with 20ml 6M HCl as preservative.

Specimens with a pH above 3 (indicating insufficient or no acid) cannot be
analysed.
In children, a spot urine can be used, delivered to the laboratory as soon as

possible for adjustment of pH.

ref. range:
Adult µmol/L/day
noradrenalin 0.08 - 0.47
adrenalin 0.00 - 0.11
dopamine 0.4 - 3.0
Different ranges are used for children.
Indications
Phaeochromocytoma 25% of the population have hypertension but only a fraction of
these can or should be screened for a phaeochromocytoma. Particular indications are:
• symptoms, including sweating attacks, severe headaches, palpitations,

nervousness, chest pain; flushing attacks are very uncommon.
• episodic hypertension (not always present)
• moderate or severe hypertension in pregnancy or in young people.
• adrenal mass
Neuroblastoma These usually present as an abdominal mass in children under the

age of 5.
Number of specimens When clinical suspicion is low, a single normal result is

sufficient but when suspicion is high, up to three specimens should be tested,
preferably collected during or just after symptoms.
Interpretation
The typical phaeochromocytoma gives a noradrenaline level of 1.0 – 2.0 µmol/day.
Occasionally the adrenaline level is elevated but usually it and the dopamine are near
normal. In malignant phaeochromocytomas (10% of the total), dopamine tends to be
elevated as well as noradrenaline.
The typical neuroblastoma shows a huge increase in dopamine.

Non-tumour elevations can be caused by anxiety, stress and exercise, particularly in
the case of dopamine where elevations can be up to twice the upper limit. Small,
isolated elevations of dopamine can usually be ignored.
Essential hypertension can be associated with a minor increase in noradrenaline,

usually less than twice the upper limit.
Medication
Noradrenaline is increased by amphetamines, alpha- and beta-blockers, vasodilators,
theophylline, phenothiazines and tricyclic antidepressants.
Noradrenaline is decreased by clonidine, methyldopa, and bromocriptine.
Dopamine is massively increased by levodopa.
Cat scratch disease

Specimens:
1. culture (slow - up to 28 days)

– blood (EDTA).
– tissue or FNA in sterile container
2. serology
– paired sera, 2-3 weeks apart
3. histology, cytology
– formalin-fixed tissue, usually lymph node, for histology
– FNA material for cytology

Cat scratch disease (CSD) is a self-limiting febrile illness with localised tender
lymphadenopathy caused by Bartonella (previously Rochalimaea) henselae which is
transmitted when a bacteraemic cat or kitten bites or scratches a human. In the
United States, where one third of households have a cat, the annual incidence of CSD
is 100 cases/million population, 80% of them in children.
Although CSD was first reported in 1931, it is only recently that B. henselae, a
fastidious slow-growing, gram-negative rod, was identified as the pathogen
responsible. A study of cats in Auckland found 17% with B. henselae bacteraemia.
Fleas transfer the organism from cat to cat and flea control is a useful preventive
measure.
Severe systemic illness can occur in immuno-compromised individuals.
Treatment. Pain relief may be required. Steroids are generally ineffective. There are
no controlled trials to help choose an antibiotic but for those with prolonged fever
and/or severe lymphadenitis, erythromycin, doxycycline, clarithromycin,
ciprofloxacin, aminoglycosides and sulphamethoxazole/trimethoprim have been used.
Therapy should be discussed with an infectious disease specialist.
CBC (complete blood count)
see Blood count
CD4 T-lymphocytes
specimen: whole bloods

lymphocytes are stable for only 6 hours in EDTA but in ACD tubes
they are stable for several days.

ref. range: adult 500-1650 cells/µl
The CD4 count (or CD4/CD8 ratio) is used to monitor the T-lymphocyte status in
HIV patients and the immune defect induced by the adenosine analogues used to treat
some haematological malignancies. As counts fall below 200/cmm, opportunistic
infections become increasingly common.
CD59
An absence of CD59 activity on the cell surface of red cells characterises paroxysmal
nocturnal haemoglobinuria (PNH).
see PNH
CEA
see Carcinoembryonic antigen (CEA)
Celiac disease
see Coeliac disease (gluten sensitive enteropathy)
Cerebrospinal fluid
see CSF (cerebrospinal fluid)

Ceruloplasmin (copper oxidase)
specimen: serum
ref. range: 0.15 – 0.45 g/L
Ceruloplasmin is reduced in hepatolenticular degeneration (Wilson's disease), and

Menke's kinky (steely) hair syndrome.
Oestrogens, anticonvulsants and inflammation cause elevations – ceruloplasmin is a

late acute phase reactant. 95% of serum copper is carried by ceruloplasmin.
see also Copper
Cervical cytology
specimen:
The specimen is collected by a spatula, a combination of spatula and cytobrush, or a

cervix broom.
The cells must be representative of the cells lining the cervix. Squamous cell cancer
of the cervix, which accounts for 60-80% of invasive cancers, begins as cervical
intraepithelial neoplasia at the squamocolumnar junction. It is important to sample
this site to detect early changes.
The ideal sample consists almost entirely of squamous cells which line the ectocervix
and a small number of endocervical glandular cells to indicate that the
squamocolumnar junction has been sampled.

A. Collecting specimens:
There are two methods:
• conventional pap (papanicolaou) test

• Thin Prep pap test
1. Conventional Pap test
Essentially unchanged for the last 50 years, this test has saved the lives
of many women reducing mortality from cervical cancer by more than
70%.
Preparation
Write the patient’s name on the frosted end of the slide in pencil (HB
is fine) and have the fixative (Cytofix or Cytospray) ready for use.
Taking the smear
Using a speculum display the cervix and ensure the external os is

accessible. Carefully wipe away excess mucus and inspect the cervix
in good light. If the cervix looks abnormal the women should be
referred for colposcopic examination regardless of the cytology report.
The specimen should be collected with either a spatula and cytobrush

or a cervix broom.
Spatula and Cytobrush
The spatula specimen is collected first because of the tendency of the

cytobrush to causebleeding.
The tip of the spatula is inserted into the cervical canal and carefully
rotated through 360º obtaining cells from the ectocervix,
transformation zone and lower endocervix. The spatula must make
sustained contact with the cervix throughout the whole rotation if
segments are not to be missed.

While an adequate sample is often obtained just with a spatula, the addition
of a cytobrush usually ensures the presence of endocervical cells and
permits good sampling of the canal if this is where the squamocolumnar
junction is situated. Adenocarcinoma of the endocervix and its precursor
adenocarcinoma in situ (AIS) may also be detected in asymptomatic
women.
Cytobrush smear
Indications for cytobrush smears are:
• repeat smears on patients with abnormalities e.g. CIN (cervial intraepithelial

neoplasia), HPV (human papiloma virus).
• where the anatomy of the canal has been altered by age as in post-menopausal
women or by treatment such as cone or Lletz biopsy.
• repeating a smear where previously no endocervical cells were obtained.
• abnormal bleeding

Cytobrush Method The Cytobrush is gently inserted into the endocervix canal and
rotated one full turn. The contents of the brush are transferred to the labelled slide
using a rolling or rotary motion along the surface of the slide. Collection of the
obligatory spatula smear must precede that of the cytobrush smear.
The specimen, once smeared, needs to be fixed within 4-5 seconds to prevent fixation
artefact.
Fixation
Two methods are commonly used.
1. Coplin jar
This is a glass or plastic jar with slots in the side of the jar to ensure the slides
stand up in the jar and do not touch their neighbours. The Coplin jar is filled
with cytofix.
It is important to keep the lid on the jar as this prevents evaporation of the
cytofix which should be changed every 3-4 days or every 15-20 slides.

The slides need to be immersed for at least 15 mins. Wet slides may be then
placed in plastic (pink) slide mailers and sent to the laboratory.
2. Cytospray
Cytospray is available in either 100 or 200ml bottles with an environmentally

friendly pump action spray. Cytospray is not the same as cytofix. Cytospray
is 95% alcohol with wax added to prevent rapid evaporation of the alcohol
once sprayed onto the slide.
It is important to hold the spray bottle at least 20 cm from the slide and
produce a good powerful fine droplet spray. If the spray bottle is held too
close to the slide or large droplets are created then the cells may be damaged
and the slide rendered uninterpretable. The slide may be placed in the plastic
slide mailers, sprayed and the mailer closed and sent to Diagnostic.
Can the cytobrush smear go on the same slide as the spatula smear?
The answer is yes, provided you take precautions to ensure there is no delay in
fixation.
Here are two methods:
• “Store” the spatula in the moist environment of the posterior vaginal

fornix after the spatula smear has been taken, while the cytobrush
specimen is taken. Spread the smears on opposite halves of the slide in
quick succession and fix immediately.
• Spread the spatula specimen on one half of the slide. Immediately cover
the other half with a layer of paper and spray the spatula smear taking care
that no fixative runs under the paper or through it onto the unused half. If
this happens cells will not stick to the slide and will be lost during
processing. Now collect the cytobrush smear and spread it on the
remaining half slide. Spray with fixative.
• Sometimes it may be necessary to use two separate slides. Collection and

fixation of the spatula smear is completed before collecting the cytobrush
smear. While this doubles the screening time, for the patient’s sake we

would rather have a good sample on two slides than a less than optimal
sample on one slide.
Cervix broom
• This device is used alone.
• The central bristles of the broom are inserted into the endocervical canal deep
enough to allow the shorter bristles to fully contact the ectocervix. Push
gently, and rotate the broom in a clockwise direction 2 to 3 times.
• Gently wipe the cell sample onto the glass slide as if one were using a
paintbrush, first n one direction then in the other direction making sure all the
bristles and both sides come in contact with the slide. Repeated brushing back
and forth is not recommended as this will damage the cells.
• Fix the slide immediately.
B. Thin Prep Pap test
This is a new way of processing cells taken from the cervix, utilising fluid-
based specimen collection.
The sample is collected in the normal way but instead of smearing the sample
on a slide, it is rinsed in a fluid containing fixative. The sample is put into a
machine which filters out most of the blood and inflammatory exudate and
prepares a smear with a thin even layer of cells. The smear is then screened in
the normal way by a cytology screener.
The advantages of this system are:
1. Nearly all the cells collected are transferred to the sample providing a
representative homogeneous smear.
2. There are no preparation artefacts such as air drying and obscuring

blood and inflammatory debris are removed.

3. Multiple slides can be prepared from one sample and part of the
sample might be used for ancillary studies e.g. molecular probes for
identifying Chlamydia, HPV, etc.
In clinical trials the Thin Prep Pap Test has been shown to have the following
advantages
• it is more sensitive than the conventional pap test in detecting

abnormalities.
• it gives better quality slides leading to a decrease in the number of

smears called unsatisfactory or less than optional.
• fewer smears are reported as atypical squamous cells of uncertain

significance.
Specimen collection
1. The specimen is collected as for a conventional smear except that a plastic

spatula is used rather than a wooden one.
2. The collection device is rinsed vigorously in PreservCyt ® solution. The

cytobrush or cervix broom should be rotated at least 10 times in the solution
and then discarded. The bristles of the cytobrush and cervix broom should
be forced apart on the side and bottom of the collection vial.
3. The cap of the vial should be tightened so that the tongue line on the cap
passes the tongue line on the vial.
4. Record the patient's name on the vial and then place with the completed
cytologyrequest form in a biohazard bag for collection by the laboratory.
This technology appears to offer an improved method of processing a cervical smear

which may have a significant impact on reducing false negative Pap smears. It
remains uncertain whether the additional cost of Thin Prep is justified. However, if
the number of repeat smears, unnecessary procedures and number of women who
develop invasive cervical cancer can be reduced using this technology, the costs of
cervical cancer screening and treatment may ultimately be reduced.

B. Cervical Cytology Reports
The Bethesda system reports under three headings:
1. Adequacy of specimen
— whether squamous cells are scanty, adequate or abundant

— whether endocervical glandular cells are present or absent
— quality of fixation
— presence of excessive blood or inflammatory exudate
2. Description of findings
The main categories of abnormalities are:
— ASCUS (abnormal squamous cells of uncertain significance)

On follow-up, many examples of ASCUS will revert to
normal, some will remain ASCUS, a few will progress to
more definite abnormality.
— Low-Grade Abnormality (formerly CIN 1)

As with ASCUS, many low-grade abnormalities will revert
to normal. Two low-grade abnormal smears six months
apart are an indication for colposcopy.
— High-Grade Abnormality (formerly CIN 2 and CIN 3)

A high-grade abnormality is an indication for colposcopy
and biopsy.
— HPV and other cytologically detectable infections will be

noted. HPV alone is managed as a low-grade abnormality.
3. Recommended follow-up
Follow-up recommendations take account of current and past

findings. Possibilities are:
— routine follow-up in three years

— follow-up in six months for ASCUS or low-grade
abnormalities

— colposcopy and biopsy for high grade abnormalities or
repeated low-grade lesions.
Cervical swabs
Swabs are collected from the cervical canal when testing for Neisseria or Chlamydia
trachomatis – see entries under these headings.
CFT (complement fixation test)
A methodology used for detecting a wide variety of antibodies.
Chicken pox
see Varicella-zoster virus (VZV)
Chilomastix mesnili
A non-pathogenic commensal flagellate found in faeces. When present it can suggest

infestation with worms which may warrant treatment.

Chlamydia pneumoniae
specimens:
1. antibodies - serum, preferably paired sera 2-3 weeks apart
interpretation:
single specimen <1:16 negative
1:16-1:32 indeterminate
>1:32 past or present infection
paired sera 4-fold or greater increase indicates current infection
2. culture – please discuss with microbiologist.

Requires a nasopharyngeal swab in special medium.
C. pneumonia has recently been recognised as an important cause of atypical

pneumonia, second only to Mycoplasma. Like the other Chlamydia it is an obligate
intracellular bacterium. It was previously called the TWAR agent.
Spectrum of disease
Many adults have antibodies indicating that the infection is common, initial infection
being typically at age 5-15 years. It can cause pneumonia, severe pharyngitis,
hoarseness, fever, cervical lymphadenopathy. Infection in young adults is usually of
mild to moderate severity but can be sub-clinical or, in immunocompromised
patients, severe. Incubation period averages 21 days and infection can recur. Its most
recent (and surprising) association is with coronary artery disease, suggested by
seroepidemiologic studies and finding the organism in atheromatous plaques.
Laboratory diagnosis is typically based on serology.
Treatment for lower respiratory tract infection is erythromycin or other macrolides in

children and doxycycline or macrolides in adults. 10 - 21 days may be required as
prolonged or recurrent symptoms are common.

Chlamydia psittaci
specimens:
1. antibodies - serum, preferably paired sera 2-3 weeks apart
interpretation:
single specimen <1:16 negative
1:16-1:32 indeterminate
>1:32 past or present infection
paired sera 4-fold or greater increase indicates
current infection
C. psittaci is a pathogen endemic in all bird species. When a human inhales dust
from fomites from infected birds, they can develop an infection which may present as
an atypical pneumonia, headache, fever, rash, myalgia. Severity ranges from mild to
moderate, occasionally severe.
Psittacosis is largely confined to bird-fanciers (the parrot family particularly) and

poultry-handlers.
Laboratory diagnosis is based on antibody findings.
Treatment – tetracyclines or the macrolides.
Chlamydia trachomatis
In New Zealand the term "chlamydia" commonly refers to genital infections with C.
trachomatis. They are widespread in the community.
Infection is diagnosed by detecting chlamydia antigen in cellular material using an

ELISA method.

Specimens: female – urethral swab and cervical swab
male – urethral swab
or first-catch urine
conjunctivitis – conjunctival swab
Each chlamydia pack has 3 swabs
– a single thin wire urethral swab

– 2 larger cervical swabs
Swabs must be placed in the purple top tube provided for transport.
Female specimens Use one of the large swabs to clean secretions away from the
cervical os. Now insert the second large swab 1-2cm into the endocervical canal and
rotate for 15-30 secs. Chlamydia are located inside cells, not secretions, hence the
need to rotate the swab against the cells lining the cervical canal.
Now insert the thin swab into the urethra and rotate to collect the second specimen.
Sampling both cervix and urethra, only one of which may be infected, increases
recovery rate by 15-20%.
Vaginal swabs are of no value.
Male specimens If there is a urethral discharge, swab the inside of the urethral
meatus. Insert the swab 2-4cm into the urethra and rotate for 3-5 seconds to ensure
adequate sampling.
As an alternative, particularly when there is no discharge, collect 10-20 mls of first-

catch urine, i.e. the first stream of urine, which flushes chlamydial discharge out of
the urethra. The patient should not have voided for several hours before providing
the first void urine.
Label this urine specimen clearly "for chlamydia".

Conjunctivitis Swab the inside of the lower eye-lid using the smaller urethral swab.
Remove any purulent material before collecting conjunctival epithelial cells by
rubbing the dry swab over the everted palpebral conjunctiva.
Other Types of Test
– culture is occasionally used e.g. for medico-legal reasons
– molecular methods such as LCR (ligase chain reaction) and PCR

(polymerase chain reaction) are alternatives to the ELISA methods.
– antibody tests are seldom used.
When to test for chlamydia
– when an STD (sexually transmitted disease) is suspected

– when a cervical smear is collected
– during pregnancy because infection can be passed to the infant during birth.
It is not necessary to do a test of cure following doxycycline treatment.
In pregnancy, doxycycline cannot be used. A test of cure should be done after

completing a course of one of the alternative agents as these have a known failure
rate.
Tests should not be performed until 3 weeks after treatment to prevent false positives
due to persisting dead antigen, or false negatives due to persisting live organisms
being too small in number to register positive.
Reliability of the antigen test
All results reported as positive have been confirmed using a different methodology to
eliminate most false positives. The current literature gives the predictive value of a
confirmed positive as >99%. As with all laboratory tests the possibility of both false
positives and false negatives needs to be kept in mind when a result seems not to fit
the clinical situation.

In Auckland the overall positivity for all people tested is 5%.
Treatment
Chlamydia is treated with doxycycline, 100mg 12-hourly, for 7–10 days except in
pregnant women where amoxycillin, 500mg 8-hourly, or erythromycin, 500mg base
6-hourly, is used. Recently azithromycin as a 1g single dose has been approved. This
is likely to become the standard treatment of genital C. trachomatis infection in New
Zealand.
C. trachomatis conjunctivitis – for neonates erythromycin 50mg/kg/day divided 6-

hourly for 10-14 days is recommended. In adults prolonged treatment for 3 weeks
with doxycycline or erythromycin is used. Regardless of age, topical antibiotics are
inadequate and are unnecessary when oral treatment is given.

Spectrum of disease:
Genital infections
• urethritis, males and females, often asymptomatic in females. 60% of non-

gonococcal urethritis is due to chlamydia.
• cervicitis, usually asymptomatic
• salpingitis and pelvic inflammatory disease, an important cause of infertility
• conjunctivitis, in infants born to infected mothers or in adults who get genital

secretions into an eye.
Other sub-types of C. trachomatis cause
• trachoma, a chronic conjunctivitis which is a major cause of conjunctival scarring

and blindness in developing countries.
• LGV (lymphogranuloma venereum), found mainly in Africa, Asia and South

America, an STD causing chronic granulomatous inguinal lymphadenopathy.
Chloride
specimen: serum
ref. range: 95 – 110 mmol/L
Formerly, chloride was measured as part of the electrolyte group but it has now fallen
into disuse except for a few specialised situations in renal medicine. Those who
calculate anion gaps will need a chloride level.
Cholesterol
Total cholesterol is made up of three fractions:

total = LDL + HDL + VLDL/IDL
Total and HDL cholesterols are measured directly in the laboratory.
VLDL/IDL is estimated from the fasting triglyceride using the formula
triglyceride
VLDL =
2.2
LDL is calculated by subtraction using the Friedewald formula.
triglyceride
LDL = total − HDL −
2.2
The formula is inaccurate and not used when the triglyceride is above 4.5.
see Cholesterol, HDL

Cholesterol, LDL
Cholesterol, total and total/HDL ratio
also Cardiovascular disease (CVD) risk assessment

Lipid disorders
Triglyceride
Cholesterol, HDL
specimen: serum

ref. range: 1.0 - 2.5 mmol/L
Female levels are on average 0.3 mmol/L higher than male.
The current NHF (National Heart Foundation) recommended level is >1.0 which is
relatively easily achieved, 80% of females being above this level and 60% of males.
HDL cholesterol is protective against atherosclerosis and a low HDL is an
independent risk factor separate from LDL cholesterol.
increased by
• exercise
• alcohol
• drugs – oestrogens
– fibrates, statins, nicotinic acid
– anticonvulsants
decreased by
• drugs – androgens, anabolic steroids, danazol, testosterone

– progestins
– beta blockers
– thiazides
– isotretinoin
– antiviral agents
• smoking
• obesity
• familial hypolipoproteinaemia
• renal impairment/proteinuria
Athletes using anabolic steroids can have dramatically low HDL levels.

Cholesterol, LDL
specimen: serum, fasting (see cholesterol, total)

ref. range: NHF (National Heart Foundation) recommended ideal level <3.0 mmol/L
LDL cholesterol is calculated using the Friedewald formula – see under Cholesterol
above.
It is a major risk factor for coronary artery disease.
Quantitatively it makes up about 80% of total cholesterol in a normal person and for
this reason the terms total and LDL cholesterol are often used interchangeably, even
though there are significant differences.
The two main determinants of LDL levels in healthy people are:
• genetic inheritance – responsible for more than half the LDL level and not
modifiable except by drugs
• diet
elevated by:
• polygenic hypercholesterolaemia
• familial hyperlipoproteinaemia
• high fat diet
• diabetes
• hypothyroidism
• alcohol
• nephrotic syndrome

• drugs: glucocorticoids, beta-blockers, thiazides, danazol, androgens,
isotretinon, anti-viral agents, cyclosporin
lowered by:
• ideal diet
• oestrogens
• drugs: statins, fibrates, nicotinic acid, bile resins
see also Cholesterol, total and total/HDL ratio

Lipid disorders
Cholesterol, total and total/HDL ratio
specimen: serum
ref. range: NHF ideal levels – total cholesterol <5.0
– total/HDL ratio <4.5
Fasting or non-fasting?
• Total and HDL can be non-fasting.

• LDL cholesterol and triglyceride should be fasting. A point worth making is
that for a person eating a healthy low fat breakfast or lunch, there will be no
significant difference between fasting and non-fasting.
A reasonable approach is to make the first profile non-fasting. If levels are higher
than ideal, a second fasting specimen is ordered to complete the baseline.

Observed ranges by age and gender
The graph below shows "observed" total cholesterol ranges in 80,000 unselected sera
in the Auckland population 1997 - 1998. It can be seen that in the 45-70 age-group,
about 70% lie above the ideal level at 5.0 mmol/L.
Female and male mean levels are shown separately but the 5th and 95th percentile
lines are for male and female combined.
Factors affecting total cholesterol
Because the LDL fraction makes up about 80% of total cholesterol, those factors
which raise or lower LDL cholesterol (qv) will have the same effect on total
cholesterol.
There are differences however:

triglyceride
total = LDL + HDL +
2.2
It can be seen that a high triglyceride has an important effect on total levels whilst
LDL is relatively unaffected by triglyceride – hence the importance of examining a
full lipid profile, not just total cholesterol.
The full profile is also essential to measure HDL as an important independent risk
factor and to measure triglyceride which is also being recognised as a risk factor, e.g.
in women and diabetics.
Total /HDL ratio
This ratio integrates the contributions of HDL and LDL into a single figure, showing
the magnification of risk when LDL is high and HDL low; and also how a high HDL
can diminish the importance of a high LDL.
ratio <4.5 — ideal

4.5-8.0 — low medium risk
>8.0 — high risk
Variance in total cholesterol when monitoring treatment
At a level of 6.5 mmol/L the biological variance is about ± 0.5 mmol which means
that changes between 6.0 and 7.0 are not necessarily significant. Serial
measurements, say monthly or 3-monthly, are necessary to smooth out these random
oscillations and show whether the trend is down, up or unchanged.
see also Lipid disorders

Cholinesterase
specimen:
• whole blood (heparin) is preferred because it can be used for both red cell and
plasma cholinesterase measurements when checking for insecticide poisoning
and can be used in detecting scoline sensitivity.
• serum can, however, be used for all tests except red cell cholinesterase.
• please include clinical details.
ref. ranges: red cell cholinesterase 9 - 16 Units

plasma or serum cholinesterase4.9 - 12.0 U/ml
dibucaine inhibition number 81 - 86
Indications:
1. Chronic exposure to organophosphate and carbamate anticholinesterase

sprays
Organophosphates Carbamates
malathion carbaryl
acephate methiocarb
coumaphos methomyl
chlopyrifos propoxur
These insecticide sprays are widely used by horticulturists.
Red cell and plasma cholinesterases should be measured before spraying

commences to establish the individual's baseline reference range and at regular
intervals thereafter.
If the baseline is unknown, estimations at 3-day intervals after removal from

exposure will show recovery towards the baseline.
Because red cell cholinesterases are irreversibly inhibited by

organophosphates (but not carbamates), levels remain low for the 4-month life

of erythrocytes. The red cell level is the preferred test for monitoring low
level chronic exposure.
2. Acute poisoning
Plasma cholinesterases fall sharply when acutely exposed to

organophosphastes or carbamates but recover to their previous levels within
less than a week.
Measure plasma (or serum) cholinesterase
3. Scoline (suxamethonium) sensitivity
Measure serum or plasma cholinesterase and dibucaine number. Do not test

within one week of scoline administration or two weeks of blood transfusion.
4. Other Cholinesterase levels are reduced in chronic liver disease, renal disease,
pregnancy/oestrogens, acute illness.
Choriocarcinoma
Chorionic gonadotrophin
Chorionic villous sampling

Prenatal diagnosis for selected inherited diseases is performed at 9-11 weeks
gestation on foetal DNA extracted from chorionic villi. This is used for the antenatal
detection of an increasingly wide range of severe, untreatable disorders where
termination is a reasonable option to consider.
Chromium
specimen: random urine with added HCl
ref. ranges : normal < 2µmol chromium/mol creatinine

exposure > 4µmol chromium/mol creatinine
When the test is being done in welders, the specimen should be collected towards the
end of the working week.
Chromosome analysis
see Cytogenetics
Chronic fatigue syndrome
This relatively common condition (1-2 per 1000) continues to attract attention in both
the lay and medical press.
We are sometimes asked by patients if there is a simple yes/no diagnostic test and so
far there is none, despite occasional claims to the contrary. The diagnosis is based on
the history of debilitating fatigue for at least 6 months in the absence of any clinical
or laboratory evidence of identifiable organic disease.

Conditions to be excluded include endocrine disease (diabetes, thyroid) specific
infections (mainly viral such as infectious mononucleosis, Coxsackie B, CMV)
connective tissue disorders and neuro-muscular disease.
Chronic lymphocytic leukaemia (CLL)
Typically CLL is an indolent disorder with a median survival of 10-14 years. In the
early stages the patient does not require therapy but regular blood counts are
performed to monitor the disease for increased activity.
Diagnosis is based on peripheral blood finding of lymphocytosis with cell marker

analysis to demonstrate a monoclonal B cell population with light chain restriction.
Bone marrow biopsy is not essential for diagnosis but is useful to determine bone
marrow reserve and possibly outcome prediction.
The indications for treatment are:
• bone marrow failure with anaemia, neutropenia or thrombocytopenia

• bulk disease with lymphadenopathy and/or hepatosplenomegaly
• constitutional symptoms such as fever, weight loss, night sweats
• autoimmune complications, usually haemolytic anaemia
Predictors of a poor outcome:
(i) clinical stage, RAI or Binet staging system

• >3 nodes with bone marrow failure: mean survival 2 years
• >3 nodes: mean survival 7-8 years
• <3 nodes with normal haemoglobin and platelets:
approaches age-matched control survival.
(ii) lymphocyte doubling time <12 months
(iii) abnormal karyotype on chromosome analyses
(iv) marrow infiltration pattern, nodular being better than diffuse

Treatment is not given on the basis of the high lymphocyte count alone. Initial
therapy usually involves the alkylating agent chlorambucil with or without
prednisone. Fludarabine is one of a new group of agents which is an alternative first
line treatment for CLL.
Chronic myeloid leukaemia (CML)
CML is predominantly a disorder of middle life but the diagnosis is being made
increasingly in younger patients. The disorder is characterised by a leucocytosis
which is left shifted, typically showing the major increases in myelocytes and
segmented neutrophils giving a bimodal differential white cell distribution. Blast
cells are also present. The majority of patients are Philadelphia chromosome positive.
The NAP score is low or absent.
CML is a state of bone marrow instability and after a variable time, median 3-4 years,
the disease transforms into an acute leukaemia which is unresponsive to standard
chemotherapy. The only potentially curative treatment is bone marrow
transplantation. This may use a matched sibling donor or a matched unrelated donor
transplant. Interferon is the treatment of choice in patients who cannot undergo bone
marrow transplantation. Hydroxyurea is frequently used for cytoreduction.
Chyluria
specimen: random urine, ask for triglyceride.
Chyluria is due to blockage of lymphatics, usually by filaria but sometimes by

malignant disease. The urine is milky due to triglyceride-rich chylomicrons in the
lymph.

Chryseobacterium
see Flavobacterium
A gram-negative bacillus resembling Pseudomonas, formerly known as
Flavobacterium. A pathogen in the urinary tract, it may also cause superficial skin
infections after contact with soil or fresh water. C. meningosepticum is known as a
cause of neonatal meningitis. Isolates are susceptible to vancomycin which is
unusual for gram-negative species.
Citrobacter
A gram-negative enteric bacillus which most commonly causes urinary tract

infection. Other types of infection include nosocomial pneumonia, septicaemia and
wound infections. Treatment is according to susceptibility results.
CK (creatine kinase) total
specimen: serum
ref. range: female 30-180 U/L
male 60-220 U/L
Elevations of CK
These are common and most arise from skeletal muscle. Clinically the elevations in
myocardial infarction are important.
From skeletal muscle

• muscular exercise – the commonest cause. Well-muscled individuals, with or
without regular exercise, tend to have levels at or above the upper end of the
reference range. Acute bouts of more severe exercise will give elevations of
variable extent and duration which may last a week after one episode. There
is wide individual variation but levels can rise as high as 4000 U/L in severe,
unaccustomed exercise.
• muscle trauma – IM injections (even 1ml), accidents, bruising, physical
violence
• acute viral infections – particularly those with myalgia
• alcoholism – even when there is no overt myopathy
• hypothyroidism – and other endocrinopathies
• muscular dystrophies
• polymyositis, dermatomyositis, connective tissue disorders
• tumours – some malignant tumours cause massive increases in CK
• surgery – levels return to normal in 1 week
• parturition – elevated for up to 6 weeks
• acute psychoses
• drugs – fibrates, statins, captopril, colchicine,
isotretinoin, lithium, beta blockers
• renal failure
From cardiac muscle
In MI (myocardial infarction), CK typically starts to rise 4-12 hours after chest pain
commences and returns to normal in 2-3 days. Myocarditis can cause more
prolonged elevations of CK.
see also CK - MB and other isoenzymes

Myocardial markers for infarction (MI) and ischaemia

CK - MB and other isoenzymes
specimen: serum, refrigerate if any delay in analysis

ref. range: <4.0 µg/L
relative index <1.0
The three isoenzymes of CK are:
• CK-MM, from skeletal muscle, makes up >94% of total CK

• CK-MB, comes from cardiac muscle but with a small contribution from
skeletal muscle
• CK-BB from brain is found in low concentration and is clinically unimportant
except occasionally in tumours.
Except when myocardial infarction is a possibility, an elevated CK total can be

assumed to be CK-MM from skeletal muscle.
CK-MB in myocardial infarction (MI)
This test has now been superseded by Troponin T or Troponin I which have better
specificity and stay high for 7-10 days.
CK-MB rises 4-10 hours after MI and stays high for 36-48 hours.
Interpretation CK-MB Rel. index

MI excluded <4.0 <1.0
MI probable >4.0 >2.0
MI inconclusive >4.0 & CK total >400 <2.0

The relative index is the CK-MB expressed as a % of total CK.
see also Troponin I (TnI) and Troponin T (TnT)

Myocardial markers for infarction (MI) and ischaemia
CLL
see Chronic lymphocytic leukaemia (CLL)
Clostridium difficile
A normal inhabitant of the bowel which can proliferate when other organisms are
suppressed by antibiotics, particularly clindamycin or ampicillin. C. difficile
produces toxins causing bloody diarrhoea and pseudomembranous colitis visible on
endoscopy. Less severe forms of antibiotic-associated diarrhoea may also be
associated with C.difficile.
Management
Stopping the precipitating antibiotic treatment may be enough. The most commonly
used treatment is metronidazole, 400mg 8-hourly for 7-10 days. Up to 20% of
patients relapse. This is not due to metronidazole resistance but is explained by the
ability of C. difficile to form antibiotic resistant spores. The treatment for relapse is
again metronidazole.
CML
see Chronic myeloid leukaemia (CML)

CMV
see Cytomegalovirus (CMV)
CO
see Carbon monoxide
CO2
see Bicarbonate
Blood gases & pH
COAD/CORD (chronic obstructive

airways/respiratory disease)
see Bronchitis, acute or chronic
Coagulation factor assays

see von Willebrand's disease (vWD)
Fibrinogen

Coagulation screen
The basic screen consists of:
• platelet count
• bleeding time for platelet function
• PR (prothrombin ratio) for extrinsic pathway
• APTT (activated partial thromboplastin time) for intrinsic pathway
• TCT or fibrinogen assay for final common pathway
Two other tests done at the same time are:
• blood count, to detect other haematological abnormalities

• liver function tests to exclude liver disease as a cause of coagulation factor
deficiency
These tests may miss mild abnormalities but they will detect major disorders. More
detailed investigations may more fully characterise an abnormality and are indicated
where there is a strong bleeding history.
What are the common abnormalities?
This laboratory does about 6000 screens each year. Diagnoses and their frequencies
are:

diagnosis % of total
bleeding history but normal laboratory tests 66
isolated long APTT 10
congenital platelet function defect 8
acquired platelet function defect 5
von Willebrand's disease 4
lupus anticoagulant 2
vitamin K deficiency 2
liver disease 2
other factor deficiency 1
The importance of the bleeding history
A careful history is the most valuable part of an assessment. If the history of bleeding
is convincing, a minor disorder may exist even if the laboratory tests are normal.
Ask specifically about
· epistaxis especially if bilateral, recurrent, or requiring repeated

cautery. Unilateral epistaxis is often due to a local
lesion.
· bruising specify size and whether spontaneous or traumatic.

Trunk and upper arm bruising are potentially more
important than lower limb bruising. Deep bruising
with central induration is significant.
· lacerations particularly recurrent and prolonged bleeding
· surgery wisdom tooth extraction, tonsillectomy, other major

surgery, blood transfusion requirement, prolonged
postoperative hospital stay
· menorrhagia a bleeding disorder may potentiate anovulatory

menhorragia
· gum bleeding when brushing teeth

· family history suggests inherited disorder
· drugs specifically ask about medication for headaches,

arthralgias, particularly aspirin, NSAIDs
Coefficient of variation (CV)
see Variation
Coeliac disease (gluten sensitive enteropathy)
Coeliac disease, affecting at least 1:3000 (1:300 in some populations) is by far the
commonest cause of intestinal malabsorption.
In severe cases it presents in infancy or childhood with failure to thrive and fatty
diarrhoea.
Milder cases are more common and can easily be overlooked, particularly as many do
not have intestinal symptoms. Features of these milder cases can be one or more of:
• anaemia
• iron deficiency
• folate deficiency
• fatigue
• diarrhoea, abdominal discomfort
The disease is due to an intolerance to gliadin (gluten) found in wheat, barley and rye.
Diagnostic antibodies are found in serum, and the mucosa of the small intestine
shows flattened villi on biopsy. Withdrawal of gluten from the diet usually results in

symptomatic improvement, normalisation of villi and disappearance of antibodies
over the course of a year or so.
Dermatitis herpetiformis, which presents as a chronic pruritis papulovesicular skin

rash, is a cutaneous manifestation of gluten sensitivity with the same diagnostic
antibodies and improvement on gluten withdrawal.
Diagnosis
1. Antibodies
These simple, relatively specific tests developed over the past few years have
improved the detection rate in patients whose symptoms do not justify
intestinal biopsy.
— anti-gliadin antibodies (AGA) are sensitive but show significant false

positives
— endomysial antibodies (EMA) are highly specific but less sensitive
— reticulin antibodies are less often used but have a high degree of pecifity
when positive
All three are measured as the IgA antibody, which correlates with disease better
than the IgG, except in patients with selective IgA deficiency (10x more
common in coeliac patients) where the IgG antibody must be used. To identify
IgA deficiency, immunoglobulins must be measured.
If both AGA and EMA antibodies are positive, predictive value for coeliac
diseaseis >99%. Where only one test is positive, the likelihood of coeliac
disease is less.
As noted above, antibodies can disappear when a gluten-free diet is successfully

implemented. Reappearance of antibodies can indicate changed dietary
compliance.
2. Other tests
– malabsorption

blood count
s. iron, IBC and ferritin
s. folate
fat: check 3-day faecal fat
– small intestinal biopsy
for definitive diagnosis
3. Trial of gluten-free diet
Cold agglutinins
specimen: serum from blood collected at laboratory and stored at 37ºC prior to
analysis.
Cold agglutinins are autoantibodies that cause red cell agglutination in the
temperature range 0-37ºC. Clinically harmless cold agglutinins in low titre may be an
incidental laboratory finding.
In cold haemagglutinin disease , higher titres of an IgM antibody lead to complement-

mediated haemolysis and may be associated with Raynaud's phenomenon.
An even rarer condition is paroxysmal cold haemoglobinuria in which the Donath-

Landsteiner antibody causes intravascular haemolysis, sometimes severe, following
exposure to cold.
These cold autoantibody diseases can be either primary, when they are usually found
in older patients, or secondary. The secondary associations are infections (infectious
mononucleosis, mycoplasma, CMV); lymphomas or CLL; or connective tissue
diseases. The prognosis of secondary cold haemagglutinin disease is that of the
underlying disorder.

Serum protein electrophoresis may show a monoclonal paraprotein, particularly when
associated with malignant disease, or the agglutinin may be polyclonal.
see also Cryoglobulin & cryofibrinogen
Complement, C1 inhibitor (C1 INH)

specimen: serum
ref. range: antigenic 0.15-0.35 g/L
functional 5-10 U/ml
C1 inhibitor is a complement inhibitor that is deficient in quantity and/or activity in

85% of patients with hereditary angi-oedema. Complement C4 is almost invariably
reduced, even between attacks.
Complement fractions C3 and C4

specimen: serum — must be separated within 1 hour and frozen
ref. range: C3 0.8 – 1.8 g/L
C4 0.2 – 0.4 g/L
The complement system is a cascading series of plasma proteins whose end-products

cause bacterial lysis and remove the immune complexes found in post-streptococcal
glomerulonephritis, SLE and other autoimmune disease. There is reduction of C3 in
PSGN and of both C3 and C4 in SLE. They are increased in most other inflammatory
states.

Complete blood count (CBC)
see Blood count
A group of inherited adrenal disorders due to enzyme defects, the commonest being
21-hydroxylase deficiency. Neonatal blood screens check for severe forms of 21-
hydroxylase deficiency by measuring 17 OH-progesterone.
Severe CAH can present as hypokalaemia and dehydration in neonates; as virilisation

in a female child; or as precocious puberty in males.
A milder and more common form of CAH can present as hirsutism in adult women.
It can be detected by measuring serum 17 OH-progesterone on a morning specimen
collected during the follicular phase of the menstrual cycle.
see also – 17-hydroxy progesterone (17-OHP)
Conjugated bilirubin
see Bilirubin, conjugated (direct) and unconjugated (indirect) fractions
Connective tissue diseases

A group of systemic autoimmune diseases characterised by the presence of fairly non-
specific autoantibodies and associated with chronic inflammation of musculoskeletal
structures. The main diseases are:
• rheumatoid arthritis (1-2% of the population)

• SLE, systemic lupus erythematosus, (0.1% of the population)
• Sjogren's syndrome
• diffuse scleroderma (0.002% of the population)
• local scleroderma (CREST)
• mixed connective tissue disease (MCTD)
• dermato/poly/myositis
Tests associated with these conditions are described under the disease headings.
Diagnosis can be difficult or impossible in the early stages of these conditions which
can evolve over months or years before enough features develop to establish the
diagnosis.
Conn's syndrome
see Aldosterone and renin, plasma
Coombs test
specimen: serum
The Coombs test detects antibodies directed against red cells.
The direct Coombs test detects antibodies or complement which are coated on red
cells as in autoimmune haemolytic anaemia, haemolytic disease of the newborn,

incompatible transfusions, or drug-induced haemolysis, particularly that due to
methyldopa or penicillin in large doses.
The indirect Coombs test detects red cell antibodies in serum, as in maternal antibody
screens in pregnancy or some autoimmune haemolytic anaemias. It is also used in
cross-matching.
Copper
specimen: serum
or urine, 24-hr in special plastic bottle from laboratory containing 25ml
purified HCl
ref. range: serum 13-22 µmol/L

urine <1.2 µmol/day
Wilson's disease is an autosomal recessive disease due to accumulation of copper in

the body in toxic amounts. It presents usually at age 5-20 with unexplained liver
disease, neurological or psychiatric symptoms, or Kayser-Fleischer corneal rings.
There is an increased excretion of urine copper, but reduced serum copper. This is
because ceruloplasmin (qv), the protein which transports copper in serum, is reduced
in Wilson's disease even though the total body load of copper, and its urinary
excretion, are markedly elevated.
S. copper is reduced in protein-losing states and raised by oestrogens, pregnancy, or

inflammatory states.
Coproporphyrin
see Porphyrias

Cord blood testing
When haemolytic disease of the newborn (qv) is suspected, Hb, blood group, direct
Coombs and bilirubin must be checked. Otherwise cord blood samples are not
routinely tested though some collect the samples and store them for up to a week at
4°C in case they should be needed.
When the direct Coombs is positive, Rh typing must be confirmed and the coating
antibody identified. The initial Rh typing will sometimes be found to be incorrect
when the direct Coombs is positive, due to interference by the antibody.
Cord blood reference ranges for a wide variety of tests differ markedly from those
found in the next few hours, days and weeks of life. See individual test entries for
particular ranges. The three commonest tests on cord blood and their reference
ranges are:
Hb 136–196 g/L
bilirubin full-term up to 50 µmol/L
premature up to 25 µmol/L
direct Coombs negative
Cortisol, serum
specimen: serum collected at 07.00 – 10.00 hrs
ref. range: 200–700 nmol/L
There is marked diurnal variation, the peak at 09.00 hrs being 50-100% higher than
the trough at 23.00 hrs.
An isolated 09.00 serum cortisol is a crude diagnostic tool. A rough guide to
interpretation:

<150 strongly suggests adrenal insufficiency
150-200 further assessment indicated for possible
adrenal insufficiency
200-550 adrenal insufficiency not excluded
Cushing's syndrome unlikely
550-700 adrenal insufficiency unlikely
Cushing's syndrome possible
>700 Cushing's syndrome possible but there
are commoner causes of raised cortisol
Decreased levels
• primary adrenal insufficiency (Addison's disease)

• secondary deficiency follows adrenal suppression by steroid therapy
• drugs – ketoconazole, phenytoin, metyrapone, steroids
• decreased cortisol-binding proteins
• hypopituitarism
• exogenous steroids (variable)
Elevated levels
• Cushing's syndrome – pituitary adenoma or hyperplasia

– adrenocortical tumour
– ectopic ACTH from malignant tumour
• stress, illness, depression, alcoholism
• oral contraceptives, oestrogens, pregnancy
• exogenous steroids (variable)
• increased cortisol-binding proteins
Cortisols are of lmited value when monitoring replacement therapy.
see also Adrenocortical insufficiency

Cushing's syndrome
Cortisol, urine free

specimen: 24–hr urine, no preservative
ref. range: 110–330 nmol/day
Because only the unbound fraction of serum cortisol reaches the urine, this is a good
screen test for Cushing's syndrome and a clearly normal result makes the diagnosis
unlikely. In perhaps 10% of cases cortisol hypersecretion is intermittent.
Elevations up to 3x normal may be found in stress, depression or alcoholism.
Urine cortisol is not used in suspected adrenal insufficiency.

Corynebacterium diphtheriae
The latest Auckland case was in July 1998. A special medium is required to recover
C. diphtheriae so the possibility of diphtheria must be specifically mentioned on the
request form.
Tonsillar diptheria is still occasionally seen in non-immunised persons. Skin

infections with C. diphtheriae occur in the tropics and can be a source of infection.
Corynebacterium haemolyticum
see Arcanobacterium haemolyticum
Corynebacterium minutissimum
see Erythrasma
Coxsackie viruses
These are widely distributed enteroviruses associated with many different types of
illness including minor febrile illnesses, the common cold, herpangina, pleurodynia,
aseptic meningitis, myocarditis, post-viral fatigue syndrome, conjunctivitis, Type I
diabetes and others. Infections are more common in summer and autumn. Virus can
be recovered from throat swabs or rectal swabs and also conjunctival or vesicular
swabs if lesions are present.

C-peptide, plasma or urine
C-peptides are fragments derived from endogenous, but not exogenous, insulin.
Formerly used to check residual islet cell function in Type 1 diabetes or in the
investigation of unexplained hypoglycaemia but now rarely used.
CPK (creatine phospho-kinase)
see CK (creatine kinase) total
C-reactive protein (CRP)

specimen: serum
ref. range:
mg/L
<5 normal
10 - 40 mild inflammation, some viral infections
40 - 200 acute inflammation, bacterial infections
>200 severe bacterial infection or extensive trauma
CRP is the most useful of the acute phase reactants, rising sharply 4-8 hours after
tissue damage by infection, infarction, inflammation or trauma. It returns to normal
2–3 days after disease activity has ceased. It can be regarded as a fast-changing ESR
which, by contrast, rises and falls more slowly. It can be used as an indication of
occult bacterial infection, suspected rheumatic fever, inflammatory bowel disease or
other conditions where there is uncertainty whether symptoms are functional or due to
organic disease. Chronic inflammatory diseases such as SLE can be monitored using
serial CRPs and for this purpose it is a more useful test than the ESR. It has also been
used in the diagnosis of myocardial infarction.

Creatine
specimen: 24-hr urine, no preservative
A disused investigation for muscle disease, CK being a better test.
Creatine kinase
Creatine phosphokinase (CPK)
Creatinine, serum
specimen: serum
ref. ranges:
age mmol/L
newborn 0.020 - 0.090
child 0.020 - 0.070
adolescent 0.040 - 0.090
adult female 0.050 - 0.105
adult male 0.060 - 0.120
Some laboratories use µmol/L which would make the adult female range, for
example, 50 - 105.

S. creatinine is widely used as a test of renal function both as a general screen, along
with urine protein, for renal disease, and as a test for serial monitoring of renal
function where there is potential or actual renal disease.
It reflects glomerular filtration rate (GFR).

1
s. creatinine α
GFR
It also reflects endogenous creatinine formation from skeletal muscle and to a much
lesser extent, exogenous creatinine excretion from cooked meat.
GFR steadily reduces with increasing age but this is offset, though not completely, by
diminishing muscle bulk and creatinine excretion.
The use of a population-based reference range is even less satisfactory for creatinine
than for other analytes because the individual creatinine range for a person remaining
in good health is narrower than the traditional population range. When monitoring a
potentially nephrotoxic process, reference should always be made to the individual's
own range, as shown by creatinine results when disease-free, rather than to the
population range.
Uses of serum creatinine
• as a crude basic screen of renal function

• for establishing an individual's baseline creatinine range
• monitoring potentially nephrotoxic drugs, particularly in the elderly–
NSAIDs
– ACE inhibitors
– aminoglycosides
– diuretics
– lithium

– and others
• monitoring potential nephropathy e.g. in diabetics
• monitoring established renal disease
• monitoring renal transplant rejection
• monitoring renal dialysis
Method interference
Cephalosporins and ketosis give a falsely high creatinine.

Hyperbilirubinaemia (>200 µmol/L) gives a falsely low value.
Cimetidine, probenecid and trimethoprim can raise creatinine temporarily by reducing

tubular secretion.
Pre-renal disease
When shock, cardiac failure, fluid & electrolyte depletion, reduce renal blood flow, s.
creatinine will rise.
Post-renal obstruction
Usually prostatic, will eventually raise s. creatinine.
Creatinine, urine
ref.ranges:
adult female 4.0 - 17.0 mmol/day

adult male 7.0 - 24.0 mmol/day

24-hr urine creatinines are used when estimating creatinine clearance.
Wide variations in creatinine output for an individual are due to biological variation
of ± 20%, sometimes compounded by incomplete (or over-complete) urine collects.
A creatinine concentration in a spot urine gives a way of compensating for urine

concentration when expressed as the ratio, analyte/creatinine e.g. ACR
(albumin/creatinine ratio) in diabetics.
Creatinine clearance
specimens: 24–hr urine, no preservative – must be accurately timed to 24 hrs, no more, no less.
plus serum obtained within collection period
ref. range: female >1.2 ml/sec/1.73m²

male >1.5 ml/sec/1.73m²
after age 40, clearance drops by about 0.1ml/sec/decade
Creatinine clearance is used as a measure of GFR (glomerular filtration rate) where

early renal impairment is suspected. Because collecting a 24-hr urine is inconvenient
and often inaccurate, the serum creatinine alone is often used as a GFR proxy.
The day-to-day variance is about 20%.
The formula for calculating clearance is :
ur .creat . conc. x volume 1.73
creatinine clearance = x
s . creat . conc. surface area
For an adult of average build, correction is unnecessary but it is essential in children.
A useful approximation in children is:

ht . in cm
GFR ( ml / sec / 1.73m 2 ) =
s . creatinine x 1500

The Cockroft & Gault formula provides an estimate of creatinine clearance based on
age, weight, sex and s. creatinine without the need for urine collection.
( 140 - age ) x weight ( kg )
male creatinine clearance = ml / sec
s . creatinine ( mmol / L ) x 50 ,000
for females, same formula x 0.85
CREST syndrome
• Calcinosis
• Raynaud's phenomenon
• Esophageal hypomotility
• Sclerodactyly
• Telangiectases
Also called limited scleroderma. The ANA is usually positive showing the
centromere pattern.
Crohn's disease
Laboratory abnormalities can include:
• iron deficiency
• vitamin B12 deficiency
• anaemia due to combinations of chronic disease and iron and B12 deficiency
• raised ESR and CRP
• reduced albumin
• hypokalaemia

Crossmatch
specimen: blood (plain tube)
For routine pre-operative cross-matches for cold surgery, the specimen must be
collected at least 24 hours in advance. There are some essential prerequisites:
• The request must be made on cross-match request forms in duplicate (one can
be a carbon copy).
• Full ID on request form – full patient name, dob, sex, NHI number if known.
• Full patient ID on specimen tube and date and time of collection.
• Doctor's name and signature and date of request on both copies.
• Time and date of specimen collection. If the patient has been transfused in the
past 14 days, specimen collection and cross-match must be done within 24
hours of operation.
• Patient's hospital
• Indicate whether 'group and hold' only
• If packed cells or whole blood required, indicate number of units
• Time and date required
• Give previous transfusion history, history of red cell antibodies, obstetric
history.
Laboratory procedure The donor red cells are tested for compatibility with the
patient's serum.

CRP
see C-reactive protein (CRP)
Cryoglobulin & cryofibrinogen
specimens: serum (plain tube) for cryoglobulins

plasma (heparin) for cryofibrinogen
and blood (EDTA)
Specimens must be kept collected at the laboratory to maintain them at 37°C prior to
analysis.
see Cold agglutinins
Cryptosporidium
Cryptosporidium is now recognised as a cause of acute gastroenteritis, particularly in

children. It is a notifiable disease. Recent figures for New Zealand show a
population attack rate of 20/105 with the highest rates for children: 35/105 for those
under 1 and 70/105 for 1-4 year olds. It is found in a variety of hosts and
transmission from farm livestock or pets to humans can occur. Person to person
transmission also occurs and has been responsible for outbreaks in child care
facilities.
Diagnosis is by use of a special stain for oocysts in faeces and will be done on
specific request. The typically watery diarrhoea usually settles without treatment
within 10 days (range 1-20 days). In immunocompromised patients (especially those

with HIV), it may cause a severe prolonged diarrhoeal illness. In this situation
specialist advice should be sought on treatment.
CSF (cerebrospinal fluid)

specimen: collect into sterile tubes
ref.ranges:
cells <5 mononuclears

no neutrophils
no red cells
glucose >5 mmol/L
protein <0.45 g/L
The microbiology department should be notified if meningitis is a possibility so that

the specimen can be handled urgently.
CSF cytology
CSF specimens for cytology need to reach the laboratory within 30 minutes of
collection. Please contact the laboratory prior to lumbar puncture if CSF cytology is
required.
Cushing's syndrome
The main causes are:
• excess ACTH (adrenocorticotrophic hormone) produced by the pituitary

• excess ACTH produced by non-endocrine tumour particularly Ca lung
• adrenal tumours
Basic screen test: 24–hr urine free cortisol (qv)

Follow-up test: dexamethasone suppression test (qv)
Isolated serum cortisol is not recommended as a screen test though a level below 500
nmol/L in a specimen collected before 10.00 hrs makes Cushing's unlikely.
Clinical features of Cushing's include obesity, diabetes, hypertension, plethora,

muscle weakness, striae and osteoporosis.
CV (coefficient of variation)
see Variation
Cyclical neutropenia
see Neutrophils (polymorphs)
Cyclospora cayetanensis
C. cayetanensis is a recently described protozoan which causes diarrhoea in travellers
to endemic areas. It is common in Nepal. The incubation period is 3-11 days,
median 8 days. It causes a protracted and relapsing diarrhoea. Range of illness is 9-
40 days. Diarrhoea may last for months in the immunocompromised. Diagnosis is by

detecting acid fast oocysts in stool. The treatment of choice is cotrimoxazole, two
tablets 12 hourly for 7 days.
Cystic fibrosis
Affects 1:3000 infants. Cystic fibrosis is carried on a recessive gene which can be
identified in 70% of carriers by DNA testing. The underlying defects of exocrine
gland function show up in respiratory tract, pancreas and sweat glands. Typically,
presentation is in infancy or childhood with recurrent pulmonary infections and
sometimes with malabsorption.
All newborns in New Zealand are screened for cystic fibrosis by measuring blood
trypsinogen on the NTC (National Testing Centre); (qv) blood spots collected in the
first week of life. Pick up rate is 98%. The test can be used up to the age of 6 weeks.
Because false positives are relatively common, positive tests must be checked at 6
weeks.
There are two definitive tests:
• Sweat electrolytes (qv) – high Na+ and Cl- levels

• Identification by DNA testing of a CF gene which is present in 70% of cases.
Tests are being developed for the remaining 30% and prenatal DNA testing is
being used to identify affected foetuses.
Cys 282 mutation
see Haemochromatosis

Cystinuria
specimen: random urine for screen test

24-hour urine for quantitation
ref. range: <420 µmol cystine/day
Cystinuria with an incidence of 1:10,000 is the one of the commonest of the inborn
errors of metabolism. Failure of the renal tubules to reabsorb cystine from urine
results in excretion of a high concentration of poorly soluble cystine which can
precipitate to form cystine stones – 1-2% of all renal calculi.
Cytogenetics
Three major areas of testing are carried out:
1. Prenatal diagnosis from:

— amniotic fluid
— chorionic villi
2. Clinical diagnostic work for cases of:

— infertility or multiple miscarriages
— stillbirth (where clinical indicators are present)
— babies with multiple malformations, with or without neurological
dysfunction
— children with an unusual appearance who are developmentally delayed
or mentally retarded, especially if there are co-existing congenital
defaults
— in some children with speech delay, behavioural problems, isolated
mental retardation
— genital abnormality, hypogonadism
3. Cancer cytogenetics:
— leukaemia
— lymphomas

— solid tumours
Cytology
see Cervical cytology
Aspirated fluids, synovial, pleural,
ascitic etc from cysts or pleural or
ascitic fluid
Bronchial brushings or washings
CSF (cerebrospinal fluid)
Fine needle aspirate (FNA)
Frozen section/rapid smears
Gastric and oesophageal
brushings/washings for cytology
Sputum cytology
Ulcer scrapings for cytology particularly
from the oral cavity
Urine cytology
Cytomegalovirus (CMV)
specimen: serum
Interpretation
IgM antibodies, reported as +ve or –ve, are detectable for a period of about 6 months
from the time of commencement of a CMV infection. False positives occur during
some other viral infections, notably those due to EBV.

IgG antibodies, reported in units/L, become detectable soon after the commencement
of infection and remain positive for life, usually at a level >20 units/L. A rising titre
in paired sera is the best evidence of current infection. Most adults are IgG CMV
positive indicating previous infection.
The virus itself persists in latent form throughout life after recovery from the initial
infection and can be reactivated in an immunocompromised patient.
Clinical infection can present in several ways:
• subclinical infection is common, particularly in childhood.

• a mononucleosis-like syndrome is found in adolescents and young adults,
spread by sexual and other intimate contact. CMV differs from EBV
mononucleosis in its absence of heterophile antibodies. Exudative pharyngitis
and cervical lymphadenopathy are rare. The illness can be severe with fevers
and profound fatigue lasting several weeks and the virus can cause hepatitis.
As in EBV infections, variant lymphocytes are a feature.
• Congenital infections range from inapparent to severe with congenital
abnormalities or intrauterine death. Diagnosis is by identifying the virus in
urine collected during the first week of life.
• Immunocompromised patients can develop severe generalised disease.

D-Dimers
ref. range: <200 µg/L
D-dimer is a fibrin break-down product and elevated levels can be found in any
situation where there is thrombosis.
Clinically the test is used when DVT (deep vein thrombosis) with or without PE
(pulmonary embolism) is suspected. A normal D-dimer level makes DVT/PE
unlikely.
Elevated levels have a poor predictive value for DVT/PE as they are found in many
clinical situations including chronic inflammatory disorders, malignancy, post-
operative states and acute rheumatic conditions.
Dehydroepiandrosterone sulphate
see DHEAS (dehydroepiandrosterone sulphate)
Demodex folliculorum
This is an extremely small mite (0.3-0.4mm), which inhabits the hair follicles and
sebaceous glands of humans. They feed on sebaceous secretions, especially sebum.
They are particularly common on the nose, eyelids and cheeks.
The life cycle from egg to larvae to nymphs to adults takes around two weeks and
occurs within the hair follicle or sebaceous gland. A high proportion of adults,

especially women, unknowingly have these mites. They are seldom found on
children or adolescents.
They do not normally appear to produce disease. There are conflicting reports on
their association with rosacea.
It has been associated with ocular itching and blepharitis in the elderly but its
importance as a cause is disputed.
Treatment: There is little to suggest that treatment is indicated for this endemic
human infestation.
Dengue antibodies
specimen: serum
Dengue, a painful febrile illness ("break-bone fever") caused by a mosquito-borne

arbovirus, is found all over the Pacific including Fiji. Typically it occurs in outbreaks
but can be sporadic.
Diagnosis is by measuring IgM and IgG antibodies preferably in paired sera.

Although both antibodies may date back to an earlier infection, the ratio of IgM to
IgG, or rising titres in paired sera, will help decide whether infection is recent.

Dermatophytes
The three dermatophytes – Trichophyton, Microsporum and Epidermophyton –

invade keratin in skin, nails and hair. They have their sites of predilection but any of
them can be found at any site.
Microsporum species are usually transmitted by animals and are the common cause of
scalp ringworm in children.
Epidermophyton is transmitted from person to person and most commonly affects the
groin.
Trichophyton has three modes of transmission from soil, animals or humans and is
found in hair, nails and skin.
The clinical picture and treatment are, however, determined more by site than by
species and in the discussion that follows, the dermatophytes will be treated as if they
were a single fungus.
The task of the laboratory is to answer the question "Is this skin lesion due to a
fungus?". False positive answers and false negatives are equally undesirable. A false
positive may subject the patient to a long and expensive course of treatment. A false
negative answer may lead to unsuitable treatment such as a steroid which will
exacerbate the underlying fungal infection. There are three important steps in
laboratory diagnosis:
Specimen collection An adequate amount of keratin must be collected from the area
of the lesion where fungal growth is most likely to be active. The importance of
collecting an optimum specimen cannot be over-emphasised.

Microscopic examination Demonstration of hyphae in a KOH wet film can
immediately establish the presence of a fungus.
Fungal culture Growth of a dermatophyte, taking up to 3 weeks, will pick up those

infections where hyphae have not been found on initial microscopy. Although the
laboratory keeps cultures for 3 weeks, most positives are reported after 1-2 weeks.
Superficial mycoses by site
The typical fungal skin infection is an irregular expanding ring with a raised
serpiginous border thought to resemble a worm, hence the old term ringworm or tinea
(latin for worm). Scrapings of keratin must be collected from the periphery where the
infection is active. Sometimes there is a secondary bacterial infection obscuring the
fungus, a situation seen particularly in athlete's foot.
Manifestations of fungal infections vary considerably by site.
Trunk and limbs – tinea corporis
These usually present the classical appearance described above. They are usually
cured within 2 weeks by topical antifungals such as terbinafine, clotrimazole,
miconazole or econazole. It is recommended to continue treatment for several days
after full resolution of the lesions. Where chronic or widespread infection is present,
oral terbinafine, itraconazole or fluconazole may be considered.
Scalp – tinea capitis
Infected hair may break leaving a bald area. Fluorescence under a Woods lamp
sometimes helps establish the diagnosis and indicates which hairs should be taken for
microscopy and culture. Treatment with an oral agent is recommended, e.g.
terbinafine or itraconazole.

Groin – tinea cruris
Lesions may be on the inside of the thighs, inguinal area, pubic hair or scrotum.
Candida infections are common here as in other moist warm folds and a swab should
also be collected and placed in transport medium. Topical imidazoles are effective
against both Candida and dermatophytes. Erythrasma (qv) may be found in the groin
and is sometimes mistaken for tinea.
Athlete's foot – tinea pedis
Although the initial infection can be dry and scaling, added bacterial infection and
accumulation of soggy debris may occur. Treatment requires attention to hygiene and
local applications. Bear in mind Candida can be implicated as well as bacterial
superinfection.
Nail – tinea unguium, onychomycosis
Dermatophytes may affect the nails alone or they may spread from a nearby skin
infection. The nail often becomes thickened, discoloured and friable. Scrapings,
clippings and debris should be collected. Collection of a good specimen is of
particular importance in this site because long-term oral treatment may be needed.
Treatment options include oral terbinafine or itraconazole. Yeast species such as
Candida (qv) and other non-dermatophyte fungi may also cause nail infections.
Palms and Soles
Dermatophytes can be the cause of dry scaly lesions of palms and soles. Specimens
need to be collected with care to avoid false negatives. Treatment is topical.
Tinea versicolor

Malassezia furfur (qv) causes this fungal infection which presents as skin
discoloration without inflammation or itching. Treatment is with a topical imidazole,
ciclopiroxolamine or terbinafine. Oral terbinafine is not effective.
Dexamethasone suppression test
specimen: serum
protocol: day 1, give 1 mg dexamethasone orally at 23.00 hrs

day 2, collect specimen at 08.00-09.00 hrs
ref. range: <130 nmol/L at 09.00 hrs post-suppression
Normal suppression, especially to <50 nmol/L makes Cushing's syndrome unlikely.

Failure to suppress is less helpful and may occur with a range of conditions including:
• Cushing's syndrome
• endogenous depression
• chronic alcoholism
• drugs – phenytoin, barbiturates, oestrogens
• significant stress or illness
DHEA
see DHEAS (dehydroepiandrosterone sulphate)
DHEAS (dehydroepiandrosterone sulphate)

specimen: serum

ref. range: adult female 0.4-5.8 µmol/L
adult male 2.8-9.6 µmol/L
DHEA and its sulphate DHEAS are the most abundant androgenic steroids secreted
by the adrenal cortex. DHEAS is more commonly measured than DHEA and for
practical purposes the two estimations provide the same information. Its uses are:
• in the investigation of virilism - levels are usually >3x upper limit of normal
• in the investigation of hirsutism when there is a more than 2-fold increase in

free testosterone
• to differentiate Cushing's disease (minor elevations of DHEAS) from adrenal

neoplasms where there are large increases
• for monitoring steroid suppression therapy in congenital adrenal hyperplasia.
DHEAS is not used as a first-line investigation in mild to moderate hirsutism. Mild

elevations up to 30% are common but do not affect management.
In people taking DHEA supplements to restore youth and beauty, the DHEAS levels
may be increased 2-3x.

Diabetes autoantibodies
specimen: serum
ref. range: antibody significant level

— GAD (glutamic acid decarboxylase) > 10 units
— IA2 (insulin antigen 2) > 8
— ICA (islet cell antibody) > 10
— IA (insulin antibody) > 3
These autoantibodies are markers for Type 1 diabetes and typically can be detected
months or years before the development of clinical disease.
Indications
As yet a generally accepted preventive treatment for pre-clinical diabetes has not been
found but when it is there will be screening programmes and preventive treatment for
those who have significant levels of one or more antibodies.
At present autoantibodies are measured in two situations:
• to help predict whether a child of a Type 1 parent will develop diabetes.
• to determine whether a newly-diagnosed adult (particularly young adult) has

Type 1 or Type 2 diabetes, though in practice antibodies are not often used
because the typing is clinically apparent.
The preferred initial screen is for GAD and IA2 antibodies which are the easier tests
technically and the ones most likely to be elevated.
see Diabetes mellitus (DM), classification

Interpretation
The autoantibody pattern is variable from one patient to the next and varies with time
for an individual patient. GAD antibodies have a higher positivity rate (~80%) than
the others and stay elevated for longer
ICA and IA appear earlier in the pre-clinical course of the disease and disappear
earlier.
One antibody just above the level of significance may disappear without diabetes
developing.
A high level – they can be up to 50 times the significant level – is more likely to
progress to diabetes.
Two or more antibodies are more predictive than one.
Risks for developing Type 1 DM (diabetes mellitus) are:
identical twin has Type 1 DM 40%

both parents Type 1 DM 20%
father Type 1 DM 8%
sibling Type 1 DM 5%
mother Type 1 DM 3%
general population 0.3%

Diabetes insipidus
The essential feature is inadequate ADH (antidiuretic hormone) from the

hypothalamus/posterior pituitary causing excessive loss of dilute urine from the
kidney; or a kidney which is unresponsive to ADH. The usual problem is to separate
compulsive water drinking or simple urinary frequency from true diabetes insipidus
in a patient complaining of polydipsia and polyuria.
• Other causes of polyuria need to be eliminated.
— diabetes mellitus
— hypercalcaemia
— renal disease
— medication: lithium, diuretics
• A 24-hr urine should be collected to check whether urine volume is genuinely

excessive e.g. >4L. In severe disease, volume can be as high as 18L.
• The final screen test is urine osmolality after 8-12 hours of water deprivation
overnight. A urine specimen is collected on waking and ½-1 hour later before
drinking anything, the osmolality in these two specimens indicating ability to
concentrate urine.
The person with diabetes insipidus will be excreting a large volume of dilute urine
throughout the night compared with the normal person's diminishing volume of
increasingly concentrated urine. An osmolality <200 mmol/kg is consistent with
diabetes insipidus whereas a value above 400, or better still above 600, makes the
diagnosis unlikely.
Water deprivation should not be attempted in the person with a very high urine
volume because of the danger of serious dehydration.

Diabetes mellitus (DM)
Classification
• Type 1 (formerly IDDM) beta cell destruction associated with

autoantibodies leading to absolute insulin
deficiency
• Type 2 (formerly NIDDM) there is insulin resistance with relative insulin
deficiency and in some cases absolute insulin
deficiency requiring insulin treatment.
• gestational diabetes (GDM)
• pancreatic diabetes – pancreatitis, haemochromatosis
• endocrinopathies – Cushing's, Conn's, hypothyroidism, phaeochromocytoma,
acromegaly
• drug induced – steroids, thiazidess
Diagnosis of diabetes
Consider under two headings:
1. Symptomatic (thirst, polyuria, weight loss, tiredness)
The symptomatic patient almost invariably has a glucose level above 15 mmol/L.
An interim diagnosis can be made immediately using a urine dipstick, followed by
a definitive laboratory blood glucose.
Where there is less urgency, a random glucose result above 11.0 mmol/L at the
laboratory will confirm the diagnosis.

2. Asymptomatic i.e. screening for diabetes
• A fasting glucose is a good screen test and can be combined with fasting
lipids to check risk factors.
• Random bloods – A level between 7.0 and 11.0 is an indication for a GTT
(glucose tolerance test) or a fasting test. Below 7.0 can be accepted as
probably non-diabetic. Above 11.0 should be followed by a second random
glucose, two values above 11.0 being diagnostic of diabetes.
• HbA1c (qv) is a useful test where a random glucose is equivocal and GTT is
impractical e.g. the very busy, the needle-shy or the elderly person in a rest
home.
• The 1-hour or 2-hour post-polycose plasma glucose is useful in population

studies but inconvenient for the individual non-pregnant adult – having gone
to the trouble they may as well do the full 2-hr diagnostic GTT.
• In pregnancy the 50g polycose (qv) screen test is used.
• Urine testing is unacceptable as a screening procedure.
Diagnostic criteria
• classic symptoms and plasma glucose ≥ 11.1 mmol/L

• fasting glucose ≥ 7.0 on two occasions (the 1985 WHO level was 7.8)
• 2-hr glucose level ≥ 11.1 in a GTT.
• two random glucose levels ≥ 11.1.
see Glucose tolerance test (GTT) for more detail

Who should be screened for diabetes?
The NZSSD recommends screening as follows:-
• 5-yearly testing of Europeans over age 40 and non-Europeans over age 30

• frequency increases to 3-yearly if the patient is obese, has a family history of
diabetes or has hypertension.
• tests should be done yearly for
– post IGT (impaired glucose tolerance)
– post GDM (gestational diabetes)
Detection of pre-clinical Type 1 diabetes
see Diabetes autoantibodies
Monitoring diabetes
Patient autonomy is central to successful management and this involves self-

monitoring using finger-prick specimens for most Type 1 diabetics and for selected
Type 2s.
Type 2s require fewer tests for monitoring, their glucose levels being generally more
stable and their treatment regimens more fixed. A four times daily insulin regimen,
by contrast, in an unstable diabetic, requires frequent monitoring.
Tests used for monitoring glycaemic controls are:
Plasma glucose Patients who are self-monitoring establish their daily glucose profile
by testing before breakfast (fasting), before lunch, before dinner and before bed.
When using the laboratory, bearing in mind its more limited availability, the most
useful times are before lunch, often the lowest level of the day, and late afternoon.

Patients who are unreliable testers will require more laboratory glucose tests than
those who are conscientious self-testers.
HbA c (qv), which gives a measure of the mean blood glucose level over the past 2
1
months, is the essential base-line measure of glycaemic control and should be done at
least annually in all diabetics.
Fructosamine (qv) may have a role when looking for more recent changes in
glycaemic control or when red cell turnover is increased as in chronic bleeding or
haemolysis but in general it is a considerably less satisfactory test than HbA c.
1
Urine glucose testing has been abandoned as a tool for monitoring.
Urine microalbumin (qv) is used at annual review for detecting early nephropathy.
Diarrhoea, infectious
The common pathogens diagnosed at this laboratory are:
Campylobacter 55%
Salmonella 17%
Giardia 14%
Yersinia 10%
Shigella 4%
Rotavirus is the most common pathogen in children under 5 years of age.

For more detail on the above organisms, see separate alphabetic entries.
Travellers' diarrhoea

Acute severe diarrhoea – ciprofloxacin 500mg 12-hrly is the treatment of choice
supported by careful attention to fluid and electrolyte intake.
Chronic diarrhoea – can be due to giardiasis. Treat with metronidazole 2g daily for 3
days, or tinidazole 2g as a single dose.
Prophylactic antibiotics – these are not recommended as a routine but some travellers
suffering repeated bouts of diarrhoea may be helped by doxycycline 100mg daily or
cotrimoxazole 480 mg daily.
Diastase
The old name for urinary amylase (qv).
Diazepam
see Drug screen – overdose
Dibucaine number
see Cholinesterase
The dibucaine number detects the qualitative difference in cholinesterase enzymes in

scoline-sensitive persons.

DIC (Disseminated intravascular coagulation)
This is an uncommon condition in which there is a generalised consumption of

plasma clotting factors and platelets resulting in fibrin deposition within the
microcirculation. Secondary haemorrhagic events are due to the consumption of
normal clotting factors and secondary fibrinolysis.
Clinical setting for DIC:
(i) Major trauma

(ii) Septicaemia (usually with acidosis)
(iii) Obstetric crises (placental abruption, eclampsia, retained dead foetus)
(iv) Malignancy (acute promyelocytic leukaemia)
Tests for DIC include FBC (with blood film for fragments), platelet count (as part of
FBC), prothrombin time (PR), APTT, fibrinogen assay and D-dimers.
Dientamoeba fragilis
specimen: faeces in PVA fixative obtainable from lab.
A flagellated amoeba recognised as a cause of acute or recurrent diarrhoea. Most

acute cases are self-limiting and do not need treatment.
Laboratory diagnosis is by recognition of the trophozoite in stained films made from

faecal material fixed in PVA.
Faecal excretion is erratic and multiple examinations, e.g. three specimens on

different days, may be required for detection. There is uncertainty about treatment.
Doxycycline 100 mg 12-hourly for 10 days has been used.

Differential white cell count
see Blood count
Digoxin
specimen: serum
therapeutic range: 1.2–2.6 nmol/L (trough level)
Specimen should be taken at least 6 hours after last dose. Half-life is 36 hours, time
to steady state 8 days. Where toxicity is suspected, digoxin administration should
cease until the serum level has been measured – the long half-life means the decline
to sub-therapeutic levels is slow whereas a move higher into the toxic range can be
lethal.
Because digoxin is 85% eliminated by the kidney, renal impairment (as in the elderly)
is a potent cause of toxicity. Low K+ and high Ca++ levels potentiate toxicity.
Hypothyroidism and some drugs raise digoxin levels.
A source of falsely high digoxin levels is an ill-defined plasma substance termed

DLIF (digoxin-like immuno-reactive factor). Levels of DLIF can be up to 0.5 nmol/L
in healthy people taking no medication or as high as 3.0 in patients with renal or
hepatic failure.
See also Errors: antibody error

Dilantin (phenytoin)
specimen: serum
therapeutic range: 40–80 µmol/L (trough level)
Dilantin's unique pharmacokinetics make measurement of serum levels important.
At sub-therapeutic levels, Dilantin is removed by the liver at a rate proportional to

serum concentration. Within the therapeutic range, however, degradative enzymes
are saturated and serum levels climb quickly. For many patients, symptoms of
toxicity appear soon after the upper therapeutic limit is passed. Several common
drugs can precipitate toxicity by displacing Dilantin from its protein binding or by
inhibiting its breakdown.
see also Anticonvulsants
Diphtheria
see Corynebacterium diphtheriae
Diphyllobothrium latum
A tapeworm found in the human small intestine where it can live for 20 years and
reach 10 metres in length. By competing for vitamin B12 it can cause megaloblastic
anaemia. It is acquired by eating larvae in raw fish flesh. Even when fish is cooked
adequately, humans may become infected by sampling the flesh during preparation.
Distribution is mainly in Scandinavia but also in Japan and the Pacific Coast of the
USA. Diagnosis is by finding characteristic eggs or proglottids in faeces. Final
control will only occur by prohibiting the discharge of untreated sewage into lakes
and streams. Treatment is praziquantel, 10mg/kg as a stat dose.

Direct bilirubin
see Bilirubin, conjugated (direct) and unconjugated (indirect) fractions(direct)
Direct Coombs test
see Coombs test
Disaccharidases
specimen: small bowel mucosal biopsy transported immediately to the laboratory
on ice – do not place on paper.
ref. ranges:
U/g
lactase 2-8
maltase 8 - 40
sucrase 3 - 18
Clinically, lactose intolerance, which can be secondary to a variety of gastrointestinal

disorders, is the most important of the dissacharidase deficiencies.
see Reducing substances in faeces for lactose intolerance in infants
Disseminated intravascular coagulation
see DIC (Disseminated intravascular coagulation)

DLE
DM
see Diabetes mellitus (DM)
DNA antibodies (anti-double-stranded DNA)
specimen: serum
interpretation: <1:20 negative
1:20 or 1:40 equivocal
>1:80 supports diagnosis of SLE
Anti-ds DNA is positive at 1:80 or higher in 60-80% of SLE. Low titres may be seen
in rheumatoid arthritis, autoimmune hepatitis and in other immunological disorders.
DNA, genetic studies
see Molecular genetics - genetic studies

DNA, paternity
see Paternity testing
Donath-Landsteiner test
Used for the diagnosis of paroxysmal cold haemoglobinuria.
see Cold agglutinins
Dopamine
see Catecholamines
Down's syndrome, (trisomy 21) pre-natal testing
Also called Down syndrome

(NTD)
Drug allergy
see Penicillin allergy

Anaesthetic allergy
Drug screen – overdose

specimen: 30 ml random urine
Overdose screens are usually for persons admitted to hospital. The panel of drugs to
be tested will depend on the history and clinical findings.
Drug screen – pre-employment screen and

drugs of abuse
specimen: 30ml random urine
A common panel includes:
• amphetamines
• barbiturates
• benzodiazepines
• cannabinoids
• cocaine
• opiates
• phencyclidine (angel dust)
Results are reported as +ve or -ve using internationally recognised cut-off limits.
Serum is not used for screening.
If alcohol is required a blood (serum) specimen should be collected to give a

quantitative result which will separate the prospective employee who had a health-
giving glass of wine the night before from the chronic alcoholic with a sustained high
alcohol level.

Pre-employment screens, common for some years in the USA, are being used more
often now in New Zealand and in some occupations, for example in public transport,
random checks may be used.
When results are to be used medico-legally, there has to be a secure audit trail
beginning with direct observation of specimen collection.
Drugs, therapeutic monitoring (TDM)
As a general rule, trough levels are measured, i.e. the low point reached before the
next dose is taken. Patients can defer their morning dose, attend the laboratory at
09.00 hrs to have blood off and then take their daily dose after that.
The exception is theophylline where the peak is monitored: the blood specimen
should be collected 4 hours after a sustained-release preparation or 2 hours after the
shorter-acting 6 hourly preparation.
The half-life (t½) is the time for a serum level to drop by 50%. When a drug is
started, or the dosage changed, the time to reach a new steady state = t½ x 5.
Reasons for drug monitoring include:

• check compliance
• guide dose adjustment
• check for toxicity
• monitor interactions if a new drug is added
see also Antiarrhythmic drugs

Antidepressant drugs, tricyclic
Anticonvulsants

individual drug entries
DVT (deep vein thrombosis)
see Venous thromboembolism (VTE)

INR (international normalised ratio)
E1 (oestrone)
see Oestrogens
E2
see Oestradiol (E2)

E3
see Oestriol (E3)

Ear swabs & infections
Otitis media
It is not possible to sample the middle ear routinely and the flora of the external
meatus bears no relation to that behind the drum. Antibacterial treatment is therefore
empirical, based on studies which show the role of H.influenzae, Strep. pneumoniae,
Moraxella (previously Branhamella) catarrhalis, and Strep. pyogenes. Amoxycillin,
cotrimoxazole and amoxycillin-clavulanate provide effective treatment. Cefaclor has
insufficient activity against Strep. pneumoniae for it to be recommended in this
situation.
Otitis externa
Ear swabs are taken from just inside the external meatus. The commonest pathogens
are Staph. aureus and Pseudomonas aeruginosa. H. influenzae and S. pneumoniae
are also frequently isolated.
Most cases respond to keeping the ear clean and dry.
% susceptible to topical agents are:
% susceptible to topical agents

chloramphenicol neomycin¹ polymyxin²
S. aureus 99 80 0
P.aeruginosa 0 0 100
1. Neomycin susceptibility predicts susceptibility to

framycetin (Soframycin) and gentamicin.
2. Polymyxin susceptibility predicts susceptibility to colistin
which is contained in Coly-Mycin S Otic ear drops.

EBV (Epstein-Barr virus) antibody
see Infectious mononucleosis
Echinococcus
see Hydatids
Echis ratio (ER)
This test is helpful in deciding whether a prolonged PR/INR is due to impaired

hepatic protein synthesis or vitamin K deficiency/warfarin. Other conditions such as
heparin therapy, severe DIC and congenital factor deficiency may affect the Echis
ratio and must be excluded before interpreting results.
PR ER cause
prolonged normal vitamin K deficiency/warfarin
prolonged prolonged reduced factor synthesis (liver disease)
The test is based on the ability of the Echinus carinatum venom, from the saw-
toothed viper, to activate factors II and X.
Echoviruses
see Enteroviruses

E. coli (Escherichia coli)
An important member of the normal flora of the intestine and the cause of 80% of
urinary tract infections.
% susceptible
norflox nitrof aug trimeth cotrim amox
E. coli 100 99 96 77 79 44
E. coli can also cause septicaemia or meningitis, particularly in infants.

Enterotoxigenic E. coli causes diarrhoea but this is not detected by routine faecal
cultures.
Culture for E.coli 0157/H7, which is associated with haemorrhagic colitis, a severe
form of diarrhoea, and with haemolytic-uraemic syndrome, can be arranged on
request.
Ectopic ACTH syndrome
see Cushing's syndrome
Ectopic pregnancy

EDTA
seeTubes for blood collects
Electrolytes
specimen: serum
The standard electrolyte group consists of Potassium (K+), serum and Sodium (Na+),
serum – see separate entries on these.
Electrophoresis (EPP) of serum proteins

specimen: serum
The main indication is suspected myeloma or macroglobulinaemia when investigating

unexplained high ESR (above 50), back-pain, unexplained anaemia, suspected
malignancy, etc.
EPP pattern
The fractions demonstrated by agarose gel electrophoresis are:-

mean concentration
(g/L)
albumin (at anodal end of EPP) 42
alpha-1 globulin alpha-1 antitrypsin 3

orosomucoid 1
alpha lipoprotein (HDL) 0.5
alpha-2 globulin alpha-2 macroglobulin 2.5

haptoglobin 1.5
ceruloplasmin 0.4
beta globulin beta lipoprotein (LDL) 5

transferrin 3
complement (mainly C3) 1.5
gamma globulin IgG 7 - 15

IgM 0.5 - 2.5
IgA 1-3
Additional Bands
• Benign or malignant paraproteins (qv) are usually in the gamma zone but
some, particularly IgA, may overlie the beta band or occasionally lie between
the alpha 2 and beta bands.
• Free light chains (Bence Jones protein) being of relatively low MW are found
mainly in urine but occasionally form a band, usually in the beta-gamma zone,
particularly in patients with renal impairment.
• If the specimen is haemolysed, Hb will show as a band between the alpha-2
and beta
• In plasma (as distinct from serum), fibrinogen forms a band between the beta
and gamma zones.
• A markedly elevated CRP can sometimes be seen as a weak band in the
gamma zone.
• Beta-gamma bridging is sometimes seen in inflammatory conditions.

Abnormal EPP Patterns
• reduced albumin – see Albumin
• reduced alpha-1 – see Antitrypsin (alpha-1-antitrypsin - AAT)
• increased alpha-1 and/or alpha-2 – usually due to increased acute phase
reactants (qv).
• reduced gamma – see Immunoglobulins, IgA, IgG, IgM
• diffuse increase in gamma – see Immunoglobulins, IgA, IgG, IgM
• nephrotic syndrome pattern – low albumin, increased alpha-2
(macroglobulin), reduced gamma.
Electrophoresis of lipoproteins
see Lipoprotein electrophoresis
Electrophoresis of urine
This is a test for free light chains (Bence Jones protein) in IgG or IgA myeloma and
occasionally with IgM-associated malignancies. After concentrating the urine, free
light chains show up as a well-defined band in the beta or gamma zone.
In Bence Jones myeloma (10-20% of all myelomas) a heavy band of free light chains
in urine is the diagnostic feature, usually with no band on serum EPP.
see also Immunoglobulins, IgA, IgG, IgM : malignant paraproteins
EPP of urine is occasionally used in generalised proteinuria to separate selective

(albumin) from non-selective proteinuria.
see Proteins, urine (proteinuria)

Elliptocytosis
Hereditary elliptocytosis, transmitted as an autosomal dominant, is a common

disorder characterised by large numbers of elliptical cells in the peripheral blood.
Usually it is a chance finding but in 15% there is a mild compensated haemolytic
anaemia.
specimen: serum
interpretation: results are given as +ve or -ve, not as a titre
Some nuclear antigens can be extracted into solution and patients’ serum tested for
presence of antibodies against those antigens. ENA screen is used as a follow-up test
on positive ANA's or where one of the connective tissue diseases other than
rheumatoid arthritis is suspected.

antigen associated disease
(with approximate % frequency of antigen)
Sm SLE (20%) - antigen is 99% specific when present
RNP MCTD
autoimmune hepatitis
SLE (30%)
RA
Ro (SS-A) Sjogren's (90%) usually associated with La (SS-B)
SLE (40%)
polymyositis (5%)
RA (5%)
neonatal lupus in pregnancy
La (SS-B) Sjogren's (80%) usually associated with Ro (SS-A)
SLE (10%)
diffuse scleroderma (5%)
neonatal lupus in pregnancy
Scl 70 diffuse scleroderma (50%)
CREST (10%)
Jo1 polymyositis (30%) - >95% specific when present
Endolimax nana
A non-pathogenic gut protozoan which does not require treatment.
Endomysial antibodies (EMA)

specimen: serum
ref. range: not detected
EMA have very high sensitivity and specificity for untreated coeliac disease and
dermatitis herpetiforms.
see Coeliac disease (gluten sensitive enteropathy) for interpretation

Entamoeba coli
A non-pathogenic amoeba of the gut which tends to be acquired in situations where

Entamoeba histolytica and Giardia are found. Symptoms of gastrointestinal
infection, if present, are likely to be due to the latter organisms.
Does not require treatment.
Entamoeba dispar
see Entamoeba histolytica
Entamoeba hartmanni
A non-pathogenic gut protozoan which does not require treatment.
Entamoeba histolytica
As far back as the early 1900s it was suspected that there were two "types" of
Entamoeba hystolytica, one which causes disease and one which was non-pathogenic.
Work over the past 25 years has proven this early suspicion to be true. There are two
morphologically indistinguishable Entamoeba species : E. histolytica, the cause of
intestinal and extra-intestinal amoebiasis; and E. dispar, its non-invasive relative.

E. histolytica is the causative organism of amoebic dysentery. Clinical infection is
due to trophozoites invading the gut wall. The spectrum of disease ranges from mild
changes in bowel habit through chronic recurrent diarrhoea to fulminant bloody
diarrhoea with invasion of the liver and other sites by trophozoites. Amoebic
dysentery is diagnosed by finding highly specific trophozoites which have ingested
erythrocytes. This is a rare finding in our laboratory. Where E. histolytica is
suspected as a cause of severe dysentery, please consult with the microbiologist to
discuss arrangements to allow examination of fresh stool for trophozoites.
Treatment of amoebic dysentery or hepatic abscess is with metronidazole, 400-800mg
8-hourly for 10 days.
Almost all reportings of E. histolytica are based on finding typical cysts. It is not
uncommon to find them in the faeces of people who have been to, or have originated
from, third world countries and it is likely that a good proportion of these are E.
dispar rather than E. histolytica. Treatment is generally not indicated because if the
cysts are E. dispar they are not pathogenic and if they are E. histolytica the risk of
developing invasive disease during asymptomatic carriage is low. Treatment of cyst
carriage is indicated if there is reason to suspect infection with E. histolytica, e.g. high
titres of specific antibody, history of close contact with a case of invasive amoebiasis,
or an outbreak of amoebiasis (unlikely in New Zealand). Some would treat cysts if
the patient was receiving steroids which are a risk factor for amoebiasis.
Treatment of asymptomatic cyst carriage is with:
diloxanide furoate,
or paromomycin,
or iodoquinol
These agents are not registered in New Zealand and can be provided only on a named
patient basis.

Enterobacter species
Gram-negative enteric bacilli, part of normal enteric flora, occasionally a cause of

urinary tract infection in the community. May cause systemic infection in
hospitalised patients. Treatment choice depends on susceptibility results.
Enterobius vermicularis (pinworm)
Common cause of pruritis ani. Spread from person to person by faecal-oral route.
Adult worms live attached to the mucosa of the caecum. Gravid females migrate to
the anus. The cream coloured adult female worm, approximately 10mm long, lays
eggs on the perianal skin. Each female deposits approximately 20,000 eggs on the
host, bed clothes and linen. Eggs are infectious shortly after laying, are relatively
resistant to drying and remain viable in linen, bedclothes, or house dust for several
days. Eggs can be demonstrated using a swab or cellotape imprint. Usually
anthelmintics are prescribed on clinical grounds alone, e.g. mebendazole or pyrantel.
Many recommend that all family members should be treated simultaneously.
Enterococcus
Previously known as S. faecalis or Group D Streptococcus.

A common cause of urinary tract infections and can be an important pathogen in
bacterial endocarditis.
% susceptible in the urinary tract

amox-clav amox trim nitrof norflox
Enterococci 99 99 0 99 82

Enteroviruses
A large group of viruses including polio, coxsackie and echoviruses affecting a wide
variety of organ systems. Their name is derived from their ability to infect the gut
and be shed in faeces.
Identification of the viruses or their antibodies is seldom required in general practice.
Eosinophils
specimen : blood (EDTA)
ref. range: 0 – 0.5 x 109/L
Eosinophilia
Eosinophil counts are part of a routine blood count. The common causes of
eosinophilia are drug effect, allergy or parasitic infestation of the gut.
The differential diagnosis includes:-
• allergic disorders
• parasitic colonisation – hookworm, filaria, hydatids, toxocara
• drug administration
• skin disease, e.g. eczema, psoriasis, pemphigus
• collagen disorders, especially polyarteritis nodosa
• infections, e.g. TB, scarlet fever
• malignant disease, e.g. lymphoma, Hodgkins disease, ovarian Ca.
• pulmonary eosinophilia

• hypereosinophilic syndrome (a rare myeloproliferative disorder)
Epidermophyton
see Dermatophytes
Epilim
see Valproic acid (Epilim)
EPP
see Electrophoresis (EPP) of serum proteins
Epstein-Barr virus
Errors
There is a distinction between errors, which are due to human fallibility, and
variance (qv) which is the sum of the unavoidable fluctuations due to biological
changes (e.g. diurnal rhythms) and the analytical imprecision of the method.

There are four main sources of error.
• Clerical error This is the commonest error, the hardest to detect and
potentially the most serious. It includes mislabelling of specimens,
transposition of specimens in an analyser rack, transcription errors when
entering data into a computer, and so on. We do our best to devise systems
that will avoid these errors but we will never, alas, achieve perfection.
• Specimen collection errors The specimen collection procedure may have
failed to pick up the cells or microorganism it was aiming for. The specimen
may have deteriorated on standing e.g. microorganisms have died; potassium
has leached out of red cells into serum
• Analytical error is where the analyst or reagent manufacturer has made a
mistake but in practice this is the least important source of error, thanks to
modern technology and use of quality control procedures.
• Antibody error Immunoassays – methods incorporating an antibody to detect
the analyte being measured, rather than using chemical reactivity – are used in
many of the exciting new assays now available, particularly for hormones,
antibodies and drugs. Specificity of the antibody is not always absolute.
Anti-digoxin antibodies are an example. The term DLIF (digoxin-like
immuno-reactive factor) is used to describe substances found in serum which
are identified by the analytical antibody as "digoxin" but which in reality are
something else. Thus a "digoxin" level may be measured in a healthy person
taking no medication at all. The same antibody error can occur potentially in
any method and can be the explanation of a result which is wildly astray as
shown by finding a much lower or higher level when repeated in a laboratory
using a different method.
Important Rule: "If an abnormal result, or a normal result, does not fit the clinical
picture, or if it has important diagnostic, therapeutic, or social consequences, don't
act on the result until the test has been repeated on a second specimen." If you
suspect an error, please phone us. We can often help – and we can make sure that
error doesn't happen again.

Erythrasma
A superficial infection of groin, axillae and toe webs caused by Corynebacterium

minutissimum leading to pigmentation of pale skin or depigmentation of dark skin. It
may fluoresce coral pink under a Woods lamp and be mistaken for a fungal infection.
Treatment is with oral erythromycin. Five days treatment is usually enough but 2-3
weeks may be required.
Erythrocyte
= red cell
Erythromycin sensitivity
This is an allergic response caused usually by the estolate of erythromycin. It

requires at least 1 week (usually 2 weeks or more) of drug ingestion before the typical
cholestatic picture develops with elevation of all liver enzymes but particularly ALP
and GGT. Clinically there may be jaundice, abdominal pain, fever and malaise. All
resolve when the drug is stopped.
Erythropoietin (EPO)
specimen: serum
ref. range: 5-30 mIU/ml
Erythropoietin (EPO), a hormone produced by the kidney in response to low renal

pO2, has an important role in the regulation of erythropoiesis.
Measurement of EPO can be used when differentiating primary polycythaemia (low

EPO) from secondary polycythaemia (high EPO).

Reduced EPO formation is a feature of the anaemia of chronic renal disease and EPO
can be used to treat the anaemia.
Escherichia coli
see E. coli (Escherichia coli)
ESR (erythrocyte sedimentation rate)

specimen: blood (EDTA)
ref. range:
mm/hr
female male
child 1-10 1-10 1-10
adult <50 yrs 1-20 1-15
>50 yrs 1-30 1-20
Levels are higher in pregnancy due to hyperfibrinogenaemia.
The ESR is an antique test that still has a place as a non-specific indicator of
inflammatory disease and abnormal protein states.
In an acute illness, the ESR may take a week or more to start to rise and stay elevated
for some weeks after its resolution. The CRP (qv) by contrast rises and falls more
quickly and is in some ways a better marker for acute inflammation.
Interpretation

• ESR within the reference range
A "normal" ESR never excludes inflammatory disease but it makes it less
likely.
• ESR 20 - 50
Values in this range may have an obvious explanation but sometimes,
particularly in the elderly, they persist for no obvious reason. In the absence
of any other leads, investigation need not be too intensive. Pregnancy
elevations are usually in this range.
• ESR 50-100
These usually have an explanation and should
be pursued.
• ESR >100
The "3-figure ESR" nearly always indicates
serious disease such as a serious infection,
malignant paraproteinaemia or connective tissue
disease.
Baseline investigations for a high ESR would

include all those relating to serious acute and
chronic infections, serum and urine protein
electrophoresis, immunoglobulins, ANA,
rheumatoid factor.
Essential thrombocythaemia
Essential thrombocythaemia is a myeloproliferative disorder characterised by a
sustained increase in the platelet count, particularly above 600 x 109/L.
Clinical features include splenomegaly, an increase in thrombotic risk and bleeding of

varying severity. Bone marrow biopsy and elevated NAP score are useful in

diagnosis. Treatment is aimed at reducing the platelet count. Therapy at counts
which are only modestly increased is controversial.
Estradiol/Estriol/Estrogens
see Oestradiol (E2) etc.
Ethanol (ethyl alcohol)
see Alcohol, ethyl (ethanol)
Ethosuximide (Zarontin)
see Anticonvulsants
Euthyroid hyperthyroxinaemia
see Thyroid disease — diagnosis and monitoring
Exposure to blood and body fluids
see Needlestick injuries

Extended GTT
see GTT
Extractable nuclear antigens
see ENA (extractable nuclear antigen) antibodies
Eye swabs
If the eye is moist, use a dry swab; if the eye is dry, moisten the swab in transport
medium. After pulling the lower lid down roll the swab across the inner part of the
lower lid. If there is pus in the corner of the eye, get some of this onto the swab as
well.
In neonates, conjunctivitis can be due to gonococci or Chlamydia trachomatis

transmitted from mother to baby during birth. When testing for Chlamydia remove
any purulent exudate before collecting conjunctival epithelial cells by rubbing the
small Chlamydia swab over the everted palpebral conjuctiva.
Bacterial conjunctivitis outside the neonatal period is most commonly caused by

Staph. aureus, H. influenzae or Strep. pneumoniae and usually resolves spontaneously
or in response to topical eye drops or ointment. Occasionally unusual bacteria are
found. A negative bacterial culture usually indicates a viral or allergic conjunctivitis.

% susceptible
chloramphenicol neomycin¹ fucidin polymyxin B tetracycline
S. aureus 98 94 99 0 97
H. influenzae 100 100 0 100 99
S. pneumoniae 100 0 — 0 76
1. Neomycin susceptibility predicts susceptibility to

framycetin (Soframycin) and gentamicin.
Factor VIII assays
see von Willebrand's disease (vWD)
Factor V Leiden (FVQ506)
The commonest of the inherited causes of hypercoagulability, first recognised in

1993, is a mutation of the Factor V gene known as Factor V Leiden. Normal Factor
V, which promotes normal clotting, is inhibited physiologically by Activated Protein
C. Factor V Leiden is abnormally resistant to this inhibitory action and the presence
of Factor V Leiden is detected by the APCr test.

Factor V Leiden occurs in 3-7% of Caucasians and is a factor in 20-40% of cases of
venous thromboembolism (VTE). Risk of VTE is increased 5-10 times in
heterozygotes compared with normal people and 50-100 times in homozygotes.
Addition of oral contraceptives increases the risk a further 3-5 times in heterozygous
individuals.
see Hypercoagulability
Activated protein C resistance (APCr)
Factor XII
Deficiency of Factor XII is a common cause of prolongation of the APTT.
Mild Factor XII deficiency causes a mild prolongation of the APTT. A significant
prolongation of the APTT (e.g. >80 seconds) which corrects with the 1+1 test and
which is not associated with bleeding symptoms is usually due to more marked Factor
XII deficiency but even low levels are of no clinical significance.
see APTT (activated partial thromboplastin time)
Faecal fat
specimen: faeces collected over a 3-day period into a container supplied by the
laboratory and stored in the refrigerator during collection. Extraneous
material such as toilet paper, plastic bags or nappies, must be excluded.
The patient should be eating 70-100g fat per day for at least three days

prior to and during collection, i.e. not on a fat-reduced diet. Laxatives
or cholestyramine interfere with the test.
ref. range:
<1 yr 1.5g/day
1-10 yrs <3g/day
>10 yrs <5g/day
1g = 3.5 mmol
Indications
• for documenting steatorrhoea
• for monitoring treatment in patients with known steatorrhoea
This is an unpleasant test for both patient and laboratory and should not be used as a
screening test in patients with chronic diarrhoea or other non-specific gastrointestinal
symptoms.
Steatorrhoea should be suspected when stools are pale, loose, bulky and greasy. It
will seldom be found in formed brown stools. In this laboratory, the mean weight of
normal 3-day faecal collects is 350g compared with a mean of 940g for those with
steatorrhoea (>5g fat/day).
see also Malabsorption.
Faeces, for culture and microscopy
specimen: 1-3 random fresh faeces collected into small clean jars, each of which
should be delivered to the lab as soon as possible, preferably within 4
hours.
We have recently analysed our results for patients who have had three specimens sent
for bacterial culture for enteric pathogens:

specimen 1 detected 85% of positives
specimen 1 & 2 detected 95% of positives
specimen 1,2 & 3 detected 100% of positives
Therefore a single specimen detects the majority of positives. Three specimens may
be requested in chronic intermittent diarrhoeas or in food handlers where it is
essential they be established as being free of infection. The three specimens should
be collected on three different days and each taken to the lab on the day of collection.
Routine examination includes culture and examination of a wet film for red or white
blood cells.
Culture will detect Campylobacter, Salmonella, Shigella, Yersinia, Aeromonas, and

Pleisomonas. If infection with a Vibrio species is suspected this should be indicated
on the form so special media will be inoculated.
Rotavirus is looked for when the patient is age 5 or less.
Examination for Giardia antigen, or of a faecal concentrate for ova and parasites, is
performed only when specifically asked for on the request form.
Faeces for occult blood

specimen: faecal smears on reagent cards
Three specimens are collected on 3 separate days and either 1 or 2 smears (from
different parts of the specimen) taken from each. They remain stable for up to a
week.
Indications

When done properly, a positive result (even one) increases likelihood of
gastrointestinal blood loss, especially from lower bowel.
However, because of low sensitivity for detecting small, often intermittent bleeding, a
negative result does not exclude GI blood loss as from a tumour. Further evaluation
(e.g. colonoscopy) is still therefore indicated in at-risk patients with unexplained iron
deficiency.
Types of test/dietary advice
Non-specific guaiac tests These, the most commonly used tests, detect the peroxidase
activity of haem whether of human or animal origin.
They can give false positives with high meat diets, peroxidase-containing foods such
as horse-radish or turnip, or sometimes with iron supplements. Gastric irritants such
as NSAIDSs can give positives because of the minor bleeding they induce.
High dose vitamin C or E supplements can give false negatives.
Specific immunochemical tests Most of these detect intact human Hb but others are
based on human haem, porphyrin or even albumin. Although these tests avoid dietary
false positives, there is still the large problem of positives due to minor benign
bleeding.
Faeces for ova and parasites

specimen: 1-3 random faeces samples
The ova and parasites box must be ticked if these are required in addition to faecal
culture.

Where Giardia (qv) is suspected, the antigen test is more sensitive than the standard
parasite screen. The antigen test is requested by ticking the Giardia box.
Fanconi syndrome
A generalised disorder of renal tubular function characterised by acidosis, amino-

aciduria and glycosuria. It can be a primary defect but is more often secondary to
some other metabolic condition or to nephrotoxins or drugs.
Fat, faecal
see Faecal fat
FBC (full blood count)
see Blood count
FDP (fibrin degradation products)

do test for D-dimers
Fe
see Iron

Ferritin
specimen: serum
ref. range:
Age µg/L
<6 mths 50-400
6 mths-15 yrs 12-140
adult female 20-160
adult male 20-250
Low levels
Ferritin is a measure of total body iron stores and levels below 12 indicate seriously
deficient or absent stores. Results between 12 and 20 suggest reduced stores. Iron
stores are often marginal in infancy, adolescence and in women during their child-
bearing years, especially if diet is deficient. At other times they should prompt a
search for sites of blood loss.
see Iron deficiency for more detailed discussion.
In the presence of inflammation, which elevates ferritins, an iron-deficient person

may have a normal result despite their lack of iron.
High levels
• haemochromatosis – (qv)
• liver disease – in viral hepatitis the ferritin can rise above 4000.
• alcohol
• chronic inflammation – connective tissue diseases, bacterial infections
• malignancy, particularly leukaemias, lymphomas and myeloma

• thyrotoxicosis
• excessive parenteral iron therapy
• multiple blood transfusions in refractory anaemias
A raised ferritin is not uncommonly found with no immediately obvious explanation.

If the fasting iron saturation is above 50% the HFE gene should be tested as a marker
for haemochromatosis.
If no explanation is found, ferritin should be checked at least annually with

appropriate follow-up of clinical developments.
Fetal
see Foetal Hb
Fetoprotein
Fibrin degradation products

do test for D-dimers
Fibrinogen

Fibrinogen is reduced in:
• afibrinogenaemia (total absence of fibrinogen)

• hypofibrinogenaemia (decreased synthesis of fibrinogen)
• dysfibrinogenaemia (structural abnormality of the fibrinogen molecule)
-
Fibrinogen is increased in inflammatory conditions.
It is measured as part of the basic haemostasis screen.
Filariasis
Filariasis occurs in Africa, Latin America, Asia and the Pacific Islands where the
most common cause is Wuchereria bancrofti. Diagnosis is by finding microfilaria in
peripheral blood. An eosinophilia may be the only evidence of filarial infestation.
Lymphatic filariasis occurs when host inflammation and fibrosis lead to lymphatic
occlusion and in patients heavily and repeatedly infected, elephantiasis may develop.
Bacterial cellulitis contributes to tissue damage. The syndrome of tropical
eosinophilia is an extreme reaction to filariasis.
Treatment with diethyl carbamazine or ivermectin clears microfilaria from the blood.
Dying microfilaria can stimulate a severe allergic reaction requiring treatment.
Fine needle aspirate (FNA)

Separate instructions for FNAs are available on request for those using this technique.
A service is also provided by our pathologists.
Flavobacterium
see Chryseobacterium
Fluoride tube for glucose
Flushing attacks
FNA
see Fine needle aspirate (FNA)
Foetal Hb
see Hb ( haemoglobin)

Foetoprotein
Folate (folic acid), serum

specimen: serum
ref. range: 8.0-35.0 nmol/L
6.0-8.0 nmol/L: borderline low
Although the terms folate and folic acid are often used interchangeably, another usage
is to apply folate to the serum analyte and naturally-occurring vitamin found
particularly in green vegetables, while using folic acid to refer to the synthetic
chemical used in vitamin supplements.
Folate deficiency is associated with three important disorders.
• macrocytic megaloblastic anaemia

As with vitamin B12 deficiency, the correlation between serum folate level
and peripheral blood findings is not close.
• birth defects, particularly neural tube defects

Studies have shown dramatic reduction in birth defects in women taking
400µg folic acid daily, commencing prior to conception.
• cardiovascular disease
The evidence is circumstantial only and concerns the plasma
homocysteine levels which appear to be a graded independent
risk factor for cardiovascular disease. When plasma folate is
maintained consistently above 15 nmol/L, using a supplement
of 400µg folic acid daily, plasma homocysteine falls to a low

plateau.
Although definitive studies are not available at the time of

writing (are under way), it seems at least possible that a daily
supplement of 400µg folic acid could be beneficial and that the
low end of the 8.0-35.0 nmol/L reference range is not as
desirable as the mid-zone.
Causes of low serum folate
• Inadequate diet – the commonest cause. Folate comes particularly from green
vegetables and is destroyed by cooking. Deficiency is associated with old
age, poverty, alcoholism, anorexia
• Malabsorption – coeliac disease, tropical sprue, giardiasis
• Drugs – anticonvulsants, pyrimethamine, methotrexate and others
High folate levels are due to vitamin supplements or a recent meal high in folate.
Total body stores in a healthy individual approximate 10mg, enough to last about 6
months if all dietary folate is removed. Recommencement of folate intake restores
serum levels in a few days but replenishment and maintenance of body stores
requires sustained intake.
see also Macrocytosis
Folate, red cell

ref. range: 400–1800 nmol/L

Red cell folate is a better indicator of tissue stores than serum folate, which is more
labile. The red cell folate method has precision problems however and is more
expensive. In practice it is not always used despite its theoretical superiority.
Interrelationship between B12 and folate deficiencies:
1° deficiency Serum B12 Serum folate Red cell folate

B12 ↓↓ n↑ n↓
folate n↓ ↓↓ ↓
Follicle stimulating hormone
see FSH (follicle stimulating hormone) and LH (luteinising hormone)
Food allergy
True IgE-mediated, immediate-response, food allergy affects about 5% of children

and 1% of adults.
In children, milk, eggs and peanuts are important.

In adults, peanuts, fish, shellfish and fruit.
Adverse reactions to food are more often non-allergic, e.g.
• transient lactase deficiency in infants causing milk intolerance

• tyramine in cheese or red wine causing headaches
• monosodium glutamate in Asian cooking causing abdominal symptoms
• metabisulphate added as preservative to dried foods or white wine

Diagnosis requires a careful history, trial of withdrawal of the suspected food and, in
selected cases, food challenge - supervised if past reactions have been serious.
Skin tests and RAST tests are less helpful in food allergy than in allergy caused by
inhaled allergens and can give both false negatives and false positives. Peanuts, cows
milk and eggs are included in most standard batteries of skin tests. Specificity is not
particularly high but a -ve test makes allergy less likely and a +ve test, particularly in
the context of a positive history, makes the diagnosis more likely. Testing the patient
with an ill-defined history of vague complaints against a wide range of foods will
seldom be productive.
Free T3
see T3, free (tri-iodothyronine)
Free T4
see T4, free (thyroxine)
Free testosterone
see Testosterone
Frozen section/rapid smears

by arrangement with Histology Department.

Fructosamine
specimen: serum
ref. range: 190-290 µmol/L
Fructosamine is glycated albumin and gives a measure of the mean glucose level over
the preceding 1–3 weeks in diabetes. For the laboratory, fructosamine is a cheaper
test than HbA1c but it has major disadvantages.
• in obese patients, who make up the bulk of the Type 2 diabetic population, it
is falsely low.
• it is lowered in any condition where there is increased albumin turnover, most
notably by the proteinuria of diabetic nephropathy.
• its correlation with HbA1c is not good.
• –diabetologists don't like it.
Should it be used at all? Provided an HbA1c is available, fructosamine should

probably be used only in patients with increased Hb turnover as in haemolysis or
chronic blood loss; or perhaps during pregnancy when rapid improvements in
glycaemic control are being sought.
Indicative levels of control in diabetes:
around 300 is the target value

280 - 330 good control
330 - 380 fair control
380 - 450 bad control
>450 requires urgent attention
In pregnancy there is a fall in fructosamine values to within a range of about 150 -

260.

see also HbA1c (glycated Hb)
FSH (follicle stimulating hormone) and LH

(luteinising hormone)
specimen: serum
ref. ranges:
FSH LH
adult female
follicular and luteal phases 1-8 IU/L 2-15 IU/L
mid-cycle ovulatory peak 6-26 20-120
post-menopausal 18-120 15-100
pregnancy/oral contraceptives <1 <2
adult male 1-9 2-12
Physiological actions
The complex cyclical variations in FSH, LH, oestradiol and progesterone in the
menstrual cycle are shown in the diagram.
Specimens are collected outside the mid-cycle peak except when timing ovulation.
Release of both hormones is episodic and can lead to biological variation throughout
the day.
In the male, FSH stimulates spermatogenesis whereas LH (also known as ICSH),

stimulates interstitial cells to release testosterone.
Applications
• Identifying the menopause – the FSH rises from a base-line of less than 8 to
above 20. FSH rises relatively more than LH. see also Menopause.
• Ovarian or testicular failure – both FSH and LH rise to menopausal levels.

Gonadal failure can be primary as in agenesis, dysgenesis, Klinefelter's or

Turners syndromes. Or it can be secondary as in premature menopause,
oophorectomy, or testicular damage.
• Identifying day of ovulation in fertility control.
• Hypopituitarism – LH and FSH are not usually undetectable in

hypopituitarism but low or inappropriately normal values in patients with low
oestradiol (women) or low testosterone (men) are suggestive. Mid-range or
high values can help exclude hyopituitarism.
• Polycystic ovary syndrome (qv) – LH is often raised relative to FSH with an

LH/FSH ratio >2.

These cyclical changes will not, of course, be found in women on oral contraceptives
which suppress LH and FSH below the reference range.
FTA (fluorescent treponemal antibody)
specimen: serum
A positive FTA indicates past or present treponemal infection. It does not

distinguish between syphilis and yaws. The FTA stays positive life-long.
see also Treponemal serology (STS, serological tests for syphilis)
Full blood count (FBC)
see Blood count
Fusobacterium
An anaerobic gram-negative bacillus, found in situations predisposing to anaerobic

(qv) infection, e.g. following a break in the integrity of mucosal surfaces.
Fusobacterium necrophorum can cause local disease of the oropharynx complicated
by septic thrombophlebitis and metastatic abscesses. Usually susceptible to penicillin
as well as other ß-lactam agents. Also susceptible to metronidazole.

G
G-6-PD (glucose-6-phosphate dehydrogenase)
specimen: blood (heparin or EDTA)

ref. range: 4.6 - 13.5 EU/g Hb
Quantitative assay is done if the screen test is abnormal.
G-6-PD deficiency is a cause of drug-induced haemolytic anaemia, commonest drugs

being nitrofurantoin, sulphonamides, nalidixic acid, anti-malarials, sulphones.
Deficiency occurs particularly in Mediterranean peoples, black Africans and some
Asiatics.
GAD autoantibodies

Galactorrhoea
Most patients are women but occasionally galactorrhoea is found in men.

Causes are:
• Hyperprolactinaemia. This is commonly, but not invariably, associated with

galactorrhoea. There may or may not be a pituitary tumour. Elevations of
prolactin (qv) can be minimal and intermittent.
• Hypothyroidism and hyperthyroidism.
• Drugs – phenothiazines, benzodiazepines, tricyclics, methyldopa,
butyrophenones, metoclopramide, H2 receptor antagonists, digoxin,
spironolactone, post-oral-contraceptive.
Galactosaemia
A screen test for galactosaemia is part of the standard neonatal screen in the first
week of life.
see Neonatal screening
Gallstones
These consist mainly of cholesterol except in chronic haemolysis when pigment

(bilirubin) stones may be formed. Analysis of a stone is of interest only when
haemolysis is suspected or when an unidentified.object ? gallstone, is found in faeces.

Gamma globulins

Electrophoresis (EPP) of serum proteins
Gamma glutamyl transpeptidase
see GGT (gamma glutamyl transpeptidase)
Gardnerella vaginalis
Formerly known as Haemophilus vaginalis and Corynebacterium vaginalis.
A common bacterial isolate from the vagina. It may be present in up to 30% of

healthy women. When found in association with "non-specific vaginosis", treatment
with metronidazole or tinidazole will eliminate odour and discharge though there is a
tendency to recurrence requiring repeat treatment.
see also Vaginal discharge.
Gastric antibodies
see Intrinsic factor antibodies and parietal cell antibodies

Gastric and oesophageal brushings/washings
for cytology
Smears should be made from brushes and fixed in Cytofix immediately. Washings
should be submitted to the laboratory as soon as possible.
Gastrin
specimen: serum, separated and frozen immediately
ref. range: 0-75 pmol/L, fasting
Gastrin, released from the gastric mucosa, is a potent stimulant of gastric acid
secretion.
Gastrin measurements are used in the diagnosis of pancreatic gastrinomas associated

with severe peptic ulceration in the Zollinger-Ellison syndrome in which there is
marked hypersecretion of gastric acid.
Vagotomy, non-fasting state, renal failure, or the gastric acid hyposecretion due to
pernicious anaemia and chronic atrophic gastritis, are associated with an increase in
gastrin levels.
GDM
see Gestational diabetes mellitus (GDM)

Genetic studies
see Cytogenetics
Molecular genetics - genetic studies
Genotype
The genetic constitution of an individual with definition of both dominant and
recessive genes in a gene pair. By contrast the phenotype defines only the dominant
member. In relation to rhesus blood grouping the phenotype CDE could have, for
example, the genotype CDE/CDE or CDe/cdE.
Gentamicin
Gestational diabetes mellitus (GDM)
GDM is a form of glucose intolerance that develops during the 2nd half of pregnancy
and disappears after parturition.
It is associated with increased foetal risk which is reduced if the GDM is treated
successfully with diet or, in the few where hyperglycaemia persists, with insulin. A
mother with GDM is at increased risk for developing diabetes in later life.
Polycose screen test for GDM

Screening at 24-28 weeks is currently recommended for all pregnant women, though
clearly at-risk patients, e.g. previous GDM, can be evaluated earlier, even before
conception.
The test is usually done in the morning. No booking is required and the patient does
not need to fast before the tests. A suspension of 50grams of polycose is given and a
single blood collected 1 hour later. If the glucose is above 7.8 mmol/L, a 2-hour GTT
is ordered as the definitive test.
If the post-polycose glucose is less than 7.8 but risk factors are present – obesity,
family history of diabetes, history of GDM, macrosomia, intrauterine or neonatal
death – another polycose screen test or a GTT should be considered at 32-34 weeks to
check whether glucose tolerance has deteriorated.
Diagnostic GTT criteria for GDM
GDM is present if:
fasting glucose ≥ 5.5 mmol/L

or 2-hour glucose ≥ 9.0 mmol/L
GGT (gamma glutamyl transpeptidase)
specimen: serum
ref. range: female 0-50 U/L
male 0-60 U/L
GGT is found almost entirely in the liver. It is elevated particularly in cholestatic

disorders, by alcohol, and also as an effect of some drugs, notably anticonvulsants.

GGT is the enzyme most reliably raised by excessive alcohol, typically in the range
60-200 but occasionally >1000. 30% of heavy drinkers have normal levels. After a
weekend binge, levels rise up to 100% over 3 days. If the cause of an elevated GGT
is uncertain, total abstinence from alcohol with weekly GGT estimations over a 4-
week period may provide the answer.
see also Liver enzymes
GH
see Growth hormone (HGH, somatotropin)
Giardia
specimen: 1-3 random faeces samples.
Giardia lamblia is a protozoan infesting the upper small bowel where it can cause
acute or chronic diarrhoea and sometimes fat and vitamin malabsorption.
It is now the commonest cause of water-borne diarrhoea in the world with vast
reservoirs in humans and wild and domestic animals and in rivers and water supplies.
Although more common in third world countries with poor sanitation it is
increasingly being found in developed countries including New Zealand. At this
laboratory it is the third commonest faecal pathogen after Campylobacter and
Salmonella.
It is commonly taught that three stool specimens are required to detect intestinal
parasites such as Giardia but several studies have shown that >85% of cases are

detected on the first specimen. When evaluating chronic or relapsing diarrhoea it
may be necessary to send up to three specimens for testing.
The two commonly-used tests for Giardia:
• Detection of Giardia antigen in faeces using an Elisa method.

• Microscopy for cysts in faecal concentrate. Occasionally trophozoites are
seen in acute infections.
The antigen method is the more sensitive.
Treatment with tinidazole or metronidazole is usually effective but may need to be

repeated.
Gilbert's syndrome
This common, harmless, inherited condition, in which the liver has reduced ability to
conjugate bilirubin, was first described in 1901 by the Frenchman Gilbert whose
name is usually, though not always, pronounced in the English fashion.
It affects somewhere between 2 and 10% of the male population depending whether
the cut-off is taken as 25 or 20 µmol/L. The male/female ratio is about 4:1.
Because a genetic test is not available, diagnosis is based on exclusion.
Features are:
• elevation of bilirubin is the only laboratory abnormality and the level seldom
exceeds 80 µg/L.
• liver enzymes are normal.

• the bilirubin is unconjugated.
• there is no evidence of haemolysis as measured by reticulocytes and
haptoglobins.
• the bilirubin level fluctuates; the condition is often first detected in the 2nd-
3rd decade.
• fasting, dehydration, fever, sea-sickness, intercurrent illnesses, can all cause
the bilirubin to rise, sometimes to the point where it becomes visible as
jaundice. At this point the patient may note malaise, blaming it on the
Gilbert's rather than the precipitating factors.
Glandular fever syndrome

This syndrome, which includes atypical lymphocytosis, lymphadenopathy,
pharyngitis and malaise, is due mainly to infectious mononucleosis, toxoplasma or
CMV – see entries under these headings.
Gliadin (gluten) antibodies (AGA)

specimen: serum
-ve borderline +ve

IgA AGA <30 30-50 >50
IgG AGA <40 40-60 >60
Anti-gliadin antibodies (AGA) have a high degree of sensitivity and specificity for
untreated coeliac disease and dermatitis herpetiforms.
see Coeliac disease (gluten sensitive enteropathy) for more detail

Globulins, total
specimen: serum
ref. range: 18-34 g/L
total globulins = total proteins — albumin

Immunoglobulins, IgA, IgG, IgM
Proteins, total, serum
Glucose
specimen : plasma (fluoride)
ref. range :
Age (yrs) mmol/L
fasting glucose 3.5-6.0
random glucose 0-1 2.0-6.0
>1yr 3.5-7.0
If the specimen is collected in a plain tube the glucose level will tend to be low by an
unpredictable amount because red cells consume glucose causing the serum level to
fall at a rate of 0.1-0.5 mmol/L/hr. Fluoride prevents this glycolysis.
see also Diabetes mellitus (DM)

Glucose tolerance test (GTT)
Hypoglycaemia
Polycose screen test for gestational diabetes (GDM)

Glucose tolerance test (GTT)
Indications
The GTT is the traditional test for the diagnosis of border-line diabetes mellitus.
For the patient who does not want to go through the 2-hour GTT, an alternative,
recommended by the American Diabetes Association in 1997, is to measure two
fasting glucoses on two separate days.
Contraindications
A GTT is unnecessary in a person who has symptoms of diabetes (thirst, polyuria,
tiredness), and random glucose levels >11.1. An HbA1c above 6% further confirms
the diagnosis in this situation and gives an indication of mean glucose level.
The GTT is not a useful test for monitoring treatment and is never used in a diabetic
on oral hypoglycaemics or insulin.
It should not be performed during intercurrent illness or periods of stress or in a

person on a low carbohydrate diet, all of which elevate glucose levels above their
usual values.
Test protocol
The patient makes an appointment and fasts overnight (10-14 hrs). Excessive fasting
worsens tolerance.
The glucose load is given in the form of polycose, a relatively non-emetic polymer of
glucose.
2-hour test for suspected diabetes or GDM

Dose for adult: 75g
Dose for child: 1.75g/kg body-weight
Bloods are collected fasting and at 1 and 2 hours. The patient stays in the collection
room throughout and should not smoke.
Urines are no longer collected except where renal glycosuria is a possibility.
4½ hr test for reactive hypoglycaemia This is discussed in more detail under

hypoglycaemia. It is not generally regarded as a useful test but if done, the dose is
100g and bloods are collected at ½-hrly or hrly intervals.
Interpretation
The current (2000) criteria for plasma measurements are:

Fasting 2 hr
normal non-pregnant <6.0 <7.8
diabetes — 1 or both of >7.0 >11.1
IGT 7.8-11.0
IFG 6.1-6.9
normal pregnant <5.5 <9.0
GDM — 1 or both of >5.5 > 9.0
IGT = impaired glucose tolerance

IFG = impaired fasting glucose (or glycaemia)
GDM = gestational diabetes mellitus
The ADA (American Diabetes Association) has recommended that the GTT be
replaced by 2 fasting glucose levels or by random glucose levels.
Diabetes is then diagnosed by

2 fasting glucoses >7.0 mmol/L
2 random glucoses >11.1 mmol/L
1 fasting glucose >7.0 and 1 random >11.1
Subsequent analyses have shown that screening based on 2 fasting glucose levels will
give a significantly lower diabetic prevalence than when the 2 hr GTT is used, the 2
hr level >11.1 being a more sensitive criterion than the fasting level of 7.0.
WHO will be making its definitive recommendation on the use of the GTT in 2000
but meanwhile the GTT retains its position as an accepted diagnostic measure for
borderline diabetes.
When diabetic symptoms (thirst, polyuria, weight loss) are present, a single random
glucose >11.1 establishes the diagnosis.
As with any biological test, glucose tolerance varies from week to week and month to
month and any result in the region of a cut-off limit can switch back and forth
between normal, impaired and diabetic under the influence of stress, illness, change
of diet, or simply unexplained variance.
Lag storage curve has a 1-hour glucose peak in the 11-15 mmol/L range, then returns
to normal at 2 hours. This is seen post-gastrectomy, and sometimes in normal people,
when a carbohydrate load rapidly reaches the small intestine and is absorbed before
insulin action has time to bring down the glucose peak.
Glucose, urine
see Glycosuria

Gluten
see Gliadin (gluten) antibodies (AGA) and Coeliac disease (gluten sensitive
enteropathy)
Glycated Hb
see HbA1c (glycated Hb)
Glycosuria
Glucose appears in the urine when the renal threshold has been exceeded; this
typically being at a blood glucose level around 11mmol/L.
With advancing age, or renal impairment, the renal threshold rises so that some
diabetics have glucose-free urine even with blood glucose levels in the 12-15 mmol/L
range.
Glycosuria is found in:
• Diabetes mellitus – once the renal threshold is exceeded.

• Renal glycosuria – in which the individual has a lowered renal threshold. The
GTT is entirely normal but urine specimens collected during the test show
glucose. The patient who is proven to have this uncommon condition can be
reassured that it is of no clinical significance and is unrelated to diabetes.
• In pregnancy – renal glycosuria is common in healthy non-diabetic women
during pregnancy, beginning during the first trimester and disappearing within
a week of delivery. A feature of this glycosuria is its variability from day to

day, throughout the course of the pregnancy and even during the course of a
day.
Uses of urine glucose tests
• As a side-room test for suspected diabetes when a blood test is not available.
• As a home test for children whose parents worry about diabetes but don't want
blood tests.
Urine glucose tests are not used for
• adult diabetic screening

• screening in pregnancy
• monitoring known diabetes
Gonadotropins

LH (luteinising hormone)
hCG (human chorionic gonadotrophin)
Gonorrhoea
see Neisseria

Gout
see Urate, serum
GPH syndrome
= gestational proteinuria and hypertension
GPT
see ALT (alaninine transaminase or amino transferase)
Gram stain
The gram stain, described as the single most useful procedure in diagnostic
microbiology, was perfected by the Danish microbiologist Christian Gram in 1884.
When a microbiological specimen reaches the laboratory there are typically two
initial procedures.
• Gram stain of the specimen smeared on a slide to determine numbers of

bacteria, whether cocci or bacilli and whether gram-negative or gram-positive.
In a case of meningitis for example the gram stain gives a presumptive
diagnosis and dictates initial antibiotic treatment.
• The specimen is cultured on a microbiological plate and the colonies gram-
stained next day.
Some examples:
gram-positive organisms
cocci Staphylococcus

Streptococcus
bacilli Corynebacterium
gram-negative organisms
cocci Neisseria
bacilli enteric bacteria: Escherichia, Salmonella, Shigella,
Enterobacter, Klebsiella, Serratia, Proteus,
Citrobacter,Yersinia
Graves disease

Thyroid antibodies
Group and hold
see Crossmatch
Growth hormone (HGH, somatotropin)
specimen: serum
ref. range: There is no defined range for random HGH which can vary between 0
and 24 µg/L in healthy people. Suppression or stimulation tests are
used in preference to random HGH.
elevated levels • pituitary gigantism

• acromegaly

• stress, exercise
• insulin-induced hypoglycaemia - used in stimulation tests
for dwarfism or hypopituitarism
low levels • pituitary dwarfism

• hypopituitarism
• glucose infusion - used in suppression tests for gigantism
or acromegaly.
GTT
see Glucose tolerance test (GTT)
Guthrie card
see Neonatal screening
Gynaecomastia
Transient gynaecomastia is normal in the newborn and in adolescence and minor
degrees of persistent gynaecomastia are common in the elderly male as testosterone
levels decline with an increase in the oestrogen/testosterone ratio.
The causes of more troublesome and progressive breast enlargement include:
• drugs - oestrogens - spironolactone

- digoxin - cimetidine
- tricyclics - diazepam
- methyldopa - anti-androgens

• hypogonadism – check LH, FSH, testosterone
• liver disease
• thyrotoxicosis
• feminising tumours
• Klinefelter's syndrome
Haematocrit (PCV)
see Blood count
Haematuria
infections)
Haemochromatosis

Haemochromatosis is a condition of iron overload which is usually sub-clinical but
which in some patients causes systemic disease due to parenchymal tissue damage.
In its common hereditary form, the diagnosis of haemochromatosis is being made

with increasing frequency because of the ready availability of tests for ferritin, iron
and iron saturation, and, recently, the HFE gene.
Iron overload can also be acquired due to repeated transfusions for refractory anaemia
or to inappropriate parenteral iron over a long period of time.
Hereditary haemochromatosis (HH)
In HH the iron overload is due to excessive absorption which steadily increases the
total body mass of iron throughout life. Women are protected during child-bearing
years by menstrual loss of iron.
HH is carried on a recessive gene with the remarkably high prevalence of 1:10 in the
general population for the heterozygous (carrier) state and 1:400 for the homozygous
(affected) state.
In 1996 the HFE gene, also known as the cys282 tyr mutation, was identified as a
marker for at least 90% of HH.
Heterozygotes may have mild or moderate elevations of ferritin and iron but will not
develop clinical disease.
Homozygotes will not always develop disease but because their risk is so much
higher, they are treated by venesection to reduce body iron, as measured by ferritin, to
normal levels.
Clinically HH is characterised by:

• lethargy, skin pigmentation, reduced sweating
• hepatic damage: elevated enzymes, cirrhosis, hepatocellular carcinoma
• endocrine damage: diabetes, hypogonadism. loss of libido, amenorrhoea,
hypopituitarism, hypothyroidism
• arthropathy
• myocardial damage: congestive cardiac failure
Diagnosis
HH is suspected when iron saturation is consistently above 55% and ferritin above
400 µg/L.
The HFE gene should be tested for and if present the test will show whether the
patient is a hetero- or homo-zygote.
Homozygotes should be further tested for tissue damage by measuring glucose, liver
enzymes, TSH, and LH, FSH and testosterone if hypogonadism is suspected.
Before the HFE test became available, a liver biopsy was taken to measure liver iron
content and also look for cirrhosis. The hepatic iron index is an expression of liver
iron that compensates for the normal increase in iron that occurs with age. An iron
index >2.0 µmol iron/ g liver/year of age is indicative of HH. Liver biopsy is seldom
performed if the ferritin is <1000 µg/l, liver enzymes are normal and there is no
hepatomegaly. Hepatic fibrosis is rare when these criteria are met. Liver biopsy
may still have a place where clinical suspicion of haemochromatosis is strong but
HFE negative.
Monitoring treatment
Venesection is performed at weekly intervals until ferritin is below 100-200 µg/L and
then frequently enough to hold the ferritin at this level.
Screening relatives of a proband

Iron, iron saturation and ferritin should be measured in siblings of whom, statistically,
1:4 will be homozygous. All of the children of a homozygote will be heterozygote
carriers and if the other parent carries the gene, statistically half of the children will
be homozygotes.
Haemoglobin whole blood concentration (Hb)
see Blood count
Haemoglobin electrophoresis (Hb EPP)

Hb EPP detects abnormal and unstable haemoglobins and gives an indication whether
HbA2 or HbF are increased.
Haemoglobin pigments
specimen: whole blood (heparin or EDTA)
This term usually refers to metHb and sulphHb which can be found following
exposure to some drugs, notably phenacetin, sulphonamides, sulphones, antimalarials;
and to some occupational and household chemicals.
When metHb and/or sulphHb exceed 15% of total Hb, the patient appears cyanosed.

Haemoglobinopathy screen
The screen consists of: Hb electrophoresis

HbA2 quantitation
HbF quantitation
HbH body stain
Hb stability test
Indications
• Suspected thalassaemia (qv) or haemoglobinopathy - hypochromic microcytic

anaemia in the absence of iron deficiency or chronic disease, particularly in
persons of Asian or Mediterranean descent.
• Unexplained haemolytic anaemia.
• The patient's partner has been diagnosed with a haemoglobinopathy or

thalassaemia and the couple are in the child-bearing age group.
see also Haemoglobins, normal and abnormal
Haemoglobins, normal and abnormal
The haemoglobin (Hb) molecule consists of two pairs of polypeptide chains with
a haem attached to each. The porphyrias are due to disorders of haem synthesis.
The haemoglobinopathies are due to disorders in the globin chain pairs which are
labelled á â ä ã etc. In the haemoglobinopathies, the amino acid sequence in a
globin chain can be abnormal, or there can be a quantitative abnormality in globin
chain production.

HbA á2â2 The normal adult Hb comprising 97% of the total. Also called HbA1.
HbA1c, of interest to diabetologists, is the non-enzymatically glycated
fraction of HbA1.
HbF á2ã2 foetal Hb comprises 70-90% of the total at birth falling to 1% by age
2. It is increased in ß thalassaemia and hereditary persistance of HbF
(HPFH).
HbA2 á2ä2 the minor component of adult Hb comprising 1.5-3.2% of the total. It
is increased in ß cell thalassaemia.
HbH ß2ß2 is increased in the α thalassaemias in which there is deletion of

deletion of 1-4 of the ã chains. In the 3-chain deletion HbH disease,
HbH comprises 5-30% of total Hb.
HbS the cause of sickle cell anaemia (HbSS) found in South Africans and
occasionally in those of Mediterranean or Middle Eastern origin. The
heterozygous state HbAS, is asymptomatic.
see also Haemoglobinopathy screen

Thalassaemias
Sickle cell test
Haemoglobinuria
Haemoglobinuria indicates intravascular haemolysis with passage of Hb from plasma

through glomeruli into urine. It does not include Hb released from intact red cells in
urine.
infections).
Causes of true haemoglobinuria include:
• strenuous exercise ("march" haemoglobinuria)

• some drugs - sulphonamides, quinine, phenylhydrazine

• infections - malaria, yellow fever, scarlet fever, septicaemias
• other - severe burns, incompatible transfusion, paroxysmal nocturnal
haemoglobinuria (PNH) or paroxysmal cold haemoglobinuria (PCH)
In chronic haemoglobinuria such as PNH, haemosiderin may be detected in urine.
Haemolysis
The features of haemolysis are:
• anaemia
• polychromasia – reticulocytosis
• haptoglobins - reduced or absent
• hyperbilirubinaemia
The blood film is used to distinguish between spherocytic and non-spherocytic

haemolytic anaemia:
spherocytes present spherocytes absent
hereditary spherocytosis hereditary elliptocytosis
autoimmune haemolysis haemoglobinopathies
(Coombs positive) enzymopathies (e.g. G-6-PD deficiency)
drug-induced haemolysis PNH
delayed transfusion reaction
ABO incompatibility in the newborn
Haemolytic disease of the newborn

Haemophilia
The haemophilias are due either to Factor VIII deficiency (classical haemophilia) or
Factor IX deficiency (Christmas disease). Spontaneous mutations account for 30% of
new cases in the absence of a family history. Severe haemophilia presents early in
infancy but mild haemophilia can present later in life following surgery or trauma.
Diagnosis is from:
• clinical bleeding history

• family history
• abnormal APTT (correcting with 1+1 test)
• reduced level of FVIII or FIX
• DNA genotyping
see also Bleeding disorders

Coagulation screen
Haemosiderin
A granular storage form of iron which can be seen histologically. Physiologically it

is the normal storage form of iron in bone marrow. Pathologically it is found in many
parenchymal tissues in iron-overload. S. ferritin levels reflect tissue haemosiderin
load.
In chronic haemoglobinuria, haemosiderin may be detected in a fresh random urine.

Hair for fungi
see Dermatophytes
Hairy cell leukaemia
This is a rare form of B cell leukaemia (1-2%) with a 5:1 male predominance. It is
characterised by pancytopenia, circulating 'hairy cells' and splenomegaly (80%).
Treatment is highly effective with ≥ 80% complete remission after one course of one
week followed by a long period of complete remission.
Ham's test
see Paroxysmal nocturnal haemoglobinuria (PNH)
Hansen's bacillus
see Leprosy
Haptoglobins
specimen: serum

Haptoglobin estimation is one of the screening tests for haemolysis. Hb released by
the haemolytic process combines with haptoglobin to form a complex which is
removed by the liver. It is also an acute phase reactant, migrating with the alpha-2
band on protein electrophoresis.
It is reduced by:
• haemolysis — haptoglobins are absent in moderate or severe haemolysis

• oestrogens, oral contraceptives, pregnancy
• acute or chronic hepatocellular liver disease
• specific genotype
• lower in first year of life — almost absent in first 6 weeks.
It is elevated by:
• biliary obstruction
• many acute or chronic inflammatory disorders – following recovery from an
infective episode the level falls to normal within 10-14 days.
• specific genotype
Hb ( haemoglobin)
see Blood count

HbA1c (glycated Hb)
ref. ranges: %
Non-diabetic range: 4-6
Diabetic range:
excellent control 6-7
good control 7-8
indifferent control 8-9
poor control 9 - 10
exceptionally poor control >10
HbA1c is a measure of the mean blood glucose level over the previous 2-3 months
and particularly the previous 4 weeks. It provides the essential baseline measure of
glycaemic control in a diabetic and should be measured at least annually in all
diabetics and more often (say 3-monthly) when assessing the affect of changes in
therapy or compliance.
Unlike fructosamine, HbA1c is unaffected by proteinuria or obesity. It may be low

however when there is shortened red cell survival as in haemolysis or bleeding.
The central role of HbA1c in assessing glycaemic control arose out of the DCCT
(Diabetes Control and Complications Trial) which followed 1441 insulin dependent
diabetics between 1983 and 1993. Intensive control compared with standard control
reduced the risk of development and progression of retinopathy, nephropathy and
neuropathy by approximately 60%. Risk of complications rose with increasing
HbA1c with a significant steepening of the curve above a value of 8%.
Correlation of HbA1c with mean blood glucose

approximate
HbA 1 c mean glucose
% mmol/L
5 5
6 6
7 8
8 10
9 12
10 14
HBV
see Hepatitis B (HBV)
hCG (human chorionic gonadotrophin)
specimen:
• quantitative hCG serum
• qualitative pregnancy test serum (preferably)
or random urine
ref. range: non-pregnant female or male <5 IU/L.
Qualitative pregnancy tests turn positive at around 25 IU/L.

hCG differs from the pituitary gonadotropin LH, only in its beta chain, hence the
prefix "beta" sometimes applied to hCG. LH is otherwise structurally and
functionally identical to hCG.

hCG in normal pregnancy
The developing placenta begins producing hCG about 3 days after implantation.
The sequence of events is:
Gestation Mean hCG

(weeks) (units)
1st day LMP (last monthly period) 0 0
fertilisation 2 0
implantation 3 0
placenta produces measurable hCG 3½ 10
1st day of missed period 4 100
gestational sac becoming visible on ultra-sound 5 1,500
peak hCG level 9 120,000
A single measurement of hCG answers the question whether a pregnancy is present or

not.
Adding a second hCG or a series and plotting them on the hCG graph gives valuable
information on the health of the embryo.
In a normal pregnancy, the hCG doubles every 1½ days between weeks 3½ and 6 and
the trajectory rises parallel to the graph's percentile lines with remarkably little
deviation.
A plot which is rising parallel to the percentile lines but outside the 5th-95th range
indicates a healthy pregnancy with incorrect dates.
A graph rising more slowly, or flattening, usually indicates the onset of spontaneous
abortion or an ectopic pregnancy and is an indication for proceeding with vaginal
ultrasound looking for an intra-uterine gestational sac.
hCG in ectopic pregnancy

hCG is nearly always detectable in ectopic pregnancy and its absence makes the
diagnosis most unlikely.
Levels may be
• low for dates – below the 5th percentile

• rising more slowly than normal
• flat or declining
hCG quantitation must be combined with ultrasound which will detect an intra-
uterine sac after 5 weeks in a normal pregnancy. Using an abdominal probe, the
intrauterine sac is visible with an hCG above 2000 units; with a trans-vaginal probe,
the sac can be visible at 1000 units. In ectopic pregnancy there is, of course, no intra-
uterine sac.
hCG after spontaneous or induced abortion

After foetal loss or death, the hCG falls over a period of 1-5 weeks depending on its
initial height and the completeness of elimination of placental tissue. The starting
hCG depends on gestational age and health of the conceptus.
hCG in hydatidiform mole and choriocarcinoma

The abnormal trophoblastic tissue produces large amounts of hCG whose levels are
usually either high normal or clearly above the 95th percentile, sometimes as high as
1,000,000 IU/L. Ultrasound will separate a hydatidiform mole from a multiple
pregnancy which can also have an hCG level above the 95th percentile.
After evacuation of a mole, the hCG is measured weekly until it has been normal (<5)
for at least a month; and then monthly for at least 6 more months.
Absolute hCG levels are more method-dependent in trophoblastic disease and

tumours than in normal pregnancy where levels should be repeatable between
laboratories with different methods. In tumours, there are varying amounts of free
beta chains and beta fragments, and different methods measure these to a varying

extent. For this reason, when monitoring a tumour, specimens should be sent to the
same laboratory.
hCG in other tumours

Ovarian and testicular germ cell tumours commonly produce hCG and a variety of
malignancies from other sites can occasionally secrete hCG. Levels are used for
monitoring treatment — but see paragraph above.
HDL cholesterol
see Cholesterol, HDL
Heaf test
see Tuberculin test (Mantoux test)
Health reforms
These are in progress all over the world, which is waiting expectantly.
Heavy metals
Heavy metal poisoning is usually industrial in origin.

see Lead, blood, Arsenic, Cadmium, Chromium

Heinz bodies
Heinz bodies are red cell inclusions seen in haemolytic anaemias due to drugs, in
haemoglobinopathies, and sometimes in normal people after splenectomy.
Helicobacter pylori
H. pylori, first described in 1984, lives in the mucus layer on the surface of the gastric
mucosa where it causes gastritis and in some people, peptic ulcer disease (PUD),
either duodenal or gastric. Antimicrobial therapy is usually curative. H. pylori is also
a significant factor in the aetiology of gastric malignancy.
The organism, confined almost solely to humans and primates, is commonly acquired
in childhood and persists for life. In Western countries the incidence of infection, like
PUD, is decreasing – <30% below age 30, whereas in developing countries, which
have high rates of PUD and gastric cancer, the incidence is above 80%, perhaps due
to poor nutrition and hygiene.
The H. pylori story is evolving rapidly, particularly where it involves gastric

infections not associated with PUD.
Tests for H. pylori
1. Endoscopy with urease test on biopsy material

This is an excellent investigation though expensive if used in all cases of
dyspepsia.
13
2. Curea breath test

A test with better than 98% sensitivity and specificity for H. pylori infection.
If it is negative, it is most unlikely the patient has PUD. If, positive and there
are other diagnostic features of PUD, e.g. past history, and endoscopy or x-
ray imaging are not available, it may be reasonable to embark on
antimicrobial therapy without further investigation.
The urea breath test is the preferred test of eradication, 4-6 weeks after anti-
microbial therapy.
To perform the test, the patient takes a measured dose of 13C urea (non-
radioactive). If H. pylori is present in the stomach its associated urease splits
the molecule releasing 13CO2. A breath sample collected after 30 minutes is
subsequently analysed for presence of 13C. The result is reported as positive
or negative.
Antibiotics, bismuth and proton pump inhibitors can give false negative
results.
3. Antibodies
A variety of tests are in use, all of them with significantly poorer
performance than the breath test. Laboratory-based tests typically have a
sensitivity/specificity of 85-95% whereas the office-based tests fall as low as
65%.
The suggestion, sometimes made in the past, that a single positive office-
based test is indication for eradication therapy, is not valid.
In their present state of development, antibody tests may provide supportive

evidence but another investigation will nearly always be necesssary.
Antibody tests are of no use as a test of eradication after therapy.
Treatment

Once H. pylori infection has been established, treatment is recommended for:
– gastric or duodenal ulcer disease, whether active or in remission

– family history of gastric carcinoma; studies are in progress to determine
whether eradication reduces risk
– MALT lymphoma of the stomach
Non-ulcer dyspepsia
There is insufficient evidence to recommend general treatment though in individual

cases it is sometimes tried.
Recommended regimens include:
Different regimens are being trialled all the time, particularly the newer short course
regimens. They can vary greatly in cost.
Here are two typical regimens.
• 2-week course
– colloidal bismuth 120mg 6hrly
– metronidazole 400mg 8 hrly
– tetracycline 500mg 6 hrly
or
amoxycillin 500 mg 6 hrly
• 1-week course
– omeprazole (or other PPI) 20mg bd
– amoxycillin 500mg 6hrly
– clarithromycin 500mg 6hrly
– metronidazole 400mg 8hrly

HELLP Syndrome
An obstetric emergency characterised by Haemolysis, Elevated Liver enzymes and

Low Platelets. Managed by early delivery and supportive care in a specialist
maternity unit.
Henoch-Schönlein Purpura
A non-thrombocytopenic purpura due to a hypersensitivity vasculitis. Platelet count

and coagulation tests are normal.
Glomerulonephritis is common, with haematuria and proteinuria.
Heparin therapy
For established deep-vein thrombosis or pulmonary embolism, anticoagulation with

heparin remains the mainstay of acute treatment, followed by warfarin therapy to
reduce the risk of recurrence.
IV Heparin
The older mode of therapy uses an IV infusion of unfractionated or standard heparin

monitored by APTT estimations.
A 1.5-2.5 fold increase in APTT relative to baseline corresponds to a heparin level of

0.2-0.4 units/ml plasma.

SC low molecular weight heparin (LMWH)
LMWH has largely superseded IV standard heparin therapy.
The dose of LMWH is calculated from body weight and is given subcutaneously once
or twice daily on an outpatient basis. Clexane (enoxaparin) and Fragmin are the two
most commonly used LMW heparins in New Zealand.
No laboratory monitoring is required.
Clinical treatment trials in venous thromboembolism indicate that LMWH is at least

comparable to standard heparin and may be superior.
Heparin tubes

Hepatitis
Hepatitis is characterised by elevations of ALT and AST and a histological picture on

biopsy which may be diagnostic. When ALT and AST are above 1000 U/L with ALP
and GGT below 300 u/L, the cause will usually be viral infection. In chronic
hepatitis, changes in ALT are used as an indication of disease activity.
Main causes of hepatitis include:-
• Viral infection
– hepatitis A virus (HAV)

– hepatitis B virus (HBV)
– hepatitis C virus (HCV)
– EB virus (infectious mononucleosis)
– other viruses – HIV
– hepatitis D, E
– CMV (cytomegalovirus)
– coxsackie virus
– sundry other viruses causing
flu-like illnesses circulating in
the community
• autoimmune hepatitis
• alcoholic hepatitis
• drug-associated hepatitis
• other
It is difficult to know the relative frequency of the common viral causes but indicative
figures from a 1992 Christchurch study are:
EB virus 50%
hepatitis A 15%

hepatitis B 15%
hepaittis C 15%
CMV 5%
Hepatitis antibodies & antigens
In general an IgM antibody develops first and then disappears within 3-12 months. It
is the marker for current or recent infection.
IgG antibodies start soon after IgM, rise more slowly, but then persist indefinitely.
They are a marker for both current and past infection but will not distinguish between
the two. IgG antibodies are used to indicate immune status – has this person been
infected in the past? Has this person's vaccination been effective?
"Total" antibodies measures both IgM and IgG in a single test. When IgM, IgG are
not specified, e.g. anti-HAV, this means "total", i.e. both IgG and IgM.
Some antibodies indicate solid immunity e.g. anti HBs.
Others do not indicate immunity, only past or current infection, e.g. anti HCV,
antiHBc.
Antigens show the presence of virus indicating current infection, carrier status or
chronic hepatitis, e.g. HBs antigen, HBe antigen, HCV-RNA, HDV-RNA.
Hepatitis A (HAV)

specimen : serum
tests : · anti-HAV IgM
· anti–HAV IgM and IgG (total antibody)
There is no test for HAV antigen.
Interpretation:
The IgM antibody appears at about the time clinical symptoms develop and persists
for 6-12 months. This anti-HAV IgM is the marker for current or recent infection.
The IgG appears not long after the IgM but persists for life and is thus the marker for
HAV immune status.
Active Immunisation:
Havrix, the HAV vaccine, became available in 1992 and provides solid immunity.
It should be recommended to any traveller going to countries where hygiene might be
suspect. Travellers with previous experience may find they are already immune, as
shown by presence of anti-HAV IgG, even though they have no recollection of
clinical disease.
Two IM injections 6-12 months apart provide immunity for many years. When there
is urgency, a single double-strength injection just before departure has been shown to
provide useful protection for up to two years. A second injection provides long-lived
immunity even when given years after the initial injection.
Passive Immunisation
Contacts of a person with active HAV infection should be given passive protection
with immune globulin 0.02 ml/kg IM provided it can be given within two weeks of
exposure.

In travellers, life-long protection with Havrix has almost completely replaced passive
protection using immune globulin.
Clinical course
Hepatitis A is spread by faecally contaminated water, or an infected food handler. It

is found frequently in third world countries and is still common in New Zealand. The
diagram shows the usual time course.
Infectivity due to faecal shedding of virus, is at its height one week before clinical
symptoms develop and persists for about 4 weeks.
Hepatitis A can relapse up to 6 (or even 12) months after the first bout but does not
persist thereafter, so is never a cause of chronic hepatitis, cirrhosis, or hepatocellular
carcinoma.

Hepatitis B (HBV)
specimen: serum
tests: HBs Ag (HBV surface antigen)

HBe Ag (HBV e antigen)
anti-HBs (antibody to HBV surface antigen)
anti-HBe (antibody to HB e antigen)
anti-HBc IgM (IgM antibody to HBV core antigen)
anti-HBc (IgM and IgG antibody to HBV core)
HBV-DNA (HBV-DNA detected by PCR)
Indications and interpretation
1. HBs antigen
If positive indicates
– acute HBV infection (enzymes elevated)
or – chronic HBV infection (enzymes fluctuate)
or – HBV carrier (enzymes not elevated)
2. HBe antigen
This should be checked whenever HBs antigen is positive. If HBe antigen
(Ag) is present, it indicates greater infectivity of the HBV infection towards
sexual partner or foetus and greater likelihood of developing chronic
hepatitis. HBe Ag is found only in association with Hbs Ag, never on its
own.

3. Anti-HBs
Indicates immunity to HBV whether naturally acquired or following
immunisation. Anti-HBs can be measured quantitatively – levels above 10
IU/L indicate immunity.
4. Anti-HBc IgM
Is measured when current HBV infection is strongly suspected but HBs Ag
and anti-HBs are both negative. Anti-HBc IgM rises early in HBV infection
and persists for about 6 months. It fills the one month "window" between
disappearance of HBsAg and the appearance of anti-HBs. Positive anti-HBc
does not confer immunity.
5. Anti-HBc total
Indicates past infection but unlike anti-HBs it does not indicate immunity and
can coexist with HBs Ag in carriers or chronic hepatitis.
Anti-HBc remains negative after HBV vaccination because the vaccine

contains s but not c antigen.
6. Anti-HBe
In chronic HBV infection, anti-HBe indicates low infectivity.
7. HBV - DNA
If positive indicates HBV viraemia which is an indication for considering
interferon treatment in chronic infections.

HBs antigen in pregnancy
HBs Ag is routinely checked antenatally. If positive, this indicates carrier state or,
less often,current infection.
The infant of an HBs Ag positive mother will need immune globulin (anti-HBV) at
birth and the first dose of a course of HBV immunisation.
Immunisation against HBV
The standard course is three IM injections at 0, 1 and 6 months. It is indicated in the

following situations:
• neonates born to carrier mothers

• sexual partners of a carrier
• health workers at significant risk from needle-stick injuries or who come in
contact with blood, e.g. nurses, doctors, laboratory workers (see Accidental
inoculation of infected blood).
• IV drug users
An initial anti-HBs test will determine whether immunisation is necessary. Presence

of anti-HBs indicates immunity. Presence of HBs antigen means that immunisation
will be ineffective. Follow-up should be provided to those found to be HBV carriers.
Opinion is divided whether the antibody response to immunisation should be

measured. The UK recommendation is to give a further booster if anti-HBs is <10
whereas American recommendations assume that protection exists even when the
level falls to <10 as long as the person has seroconverted to the vaccine.

Some people fail to seroconvert at all to the standard course. If they are considered at
particular risk, alternative protocols can be discussed with a clinical microbiologist.
Epidemiology of HBV
4% of the world population carry HBV but most of those infected are in Asia. In
New Zealand about 0.4% of European blood donors are HBV positive compared with
about 5% of Maori and Pacific Islanders.
Infection is by mother-to-neonate, sexual transmission, IV drug use, infection, or

administration of infected blood products. Often the mode of infection cannot be
identified and it is assumed there has been some less obvious transmission such as
inoculation of blood or saliva into lacerations or abrasions in childhood or during
contact sport or whatever.
About 1-2 % of HBV infected adults fail to eradicate infection and become carriers or
develop chronic hepatitis with its possible sequelae of cirrhosis and hepato-cellular
carcinoma. The risk of developing chronic infection is much higher in children and
particularly in neonates.
Follow up on HBs Ag +ve patients
ALT is the test used to decide whether the patient has active disease that should be
considered for anti-viral therapy.
If the ALT >60 units, it should be repeated in 4 months. If the elevation >60 persists,
the patient should be referred for specialist follow-up.
HBe Ag should also be checked and repeated annually if found to be positive.

Hepatitis C
specimen : serum
tests : · anti HCV (total antibody to HCV)

· HCV-RNA
Indications and interpretation
1. Anti-HCV
Used when hepatitis C is a possibility, e.g. IV drug users, raised liver
enzymes of unknown cause.
Anti-HCV starts to rise 1-6 months after the initial infection and persists for
life. Presence of anti-HCV indicates either past infection or continuing
chronic infection.
2. HCV-RNA
This is a follow-on test when anti-HCV is positive. It is also used when
clinical suspicion of HCV infection is high but anti HCV is negative because
infection is recent or the patient immuno-suppressed.
It indicates current active HCV infection and is an indication for considering

interferon and ribavirin therapy.
Clinical course & epidemiology
HCV was identified in 1989 having previously been included in the non-A non-B
hepatitis category. 0.25% of people presenting as blood donors in New Zealand are
positive for HCV. A random population sample in the United States shows 1.8%
positiviity.

Transmission in blood products has been largely eliminated, leaving contaminated
needles in drug users as the main source of new infections. In New Zealand HCV
antibodies have been found in 80% of injecting drug users, 65% of haemophiliacs,
15% of homosexual men, 11% of patients with cirrhosis. It is the cause of 5-15% of
acute non-A, non-B hepatitis.
Mother-to-foetus transmission occurs but is infrequent, <5%. Sexual transmission is

believed to be uncommon.
More than 50% of HCV infections become chronic with potential to develop cirrhosis
and hepatocellular carcinoma.
Treatment with a combination of interferon and ribavirin clears the virus in about
50% of patients.
There is no vaccine yet.
Follow up on HCV +ve patients
A positive HCV Ab test should be followed by HCV RNA test and ALT.
If HCV RNA is positive, the patient should be referred for consideration of anti-viral
therapy.
An ALT >60 units indicates active disease but a level <60 does not exclude activity.
The patient who is HCV Ab +ve but HCV RNA –ve is presumed to be free of active
hepatitis provided the ALT is <60. The ALT should be monitored annually and the
HCV RNA for at least 2 years to confirm it is staying -ve.

Hepatitis D (HDV - Delta)
specimen : serum
tests : · anti Delta IgG
· HDV RNA
HDV infections are found only as a co-infection or superinfection in HBV positive

patients. HDV is associated with more severe acute disease and a greater risk of
developing chronic hepatitis and its complications.
HDV infections once established, will persist for as long as HBV carriage continues,
but if HBV is eliminated HDV will go with it.
Anti-delta antibodies indicate either current active infection or past infection with
immunity.
Positive HDV RNA indicates current active infection.
Hepatitis E (HEV)
specimen: serum
test: anti HEV IgG
Hepatitis E resembles hepatitis A in its faecal-oral mode of transmission. It is

endemic in India, SE Asia, China, Mexico and parts of Africa.
Presence of HEV antibodies does not distinguish current from past infection.

Identifying the virus in a small specimen of faeces may identify current infection.
Hepatitis due to EB Virus
Hepatitis, autoimmune
specimen: serum
tests: • smooth muscle antibodies
• antimitochondrial antibodies
• liver/kidney microsomal antibodies
• ANA
• anti ds DNA
• immunoglobulins
Autoimmune hepatitis, formerly known as chronic active hepatitis and before that
lupoid hepatitis, affects predominantly young women. The hepatitis can be of all
grades of severity ranging from minor enzyme elevations in a well person to a clinical
laboratory picture like that of severe viral hepatitis. Diagnosis is by excluding viral
causes; by finding specific autoantibodies; by markedly elevated IgG; and by liver
biopsy.
Smooth muscle antibodies (SMA) in high concentration (>80) define autoimmune

hepatitis.
Antimitochondrial antibodies (AMA) and total IgM may be elevated but these are
typically the markers of the other autoimmune liver disease, primary biliary cirrhosis.
Liver/kidney microsomal antibodies (LKM) are uncommon but help in disease
classification. Titres tend to be lower in viral hepatitis than in autoimmune hepatitis.

Hereditary elliptocytosis
see Elliptocytosis
Hereditary spherocytosis
A relatively common haemolytic disorder found in all races and typically inherited as
an autosomal dominant. In the 25% of individuals who have unaffected parents, the
disease is assumed to be due to autosomal recessive inheritance or a spontaneous
mutation.
More severe forms present in the first 10 years of life but milder forms may be
discovered incidentally either on a blood count or because of a minimally elevated
bilirubin resembling Gilbert's Syndrome.
Laboratory tests typically show the features of a haemolytic disorder – increased

reticulocytes, reduced haptoglobins, hyperbilirubinaemia, anaemia.
The more specific findings are:
• spherocytes on the blood film

• increased osmotic fragility (qv) of red cells
Herpes simplex virus (HSV)
specimen: air-dried smear of vesicular cells on a glass slide

Virus is found in tissue cells at the base of the vesicle. A sharp needle can be used to
rupture a newly-formed vesicle and scrape tissue cells from the base. The scrapings
are smeared on a glass slide as two spots, 1cm in diameter, one each for herpes 1 and
2. If the lesions are already crusted, the crust must be removed before taking smears
using needle or spatula.
The spots are air-dried and the slide labelled with the patient's name, date of
collection and the word 'herpes'. In the laboratory, an immunofluorescent stain is
used to detect virus.
There are two types of herpes simplex, HSV1 and HSV2.
HSV 1 commonly gives rise to recurrent oral infections ("cold sores") and HSV 2 to
recurrent genital infections but either can be found at either site.
Other tests – the virus can be cultured (use the special transport swab) and antibody
tests can differentiate HSV-1 from HSV-2.
Herpes zoster
see Varicella-zoster virus (VZV) virus
Heterophile antibodies

HFE gene for hereditary haemochromatosis
specimen: ACD tube for genetic studies
interpretation – see Haemochromatosis
HGH (human growth hormone)
HIAA (5-hydroxy indole acetic acid)
specimen: 24-hr urine collected into acid

ref. range: <50 µmol/day
Avoid the following drugs and foods for 3 days before collecting the urine.
phenothiazines bananas tomatoes

methyldopa plums egg plant
naprosen pineapple avocado
cough mixture fruit juices walnuts
acetaminophen kiwifruit pecans
In carcinoid syndrome the HIAA is usually >80. Results in the 50-80 range should be
repeated.
Carcinoid syndrome, due to release of serotonin from a carcinoid tumour, is

characterised by cutaneous flushing, diarrhoea, valvular heart disease, and less often
by wheezing, paroxysmal hypotension and telangiectasia. HIAA is the breakdown
product of serotonin and is usually measured in response to a history of flushing
though this is more commonly due to menopause, alcohol (particularly in

combination with a sulphonylurea or disulfiram). Phaeochromocytoma is
infrequently a cause of flushing.
Hirsutism/virilism
The spectrum of hirsutism ranges from the upper percentiles of normal hair growth
through to the male-pattern hair growth, amenorrhoea and genital virilisation of
androgenic tumours.
The common cause of hirsutism is polycystic ovary syndrome (qv).
Rarer causes of hirsutism/virilism and tests for them are:
— adrenal tumours testosterone, DHEAS, androstenedione

— ovarian tumours testosterone, androstenedione
— adult onset adrenogenital syndrome 17-OH progesterone
— Cushing's syndrome 24-hr urine free cortisol
— hypothyroidism TSH, T4
— drugs - danazol, phenytoin,
cyclosporin, minoxidil
Histology – specimen preservation
Specimens should be placed in 10% formal saline fixative in a container of sufficient

size to allow a ratio of volume of fixative to specimen of at least 5 to 1.
Containers must be carefully labelled with name of patient, date of birth, nature of
specimen, date, name of doctor.

Biopsy specimens of small size require special care and should be placed in 10%
formal saline as quickly as possible to prevent drying artefact. Small biopsies should
not be placed on gauze or paper as this causes drying.
Special fixatives for biopsy specimens, e.g. Bouins fixative for testicular biopsies, are
also available.
Oestrogen and progesterone receptors on breast cancers are now routinely performed
on formalin fixed tissue rather than using a specimen forwarded on ice.
Skin for direct immunofluorescence microscopy (DIF), usually for the investigations
of blistering or bullous disorders, needs to be submitted to the laboratory fresh on
damp saline-soaked gauze inside a specimen pot packed in ice. The specimen needs
to be snap frozen in the laboratory within 2 hours of the specimen being taken. The
pathologist should be contacted 24 hours before taking the biopsy to ensure rapid
handling of the specimen.
see also Skin biopsy

Malignant melanoma
Prostate cancer – histological grading
HIV (human immunodeficiency virus)
specimen: serum
tests: an initial screen test with >99% sensitivity followed by a
confirmatory test for those who screen positive. The screen test
detects both HIV-1 (the commonest) and HIV-2. A DNA-based test
is available for babies born to seropositive mothers.
Patient ID

If anonymity is required, the patient is identified by a code using the first 2 letters of
the patient's surname, first initial, sex and date of birth, e.g. John Harris, male, d.o.b.
18/9/47, becomes HAJM180947. If you are unsure about the need for anonymity or
forget to ask, assuming it is required is a good philosophy.
Test interpretation
The screen test has a cut-off level of 1 unit.
Below this the test is reported as negative. Above 1 unit, the serum is referred for the
more specific Western Blot test. Results in the 1-1.5 unit range can be false positive
screen results due to cross-reactivity with other viral antigens and the level may fall
below 1, i.e. become negative, on subsequent testing. Patients with established HIV
infection typically have results in the 5-20 range. A screen result of 1-2 with negative
Western Blot should be repeated in a month.
A negative antibody test does not exclude HIV infection during the first few months
after transmission of the virus but for practical purposes, all those infected will test
HIV positive within 6 months.
The median time from infection to the development of AIDS is about 10 years.
Prevalence of HIV in New Zealand

By mid 1999, 1,355 patients had been reported with HIV infection since the
beginning of the epidemic and 678 with AIDS. Currently there are about 700 HIV
infected people living in New Zealand of whom 107 have AIDS. Homosexual males
remain the biggest identifiable risk group (63% now) but in the last 18 months
infected heterosexual immigrants, particularly from Africa, are the most rapidly
increasing group. After falling for several years, the number of newly reported HIV
infected people rose in 1998, significantly contributed to by this immigrant group.
Presentation
GPs are the group who most frequently test for and diagnose HIV infection in New
Zealand, far more than hospital, sexual health clinics or special clinics combined.

Sometimes an HIV screen is requested "as an outside possibility", without mentioning
the test to the patient. The current advice and recommendation is that an HIV test
should always be discussed prior to testing with pretest counselling as seems
appropriate.
Early symptoms of HIV include exacerbation of previous skin disease, e.g. eczema,
somewhat recalcitrant tinea, surprising shingles, oral candidiasis, recalcitrant vaginal
candidiasis : in other words, common or ordinary events occurring oddly or
excessively.
Lymphoma predisposes to HIV infection and HIV is an uncommon cause of acute

immune thrombocytopenia.
Pneumocystis carinii pneumonia (found only when patients have CD4 counts
<200/cmm and essentially preventable) is most often a creeping, slow illness with dry
cough, fever and shortness of breath which may not be easy to diagnose or confirm.
Monitoring
Viral load The concentration of virus in the plasma can now be measured. As a
generalisation the higher the concentration (max. 1,000,000 or 10 6 copies/ml) the
more rapid will be progression in time to clinical illness and AIDS. The lower the
concentration (at present the lowest level of detection is 500 or 10 27 copies/ml), the
slower the disease progression.
The aims of treatment are to suppress this level as low as possible.
CD4 counts The concentration of this lymphocyte subset correlates with the stage the
patient's immune system has reached in its battle with HIV. The lower it is (normal
>500 cells/cmm) the more likely will that individual have illness, with the risk rising
progressively as it falls below 200 and then below 100 cells/cmm.
Treatment

Treatment requires use of at least two agents and most commonly three, to slow virus
replication, minimise development of resistance, preserve and augment immune
function and thus minimise clinical illness and prolong life.
The moment to begin treatment is ill defined : with CD4 counts <350 cells/cmm and a
high viral load, few would not wish to treat or be treated. At higher CD4 counts and
lower viral loads, everyone has a different opinion and individual patient views are
often the ultimate determinant for the decision.
see also CD4 T-lymphocytes

Microglobulin
Needlestick injuries
Pancytopenia
Liver enzymes
HLA-B27 antigen (human leucocyte antigen

B27)
specimen: blood (CPD tissue typing tube)
HLA B27 has a frequency of 7-10% in the general population but a much higher
frequency in the sero-negative spondyloarthropathies which are characterised by:
– sacroileitis and spondylitis, causing low back pain and loss of lumbar
mobility
– tendonitis, including heel pain and other pain at muscle and tendinous
insertion
– oligoarthritis
– urethritis
– iritis and conjunctivitis

As indicated by the term seronegative, all of these disorders are negative for
rheumatoid factor.
The principal members of the group with the % positivity for HLA B27 are:
• ankylosing spondylitis (95%-98%)

• Reiter's disease (90%)
• arthropathies associated with ulcerative colitis and Crohn's disease (70%)
• post-enteric and post-venereal reactive arthritis (70%)
• psoriatic arthritis (30%)
HMMA (hydroxy methyl mandelic acid)

specimen: 24-hr urine collected into acid
ref. range: <40 µmol/day
Also known as VMA, vanilly mandelic acid. This is a follow-up test for suspected
phaeochromocytoma, usually used only when catecholamine fractions, particularly
noradrenaline, have shown equivocal elevations.
see also Catecholamines
Homocysteine, plasma
specimen: fasting plasma (EDTA) stored on ice prior to centrifugation

ref. range: 5-15 µmol/L

Previously, clinical interest in homocysteine in blood was confined to the rare inborn
error of metabolism homocystinuria (qv) in which plasma homocysteine is markedly
elevated to above 100 µmol/L.
More recently an association has been described between mild to moderate

hyperhomocysteinaemia (15-100 µmol/L) and cardiovascular disease and many now
regard it as an independent risk factor for coronary, cerebral and peripheral arterial
disease.
Increasing intake of folic acid and to a lesser extent vitamin B6 and perhaps B12 may
lower homocysteine levels. A daily supplement of 400 µg folic acid will in most
patients increase serum folate above 15 nmol/L and drop plasma homocysteine to a
low plateau. As yet there is no proof of a favourable affect on cardiovascular
outcomes.
Homocysteine elevation above 20 µmol/L is also a risk factor for venous thrombosis
(2-3 x increase).
Homocystinuria/homocysteinuria
A rare (1:50,000) recessive inborn error of metabolism characterised by markedly

elevated levels of homocysteine (qv) in blood and homocystine in urine.
Clinically it can present as tall marfanoid stature, arachnodactyly, myopia, lens

subluxation, premature atherosclerosis, thromboembolic events.
The screen tests are plasma homocysteine and a urine screen test for elevated
homocystine/cystine.

Homovanillic acid
see HVA (homovanillic acid)
Hookworm
Hookworm refers to intestinal infestation with Ancylostoma duodenale (found in the

Mediterranean basin, the Middle East, India and China) or Necator americanus
(found in the Americas, sub-Saharan Africa and SE Asia). Heavy infestations are an
important cause of iron-deficiency anaemia.
Diagnosis is by identifying eggs in faeces.
Treatment is with mebendazole 100mg, 12-hourly for 3 days.
Howell-Jolly bodies
These are residual nuclear remnants seen in red cells after splenectomy and
sometimes in megaloblastic anaemia or haemolysis.
see also Hyposplenism
HPV (human papilloma virus)
HPV causes sexually transmitted genital warts and is associated with dysplastic
changes and sometimes carcinoma in the cervix.

Human chorionic gonadotropin
Human genome
Some statistics:-
3.3 x 109 base pairs

3 x 1012 cells in the body
2 metres of DNA/cell
6 x 1012 metres of DNA/individual which is 8,000 times the distance between earth
and moon.
There are 50,000 - 1,000,000 different genes of which 3,000 have been mapped.
The human genome project aims to develop a powerful genetic and then physical map
and subsequently to determine the complete nucleotide sequence.
HVA (homovanillic acid)

specimen: 24-hr urine with acid preservative
ref . range: 3-42 µmol/day
HVA is the urinary metabolite of dopamine and is measured when investigating or

monitoring neuroblastomas or malignant phaeochromocytomas.
see also Catecholamines

Hydatidiform mole
Hydatids
specimen: serum
ref. range: negative
Positives are now rare in New Zealand.
25-hydroxy calciferol
see Vitamin D
17-hydroxy corticosteroids
Test no longer done. It has been replaced by the 24-hr urine free cortisol in the
diagnosis of Cushing's syndrome.
5-hydroxy indole acetic acid

5-hydroxy methoxy mandelic acid
see HMMA (hydroxy methyl mandelic acid)
17-hydroxy progesterone (17-OHP)

specimen: serum
ref. range:
nmol/L
male female
before puberty 0.4-1.0 0.6-2.0
adult 0.6-5.5 0.6-2.5 (follicular)
1.5-15 (luteal)
17-OHP has replaced urinary pregnanetriol as the best screening test for the most
common form of congenital adrenal hyperplasia (CAH) and is checked in the
National Testing Centre neonatal screening programme.
17-OHP is a precursor of cortisol, androgens and oestrogens. In CAH, a block in the

cortisol pathway leads to overproduction of 17-OHP and androgens.
see also Congenital adrenal hyperplasia (CAH)
Hydroxybutyrate
see Beta-hydroxybutyrate

Hydroxyproline
specimen: 24-hr urine with acid preservative.
ref. range: <0.38 mmol/day
This marker for bone turnover has been superseded by N-telopeptide.
see Bone turnover markers

N-telopeptide
Hyper
Greek for over, beyond.
Most hyper- entries are listed under the term they qualify, e.g. hypermagnesaemia is
described under magnesium.
Hyperbilirubinaemia
Hypercoagulability
Hypercoagulability (thrombophilia) is the term used to describe an increased risk of

thrombosis. The risk factors causing hypercoagulability can be primary (inherited) or
secondary (acquired) and when considering the aetiology of a thrombolic event, both
types need to be considered. Risk is compounded when two or more factors are
present.

A. Acquired risk factors
• immobility
• surgery
• trauma
• pregnancy
• oral contraceptives
• malignancies
• antiphospholipid antibody syndrome
• SLE
• myeloproliferative disorders
• PNH
B. Inherited risk factors

• activated Protein C resistance due
to Factor V Leiden mutation
• antithrombin III deficiency
• Protein C deficiency
• Protein S deficiency
• other
One of the first four of these inherited abnormalities is found in about 50% of cases of
thrombosis. The Factor V Leiden abnormality is ten times more common than each
of the other three.
The "other" category includes rare disorders such as homocysteinuria and the
prothrombin 20210 G-A variant. There are also other as yet unidentified
abnormalities which are presumed to exist.
Thrombotic Risk (Leiden Thrombophilia Study)

Approximate DVT incidence
category relative risk (% per year)
normal 1 0.01% (1:10,000)

OCs 2-4 0.02 - 0.04%
FV mutation (heterozygous) 5-10 0.05 - 0.1%
FV mutation + OC 30-50 0.3 - 0.5%
FV mutation (homozygous) 100 1.0%
ATIII, PrC, PrS 100 1.0%

Which patients should be tested for a genetic hypercoagulability?
• thrombosis in a patient <45 years

• recurrent thrombosis
• family history of thrombosis
Who should not be tested?
Screening is not recommended:
– as a routine before starting oral contraceptives : the absolute risk of

thrombosis is low, cost of screening is high, false positives occur, and an
unwanted pregnancy may be blamed on withholding OC.
– before surgery when there are no other risk factors.
– before pregnancy when there are no other risk factors.
– in a patient over 45 with a first thrombosis which has been provoked by an
identified correctible risk factor.
Hyperparathyroidism
see Calcium (total)
Hypersplenism

Splenomegaly, whatever the cause, leads to pooling of blood cells in the enlarged
spleen and sometimes to increased cell destruction. The net effect can be anaemia,
neutropenia or thrombocytopenia, either singly or in combination.
Hyperthyroidism
Hypertension – endocrine causes
These include: Conn's syndrome

Cushing's syndrome
phaeochromocytoma
renal artery stenosis
acromegaly
hyperthyroidism
Hypo
Greek for under, below
Hypo-words are mainly entered under the terms they qualify, e.g. hypocalcaemia is
under calcium.
Hypochromia
see Microcytosis

Iron deficiency
Percentage hypochromia
Hypogammaglobulinaemia
Hypogammaglobulinaemia can be found in:
myeloma
chronic lymphocytic leukaemia
lymphoma
non-selective protein loss
transiently with a recent viral infection
congenital deficiency
Hypoglycaemia
The glucose threshold at which symptoms of hypoglycaemia develop varies widely

between individuals but in general a glucose level <3.0-3.5 mmol/L can be described
as hypoglycaemic except in neonates where the lower limit of "normal" is about 2.5
mmol/L.
Hypoglycaemia in diabetics treated with insulin or sulphonylureas
Symptoms are common, diverse and often misinterpreted or overlooked. The

transient nature of the hypoglycaemia means that laboratory collects usually miss the

trough but any value below 4.0 is suspicious. Symptoms and signs include
irritability, tremulousness, faintness, sweating, pallor, hunger, weight gain, headache
(headache on waking may be due to nocturnal hypoglycaemia), personality change,
deterioration in level of consciousness, coma.
Reactive (functional) hypoglycaemia
This common but elusive syndrome with its symptoms of irritability, tremulousness
and hunger ("faint with hunger") is not easily diagnosed by the laboratory. It is seen
in children, young adults, and to a lesser extent older people. The symptoms are felt
some 2-5 hours after food, not while fasting.
The extended GTT (4½-5 hrs) has been the traditional test but is a burden to the
patient and has too many false positives and false negatives.
A marginally more useful test is the measured blood glucose during an attack but the
logistics of this are often not easy.
The best test is a trial of diet which, if successful, combines diagnosis with therapy.
Sweet refined carbohydrates are changed to unrefined carbohydrates with one or two
snacks added between meals.
Fasting hypoglycaemias
These are much less common than the non-fasting varieties and much more likely to
have an identifiable organic basis.
The first test is to measure a fasting glucose. If low it should be followed by a fasting
insulin and repeat glucose:
• raised or inappropriately normal fasting insulin
— insulinoma

— exogenous insulin or sulphonylureas
• low fasting insulin
— advanced liver disease
— malignancy
— isulin autoantibodies
— alcohol
— pituitary/adrenal insufficiency
Neonatal hypoglycaemia
The at-risk infants are
• low birth-weight
• infants of diabetic mothers
In both, blood glucose levels should be monitored, beginning an hour after birth, and
treatment given if levels are below 2.0-2.5 mmol/L. Glucose levels can rise and fall
quickly during the neonatal period. Clinical signs are an inadequate indication of
hypoglycaemia.
Hypopituitarism
Usually due to a tumour of the pituitary or hypothalamus but pituitary infarction or

haemorrhage can occur in a normal pituitary, classically as Sheehan's syndrome after
obstetric haemorrhage but also in other situations including bleeding disorders,
cardiac by-pass surgery and some imaging procedures.
Clinically hypopituitarism may present as amenorrhoea, hypogonadism,

hypothyroidism, adrenal insufficiency, hyponatraemia. Useful tests include:

Adrenal Synacthen test. A peak cortisol >700 nmol/L makes chronic
hypopituitarism very unlikely though it may not exclude partial or very recent onset
of hypopituitarism.
Thyroid T4 low but TSH usually normal. The TSH measured in this situation can
co-exist with clinical hypothyroidism so is assumed to be biologically inert.
Gonads FSH and LH may be low, particularly in post-menopausal women who

otherwise have high levels. Testosterone may be low in men.
Hyposplenism
After splenectomy, red cells show Howell-Jolly bodies, targeting and spherocytosis
and there is thrombocytosis and leukocytosis which may or may not persist.
A hyposplenic blood picture can also be seen in other conditions associated with
splenic atrophy :
• coeliac disease
• inflammatory bowel disease
• autoimmune disease, particularly with haemolysis
• sickle cell disease
After splenectomy a patient may have increased susceptibility to infection which can
be overwhelming in children. Pneumococci are the usual cause but other organisms
such as Haemophilus or meningococcus may be responsible. Pneumococcal and
meningococcal vaccines can be given every 5-7 years or penicillin prophylaxis in
susceptible patients.

Hypothyroidism
IA autoantibodies (insulin antibodies)
see

Diabetes autoantibodies
IA2 autoantibodies (insulin antigen 2)
IBC
see Iron-binding capacity (IBC) and saturation
ICA autoantibodies (islet cell)
Idiopathic immune thrombocytopenic purpura
see ITP (idiopathic immune thrombocytopenic purpura)
IEP

see Immunoelectrophoresis (IEP)
IF (immunofixation)
see Immunoelectrophoresis (IEP)
IgA, IgG, IgM
IgA deficiency
A selective reduction in IgA is a common congenital immune deficiency syndrome

occurring in 1:700 people. It is usually detected by blood donor screening. Most
individuals are asymptomatic. IgA deficiency is associated with autoimmune
disorders including coeliac disease, SLE, autoimmune haemolytic anaemia,
rheumatoid arthritis and thyroiditis.
Anaphylaxis may occur as a result of IgG antibodies to IgA when the individual is
exposed to blood transfusion or gammaglobulin therapy.
see also Immunoglobulins, IgA, IgG, IgM
IgE total
specimen: serum

ref. range: 0 - 100 IU/L
IgE antibodies mediate Type I allergic reactions – allergic rhinitis, asthma, atopic
dermatitis, anaphylaxis.
Total IgE is elevated in patients with multiple allergies and parasitic infestations.
Very high levels, above 1000 IU/L, are found with atopic dermatitis, fungal sinusitis
and allergic pulmonary aspergillosis.
see also RAST (Radioallergosorbent test) for specific IgE antibody tests
IGF-1 (insulin-like growth factor-1,

somatomedin C)
specimen: serum or plasma (EDTA)

ref. range:
age males females

years ng/mL ng/mL
0-5 17 - 248 17 - 248
6-8 88 - 474 88 - 474
9 - 11 110 - 565 117 - 771
12 - 15 202 - 957 261 - 1096
16 - 19 182 - 780 182 - 780
20 - 39 122 - 400 122 - 400
40 - 54 75 - 306 75 - 306
>54 48 - 225 48 - 225
Levels peak at puberty during maximum growth
The action of human growth hormone (HGH) from the pituitary is mediated through
IGF-1 which is formed in the liver. As well as its effects on growth, it has insulin-

like actions. IGF-1 synthesis is suppressed by malnutrition as well as HGH
deficiency.
IGF-1 and HGH are measured in suspected acromegaly and in pituitary dwarfism.
Immune paresis
This term refers to reduction in normal immunoglobulins
Immunoelectrophoresis (IEP)
see Immunofixation (IF), serum
Immunofixation (IF), serum
specimen: serum
Immunofixation is used:
• to confirm the presence of a paraprotein when an abnormal band has been

found on serum EPP
• to determine whether it is IgG, IgA or IgM, light chain only or, rarely, IgD or
IgE
• to establish whether the light chain component is kappa or lambda
see also electrophoresis of urine

Immunoglobulins, IgA, IgG, IgM, Monoclonal bands
Immunofixation, urine
specimen: urine, random
A test for free light chains (Bence Jones Protein), whether they are present and
whether kappa or lambda.
see also Electrophoresis of urine

Immunoglobulins, IgA, IgG, IgM, Monoclonal bands
Immunoglobulin G subclasses
The four IgG subclasses are numbered 1 to 4. In some patients, recurrent respiratory
tract infections are associated with Ig subclass deficiency even though the total IgG is
within the usual range.
Immunoglobulins, IgA, IgG, IgM

specimen: serum
ref. ranges:

Age IgG IgM IgA
0 - 14 days 6.0 - 16.0 0.1 - 0.6 0.0 - 0.1
2 - 6 weeks 2.0 - 6.0 0.2 - 0.8 0.0 - 0.5
7 weeks - 6 months 2.0 - 7.0 0.2 - 1.0 0.0 - 0.8
7 - 24 months 3.0 - 10.5 0.3 - 1.5 0.1 - 1.2
2 - 5 years 4.5 - 11.5 0.5 - 1.9 0.3 - 1.6
6 - 10 years 6.0 - 13.0 0.5 - 2.1 0.4 - 2.2
11 - 16 years 6.0 - 15.0 0.5 - 2.2 0.7 - 2.3
Adult 7.0 - 16.0 0.4 - 2.5 0.8 - 4.0
70+ yr 6.0 - 15.0 0.4 - 2.4 0.8 - 4.0
Quantitation of immunoglobulins, particularly paraproteins, is method-dependent so

when monitoring a patient with myeloma or an apparently benign paraprotein, the
immunoglobulins will ideally be measured by the same laboratory using the same
method. In practice, laboratories change methods at times so when a result shows an
unexpected rise or fall, the laboratory should be consulted.
Immunoglobulins are antibodies and constitute the gamma fraction of serum

globulins. Abnormalities of immunoglobulins include:
– monoclonal increases, benign or malignant

– polyclonal increases as seen in chronic inflammatory disorders
– polyclonal decreases : immune paresis
Serum protein electrophoresis (EPP) is an essential test when interpreting a raised

total globulin or immunoglobulin to determine whether a paraprotein is responsible
for the increase.
A. Monoclonal bands, paraproteins, M-bands

A paraprotein, which appears as a sharply defined abnormal band on serum
EPP, consists of a single population of identical immunoglobulin molecules
formed by a clone of neoplastic plasma cells. They can be benign (MGUS) or
malignant (myeloma, macroglobulinaemia or lymphoma).

Occasionally an M-band is due to an extra-medullary plasmacytoma.
Benign paraproteins (MGUS – monoclonal gammopathy of uncertain significance)

These paraproteins, composed of IgG, IgA, or IgM, appear with increasing
frequency in the elderly – 8% of patients over age 70. They can be transient,
particularly in younger individuals. Characteristics are a relatively low
concentration (total IgG <20g/L, IgA or IgM <10 g/L), normal blood picture,
no depression of normal immunoglobulins, no urine Bence-Jones Protein.
Bone marrow examination is not usually indicated but if done will show
<10% plasma cells with no atypical cells.
MGUS can be regarded as a "carcinoma in situ" of the immune system and

like any in situ lesion it has the capacity to progress to malignancy, quickly or
slowly, or it can remain largely static for the life of the individual, hence the
need for monitoring at least annually. Evolution to multiple myeloma (or
macroglobulinaemia) occurs in 25% of patients.
Malignant paraproteins
These consist either of IgG or IgA (multiple myeloma) or IgM
(Waldenstrom's macroglobulinaemia or lymphoma) and show the invasive
characteristics of malignancy with infiltration and destruction of bone
marrow.
Characteristics of a malignant, as compared with a benign paraprotein are:
– anaemia, thrombocytopenia, neutropenia

– immune paresis, i.e. reduction of normal IgG, IgA and IgM
– high and rising concentration of paraprotein
– Bence Jones protein (free light chains) typically appears in the urine in
myeloma.
– myeloma causes diffuse osteoporosis or lytic lesions, either of which
can cause back
pain, compression fractures or bone pain in other parts of the body
such as ribs or pelvis.
– hypercalcaemia, raised ALP

– renal impairment
– hyperviscosity syndrome, particularly with macroglobulinaemia
Bone marrow examination and skeletal survey establish the diagnosis.
Where there is a strong clinical suspicion of myeloma (pancytopenia, osteolytic

lesions, bone pain, immune paresis) but no serum M band, urine EPP may show
Bence Jones myeloma in which the band (of free light chains) is found only in
urine.

Treatment of myeloma
Asymptomatic or stable myeloma does not benefit from early therapy which is
indicated only for progressive disease with symptoms. Treatment involves the
use of alkylating agents such as melphalan with a trend in younger (<55 years)
patients to high dose therapy with autologous bone marrow transplantation.
B. Polyclonal increases or decreases in immunoglobulins
Polyclonal increases
These are reflected in serum proteins as an increase in total globulins and in

the EPP as an increased density in the gamma zone.
They are caused by any chronic inflammatory or liver disorder:
– chronic hepatitis, viral, alcoholic or autoimmune

– connective tissue diseases
– chronic inflammatory bowel or pulmonary disease
– parasitic infestations
Pacific Islanders and South East Asians almost invariably show a moderate
polyclonal increase in immunoglobulins reflecting exposure to a different
range of microbiological antigens compared with temperate climates.

In two conditions a single immunoglobulin is markedly elevated:
– IgG in chronic active autoimmune hepatitis

– IgM in autoimmune biliary cirrhosis
Polyclonal decreases
There are three main syndromes -
Acquired idiopathic hypogammaglobulinaemia This can occur in childhood or adult

life, is associated with recurrent bacterial infections and can be of all degrees of
severity. Sometimes it is transient; associated with recent viral infection.
Secondary hypogammaglobulinaemias (immune paresis) These are usually

secondary to chronic lymphatic leukaemia, multiple myeloma, macroglobulinaemia,
lymphomas or nephrotic syndrome.
Selective IgA deficiency This is common (1:700) and usually asymptomatic.

Sometimes it is associated with coeliac disease, allergies, respiratory infections, or
autoimmune disorders.
Imprecision
A word now replacing the older term "precision" which refers to the analytical scatter
(variance) of results when a single sample is tested repeatedly. The imprecision of a
test is expressed as the coefficient of variation (qv).
see also Variation.

Inappropriate ADH
see Sodium (Na+), serum
Indirect bilirubin
Infection control
see MRSA (methicillin resistant Staphylococcus aureus)

Infectious mononucleosis
specimen: – serum for heterophil antibodies, liver enzymes, EBV antibodies.

– whole blood (EDTA) for blood count
Epstein-Barr Virus is the causative agent in infectious mononucleosis which is

characterised by lymphadenopathy, pharyngitis, fever, variant lymphocytosis in the
blood film and transient heterophil antibodies in serum. Fatigue can be profound and
continue for months.
Although EBV infections are common in children, they are often mild and pass
undiagnosed. The peak incidence for infectious mononucleosis is in adolescence and
early adult life, but a few individuals who remain uninfected succumb in later life.

EBV, along with hepatitis A, B and C, is one of the four common causes of viral
hepatitis.
Although typically immunity is secure, EB virus remains latent in a small proportion

of B lymphocytes and can be reactivated in the immunosuppressed state.
Blood picture
Variant (atypical) lymphocytes appear in the film during the first week of illness
increasing typically to more than 20% of the total WBC during the second week and
declining over ensuing weeks.
Variant lymphocytes are found in many viral illnesses including CMV and infectious
hepatitis and the protozoan illness toxoplasmosis. Because CMV and toxoplasmosis
have a similar clinical picture to infectious mononucleosis, they are sometimes
included in the "glandular fever syndrome".
Neutropenia and thrombocytopenia are common and occasionally an autoimmune

haemolytic anaemia.
EBV can invade the liver causing elevation of liver enzymes to levels of 200-500
units/L or occasionally higher. Alkaline phosphatase and GGT often show relatively
greater elevations than the AST and ALT when compared with infectious hepatitis.
Heterophile antibodies ("Paul Bunnell test")
Heterophile antibodies, so-called because they agglutinate animal as well as human

red cells, appear in 90% of cases by the 3rd week of illness. After an infection they
persist for 3-6 months.

A first test that is negative should be repeated in a fortnight or so. Persistently
negative results can occur in cases of proven EBV infections; they are more common
in the younger or older age groups and in those with severe disease. Where clinical
suspicion remains despite negative heterophile antibodies, EBV antibodies should be
requested.
EBV antibodies
Where EBV infection is suspected but heterophil antibodies remain negative – as

happens in 10% of young adults, and 50% of children – the measurement of EBV
antibodies will provide a definitive answer.
VCA (viral capsid antigen) IgM antibodies appear at 4-7 days after symptoms
develop and persist for 2-4 months, occasionally up to 1 year. Their presence
indicates current or recent infection.
VCA IgG antibodies appear at the same time as IgM but persist for life.
EBNA (anti EB nuclear antigen) antibodies appear 3-6 weeks after onset and also
persist for life. 80% of the population are EBNA +ve, indicating past infection. A
minority of people infected with EBV never develop EBNA antibodies but will have
a positive VCA IgG test to indicate their past exposure.
Infertility
see Amenorrhoea
FSH (follicle stimulating hormone) and LH (luteinising hormone) for ovarian
failure
Progesterone for confirmation of ovulation
Prolactin for hyperprolactinaemia
Polycystic ovary syndrome (PCOS)

Seminal fluid
Influenza
Virus can be recovered from a posterior pharyngeal swab during the first 3 days of
illness. The swab must be placed in viral transport medium and transported on ice.
Antibodies can be measured in paired sera.
Inorganic phosphorus
see Phosphate
The INR is the test used to monitor warfarin anticoagulant therapy which is being
increasingly widely used across the range of thromboembolic disease. Warfarin is a
vitamin K antagonist and acts by reducing levels of Factors II (prothrombin) VII, IX
and X. The INR is a standardised prothrombin ratio calibrated so that INR results
from one laboratory are directly comparable with those from another.
A. Warfarin dosing regimens
The ½-life of warfarin is 36 hours and those of Factors II, VII, IX and X vary
between 7 and 60 hours and for this reason, response to a dose change is slow
with a lag of 3-4 days before a new equilibrium is achieved.

Although the INR is often requested as a semi-urgent test so that specimen
collection, testing, reporting and dose change can all be done on the same day,
the 3-4 day lag in INR response makes this urgency unnecessary. Dose
changes can wait till the next day.
1. Standard warfarin regimen for rapid anticoagulation.
Standard dosing regimen:

day INR Warfarin dose (mg)
1 <1.4 10 (5 in older patients)
2 <1.8 5
3 <2.0 5
2.0-2.2 5
2.3-2.4 4
2.5-2.7 3
2.8-3.0 2
3.1-3.5 1
>3.5 —
predicted
maintenance dose
4 <1.4 >8
1.4-1.7 6-8
1.8-2.3 5
2.4-3.0 4
3.1-3.5 <3
3.6-4.0 <2
Note: If 3.6-4.0, miss next day's dose, then give 2.0 mg.
If >4.1, miss 2 days' doses, then give 1.0 mg.

2. Alternative slower regimen
Can be used in older outpatients with chronic atrial fibrillation (except
when on amiodarone).
Day INR Warfarin dose Time to next
(mg) change/INR
Day 1 <1.4 3 mg 1 week

Day 8 <1.8 4 mg 1 week
1.8 - 2.5 3 mg 2 weeks
2.5 - 4.0 2 mg 1 week
>4.0 specialist 1-3 days
advice (depending
on INR level)
B. Target INR
The recommended target in the table below is a guide only and in selected
patients a different level may be recommended.
Indication Recommended INR

Target
DVT prophylaxis in high risk situations 2-3
Treatment of VTE 2-3
Prevention of systemic embolism: 2-3
atrial fibrillation
valvular heart disease
following mycocardial infarction
tissue heart valves (<3 months)
Mechanical bileaflet or tilting disc heart valve. 2.5 - 3.5

- older caged ball valve may need higher target
Recurrent thrombosis on Warfarin 3.0 - 4.0 (?)
Thrombosis in antiphospholipid syndrome 3.0 - 4.0 (?)

C. Excessive INR Respon
Sometimes a patient with a stable INR shows a marked change. Possible
causes are:
• incorrect dosage (often associated with a prescription change) accounts

for half of these unexpected changes.
• drugs
antibiotics cardiac anti- gastrointestinal

inflammatory
cotrimoxazole amiodarone phenylbutazone omeprazole
erythromycin clofibrate piroxicam cimetidine
fluconazole propanolol paracetamol
miconazole sulfinpyrazone
metronidazole
isoniazid
• gastrointestinal disease – diarrhoea

• hepatic disease, congestive cardiac failure
Bleeding risk while on warfarin
Composite figures for overall risks:
fatal bleeding 0.25%

major bleeding 1-3%
minor bleeding 6-7%
INR level v patient bleeding risk

INR events/100 estimated risk
pt years over 48hr period
2 - 2.9 4.8 1 in 4,000
3 - 4.4 9.5 1 in 2,000
4.5 - 6.9 40 1 in 500
>7.0 200 1 in 100
D. Management of overcoagulation
The urgency of correcting a high INR (above 4 if the target is 2.5) will depend
on whether there is any bleeding and whether major or minor.
Therapeutic options are:
1. For all high INR's:

Stop warfarin, then restart at a lowered dose when INR is higher than
target but <5.
INR % dose reduction Usual number (days)

of omitted doses
4-5 25 0
5-6 25 1
6-8 33 2
>8 50 3
2. Vitamin K
Low dose vitamin K replacement (usually 1-2 mg initially) is used

where the INR is excessively prolonged by warfarin as a consequence
of vitamin K depletion. Replacement of vitamin K stores should
make the subsequent response to warfarin more predictable. Vitamin
K is usually administered orally or sc, occasionally IV. For oral

replacement the appropriate volume can be drawn up into a tuberculin
syringe from an ampoule (1 mg/0.5ml or 10 mg/ml) of vitamin K in a
dose of 0.5-2 mg (see below). Larger doses of vitamin K (e.g. 5-10
mg) may make the patient resistant to further warfarin.
3. Prothrombin complex concentrate
Prothrombinex 25 u/kg or FFP 15 mls/kg is given for immediate

correction when there is major bleeding.
Guidelines for severe overcoagulation
clinical guideline
INR 6-8 without bleeding • stop warfarin
• restart in reduced dose when INR <5
• give 0.5-1mg oral/sc vitamin K if INR
fails to shorten, or if reversal required
within 24-48 hrs.
INR >8 with bleeding • stop warfarin
• restart in reduced dose when INR <5.
• give 1-2 mg oral/sc vitamin K (repeat
in 24hrs if necessary).
High INR and major bleeding • stop warfarin

• admit to hospital.
• give vitamin K 5 mg sc/iv.
• give prothrombin complex concentrate
(prothrombinex) 25 units/kg or
FFP 15 mls/kg.
Insecticides
see Organophosphate toxicity

Cholinesterase
Carbamates

Insulin
specimen: serum or plasma (EDTA or heparin)

The specimen needs to be stored at 4ºC and
separated in less than 4 hours. A fluoride
specimen for plasma glucose is collected at
the same time.
ref. range: 5 - 13 mU/L (fasting).
The principal use of insulin levels is in the investigation of fasting hypoglycaemia

(glucose <3.0 mmol/L) due to insulinoma or undeclared use of sulphonylureas or
insulin.
Insulin-like growth factor 1
see IGF-1 (insulin-like growth factor-1, somatomedin C)
Intestinal biopsy for enzymes
see Disaccharidases
Intrinsic factor antibodies

specimen: serum

80% of pernicious anaemias give a positive test. False positives are infrequent.
Iron
specimen: serum
ref. range: child 7-21 µmol/L
adult 10-30 µmol/L
Serum iron levels show a marked diurnal variation with morning levels higher by
30%.
They are also rapidly depressed to low levels by acute or chronic infections or any
other chronic disorder.
Because of these large fluctuations, serum iron is of little diagnostic use on its own
but when combined with iron-binding capacity/transferrin and ferritin, total body iron
deficiency or excess can usually be defined.
Serum iron is elevated by:
• oral or parenteral iron supplements

• haemochromatosis
• alcohol
• hepatitis
• oestrogens/oral contraceptives
• iron poisoning – children absorb oral iron easily and in acute poisoning can
present with levels in the 100-500 µmol/L range.
Iron-binding capacity (IBC) and saturation

specimen: serum
ref. range: IBC: 45-72 µmol/L
saturation: 20-40% (or 0.20-0.40)
Fe
saturation = x 100%
IBC
IBC and saturation are routinely done with requests for iron. IBC reflects the iron
transport protein transferrin, a globulin travelling in the beta band on electrophoresis.
Transferrin (and IBC) are elevated by:
• iron deficiency
• oestrogens, oral contraceptives and pregnancy, to an upper level of about 90
µmol/L
• hypothyroidism
• ineffective erythropoiesis e.g. B12, folate deficiency
Transferrin is a negative acute phase reactant and is reduced by chronic inflammatory

disease, malignancy, renal disease, thyrotoxicosis, and haemochromatosis.
The two main indications for measuring IBC/transferrin are:
• haemochromatosis (qv) in which saturation is typically above 60% when the

disease becomes symptomatic.
• in the investigation of iron deficiency when a serum ferritin is not available or
has been elevated by coexisting inflammatory or liver disease.

Iron deficiency
Useful tests
• ferritin the most sensitive and specific test. If low it is almost
pathognomonic of iron deficiency, latent or overt, but
a normal result does not exclude iron deficiency as
coexisting inflammatory disease can elevate ferritin
independently
• MCV & MCH reduced, but not until ferritin is <10
• Hb reduced, but anaemia develops later than
the other changes
• blood film oval cells, hypochromia, microcytosis
• iron reduced, but many other conditions cause
a fall in serum iron
• IBC increased (may be normal if inflammation coexists)
• % saturation reduced
Aetiology of iron deficiency
The treatment of iron deficiency must always be accompanied by a search for the
cause. Deficiency is so common in women of child-bearing age that it is easy to
attribute all deficiencies in women to menstrual loss while forgetting this is not
possible after the menopause – nor in males of any age. Deficiencies fall into three
broad groups.
Chronic blood loss

female genital tract:
• menstrual loss
• pregnancies
• tumours of female genital tract with abnormal bleeding
gastrointestinal loss:
• oesophagus, stomach, duodenum – peptic ulcer,
NSAIDS, hiatus hernia,varices
• large bowel – tumours (iron deficiency is a common
presentation), ulcerative colitis, haemorrhoids
• small bowel – hookworm, congenital vascular
malformations, Meckel's diverticulum
other:
• epistaxis, haematuria, haemoptysis, telangiectasia
Dietary insufficiency
Mainly in infants, adolescents and the elderly.
Malabsorption
Coeliac disease particularly.
Iron deficiency in athletes

Iron deficiency is more common in athletes for three reasons:
– they may be on relatively low iron diets

– they frequently suffer occult gastrointestinal blood loss
– they may suffer march haemoblobinuria with urinary iron loss
For these reasons many athletes take oral iron supplements when their ferritins are
towards the lower end of the reference range.

Iron saturation
see Iron saturation
Islet cell antibodies (ICA)

ICA precede the development of Type I diabetes (IDDM) by a variable period of
years and have been used for predicting risk in relatives of Type 1s and in population
studies.
They are measured in JDF units
>80 units or above almost invariably associated with development of IDDM,

usually within 10 years.
40 units moderate to high risk
20 units low to moderate risk
5-20 units low risk. These levels may disappear; may persist without
progression; or may progress to IDDM.
ITP (idiopathic immune thrombocytopenic

purpura)
A relatively common autoimmune disorder characterised by an isolated

thrombocytopenia in the absence of drugs, chemicals or any haematological or non-
haematological disorder.
Acute immune thrombocytopenia is distinguished from acute viral thrombocytopenia

by the clinical course with the latter usually recovering within a few days without the
requirement for specific therapy. Chronic immune thrombocytopenia is diagnosed

when the thrombocytopenia persists for more than 6 months. It may have a viral
trigger, occur as part of an autoimmune disorder (e.g. SLE), arise in association with
a lymphoproliferative disease or as an idiopathic finding.
ITP is usually a diagnosis of exclusion. Appropriate investigations may include a

coagulation screen with bleeding time (to evaluate a possible associated platelet
dysfunction), autoimmune investigations (ANA, anti DNA rheumatoid factor,
anticardiolipin antibodies, platelet antibodies), lupus anticoagulant screen, protein
electrophoresis and immunoglobulins, HIV.
Treatment is either with prednisone or intravenous immunoglobulin, particularly

when the platelets fall below 20 x 10 9 / L .
see Thrombocytopenia
IUCD
see Actinomyces

Jaundice
Hyperbilirubinaemia becomes visible in the skin and sclera of most individuals when
the bilirubin is above 40 µg/L. The skin is yellow in carotenaemia also, but not the
sclera.

Liver enzymes

Carotene
Joint aspirate
see Synovial aspirate
K+ (kalium)
see Potassium (K+), serum
Karyotype
The number and structure of an individual's chromosomes

see Chromosome analysis

Ketones
specimen: random urine or serum
This test, which is part of routine urinalysis, is usually done by a dipstick method.
Mild positives occur with starvation or illness. Moderate or strong positives in Type I
diabetics indicate poor control requiring additional insulin and rehydration - urgently
if there is significant acidosis.
"Ketostix" detects acetoacetate which accounts for only a small percentage of "ketone
bodies", the greater portion being beta-hydroxy-butyrate (qv).
Klebsiella pneumoniae
An aerobic gram-negative enteric bacillus. Found on mucosal surfaces and in the

faeces of about 5% of healthy people. It occasionally causes pneumonia as well as
biliary and urinary tract infections.
Kleihauer stain for HbF
see Thalassaemias
Klinefelter syndrome
XXY is the usual karyotype. Testosterone levels are typically reduced and FSH and
LH increased. Other pituitary tests are usually normal.

Clinically, patients are often unusually tall with long legs. Testes are small, pubic
hair scant and there may be gynaecomastia.
Laboratory error
see Errors
Variation
Lactase deficiency
see Disaccharidases
Reducing substances in faeces
Lactose tolerance test (LTT)

Lactate dehydrogenase
see LD (lactate dehydrogenase)
Lactose intolerance in infants
see Reducing substances in faeces
Lactose tolerance test (LTT)
Protocol
A fasting blood glucose is taken and then a loading dose of lactose is given, 1.5g/kg
to a maximum of 50g and blood samples taken each quarter hour for 1 hour with a
final sample at 2 hrs. The test cannot be used in diabetics.
Interpretation
In a normal person, s. glucose (derived from the lactose) rises more than 1 mmol/L
above the fasting level, usually peaking at 15 or 30 mins. Because of its indifferent
sensitivity and specificity, the LTT is not often performed.
Acquired lactase deficiency in adults is not uncommon, usually secondary to

malabsorption syndromes, Crohn's disease, giardiasis, bacterial gut infections etc.
Trial of a lactose-free diet can assist with the diagnosis.
Lag storage GTT

see GTT
Laxative abuse screen

specimen: 50 ml random urine
The method detects only stimulant laxatives.
LD (lactate dehydrogenase)
specimen: serum
ref. range: 120 - 250 IU/L
LD is an enzyme of low specificity found in liver, myocardium, skeletal muscle and

red cells. It is also found in some malignancies, notably lymphomas and particularly
non-Hodgkin's lymphoma.
Elevations can be due to:
• lymphomas, up to 2-3x the upper limit of the reference range. The level gives
an estimate of tumour bulk.
• other tumours, especially germ cell
• myocardial infarction, increase commences 12-24 hrs after infarction,
disappearing after 7-12 days
• megaloblastic anaemias due to B12 or folate deficiency
• haemolytic anaemia
• artefactual haemolysis due to faulty specimen storage or collection
• liver disease, particularly hepatitis
• skeletal muscle damage

Of the LD isoenzymes, LD1 is derived from myocardium or erythrocytes, LD5 from
liver.
LDH
see LD (lactate dehydrogenase)
LDL cholesterol
see Cholesterol LDL cholesterol
Lead, blood
ref. range: normal: adults <0.7 µmol/L whole blood

children <0.5 µmol/L whole blood
toxic: adults >3.7 µmol/L whole blood

children >2.2 µmol/L whole blood
Industrial workers exposed to lead are put off work if their blood lead is >3.2 on one
occasion or >2.6 on three consecutive occasions.
Domestic exposure occurs when old lead-based paints are being sanded or burnt off.
Children are at risk when they ingest paint fragments or dust; as are pets when they
lick their fur.

High levels should be repeated in 3-4 weeks.
Lead poisoning interferes with porphyrin metabolism causing elevation of urinary

coproporphyrin, PBG and ALA. The porphyrin changes are a better indicator of
toxicity than the blood lead on its own but are not used for routine industrial testing.
Red cells may show basophilic stippling.
Lead, urine
specimen: 24-hr urine in special container with added HCl
ref. range: <0.25 µmol/day
Urine leads are used for monitoring chelation therapy in lead poisoning after the
diagnosis has been established using blood lead levels.
LE cells
ANA and anti-DNA (qv) antibodies have replaced this test in the diagnosis of SLE.
Legionella
specimen: sputum for culture
serum for antibodies
ref. range: antibody level
There are more than 30 species of Legionella, the cause of Legionnaire's disease.

The organism, is found in hot water systems or the humidified air of air-conditioning
systems, causing both sporadic cases and institutional outbreaks of atypical
pneumonia. Since the disease was first described in New Zealand in 1980 there have
been about 700 cases. In two New Zealand studies it was the cause of 5-10% of
community acquired pneumonia.
Culture is the diagnostic method of choice. Legionella culture must be asked for
specifically as it requires the use of specially prepared media. Specimens
contaminated with sodium e.g. saline-induced sputum and bronchial washings, are
not suitable for Legionella culture.
Most healthy adults have an antibody titre of <1.128. Rising antibodies in paired sera
provide good evidence of active infection. Paired sera should ideally be collected two
weeks apart.
Please consult microbiologist for suspected infections.
Leprosy
Diagnosis is by identification of acid-fast bacilli in histological sections or in

scrapings from incised lesions or nasal septum.
Please consult microbiologist if tests are required.
Leptospirosis
specimen: serum
Since vaccination of cattle was introduced several years ago, the incidence of
leptospirosis has dropped to the point where it is now rare in Auckland and

uncommon in New Zealand, <2 cases/105. Host animals include cattle, pigs, horses
and rodents. Human infection typically follows exposure to blood of infected animals
or water contaminated with their urine.
For diagnosis an antibody screen test is performed followed by (on sera that are
positive) specific agglutination testing against the common strains of leptospira.
Titres of 1:200-1:400 are borderline.
After infection, titres rise sharply into the thousands in those who have been infected
in the past. The highest titre may not indicate the cause of the latest illness.
Consultation with the microbiologist is suggested when acute leptospirosis is a

possibility so that blood culture in special medium can be arranged.
Leucocyte count
see Blood count
Leucocytosis
Refers to an increase in the total white cell count. Its significance depends on which
cell type is increased.

Lymphocytes
Monocytes
Eosinophils

Leuco-erythroblastic blood picture
Immature myeloid cells (myelocytes, metamyelocytes, band neutrophils), and

immature red cells (nucleated red cells), are present due to invasion or disturbance of
the normal marrow. Causes include:
• metastatic malignancy
• primary haematological malignancy
• myelofibrosis
• acute haemolysis
• thalassaemia major, especially after splenectomy
Leukaemias
see Acute leukaemias, Chronic myeloid leukaemia (CML)
Leukaemoid reaction
A peripheral blood picture resembling leukaemia in a patient who does not have
leukaemia. The increased numbers of white cells can be of either lymphoid or
myeloid type. Atypical response to infection in a child is the commonest cause. It is
seen particularly in Down's syndrome. Other causes include non-haematological
malignancies and acute haemolysis.
LFT (liver function tests)

see Liver enzymes
LH (luteinising hormone)
Light chains in urine
see Bence Jones protein (BJP)
Lignocaine
see Antiarrhythmic drugs
Lipaemia
After a fat-containing meal, and in the primary or secondary hypertriglyceridaemias,

the serum is turbid or creamy due to fat particles. A severe degree of lipaemia can
cause technical interference with some tests to the point where they become invalid.
see also Triglyceride

Lipase
A test used in some centres in addition to amylase in the diagnosis of acute

pancreatitis.
Lipid disorders
When classifying a lipid disorder for the purposes of treatment, two questions need to
be asked:
• is it a primary lipid disorder or secondary to some other metabolic

abnormality?
• which lipid fractions are elevated
- cholesterol only
- cholesterol and triglyceride
- triglyceride only
Secondary disorders
These are easily identified and when treated may entirely correct the lipid
abnormalities.
The common causes are:
• obesity
• alcohol
• diabetes

• hypothyroidism
• liver disease
• drugs: oestrogens, oral contraceptives, beta blockers, corticosteroids,
thiazides, isotretinoin, antivirals, valproate
Primary disorders
If no secondary causes are identified the disorder is presumed to be primary. There is

a range of familial disorders which are presumptively identified by the family history
or by physical signs such as xanthomata, corneal arcus.
The commonest familial disorders are familial hypercholesterolaemia and familial

combined hyperlipidaemia. There are many others.
However, the commonest primary dyslipidaemia by a wide margin is polygenic

hypercholesterolaemia, which is not familial. It is identified mainly by exclusion –
no significant family history, no abnormal physical signs. Presumed to result from a
combination of genetic and environmental factors, it provides a convenient diagnostic
refuge.
Which lipid fractions are elevated?

Defining the abnormal fractions is important in both diagnosis and treatment.
The feature of familial hypercholesterolaemia is very high serum cholesterol.
The familial elevation of familial combined hyperlipidaemia may be cholesterol only

(1/3), triglyceride only (1/3), or both (1/3).
Causes of secondary dyslipidaemias do not reliably produce a constant picture. For

example, though hypothyroidism typically causes elevation of cholesterol only, it can
at times raise the triglyceride also.

Treatment
Dietary modification is common to the treatment of all dyslipidaemias.
Drug treatment, if required, will depend on whether the abnormality is cholesterol

only (statins being the agent of choice), triglyceride only (fibrates usually first choice)
or both.
Lipid tests
A "fasting lipid screen" consists of:
NHF ideal level

total cholesterol <5.0
HDL cholesterol >1.0
LDL cholesterol <3.0
fasting triglyceride <2.0
total/HDL ratio <4.5
NHF = National Heart Foundation
see Cholesterol
Triglyceride
Lipoproteins
Lipoproteins
In serum, lipids are carried as lipoprotein particles which are grouped in four
fractions:

Lipoprotein Cholesterol Triglyceride
fraction
chylomicrons small ++++
LDL ++++ small
VLDL/IDL ++ ++++
HDL ++ small
Diagnosis of the hyperlipoproteinaemias requires a fasting specimen to eliminate the

contribution of dietary triglyceride in both chylomicrons and the VLDL fraction.
Hyperlipoproteinaemias can be familial or secondary (see separate entries under

triglyceride and cholesterol for aetiology of the secondary disorders) or, commonly, a
mixture of both. Occasionally the diagnosis is obvious, e.g. the clear-cut familial
hypercholesterolaemias causing severe coronary artery disease in early adult life – but
most of the common hypercholesterolaemias and hypertriglyceridaemias are part of a
large amorphous population, deeply affected by diet and life-style and mixed
inextricably with the "normal" population, whoever they are.
Typing of hyperlipoproteinaemias
The WHO classification is that of Fredericksen who recognised six types: I, IIa, IIb,
III, IV, V. The classification has limitations. Familial hyperlipoproteinaemias can
present as different types in different family members. A single aetiology (e.g.
hypothyroidism) can be associated with several types. Treatment can convert one
type to another. Nevertheless the terms are still used. Types II and IV, and to a lesser
extent V, are the commonest.
IIa IIb IV V
total cholesterol +++ +++ + +
triglyceride n ++ +++ +++
LDL cholesterol ++ ++ n n
VLDL cholesterol n + +++ ++
chylomicrons - - - ++
turbid serum - ++ ++ ++

Note that the classification does not use HDL cholesterol.
see also Apolipoproteins

Lipoprotein electrophoresis
Cholesterol
Triglyceride
Lipid disorders
Lipoprotein (a)
specimen: serum
ref. range: <300 mg/L
Lipoprotein (a), not to be confused with apolipoprotein A which is the protein

component of HDL, is an independent risk factor for coronary artery disease (CAD).
It can be of particular interest in patients whose CAD is not explained by other risk
factors.
Levels are largely genetically determined but tend to rise after the menopause or with
renal impairment. Fasting, exercise or statins have little effect. Levels may be
lowered by niacin and perhaps by fibrates. Acute illness can have an effect
andlipoprotein (a) should not be measured within 3 months of a myocardial
infarction.
Lipoprotein electrophoresis
specimen: serum
Four fractions are identified:

alpha-I contains HDL
pre-beta contains VLDL, elevated in Type IV, IIb or III
beta contains LDL, elevated in Type IIa or Iib
chylomicrons found in non-fasting serum or Type V
Lipid EPP is a specialist investigation. For most clinical purposes a lipid abnormality
is defined by quantitation of cholesterol fractions and triglyceride on a fasting
specimen.
Listeria monocytogenes
specimen: blood cultures, CSF, for acute infection stool for carrier state
Listeria, an aerobic gram-positive bacillus, is widely distributed in soil, water and

many animals. It is occasionally found in the human gastrointestinal tract. Spread to
humans is mainly via contaminated food. Food borne outbreaks due to contaminated
coleslaw, milk, soft cheese and mussels have been reported. Although most
infections are mild and harmless, septicaemic infection in pregnant women,
presenting as a flu-like illness, may lead to serious foetal infection leading to still-
birth or neonatal meningitis. Immunocompromised persons and the elderly are also at
risk of invasive disease.
Treatment is penicillin (or amoxycillin) with or without gentamicin. Erythromycin or

cotrimoxazole are less desirable alternatives. Treatment should be for at least 14
days. L. monocytogenes is resistant to all cephalosporins.
Lithium

specimen: serum
therapeutic range: mmol/L 12 hrs post-dose
0.4-0.9 desired range
1.0-1.5 sometimes toxic
>1.5 usually toxic
The specimen must be taken 12 hours after the last dose. Steady state levels are
achieved 2-5 days after a dose change, or longer in older patients with renal
impairment. When lithium is stopped, the level falls with a ½-life of 1-3 days.
Because of the high incidence of toxic effects, monitoring is regarded as essential

every 3 months, and more often if clinically indicated. Base-line TSH, T4, and
creatinine levels should be measured before commencing therapy and 6 to 12 monthly
thereafter.
Manifestations of toxicity
• a wide range of CNS and GI effects

• hypothyroidism – relatively common
• nephrogenic diabetes insipidus
• serum potassium maybe elevated
• renal damage with raised s. creatinine may occur when serum levels have
been consistently in the toxic range over a long period.
• high serum calcium
• cardiac toxicity: AV block, T wave changes, premature ventricular
contractions.
Drugs that elevate lithium: diuretics

NSAIDs
metronidazole
ACE inhibitors

Liver enzymes
specimen: serum
ref. ranges: see under individual constituents
General
ALP and GGT are the cholestatic enzymes so are particularly elevated in:
• biliary obstruction by gallstone or carcinoma of head of pancreas

• secondary or primary carcinoma of the liver
• drugs causing cholestasis
AST and ALT are the hepatocellular enzymes and are particularly elevated in viral
hepatitis.
Non-specific elevations of liver enzymes
Typical presentations of a disease are easily diagnosed but a common problem is

finding unexpected elevations of one or more liver enzymes. For any single
aetiology, the enzyme patterns may vary from what is usually described as typical.
With alcohol, for example, GGT is said to be affected particularly, but not
infrequently one of the others is raised on its own, or any two of them, or all.
Here is a checklist, not exhaustive, of aetiologies to be considered. Many of these

conditions are described in more detail under their own alphabetic listings.
1. acute viral hepatitis
• hepatitis A
• hepatitis B
• hepatitis C

• infectious mononucleosis
• CMV and other viruses causing an acute viral syndrome
2. chronic viral hepatitis
• hepatitis B
• hepatitis C
• HIV
3. other infections
• malaria
• leptospirosis
• typhoid
• TB
• brucellosis
4. drugs - the list includes:
• analgesics salicylates
paracetamol
propoxyphene
• antibiotics erythromycin estolate

tetracyclines
flucloxacillin
amoxycillin ± clavulanate
sulphonamides
• anticonvulsants phenytoin
carbamazepine
sodium valproate
phenobarbitone
• anti-TB drugs rifampicin

isoniazid
para-aminosalicylic acid (PAS)
• hormones oestrogens

oral contraceptives
androgens
• other phenothiazines
halothane
cytotoxic drugs
allopurinol
methyldopa
chlorpropamide
some herbal remedies
5. alcohol:
affects range from minor elevation of one (classically GGT) enzyme, through
massive elevations in acute alcoholic hepatitis down to minor or no elevations
in end-stage cirrhosis.
6. obesity:
elevates ALT particularly and other enzymes as fatty liver develops.
7. diabetes:
enzyme elevations are common in association with poor glycaemic control,

obesity, hypertriglyceridaemia and fatty liver.
8. gall-stones:
causing obstruction and cholangitis
9. malignancy:
• metastases from a distant primary

• carcinoma head of pancreas causing obstruction
• primary hepatic malignancy
10. autoimmune liver disease:
• autoimmune hepatitis (formerly chronic active hepatitis)

• primary biliary cirrhosis
• sclerosing cholangitis
11. other chronic inflammatory disease:
• SLE
• rheumatoid arthritis - raised ALP
• ulcerative colitis
• Crohn's disease
12. haemochromatosis
13. heart failure
with hepatic congestion
14. muscle disease:
AST and ALT rise when CK is substantially elevated.
15 Wilson's disease
16. industrial or other toxins
17. isolated non-hepatic elevations of ALP
– see alkaline phosphatase
18. macro-molecular enzyme variants:
the enzyme molecule is too large to leave the circulation via the glomerulus
with the result that an enzyme level is permanently elevated in the absence of
any disease process.
19. idiopathic benign elevations:
when no other explanation can be found.

Summary
It is a matter of clinical judgement how many tests should be done as investigations

for these conditions.
— if the patient has a symptomatic illness an answer needs to be found

— ultrasound is mandatory where obstructive or malignant disease is a
possibility
— a screen for chronic asymptomatic enzyme elevations might include:-
• hepatitis B surface antigen

• hepatitis C antibodies
• glucose (diabetes)
• TSH (hyper- or hypothyroidism)
• lipids (hyperlipidaemia, fatty liver)
• iron, IBC, % saturation, ferritin (haemochromatosis)
• smooth muscle antibodies (autoimmune hepatitis)
• anti-mitochondrial antibodies (primary biliary cirrhosis)
• CK (skeletal muscle disease)
• immunoglobulins
– serial tests over weeks, months or years will define the time-course of the
underlying process. Is it:
• progressive (e.g. malignancy)?

• constant or oscillating about a mean (e.g. alcohol, chronic hepatitis)?
• returning to normal (e.g. resolving hepatitis or a drug effect when the
drug is stopped)?

Even after all this there may be no answer. Repeat tests at least yearly,or earlier if the
clinical picture changes. If the patient is clinically well, classify it as idiopathic
meanwhile. There seem to be quite a lot of these around.
Liver-kidney microsomal (LKM) auto-antibodies
specimen: serum
LKM antibodies are sometimes found in autoimmune hepatitis.
LKM antibodies
see Liver-kidney microsomal (LKM) auto-antibodies
Low density lipoproteins (LDL)

see Cholesterol
Lipoproteins
Low molecular weight heparin (LMWH)
see Heparin therapy

LSD (lysergic acid diethylamide)
specimen: random urine, no preservative

range: a result is reported positive if above a cut-off level of 0.5 ng/ml
Chlorpromazine ingestion will give a false positive result.
The lupus anticoagulant is an acquired coagulation inhibitor which is associated with

SLE and thromboembolic disorders. It is associated, but not synomynous with,
cardiolipin (qv) antibodies. In the context of thrombotic disease or recurrent
abortions, a positive lupus anticoagulant detected on two occasions at least three
months apart, with or without anticardiolipin antibodies, defines an antiphospholipid
antibody syndrome. Anticardiolipin antibodies are sometimes found transiently in
healthy people.
The APTT is prolonged in patients with LAC and fails to correct in the APTT 1+1
test.
The tests performed routinely as the LAC screen are KCT (Kaolin Clotting time),
APTT, PR, DRVVT (dilute Russell's viper venom time) and DTTA (dilute tissue
thromboplastin assay).
Luteinising hormone (LH)

Lyme disease
see Borrelia
Lymph node histology and cytology
Where malignant lymphoma is suspected, cytology imprints are useful in addition to

the formalin-fixed specimen.
• Lymph node imprints These may be made at the time of surgery by

bisecting the node and gently placing the cut surface for a few seconds on a
glass slide. Up to four slides should be imprinted. Pressure should not be
applied and the resulting imprints should be allowed to air-dry for 15
minutes.
After air drying, the imprint slides should have the patient's name written in
pencil on the frosted end and be placed in a cytology request envelope or
other envelope.
• Tissue specimen Half of the bisected node should be placed in 10%

formal saline while the remaining half should be placed in normal saline.
Lymphocyte antibodies
specimen: serum
Please give details of previous transfusions or transplant.

T-lymphocyte count in HIV
see CD4 T-lymphocytes
Lymphocytes
Lymphocytes play a central role in the immune response. The two main types of cell,
identified by cell marker studies are:-
T cells, primarily responsible for cell-mediated immunity

B cells, primarily responsible for humoral immunity (immunoglobulin production).
Lymphocytes are also classified by their CD (cluster designation) number. For

example,CD4 (qv) cells are T cells used as a marker for immune system damage in
HIV infections.
Lymphocytosis
An absolute lymphocytosis (>4.0 x 109/L) is typically found in two situations.
• viral infections, particularly infectious mononucleosis, acute viral hepatitis

and CMV infections.
• CLL (chronic lymphatic leukaemia), in which the proliferating lymphocytes
are monoclonal B cells with light chain restriction. CLL should always be
suspected when there is an unexplained progressive lymphocytosis at or
beyond middle age.
Lymphopenia

Causes include:
• viral illnesses
• pancytopenia due to any cause
• advanced Hodgkin's disease
• congestive heart failure
• steroid therapy
• AIDS
Variant lymphocytes
These cells, also called reactive lymphocytes, transformed lymphocytes or atypical

lymphocytes, are small lymphocytes which have undergone antigenic stimulation
(e.g. by a virus) that has transformed them into larger cells readily recognised in a
blood film. The commonest causes of variant lymphocytes are:
• infectious mononucleosis (EBV)

• acute viral hepatitis A, B or C
• CMV infections
• toxoplasmosis
Less common causes are:
– other viral infections

– immune disorders
– chronic non-viral infections

M-band
see Immunoglobulins, IgA, IgG, IgM: Monoclonal bands
Macroglobulinaemia
Multiple myeloma
Macrocytosis
Macrocytes are red cells with an MCV (mean cell volume) be divided into three
groups:
1. The megaloblastic macrocytic anaemias

These are distinguished by the presence of megaloblasts in the bone marrow
as precursors of the peripheral blood macrocytes. Megaloblastic anaemias
are due to B12 or folate deficiency. The macrocytes are oval in shape rather
than round. With well-established deficiency there are hypersegmented
neutrophils, neutropenia and thrombocytopenia.
see also Folate (folic acid), serum

Vitamin B12
2. Macrocytosis due to reticulocytosis

Reticulocytes are somewhat larger than older red cells. They are an
important feature of haemolytic and post-haemorrhagic anaemias.
3. Other
In this large group of normoblastic processes, the macrocytes are round. The
list includes:
- alcoholism

- liver disease
- hypothyroidism
- malignant infiltration
- cytotoxic drugs (especially hydroxyurea)
- myeloma
- aplastic anaemia
- myelodysplastic syndromes
- chronic obstructive airways disease
Macroglobulinaemia
IgM paraproteins are present in three conditions:
Benign IgM paraproteinaemia The commonest cause. The blood picture is normal,
the patient asymptomatic and IgM levels are static and usually <10g/L.
Waldenstrom's macroglobulinaemia A malignant process in which the IgM band is

heavy, the blood picture is abnormal and the marrow infiltrated with abnormal
plasmacytoid lymphocytes.
Malignant lymphoma or CLL (chronic lymphatic leukaemia) These should always be

searched for clinically, and on the blood film, when an IgM paraprotein is found.
see also Immunoglobulins, IgA, IgG, IgM
Magnesium (Mg)
specimen: serum

ref. range: 0.7–1.0 mmol/L
decreased by
• excessive loss of fluid and electrolytes, diarrhoea etc.

• inadequate intake : inadequate parenteral nutrition, low levels in diet and
water, (very uncommon) malabsorption
• drugs diuretics, aminoglycosides, digoxin, cytotoxics, laxative abuse
• alcoholism
• endocrine : hyperthyroidism, hyperparathyroidism, diabetic ketoacidosis,
SIADH
• hypokalaemia
• redistribution of Mg into cells, e.g. alkalosis, acidosis, severe illness
increased by
• renal insufficiency
• dehydration
• Addison's disease
• haemolysis
Severe magnesium deficiency affects neuromuscular function and the cardiac

conduction system. Clinically this can be manifested as tetany, convulsions, cardiac
arrest. Epidemiologically, magnesium deficiency in water supplies has been linked to
cardiac dysrhythmias and myocardial infarction.
Malabsorption
The aetiology of malabsorption can be considered under four headings:-

• mucosal defects – coeliac disease, the commonest cause
– Crohn's disease
– severe lactose intolerance
• pancreatic disease – cystic fibrosis
– chronic pancreatitis
• post-infectious – Giardia
malabsorption – tropical diarrhoea
• previous gastro-intestinal surgery on
stomach or small bowel
Malabsorption particularly involves iron, folic acid, vitamin B12, vitamin K, vitamin
D and fats.
Basic screen tests
• blood count, looking for macro- or microcytosis

• iron studies
• B12 and folate
• stool for Giardia and other pathogens
• INR
• gliadin and endomysial antibodies for coeliac disease
• vitamin D (25-OH-D) especially if ALP is raised
Follow-up tests
• jejunal biopsy is definitive in the diagnosis of coeliac disease

• 3-day faecal fat (qv) is used for documenting steatorrhoea and for assessing
response to therapy such as pancreatic enzyme medication

Malaria
Malaria is endemic in:–
• the Pacific west of Fiji. This includes Papua New Guinea, the Solomon
Islands, Indonesia. It does not include Fiji, Samoa, Tonga, New Caledonia,
Niue, Tahiti or Hawaii.
• SE Asia and India
• Africa and S. America
The diagnosis needs to be considered in any visitor to these areas with unexplained
fever, sweats, headache, malaise, anaemia, abnormal liver enzymes.
Diagnosis is established by detecting parasites in thick and thin films. Serial blood
specimens may be required. Leucopenia is usual but there can be leucocytosis.
Variant lymphocytes are occasionally seen. Malaria can be accompanied by anaemia
which may be caused by haemolysis, marrow depression or hypersplenism.
Of the four subtypes of Plasmodium, only two, P. falciparum and P. vivax, are
commonly identified in New Zealand.
P. falciparum causes severe, sometimes lethal, illness.
P. vivax is less severe but can relapse.
P. ovale and P. malariae are the two less commonly found subtypes.
Treatment should be discussed with those who have experience in treating malaria.

Malassezia furfur
A fungus causing tinea versicolor (pityriasis versicolor) which shows as brown scaly
patches on white skin or pale patches on dark skin. Microscopy of skin scrapings
shows grape-like clusters of cells. The organism is not readily cultivated. Diagnosis
is based on clinical features, direct microscopy and absence of fungal growth on
culture.
Treatment is with a topical imidazole, ciclopiroxolamine or terbinafine. Oral

terbinafine is not effective.
Malignant melanoma
Classification
1. In situ
– this is melanoma before it has invaded the dermis. It has 100% 5-year
survival.
2 Invasive radial growth phase
– this is early melanoma which has invaded the superficial dermis but
still has an excellent prognosis.
3 Invasive vertical growth phase
– this is melanoma which invades the dermis and may invade deeper
tissues. Prognosis is dependent mainly on tumour thickness which is
reported as both Clark level and Breslow thickness. Breslow thickness
is more important than Clark level. Few melanomas less than 0.76mm
in thickness give rise to metastases. Other prognostic factors of
importance are sex of the patient, anatomic site, mitotic rate,

histological evidence of regression and the presence of lymphocytes
amongst the melanoma cells.
Mantoux
see Tuberculin test (Mantoux test)
Maternal serum testing for foetal Down's

syndrome and neural tube defects (NTD)
specimen: serum
Maternal testing programmes require careful pre-test discussion with the mother to
explain diagnostic limitations and consideration of termination of an affected foetus.
The specimen should be collected at 15-16 weeks gestation (up to 20 weeks at latest)
and ideally an ultra-sound will be performed at about the same time to confirm
gestational age.
The combination of foetal age, maternal age and 2-4 maternal serum constituents are
entered into a computer programme which estimates foetal risk. Maternal serum tests
can include:
• AFP (alpha foetoprotein, elevated in NTD, decreased in Down's)

• free ß hCG
• free hCG
• total hCG
• unconjugated oestriol

• PAPPA (pregnancy associated plasma protein A – used only in 1st trimester
screening)
First trimester screening at 9-13 weeks has been shown to be as effective as 2nd
trimester screening in some centres and allows a decision to be made several weeks
earlier.
The result is presented as an estimated risk for discussion with the mother who may
elect to proceed with amniocentesis for possible Down's syndrome or ultra-sound for
NTD.
Maternal serum testing detects about 60% of Down's and 80% of NTD.
Down's has an overall incidence of 1:650 pregnancies rising quickly after 35 years to
1:100 at age 40. Two thirds of Down's occur at a maternal age below age 35.
MCH (mean cell Hb)
see Blood count
MCHC (mean cell Hb concentration)
see Blood count
MCTD (mixed connective tissue disease)
A connective tissue disease characterised by features of SLE, systemic sclerosis and

polymyositis.

Tests that will often be positive are:
ANA (95% positive) usually with a speckled pattern

RF (50%)
ENA, anti-RNP – a relatively specific feature
MCV (mean cell volume)
see Blood count

Macrocytosis
Microcytosis
MDS
see Myelodysplastic syndromes (MDS)
Mean platelet volume
see MPV (mean platelet volume)
Measles (morbilli, English measles, rubeola)

specimen: serum
The test can be for immune status (IgG antibody) or acute illness (IgM).

IgM antibodies appear about two days after the rash and peak about 2 weeks later.
IgM antibodies disappear after the acute illnesses. IgG antibodies persist for life.
Measles, German
see Rubella
Megaloblastic anaemia
see Macrocytosis
Folate (folic acid), serum
Vitamin B12
Melanin
specimen: urine, random
Melanomas sometimes produce enough melanin, or its colourless precursor

melanogen, for these to be detected in urine. The urine may be either pigmented or
colourless when first passed but darkens on exposure to air and sunlight.
MEN (multiple endocrine neoplasia)
These are familial clusters of endocrine adenomas or hyperplasias:

Type I parathyroid adenoma (95%)
pancreatic islet cell adenoma or hyperplasia (80%)
pituitary adenoma (50%)
Type II medullary thyroid carcinoma (95%)
phaeochromocytoma (50%)
parathyroid adenoma/hyperplasia (40%)
Meningitis
Patients with suspected meningitis belong in hospital but if you have a CSF which
might show infection, please notify us so that it can be handled urgently.
see Neisseria
Menopause
The term menopause refers to cessation of menses, a diagnosis that can be made only
in retrospect.
The interval between regular menstrual cycles and the menopause is the peri-
menopause, usually of about 2-3 years duration and variably associated with
symptoms of reduced oestrogen secretion.
Although fertility is greatly reduced during the peri-menopause, occasional ovulatory

cycles occur with FSH and LH at normal levels. During the post-menopausal period
the FSH is consistently elevated into the 20-120 IU/L range while the serum
oestradiol is <160 pmol/L.

The median age at menopause is around 50 years but in 10% of women it occurs
below age 46. In a few women the peri-menopause starts in their thirties and can be
prolonged over 3-8 years.
During HRT (hormone replacement therapy) it is not usual to monitor FSH or

oestradiol. The doses of oestrogen used do not suppress FSH and would not provide
contraception in a pre-menopausal woman.
Menstrual disorders
see Amenorrhoea
Mercury
specimen: 24-hr urine in special plastic container with HCl
ref. range: acceptable <0.25 µmol/day
toxic >0.5 µmol/day
Most of the public interest in mercury toxicity centres on amalgam in teeth but studies
have not shown harmful effects. After an exhaustive investigation, the U.S. Public
Health Service concluded there is no serious health risk. Urine mercury levels in
people with filled teeth are less than 5% of the stated acceptable limit.
Organic mercury compounds have been used as fungicides with wide-spread

poisoning in Iraq in 1971 when bread was accidentally made from seed wheat
preserved with methyl mercury. Mercury-contaminated waste in sea-water is passed
up the food chain to reach its most concentrated levels in large predatory fish such as
shark, tuna and sword-fish. The Miranda Bay disaster in Japan in 1955 was due to
industrial waste discharge being concentrated in edible fish.

Mercury as calomel in children's teething powders and in laxatives was found to be
the cause of acrodynia (pink disease) as late as the 1940's.
Mercury poisoning causes renal damage and neurotoxicity.
ME syndrome
see Chronic fatigue syndrome
Metanephrines
specimen: 24-hr urine collected into HCl.
A test formerly used in suspected phaeochromocytomas.
Methadone
Methaemalbumin
specimen: serum

The presence of methaemalbuminaemia is diagnostic of intravascular haemolysis.
Methaemoglobin
see Haemoglobin pigments
Methicillin resistant S. aureus
see MRSA (methicillin resistant Staphylococcus aureus)
Methyl bromide
Methyl bromide is used for fumigation. Agricultural officers who use these
chemicals are checked annually.
Mg
see Magnesium (Mg)

MGUS (monoclonal gammopathy of uncertain
significance)
Microalbumin

or early morning urine
or 24-hr urine
or timed urine – overnight or other timed period
ref. range:
ACR - albumin- 24-hour AER - albumin

creatine ratio output excretion rate
mg/mmol creat. mg/day µg/min
normal <2.5 <30 <20
microalbuminuria 2.5-25 30-300 20-200
macroalbuminuria >25 >300 >200
Microalbumin is a test currently used only in diabetics where it is a marker for early
nephropathy at a stage where it is reversible with good control of hypertension and
hyperglycaemia. In Type 2 diabetes, it is a powerful risk marker for vascular disease.
The term microalbumin refers to ordinary albumin (not a tiny albumin) found in urine
at concentrations below 300 mg/L, the cut-off point for conventional urine dipsticks.
Concentrations above this are called macroalbuminuria or persistent proteinuria or
clinical proteinuria and indicate irreversible nephropathy.

Because biological variance of urine microalbumin is high (± 50%) and because
transient increases in microalbumin can be due to urinary tract infection, exercise,
intercurrent illness etc, a first abnormal result should be followed by others over a 2-
12 month period and include an MSU looking for UTI. The possibility of non-
diabetic nephropathy also needs to be considered.
Presence of microalbuminuria above 70-100 mg/day in diabetes, particularly Type I,

is usually an indication for scrupulous control of even mild degrees of hypertension
using an ACE inhibitor as the agent of first choice in most patients.
Microcytosis
Microcytes are red cells with an MCV mean cell volume below 80. Causes are:
Iron deficiency The commonest cause. In severe cases the MCV can be in the 50-60
range.
Thalassaemia The MCV, which lies in the 63-80 range, is disproportionately low,
relative to the degree of anaemia and is not altered by iron therapy.
Anaemias of chronic disorders The MCV is usually normal but sometimes falls in the
75-80 range.
Sideroblastic anaemias The blood film is characteristically dimorphic.
Microfilaria
see Filariasis

Microglobulin
see Beta 2 microglobulin
Microhaematuria
infections): haematuria
Microsomal antibodies
see Thyroid antibodies
Microsporum canis
see Dermatophytes

Minimal bleeding disorders
Patients with a bleeding history but with a variable prolongation of the bleeding time
are often classified as having a "minimal bleeding disorder". The isolated long
bleeding time is presumed to be secondary to a platelet function defect. The same
condition is sometimes referred to as a long bleeding time syndrome. Patients with
suspected von Willebrand's disease can be placed in this group if they do not fulfill all
the criteria for von Willebrand's but have a bleeding syndrome characterised by
cutaneous bleeding.
see also von Willebrand's disease (vWD)
Mitochondrial antibodies
specimen: serum
Mitochondrial antibodies are seldom found in normal people. Their main use is in the
diagnosis of primary biliary cirrhosis - 90% of patients are positive. They are
sometimes present in chronic active hepatitis and occasionally in other autoimmune
disorders.
Mixed connective tissue disease
see MCTD (mixed connective tissue disease)
Molecular genetics - genetic studies

Increasing numbers of inherited diseases are now identifiable using genetic studies.
The local genetic laboratory should be consulted.
Tests are available or are being developed for:
Fragile X syndrome
Myotonic dystrophy
Prader Willi syndrome & Angelman syndrome
Huntington disease
Spinocerebellar ataxia
Familial adenomatous polyposis
Multiple Endocrine Neoplasia Type 2
Spinocerebellar muscular atrophy
Spinal muscular atrophy
Duchenne muscular dystrophy
Cystic fibrosis
Breast cancer testing
Adrenoleukodystrophy
Hereditary haemochromatosis
Monoclonal bands
Monoclonal gammopathy of unknown

significance (MGUS)

Monocytes
Causes of monocytosis include:
• subacute and chronic bacterial infections – TB, endocarditis, syphilis,

rickettsial infections
• protozoan infections – malaria
• non-infectious inflammatory disorders – vasculitis, collagen disorders, non-
infective granulomas such as sarcoidosis, ulcerative colitis, Crohn's disease
• chronic myelomonocytic and monocytic leukaemias
Mononucleosis
Moraxella catarrhalis
Previously known as Branhamella and Neisseria catarrhalis. Once considered to be

non-pathogenic but now a proven cause of upper respiratory tract infection. It is a
common cause of otitis media and sinusitis in children and is frequently recovered
from the sputum of patients with chronic obstructive airways disease. Most strains,
>95%, produce a beta-lactamase which confers resistance to penicillin and
amoxycillin. Most strains are susceptible to amoxycillin-clavulanate, erythromycin,
cotrimoxazole and tetracyclines.

Morbilli
see Measles (morbilli, English measles, rubeola)
Morphine
MPV (mean platelet volume)
specimen: blood (EDTA)

ref. range: 6.4 - 9.7 fl
The mean platelet volume is routinely measured by electronic blood counters.
Elevated MPV may be found in:
• increased platelet turnover : ITP, hypersplenism

• GPH (gestational proteinuria and hypertension) A sudden rise in MPV can
indicate onset or worsening of GPH
• DIC
• hyperthyroidism
• as an artefact in stored EDTA blood

MRSA (methicillin resistant Staphylococcus
aureus)
see Staphylococci
MSU (mid-stream urine)
infections)
Multiple endocrine neoplasia
see MEN (multiple endocrine neoplasia)
Multiple myeloma
see Immunoglobulins, IgA, IgG, IgM: malignant paraproteins
Mumps
specimen: serum
interpretation:

IgM IgG
current or recent infection + +
previously infected, now immune — +
never infected — —
The diagnosis of mumps is usually an easy one on clinical grounds without a blood
test.
Serum amylase levels rise sharply.
Muscle disease
see CK - MB and other isoenzymes
Myasthenia gravis
This is an autoimmune disorder in which neuromuscular transmission is reduced to a

varying extent by acetylcholine receptor autoantibodies (anti-ACLR) which are
detectable in about 80% of cases.
Diagnostically the Tensilon (edrophonium) test is used, an injection of

anticholinesterase which restores neuro-muscular function.
Mycobacteria

Mycobacterium avium
Mycobacterium avium complex (MAC) infection is seen predominantly, but not

exclusively, in patients with HIV infection. In that group it usually presents with
dramatic fever spikes, rigors, malaise, often hepatosplenomegaly, anaemia and
cholestatic liver function tests.
Otherwise normal children may also present occasionally with cervical adenopathy
due to MAC. It is sometimes recovered from sputum specimens sent for TB culture.
Although it can cause true respiratory tract disease it is often just a coloniser in an
abnormal respiratory tract. Evidence for it being a pathogen includes repeated
isolation, a positive smear result and CXR changes. Treatment regimens include
ethambutol and clarithromycin with or without rifabutin. Decisions on whether to
treat and with what, require specialist advice.
Mycology
see Dermatophytes
Candida
Malassezia furfur
Mycoplasma pneumoniae
specimen: paired sera

Mycoplasma is a bacterium not demonstrable with usual stains or growth media. It is
the commonest cause of atypical pneumonia, particularly in children and young
adults, and can spread as a low-grade epidemic. It responds well to erythromycin or
tetracycline but not to penicillin.
Diagnosis is by exclusion, by response to therapy, and by demonstrating a rising titre

in paired sera, the first collected as soon as possible in the illness, the second 2 weeks
later. Not infrequently the antibody titre has already plateaued by the time the first
specimen is collected.
see also Pneumonia
Myelodysplastic syndromes (MDS)
Also known as evolving leukaemia or preleukaemia.
These conditions are primary bone marrow disorders which usually behave as slowly
evolving bone marrow failure syndromes. Most often they present insidiously and in
an older population. A variety of peripheral blood findings may be noted including
pancytopenia, refractory anaemia, macrocytosis with anaemia, neutropenia and
thrombocytopenia. Diagnosis is by excluding vitamin deficiency (B12, folate) and
demonstrating dysplastic features in the bone marrow. Chromosome analysis and cell
marker studies may also be performed on the bone marrow. Management is usually
by supportive care but in selected patients more aggressive therapy maybe indicated.
Myelofibrosis
Myelofibrosis is a chronic myeloproliferative disorder characterised by bone marrow

fibrosis, extramedullary haemopoiesis, splenomegaly and a leucoerythroblastic blood

film. The condition may present as myelofibrosis at the outset or be the endstage of
another myeloproliferative disorder such as polycythaemia vera or essential
thrombocytopenia. Survival varies with a median of four years. Therapy includes
blood transfusions, cytoreductive therapy (usually hydroxyurea) for thrombocytosis,
and splenectomy in selected cases.
see also Myeloproliferative disorders (MPD)
Myeloma
see Multiple myeloma
Myeloproliferative disorders (MPD)
These conditions are characterised by excessive production of erythroid, myeloid and

megakaryocytic cell lines (panmyelosis). In many situations only one cell line may
predominate, e.g. platelet proliferation causing essential thrombocythaemia. In
polycythaemia rubra vera (primary polycythaemia), erythroid hyperplasia is the most
prominent feature with variable increases in myeloid cells (neutrophils) and platelets.
There may also be excessive proliferation of reticulin and fibroblasts within the bone
marrow giving rise to myelofibrosis. Acute myeloid leukaemia can develop as a
terminal event, usually untreatable, in any of the MPDs.
see also Myelofibrosis
Myocardial enzymes
see Myocardial markers for infarction (MI) and ischaemia

CK (creatine kinase) total
Troponin I (TnI) and Troponin T (TnT)
Myocardial markers for infarction (MI) and

ischaemia
specimen: serum
Because a patient with the typical clinical picture of an MI is admitted forthwith to a
coronary care unit, community laboratories do not often have to make the diagnosis.
There are, however, a few patientes who want to stay wherethey are or have had an
unreported episode of chest pain during the past week and in these tests will be
required.
The markers of myocardial damage are, in decreasing order of specificity, troponins I

& T, CK - MB, total CK, myoglobin, AST and LD.
AST and LD no longer have a useful role.
Myoglobin, though relatively nonspecific, is the earliest to rise and can appear within
the first 6 hours.
The remaining four typically start to rise 4-12 hours after infarction, reach a peak and
return to baseline over a period which differs between the four.
elevated for
CK - MB 2-3 days
total CK 2-3 days
troponin I 4-7 days
troponin T 4-10 days

Of these, the troponins are the most specific and usually, when elevated, indicate
infarction. Small elevations found in unstable angina may indicate ischaemic damage
and carry a poorer prognosis than a normal level.
Troponins do not rise earlier than CK but their longer period of elevation is useful,
e.g. when chest pain occurred several days earlier.
CK-MB is falling into disuse since the troponins arrived, though it may be useful in
plotting successive reinfarctions.
An elevated total CK is non-specific but if serial CK measurements follow the typical

time-course of an MI, they support the diagnosis. A small MI may occasionally be
suggested by CK changes that stay within reference range but show a typical peak
over 2-3 days.
Mycoplasma hominis
A cell-wall defective bacterium resident in the female genital tract in 5-10% of

healthy women. It is commonly found in bacterial vaginosis. M.hominis is a cause of
salpingitis as well as post-abortal or post-partum fever where it has been isolated
from the blood of 10% of women. The latter two conditions appear to be self-limiting
though antibiotic treatment may decrease the duration of fever. The agent of choice

is doxycycline. In contrast to Ureaplasma urealyticum and M. pneumoniae, M
hominis is resistant to erythromycin.
Myoglobin
specimen: 10ml random urine
Myoglobinuria occurs after skeletal muscle trauma or myocardial infarction (MI).

After major trauma, myoglobin imparts a coffee colour to urine but small amounts, as
in MI, are detectable only by chemical tests
see Myocardial markers for infarction (MI) and ischaemia
Mysoline (primidone)
specimen: serum
Mysoline is metabolised to phenobarbitone which is responsible for much of the

drug's anticonvulsant activity. Mysoline drug levels are monitored as
phenobarbitone, whose therapeutic range is 60-170 µmol/L.

Na+ (natrium)
NAP (neutrophil alkaline phosphatase) score

specimen: blood (EDTA or heparin)
ref. range: 20 - 80
Films must be made within a few hours of collecting the specimen. Although the test
is of low specificity it is of some value in the following conditions:
elevated NAP polycythaemia vera (NAP up to 300)

myelofibrosis
infections
other inflammatory conditions
pregnancy
reduced NAP chronic myeloid leukaemia

PNH
Neutrophil alkaline phosphatase activity is present in the specific granules of all

myeloid cells with highest activity in the youngest neutrophils.
Narcotic screen

Nasal swabs
After moistening the swab with transport medium, it is gently inserted up to 2cm into
the nostril, upwards and backwards, and rotated against the midline nasal septum.
Nasal swabs are taken when looking for carriers of Staph aureus, particularly MRSA.
Usually only one swab is collected per patient, inserted consecutively into each
nostril.
Nasopharyngeal swab
see Bordetella pertussis
National Testing Centre
ee Neonatal screening
Necator americanus
see Hookworm

Needlestick refers to the risk of hepatitis B (HBV) hepatitis C (HCV) or HIV

infection when a blood-contaminated needle or sharp object punctures the skin.
Investigations
Bloods from the exposed workers and the source specimen should be tested for
markers of infection and immunity.
• HIV antibody
• HBs antigen
• HBs antibody
• HCV antibody
The event must be fully documented and the exposed worker counselled and kept
informed.
Hepatitis B
• No action is required if
worker is antibody +ve – they are already immune
source is antigen –ve – the blood is not infective for HBV
worker is antigen +ve – they are already infected from some other
source, follow-up is as for any HBs ag
positive patient.
• Action is required if worker is antibody -ve and antigen -ve AND source is
antigen +ve or not known
– 400 IU of hepatitis B immune globulin within 3 days, preferably within 2

days
– start course of HBV vaccine

Hepatitis C
• no prophylaxis is available
• if the source is HCV -ve – no risk for HCV
• if source is +ve and worker -ve, the worker is at risk. Do follow-up tests at 3
and 6 months. If they seroconvert, refer for specialist follow-up.
• if worker is HCV +ve, they are already infected.
Refer for specialist follow-up.
HIV
• if source is HIV -ve – no risk for HIV

• if worker is HIV +ve – they are already infected
• if source is HIV +ve, refer immediately to an HIV specialist. PEP (post-
exposure prophylaxis) should ideally commence within 2 hours of exposure.
PEP reduces risk of infection by 80%. The agents in use in 2000 are
zidovudine, lamivudine and indinavir.
• if the source is unknown, e.g. a needle in a bag of discarded needles, the risk
should be estimated and discussed with the worker. If both agree risk is
negligible, no further action is required.
• If the risk is believed to be significant, immediately contact an HIV specialist

for a further opinion on whether PEP should be commenced.
What is the risk?
Of the three viruses, HBV is the most infective (30%) followed by HCV (3%), then
HIV (0.3%).
This means, for example, that if no PEP is used in a known HIV +ve needlestick, the
risk to the worker is 0.3%.

Prevention
All health care workers should be immunised against HBV.
Venepuncturists and nurses giving injections should be trained in safe practice.
Needles and other blood-contaminated sharps must be disposed of into puncture-

proof containers.
Neisseria
These gram-negative diplococci are typically found inside neutrophils in direct

smears from lesions. The two main pathogens are N. gonorrhoeae and N.
meningitidis.
N. catarrhalis, a member of the normal flora of the throat, was known as

Branhamella catarrhalis and is now known as Moraxella catarrhalis (qv). It is a
recognised respiratory tract pathogen.
A. Neisseria gonorrhoeae
specimens: swabs must be placed in transport medium immediately after

collection. Store at room temperature, not in the fridge, and
transport to the laboratory as soon as possible – they will survive
24-hours in transport medium. In general, Neisseria are sensitive
to drying, sunlight, heat, cold and many disinfectants.
The main infections are:
Male STD Urethritis and sometimes epididymitis. The organism can also
sometimes be recovered from the rectum and throat.

Female STD Endocervicitis is the initial infection with variable spread upwards
to fallopian tubes and downwards to urethra and perianal skin. As with males,
gonococci also grow in the throat and rectum.
Neonatal conjunctivitis Acquired during birth from an infected mother.
Gonococcal arthritis A suppurative arthritis. Synovial fluid aspirate establishes

the diagnosis.
Treatment
Until recently 96% of gonococci in New Zealand have been susceptible to

penicillin but in 1991 there was a sudden increase in penicillin-resistant strains.
Penicillin resistance resistance now runs at approximately 15%. The most
commonly used treatment for uncomplicated gonorrhoea is ciprofloxacin 500
mg as a single dose. Less than 2% of New Zealand isolates are resistant to
ciprofloxacin and at the time of writing all resistant strains have been acquired
outside the country. Ceftriaxone 125 mg intramuscularly as a single dose is an
alternative treatment.
As with any STD, treatment of partners is essential. Concomitant infection with

Chlamydia is common and empirical treatment for this is recommended, e.g. 1g
azithromycin stat.
B. Neisseria meningitidis
The causative organism of meningococcal meningitis and septicaemia which can

occur sporadically or in epidemics. Travellers to countries where epidemics
occur, e.g. Nepal, should be vaccinated according to recommendations current at
the time of travel. There are three main sub-groups, A, B and C. Most
infections in New Zealand are group B for which there is currently no
commercially available vaccine.
Suspected meningococcal meningitis is a medical emergency and in the

community situation, parenteral antibiotics, e.g. IM amoxycillin or penicillin,
should be given by the diagnosing doctor before sending the patient to hospital.

Neonatal group tests on cord blood
specimen (cord blood): · blood (EDTA)

· serum
tests: · blood count

· blood group
· direct Coombs
· bilirubin
These tests are usually done only when the infant is at risk for haemolytic disease
(qv), not as a routine.
Neonatal jaundice
see Jaundice
Neonatal reference ranges
The drama of transition from an intrauterine to independent existence is reflected in

laboratory values which change rapidly during the first week of life and to a lesser
extent in the weeks that follow. Where an unexpected result is obtained, it should be
checked against the appropriate neonatal reference range. An extreme example is
TSH which surges from a mean level of 9 units at birth to an average peak of 85 half
an hour later before falling back to near adult levels at 5 days.
Neonatal screening

specimen: dried blood spots on "Guthrie" card –allow to dry before placing in
plastic bag.
Tests are performed at the National Testing Laboratory, National Women's Hospital,
phone (09) 6310 705. All infants born in New Zealand, about 60,000/year, are tested
for the following:
Condition Test Incidence
cystic fibrosis trypsin 1 : 3,000
hypothyroidism TSH 1 : 5,000
phenylketonuria phenyl alanine 1 : 15,000
galactosaemia galactose 1 : 50,000
biotinidase deficiency biotinidase 1 : 60,000
congenital adrenal hyperplasia 17-OH progesterone 1 : 225,000
maple syrup urine disease leucine 1 : 250,000
The infant must have been feeding on milk for at least 2 days before specimen
collection, the usual age being 5 days. Cards collected up to the age of 1 month give
valid results or up to 2 months for cystic fibrosis.
Blood spot cards can be tested by the lab up to 1 month after collection. The NTL
completes the tests within 1 week of arrival at the lab. At present they notify positive
results only.
A single screening test giving an apparently normal result can never exclude the
above conditions. If a neonate or infant is unwell or not developing normally,
appropriate tests should be repeated or added.
Netilmicin
see Aminoglycoside, serum levels

Neuroblastoma
see Catecholamines
Neutrophil alkaline phosphatase
see NAP (neutrophil alkaline phosphatase) score
Neutrophils (polymorphs)
Neutrophil counts are expressed and interpreted in terms of the absolute count rather
than % of total white cell count.
A. Neutropenia
The usual adult reference range is 2.2 - 7.5 x 109/L.
Mild neutropenia, 1.5 - 2.2 x 109/L is a common finding, often suspected to be caused by
an immune mediated mechanism (immune neutropenia) when drugs are not implicated.
Below 0.5 x 109/L there is an increase in spontaneous infection with a dramatically

increased risk below 0.2 x 109/L (= agranulocytosis).
Common causes of neutropenia:
- viral infection, sometimes with an associated thrombocytopenia

- some bacterial infections, e.g. typhoid

- overwhelming sepsis, often with toxic granulation of neutrophils and a shift to
the left.
- B12 or folate deficiency
- aplastic anaemias
- malignancy – haematological malignancy or metastatic deposits in bone
marrow.
- immune-mediated – post viral, Felty's syndrome, SLE
- hypertension
- thyrotoxicosis
- chronic benign neutropenia, including cyclical neutropenia
• drugs those more commonly implicated are:
– phenylbutazone, indomethacin
– chlorpromazine, promazine, other phenothiazines
– carbamazepine
– propylthiouracil, carbimazole
– sulphonamides, cotrimoxazole
– dapsone
– thiazides
– captopril
Cyclical neutropenia
Characterised by periodic fluctuations in the neutrophil count with the nadir occurring
usuallyat three weekly intervals. In the most severe cases the neutropenia may be
extremely low, < 0.1x10.9/L , with infective complications, malaise and fever.
Hospital admission may be required as occasionally these may be life-threatening
events. In some patients, due to the severity of the neutropenic episodes and the
infective complications, growth factor support with granulocyte colony stimulating
factor (G-CSF) is required.
B. Neutrophilia
A neutrophil count >7.5 x 109/L.

Minor degrees of neutrophilia are a common response to almost any disease process.
In more serious disorders, neutrophil precursors may be present, the sequence from

cell division to maturity being myeloblast, myelocyte, meta-myelocyte, band
neutrophil, segmented neutrophil. An increase in band neutrophils, meta-myelocytes
and eventually myelocytes, i.e. a "shift to the left", should prompt a search for serious
disease.
Causes of neutrophilia
- Bacterial infection – there may be a shift to the left and with more severe
infections there may be toxic granulation and eventually neutropenia as the
marrow is overwhelmed.
At the other end of the scale is the leukaemoid reaction, a massive outpouring
of cells in response to infection with counts up to 80 x 109/L and a striking
shift to the left.
- Tissue injury – due to infarction, burns, surgery, trauma and other processes
causing necrosis.
- Other inflammatory disorders – connective tissue disorders, etc.
- Malignancy
- Drugs – steroids, epinephrine, heparin
- Other – haemorrhage, stress, metabolic disorder
Non-gonococcal urethritis (NGU)
Chlamydia is the main pathogen but Trichomonas vaginalis can also cause symptoms.
In about half of NGU's an organism is not isolated.
Treatment is doxycycline, 100mg 12-hourly for 7-10 days.
see also Chlamydia trachomatis

Non-thyroidal illness
see Thyroid disease — diagnosis and monitoring, paragraph D
Noradrenaline
see Catecholamines
Normal range
see Reference ranges and the concept of normality
Nose
see Nasal swabs
Nosocomial infection
An infection acquired in hospital, e.g. some MRSA or pseudomonas infections.

NSAIDs and renal toxicity.
NSAIDs can cause acute renal insufficiency, usually reversible, due to inhibition of
vasodilatory prostaglandins.
Susceptible patients are the elderly and those with pre-existing renal disease,
cardiovascular disease, an oedematous state or concomitant use of diuretics or aspirin.
These should be monitored 1-3 weeks after commencing NSAIDs and then 3-monthly
for long-term use, looking for:
• rising s. creatinine
• hyperkalaemia
• proteinuria
N-telopeptide
specimen: second morning spot urine

Do not add preservative.
ref. range: female 14-74 BCE/mmol creatinine

male 3-51 BCE/mmol creatinine
(BCE = bone collagen equivalent)
Excretion of N-telopeptide varies through the day being highest at night. In an
attempt to improve standardisation, a second morning urine collect (urine formed
after rising) is usual. A change of 50% is needed to show benefit of treatment.
The female range is for pre-menopausal women. After the menopause, developing
osteoporosis can double N-telopeptide levels.
N-telopeptide is a marker for bone turnover in conditions such as Paget's disease

where there is increased bone resorption. Reduction of N-telopeptide is a measure of
therapeutic effect of biphosphonates or other medication.

see also Bone turnover markers

O
Occult blood
see Faeces for occult blood
Oestradiol (E2)
specimen: serum
ref. range:
pmol/L
adult female during cycles —
see diagram under FSH
early follicular <300
ovulatory surge 500-2000
luteal phase 150-1400
post-menopausal <160
adult male <160
• oral contraceptives are associated with very low levels

• pregnancy is associated with very high levels

The assay is specific for oestradiol. Other oestrogens such as ethinyl oestradiol or
conjugated equine oestrogens (premarin) are not detected.
Oestradiol is the major endogenous oestrogen in ovulating women. It rises to a pre-

ovulatory peak mid-cycle, falls and then returns to a luteal phase plateau before
falling again prior to menstruation. Indications for estimating oestradiol are strictly
limited:
• during artificial induction of ovulation

• investigation of feminising states including precocious puberty, gynaecomastia
• investigation of possible pituitary-gonadal deficiency states in women.
It is not used during the early investigation of infertility, for diagnosing menopause,
for monitoring HRT (hormone replacement therapy), or for investigating irregular
menstruation.
see also FSH (follicle stimulating hormone) and LH (luteinising hormone)/LH
Oestriol (E3)
Serum or urine oestriols were once used for 3rd trimester foeto-placental monitoring.
They have not been replaced routinely by any other biochemical test.
Unconjugated serum oestriol is used when testing for Down's syndrome during the
first or second trimester.
(NTD)

Oestrogen receptors in breast tissue
see Breast tumour hormone receptors
Oestrogens
- Oestradiol (E2) (qv), is the major endogenous oestrogen during child-bearing
years
- Oestriol (E3), is the most abundant oestrogen during pregnancy
- Oestrone (E1), is the major circulating oestrogen after the menopause
Oestrogens are now measured in serum, not urine.
OH
see 17-hydroxy progesterone (17-OHP)
OGTT
see GTT (O = oral)
Onychocola canadensis

This is an uncommon cause of onychomycosis (qv), usually occurring in elderly
women and frequently involving all nails. There are reports of it causing skin
infection.
Treatment: itraconazole or terbinafine.
Oral contraceptives
These can affect a wide range of laboratory tests:
clotting factors increase

FSH suppressed
glucose tolerance may decrease a little
haematinics B12 and folate decrease, transferrin & IBC increase
immunological tests false +ve ANA and rheumatoid factor
LH suppressed
lipids triglyceride and HDL increase, LDL cholesterol can
show minor decrease
liver functions bilirubin, AST, ALT, GGT,ALP can all increase
oestradiol suppressed
progesterone suppressed
prolactin can be elevated up to 2x
proteins carrier globulins for cortisol, T4, iron and copper all
increase; albumin and bound calcium decrease; alpha-1
antitrypsin and alpha-2 macroglobulin increase

Organophosphate toxicity
see Cholinesterase
Osmolality
specimen: serum plain tube

urine early morning, or random, or timed collect, or 24-hr urine.
Preservative is not required.
ref. ranges: serum 280-300 mosmol/kg water

urine 50-1200 mosmol/kg water
Urine osmolality, which is under the control of pituitary ADH, varies over a wide
range to ensure that alterations in fluid intake have little effect on the tightly
controlled serum osmolality. Urine osmolality is typically highest on rising in the
morning because of the absence of fluid intake during sleep. An osmolality >600
(especially >800) makes diabetes insipidus unlikely.
An approximate serum osmolality is given by the formula:

+
osmolality = 2 x Na + urea + glucose
The normal physiological response to hyponatraemia is the secretion of a dilute urine
with osmolality <100. A higher osmolality suggests SIADH.
Osmotic fragility of red cells

specimen: blood (heparin)
ref. ranges:

fresh blood incubated blood
initial haemolysis 0.50-0.45 0.70-0.55
complete haemolysis 0.40-0.20 0.40-0.20
This is a test for spherocytes which are more sensitive to lysis in hypotonic saline
solutions than are normal red cells. The figures refer to strength of saline solutions at
which initial and complete haemolysis occur, 0.9% being isotonic. Sensitivity is
increased by pre-incubation of red cells for 24 hours at 37°C.
The test is useful in the diagnosis of hereditary spherocytosis.
Osteoporosis/Osteomalacia
Osteoporosis, a reduction in the quantity of normally mineralised bone, is seen

mainly in post-menopausal women who in old age can have problems with fractures,
particularly of neck of femur, wrists and vertebral bodies.
In osteomalacia, bone shows defective mineralisation. Vitamin D deficiency in

childhood (rarely) or old age are the usual causes along with renal osteodystrophy in
chronic kidney disease.
In old age, osteoporosis and Vitamin D deficiency can act together to accelerate loss
of bone density.
Laboratory tests in the common metabolic bone diseases are:
S. calcium S. phosphate S. ALP

osteoporosis N N N
osteomalacia ↓ or N ↓ ↑
Paget's disease N N ↑↑↑
renal osteodystrophy ↓ N
or ↑ ↑
1° hyperparathyroidism ↑ N or ↓ N or ↑
tumour metastases N or ↑ ↓ N or ↑ ↑

Because multiple myeloma can cause generalised oseteoporosis as well as discrete
lytic lesions, protein EPP should be performed.
Bone turnover markers (qv) give a measure of disease activity.
Osteoporosis/osteomalacia and their associated fracture risks in post-menopausal

women, can be actively prevented using physical activity, HRT, calcium and vitamin
D supplements, and biphosphonates.
Otitis
see Ear swabs & infections
Ova in faeces
see Faeces for ova and parasites
Ovarian function
see FSH (follicle stimulating hormone) and LH (luteinising hormone) for ovarian
failure and menopause
Progesterone for detection of ovulation
Oestradiol (E2) for oestrogenic activity

Overdose screen
see Drug screen – overdose
Ovulation
see Progesterone
Oxalate
specimen: 24hr-urine collection with HCl preservative
ref. ranges : female 0.04-0.31 mmol/24hr

male 0.10-0.41 mmol/24hr
Hyperoxaluria, with or without formation of oxalate stones, can be due to fat

malabsorption, dietary oxalate excess, Vitamin C overdose, hereditary hyperoxaluria
(rare) or industrial toxicity.
About 10% of urine oxalate normally comes from the diet but this fraction increases
with excessive intake of oxalate rich foods including spinach, rhubarb, strawberries,
tomatoes, prunes and tea.

P4
see Progesterone
Paget’s disease of bone
Asymptomatic Paget’s is a common cause of elevated ALP (150-500 units or higher)

in the elderly and the ALP level is an indication of disease activity and response to
treatment. 24-hour urine N-telopeptide is another indicator used in monitoring
treatment.
A bone scan is a sensitive method for identifying foci of Paget's disease.
see also Alkaline phosphatase (ALP)
Pancreatitis
see Amylase, serum
Pancytopenia
A reduction in all three cellular elements in blood i.e. anaemia, leucopenia
(neutropenia) and thrombocytopenia. An unexplained pancytopenia is always an
indication for a bone marrow biopsy.
Causes include:
• haematological disorders requiring bone marrow examination – aplastic

anaemia, leukaemias, myeloma, myelodysplastic disorders, metastatic tumour

• drug effects
• B12 or folate deficiency
• hypersplenism
• SLE, PNH
• overwhelming infection, HIV
see Neutrophils (polymorphs),

Thrombocytopenia, and individual disorders for more detail.
PAP
see Cervical cytology (PAP smear)
Acid phosphatase, prostatic (PAP) (prostatic acid phosphatase)
Paracetamol (acetaminophen)
specimen: serum, for quantitative measurement and assessment of risk
urine, a qualitative test where ingestion is suspected but not known
About 4 hours after an overdose of paracetamol, the serum level reaches its peak and
then declines. Charting the serum level against time elapsed since ingestion gives a
measure of risk of liver toxicity and determines whether antidote should be given. At
4 hours, a paracetamol level above about 1mmol/L is an indication for giving N-
acetylcysteine.
Paraprotein
Paraquat
specimen: • random urine for screen test

• plasma (heparin), for quantitation
- must be centrifuged immediately
Horticultural workers are not monitored on a routine basis.

After suicidal ingestion of large amounts of paraquat, the plasma level in relation to
time of ingestion will give an estimate whether the outcome is likely to be fatal.
Paraquat will be undetectable within a week of even a large intentional overdose.
Parasites in faeces
see Faeces for ova and parasites
Parathyroid hormone (PTH)

ref. range: 1-5 pmol/L
Elevations of PTH with elevated calcium:-
• primary hyperparathyroidism due to solitary adenoma (85%) or hyperplasia

(15%) is the commonest cause. Management of lesser degrees of abnormality
is usually conservative, surgery being required only when the hypercalcaemia
is causing symptoms or tissue damage.
see also Calcium (total)

MEN
• lithium therapy

• familial benign hypocalciuric hypercalcaemia is a rare autosomal dominant
disorder in which excessive renal calcium reabsorption is associated with
relatively small elevations in PTH. Parathyroid surgery is contraindicated.
Elevations of PTH with normal or low calcium
• renal failure — 2° hyperparathyroidism
• vitamin D deficiency
Parietal cell antibodies

specimen: serum
About 90% of patients with pernicious anaemia have parietal cell antibodies. These
can be found in other organ-specific autoimmune disorders such as thyroiditis and in
10-15% of apparently healthy elderly people.
see also Pernicious anaemia
Paroxysmal nocturnal haemoglobinuria (PNH)

PNH is a rare, acquired haematological disorder usually presenting in adult life.
Its features include:
• intravascular haemolysis
• venous thrombosis
• marrow hypoplasia
PNH is due to an acquired mutation giving rise to a clone of abnormal stem cells
affecting erythrocytes, leucocytes and platelets.

The haemolysis, though chronic, is intermittent, occasionally paroxysmal with severe
anaemia. It is mediated by complement and is made worse by reduction in blood pH
as occurs at night, during exercise, or in vitro as in Ham's test which is used in
diagnosis.
The non-specific laboratory abnormalities include:
• anaemia, neutropenia, thrombocytopenia

• reduced haptoglobins, reticulocytosis
• haemoglobinuria, haemosiderinuria
More specific tests for PNH are:
• absence of CD59 (qv) activity on the erythrocyte cell surface

• Ham's (qv) acidified serum lysis test
• sucrose lysis test
Pasteurella multocida
A gram-negative bacillus that is isolated from skin lesions. The organism is a
common inhabitant in the mouths of cats and dogs and infection is frequently
associated with animal bites or scratches. Regional lymphadenopathy, chills and
fever can result. It is susceptible to penicillin and amoxycillin. Wound debridement
may also be necessary.
Paternity testing
specimen: whole blood (EDTA) from:
- baby (requires mother's permission)

- father
- mother – not essential but desirable

Blood is preferably stored at 4ºC but room temperature for a day or two is acceptable.
The method involves DNA identification using white cells as the source of nuclear
material. Where the result has legal implications, a recognised collection protocol
must be observed.
Paul Bunnell test for heterophile antibodies

seeInfectious mononucleosis
PBG (porphobilinogen)
see Porphyrias
pCO2
PCOS
see Polycystic ovary syndrome (PCOS)
PCR
Polymerase chain reaction

A molecular method to amplify genetic material. The amplified sequence can then be
detected by a variety of methods. Often used to detect small numbers of organisms in
a specimen, e.g. Toxoplasma gondii in amniotic fluid or M. tuberculosis in CSF.
PCR is also used to amplify sequences for human gene studies, e.g. paternity testing
and some inherited genetic disorders.
PCT (prothrombin clotting time)
see PR (prothrombin ratio)

PCV (packed cell volume)
see Blood count
Penicillin allergy
When a patient says they are allergic to penicillin, the diagnosis can be confirmed by
skin tests conducted in a specialist setting and desensitisation achieved if penicillin
therapy is regarded as essential.
It is more usual to accept the patient's diagnosis and avoid penicillin, particularly
injections which cause more severe reactions than oral forms.
Penicillin allergic status can change over time, from positive to negative and back
again and for this reason even a negative skin test in a person who claims sensitivity,
cannot be relied on to stay negative.

Approximately 10% of penicillin-allergic patients will be allergic to cephalosporins
also. It is prudent to avoid cephalosporins in patients with immediate-type reactions
to penicillin and vice versa.
Percentage hypochromia
ref. range: <3%
The percentage of hypochromic red cells is a useful guide to iron status in patients
with chronic renal failure who are being treated with recombinant erythropoietin
(EPO).
Peripheral neuropathy
Pathologies to consider include:

– diabetes
– viral infection: Guillain-Barré
– alcoholism
– connective tissue disorders
– paraproteinaemias
– toxins: lead
– drugs: amiodarone, phenytoin, nitrofurantoin and others

Pernicious anaemia
An autoimmune disease, rare before the age of 40, causing destruction of gastric
parietal cells and intrinsic factor and hence reduced absorption of Vitamin B12.
Laboratory features include some or all of the following:
• anaemia, thrombocytopenia, neutropenia

• serum vitamin B12 reduced
• blood film features – oval (not round) macrocytes
– hypersegmented neutrophils
• macrocytosis – MCV up to 120
• intrinsic factor and/or parietal cell antibodies – 90% are positive for one or both of
these
• folate – serum levels normal or increased
– red cell levels normal or reduced
• bone marrow – megaloblastic change
• prominent increase in reticulocytes 10 days after commencing therapy with B12
• Schilling's test positive – not an essential test if other typical features are present
Pertussis
pH, blood
pH, urine
A non-contributory test except in renal tubular acidosis where a useful screen is to
collect a first morning urine in a filled, well-sealed container which should be
delivered to the laboratory without delay. A urine pH below 6.0 makes renal tubular
acidosis very unlikely.

Normal urine is acid but, on standing, contaminating organisms convert urea to
ammonia and the urine turns alkaline, a process which accelerates haemolysis of red
cells if present.
Phaeochromocytoma
see Catecholamines
Phenobarbitone
specimen: serum
therapeutic range: 65-170 µmol/L trough level
The half-life of phenobarbitone is 4 days.

see also Anticonvulsants
Phenylalanine
specimen: blood spots on Guthrie card
screening for PKU – see Neonatal screening
monitoring PKU – quantitative phenylalanine levels are also done on blood spot
specimens
Phenylketonuria (PKU)
see Phenylalanine

Phenytoin
see Dilantin (phenytoin)
Phosphatases
see Acid phosphatase, prostatic (PAP)

Alkaline phosphatase (ALP)
Phosphate
specimen: serum
ref. range:
Age (yrs) mmol/L
0-1 1.4-2.4
2-10 1.0-2.0
>10 0.7-1.5
Phosphate, also called inorganic phosphorus, is used diagnostically in two main

situations.
• hypercalcaemia – levels are reduced or low normal in primary

hyperparathyroidism and vitamin D deficiency, but are usually increased or
normal in other hypercalcaemias.
• renal failure – phosphate is elevated.
A wide range of other disorders cause hyper- or hypo phosphataemia but diagnostic
value is limited.

Phosphate levels can be falsely raised if the specimen is haemolysed.
Phospholipid antibodies
see Anticardiolipin
Pinworm
see Enterobius vermicularis (pinworm) vermicularis
Pituitary hormones
see Hypopituitarism
PKU (phenylketonuria)
see Phenylalanine
Plain tubes for blood collects
Plasma renin activity

Plasma volume
see Blood volume
Platelet aggregation
Performed in selected patients presenting with platelet function defects suspected on

the basis of a prolonged bleeding time or a clinical history not otherwise explained.
Platelet function abnormalities such as release type defects or Glanzmann's
thrombasthenia are diagnosed in this way.
Platelet antibodies
specimen: serum
blood (EDTA)
Platelet antibody tests are most often performed in the investigation of an isolated
thrombocytopenia. Both platelet-associated (PAA) and serum platelet (SPA)
antibodies are measured. A positive result for either test supports an immune
aetiology though immune thrombocytopenia may be present in patients with negative
PAA and SPA.
Platelet count
ref. range:

9
Age (yrs) x 10 /L
0-12 150-
>12 150-
>12 150-
reduced platelets – see Thrombocytopenia
raised platelets – see Thrombocytosis

mean platelet volume – see MPV (mean platelet volume)
Platelet dysfunction
This is suspected in patients presenting with a bleeding history and a normal platelet
count, normal coagulation factor screen but prolonged bleeding time. The term
“minimal bleeding disorder” (qv) is sometimes used. Occasionally, platelet
aggregation and other studies are used where further investigation is required.
Platelet function disorders can be:
congenital rare defects of aggregation, adhesion or the platelet release reaction
acquired drug effects (especially ASA; NSAIDs)

haematological malignancies (especially MDS)
myeloma, macroglobinaemia or other paraproteinaemia uraemia
immune thrombocytopenia (ITP)
myeloproliferative disorders

Plesiomonas
A gram-negative bacillus related to Aeromonas (qv) and occasionally isolated from
patients with diarrhoea. Although there are no data on the benefits of treating
Plesiomonas-associated diarrhoea there may be benefits for those with severe disease.
Options include cotrimoxazole or norfloxacin for 3 days.
Pleural fluid
see Aspirated fluids, synovial, pleural, ascitic etc
Pneumococcus
see Streptococci
Pneumonia
Pneumocystis carinii
Pneumocystis carinii was considered to be a protozoan parasite but genetic studies

suggest it is most likely related to the fungi.
It causes an acute to sub-acute, often fatal, pulmonary disease in the

immunocompromised. It is a major disease problem in those infected with HIV.
Diagnosis is by detecting organisms in bronchial brushings, open lung biopsy and

lung aspirates. A variety of stains may be used to show the organism.

Treatment is high dose cotrimoxazole and should be discussed with those who have
experience in treating this condition.
Pneumonia
At the time of clinical diagnosis an attempt, often unsuccessful, should be made to
obtain a sputum sample. Culture may show Strep. pneumoniae in classical lobar
pneumonia; or Haemophilus influenzae and/or S. pneumoniae in pneumonia
associated with chronic bronchitis.
Antibiotic therapy is usually started immediately on an empirical basis. A sputum

specimen obtained after antibiotic treatment has started, will not be useful.
% susceptible
amox tetra cotr amox-clav eryth pen
H. influenzae 81 99 91 100 0¹ —
S. pneumoniae —² 71 67 —² 76 68
1. The newer macrolides roxithromycin and to a greater extent

clarithromycin have activity against H. influenzae.
2. While pneumococci with reduced susceptibility to penicillin
are also less susceptible to other B-lactam agents they usually
respond to amoxycillin treatment for lung infections. Recent
New Zealand data indicates that approximately 93% of
pneumococci are susceptible to amoxycillin.
Atypical pneumonias These are almost as common as the classical bacterial

pneumonias.
• Mycoplasma pneumoniae (qv) is the commonest particularly in children and

young adults.
• Psittacosis (qv) affects those who have occupational contacts with birds,
including poultry.
• Legionnaire’s disease – see Legionella
• Chlamydia pneumoniae causes approximately 3% of community acquired
pneumonia in New Zealand.

• Viruses, e.g. influenza A, adenovirus, respiratory syncytial virus, cause
approximately 10% of community-acquired pneumonia in New Zealand.
Treatment: With the exception of viruses, the agents causing atypical pneumonia are
susceptible to erythromycin, though doxycycline is the preferred treatment for
psittacosis.
PNH
see Paroxysmal nocturnal haemoglobinuria (PNH)
Polychromasia
Bluish staining of some red cells in a blood film suggesting an increase in
reticulocytes (qv).
Polycose screen test for gestational diabetes

(GDM)
see Gestational diabetes mellitus (GDM)

This common endocrine disorder is characterised variably by:
• amenorrhoea or oligomenorrhoea
• infertility / anovulation with oestrogen present
• hirsutism, acne, alopecia

• mildly elevated testosterone — produced by the ovaries
• increased extra-ovarian production of oestrogen
• LH elevated, FSH depressed, LH/FSH ratio >2
• prolactin elevated
• obesity
• ovaries enlarged with multiple cysts visible on ultrasound
• insulin elevated due to insulin resistance
• family history of PCOS
Not all these features are necessarily present. The combination of androgen excess
and obesity leads to increased extra-ovarian oestrogen production which increases LH
and decreases FSH.
Treatment includes weight loss, exercise, oral contraceptives, anti-oestrogens such as

clomiphene, and local treatments, e.g. electrolysis, for hirsutism. Anti-oestrogens
enhance FSH secretion and may restore normal ovulatory cycles.
see also Hirsutism/virilism
Polycythaemia
Is defined as a haemoglobin concentration above the reference range for age and sex.
The approach to diagnosis is to distinguish between polycythaemias due to an

increased red cell mass (primary and secondary polycythaemias) and those due to a
reduced plasma volume (relative polycythaemias).
A. Polycythaemia rubra vera (primary erythrocytosis)
A myeloproliferative disorder usually occurring in middle or older age in which red

cells, and often white cells and platelets, are increased.
Laboratory features

• Red cells – Hb and PCV are increased
The red cell mass is elevated (usually >36mls/kg in males) but the plasma
volume is normal. By convention the packed cell volume is used to monitor
the treatment response.
• White cells – there is an increase in neutrophils often with a shift to the left
with band neutrophils, metamyelocytes and occasionally myelocytes.
• Platelets – 400 - 800 x 109/L in most cases with counts over 1000 x 109/L
occasionally. Giant forms may be present.
• NAP score – increased in 70%.
B. Secondary polycythaemia
Increase in the red cell mass due to tissue hypoxia caused by:
• chronic respiratory disease
• congenital heart disease
• high altitude
Secondary polycythaemia also occurs in some renal disorders, particularly tumours,

where there is increased erythropoietin production.
C. Relative or “stress” polycythaemia
The commonest form of polycythaemia, the elevated haemoglobin being secondary to

a depletion in the plasma volume. By definition the red cell mass (volume) is normal.
Clinical associations are:
• smoking
• alcohol
• stress
• dehydration
• diuretics

This condition is diagnosed by demonstrating a normal red cell mass and a reduced
plasma volume.
Polydipsia/polyuria
Urinary frequency due to UTI (urinary tract infection) or lower urinary tract
problems, can be distinguished from polyuria by collecting a 24-hr specimen to
document urine volume. Causes of polyuria include:
• diabetes mellitus (random glucose levels usually above 15 when

polydipsia/polyuria are present).
• hypercalcaemia
• hypokalaemia
• lithium therapy
• psychogenic polydipsia (compulsive water drinking) – not uncommon
• diabetes insipidus
To differentiate between the latter two, see

Diabetes insipidus.
Polymerase chain reaction
see PCR
Polymorphonuclear leucocytes (polymorphs)
Polymyalgia rheumatica
A relatively common disorder, particularly in the elderly, characterised by distressing

shoulder and pelvic girdle pain originating from muscles rather than joints. It is often
associated with temporal arteritis.
ESR and CRP are almost invariably (but not always) raised.
Response to steroids is dramatic.
Porphyrias
specimens: all must be protected from light and delivered to the lab as soon as
possible.

urine: – during an attack of suspected acute porphyria, collect a
random urine for PBG and deliver to the laboratory
immediately.
– 24-hour urine, in dark bottle with sodium carbonate as

preservative.
faeces : casual specimen delivered to the laboratory within 5 hours.
red cells : heparin tube

ref. ranges :
urine red cells faeces

(µmol/day) (nmol/L) (µmol/kg)
porphobilinogen <8.8 - -
uroporphyrin <36 - -
coproporphyrin <300 <38 <30
protoporphyrin - <925 <135
There are two main syndromes:
• Acute porphyria
– abdominal pain (autonomic neuropathy)

– peripheral neuropathy
– neuropsychiatric manifestations
Attacks are provoked by drugs that induce liver enzymes – barbiturates, alcohol,
oestrogens, sulphonamides, anticonvulsants, and others. In women, neuropathic
symptoms may be cyclical, associated with oestrogen peaks.
• Cutaneous porphyria

Presents with photosensitivity and blistering in sun-exposed areas, notably backs
of hands, forearms, face, where accumulated porphyrins react with light to
produce skin damage.
Symptoms are provoked and exacerbated by oestrogen, alcohol, and iron
supplements.
Investigations
During a suspected acute attack, e.g. recurrent acute abdominal pain not otherwise
explained, a fresh urine sample should be taken to the lab urgently for PBG.
During latent phases of acute porphyrias, abnormalities may be undetectable.
Cutaneous photosensitivity is most often due to PCT (porphyria cutanea tarda) which
is diagnosed by increases in urine and faecal porphyrins. Diagnosis of the rare
erythropoietic porphyrias requires a blood specimen.
The table below lists the names of the main porphyrias in their order of frequency –
PCT is the commonest, then variegate porphyria and so on.
The second column indicates whether that porphyria is cutaneous or acute or both.
The test columns show the tests that should be ordered in the acute and latent phases
of each porphyria.

Named porphyria Syndromes Tests
urine faeces red cells
uro-& copro-&
acute/ copro- proto- proto-
cutaneous neuropathic PBG porph. porph. porph.
porphyria cutanea tarda (PCT) + — — + + —

variegate porphyria
- acute + + + + + —
- latent — — + —
hereditary coproporphyria
- acute + + + + + —
- latent +/— — +/— —
acute intermittent porphyria
- acute — + + + — —
- latent — + — —
erythropoietic protoporphyria + — — — + +
(rare)
congenital erythropoietic + — — + + +
porphyria (v. rare)
Post-splenectomy blood film
see Hyposplenism
Potassium (K+), serum

specimen: serum
ref. range: 3.5-5.0 mmol/L
A. Elevated potassiums – hyperkalaemia
Elevated potassiums are one of the most vexing problems faced by a laboratory
because of the difficulty knowing whether a level of 7.5 mmol/L, for example,
is harmless artefact or imminently lethal hyperkalaemia.

It is not uncommon to find unexplained elevations of K+ in healthy people in
the range 5.0 - 6.0 mmol/L and, for lack of better explanation, these are usually
attributed to artefact.
• Artefactual elevation
These are comon due to leakage of potassium from red cells into serum or
plasma. Causes are:
— prolonged application of tourniquet with repeated hand-clenching. In

cachectic patients, the elevation of serum potassium can be
accentuated.
— slow, difficult blood collect causing damage (haemolysis) to red cells.
— long delay (>5 hours) between collecting and centrifuging the
specimen.
— putting the specimen in the fridge; this inhibits the red cell ion pump
that maintains the normal K+ gradient.
— individual patient variation in the extent of potassium leakage.
If you suspect artefactual elevations:-
• iscard elevated potassium results when the specimen has been stored
more than 5 hours.
• never put electrolyte specimens in the fridge.
• have the repeatd specimen collected by a skilled venepuncturist before
the morning courier collect and label it "Immediate" so that it will be
analysed soon after arrival at the lab.
• Physiological elevations
– exercise can cause elevations of up to 1.0-1.5 mmol, falling over 6-8

hours.

– pregnancy serum K+ rises from a mean of 4.3 in the 1st trimester to
5.9 in the 2nd and 3rd trimesters.
– posture 0.5 mmol lower in supine compared with standing position.
– time of day levels are slightly higher in early morning and fall after
meals.
• Drugs are a common cause of hyperkalaemia, particularly in the elderly
– diuretics: amiloride, triamterene, spironolactone

– potassium supplements
– NSAIDs
– ACE inhibitors
– beta blockers
– digoxin in toxic doses
– lithium
– cytotoxics
– antibiotics: trimethoprim, cephaloridine, methicillin, some penicillins,
tetracyclines, isoniazid
– heparin
– dietary salt substitutes which use potassium, rather than sodium,
chloride
• Pathological states
– renal failure
– adrenocortical insufficiency
– metabolic acidoses
– very high platelet or white cell counts
What levels of hyperkalaemia are dangerous?
- Levels between 5.0 and 6.0 will seldom be a danger. Between 6.0 and 7.0 risk
is increasing, particularly when the hyperkalaemia is of acute onset, as when starting

one of the drugs listed above. Patients on dialysis become acclimatised to their
hyperkalaemia and can usually tolerate levels up to 7.0 or even 7.5.
-
B. Decreased potassium – hypokalaemia
Values in the range 3.0-3.4 are common, and may remain unexplained even
after investigation. Below 3.0, the cause needs to be found.
• Drugs diuretics: thiazides, loop diuretics

purgatives
antibiotics: some penicillins, PAS, gentamicin
steroids
vit B12, folate, iron
• Liquorice
• Diarrhoea and vomiting
• Metabolic alkalosis
• Corticosteroid excess – Conn's syndrome
Cushing's syndrome
steroid medication
• Oedematous states – hepatic failure
renal disease
congestive heart failure
• Anorexia nervosa/bulimia
Potassium, urine
specimen: 24-hour urine, no preservative

ref. range: 30-130 mmol/day

The daily output depends on dietary intake but is commonly about 60-80 mmol/day.
When there is hypokalaemia, normal renal and adrenal function will reduce output to
<30 mmol/day after 2-3 days. A higher value is consistent with adrenocortical excess
(e.g. Conn's syndrome), vomiting or diuretic therapy.
With hyperkalaemia, normal homeostatic mechanisms should raise output to >130

mmol/day.
PR (prothrombin ratio)
PCT (patient )
PR =
PCT (normal plasma pool)
The term prothrombin ratio (PR) is still retained when referring to the extrinsic
pathway test for Factors II, VII, IX, X when the patient is not on a vitamin K
antagonist such as warfarin. It is used for evaluating coagulation disturbances in liver
dysfunction and clotting factor deficiency due to vitamin K depletion. For practical
purposes, PR and INR are the same test.
For monitoring warfarin therapy, see INR (international normalised ratio).
PRA (plasma renin activity)

Precision
see Imprecision
Variation
Predictive value
The predictive value of a test gives the probability that it will give the correct answer
for a population. It combines sensitivity or specificity of the test with prevalence of
the condition being tested for.
A test with a positive predictive value of 80% for a population, will give 80% true
positives and 20% false positives.
A test with a negative predictive value of 97% will give true negatives in 97% and
false negatives in 3%.
Pregnancy reference ranges
Pregnancy has a profound effect on many reference ranges.

Effect of Pregnancy
albumin decreased by 10 g/L
alkaline phosphatase steady increase up to 400 u/L by end of 3rd trimester
(from placenta)
AST may increase 10-15 u/L
blood volume increases 20-30%
cholesterol on average increases 40% but can be double its
non-pregnant level
creatinine clearance increases
glucose in urine glycosuria is common in healthy non-diabetic women
because of the drop in renal threshold during pregnancy
ESR steadily increases, up to 30-60 mm/hr in 3rd trimester
fructosamine is 5-10% lower
haemoglobin decreases due to haemo-dilution by increased plasma
volume. 100 g/L is the approximate lower limit
hCG rises to a peak of 40,000-300,000 units by 8-10 weeks
and then falls back to a plateau some 60% lower
iron-binding serum iron-binding capacity increases markedly
oestrogens increase to very high levels throughout pregnancy
potassium rises from a mean of 4.3 in the 1st trimester to 5.9 in the
2nd and 3rd trimesters
progesterone increases throughout pregnancy
prolactin increases throughout pregnancy to levels of up to 10000 U/L
protein in urine up to 0.3 g/day
T4 (free) decreases up to 20% in late pregnancy
triglycerides considerably elevated due to Increase in the VLDL
fraction. Serum is often milky in appearance because of
this, a finding first noted by Virchow in 1847
TSH often falls in 1st trimester but returns to non-pregnant
levels in 2nd to 3rd trimester
urea decreases due to increased glomerular filtration rate
uric acid decreases except in association with hypertension
(further details under uric acid)
white cell count total count increases up to 15-18,000 due to increase
in neutrophils
Pregnancy tests

Pregnanediol, urine
The old method for assessing progesterone, now replaced by serum progesterone.
Prevalence
The prevalence of a disorder is the number/100,000 of a population who have it at a

given time.
The incidence is the number of new cases/year.
Primidone
see Mysoline (primidone)
Procainamide
see Antiarrhythmic drugs
17-OH progesterone
see 17-hydroxy progesterone (17-OHP)

Progesterone
specimen: serum
ref. range: (adult women on days 20-23 of 28-day cycle):
nmol/L
0-6 not indicative of ovulation
6-10 possibly ovulating
10-25 probably ovulating
25-80 ovulating
• To detect ovulation a specimen is taken 6-9 days after presumed ovulation, i.e.
days 20-23 of a 28-day cycle. Serum levels rise sharply during the luteal
phase to reach a plateau. See diagram under FSH.
• Because hormone release is episodic, levels can vary considerably throughout
the day.
• Pregnancy – levels rise steadily to reach a peak of 200-700 nmol/L by term.
• Ectopic pregnancy – the diagnosis of ectopic pregnancy is supported by a
level below 15 nmol/L in the presence of symptoms.
Prolactin
specimen: serum
ref. ranges: adult female 40-600 mU/L
adult males 30-450 mU/L
Specimens should be collected at least 3 hours after awakening. Elevations of up to

1000 can usually be ignored or even up to 2000 in normally menstruating women.
Repeat sampling 30 and 60 mins after the first specimen will help show up elevations
due to stress alone. Prolactin levels above 5000 are almost always associated with
prolactinomas or pregnancy.
In women, hyperprolactinaemia is an important factor in infertility, amenorrhoea and

galactorrhoea (though 2/3 of women with galactorrhoea have a normal serum
prolactin).

In men, hyperprolactinaemia lowers testosterone levels and is an uncommon cause of
impotence or galactorrhoea as well as infertility.
Causes of hyperprolactinaemia
Physiological
• stress
• sleep
• pregnancy – starts to rise at 6 weeks, peaks at up to 10,000 mU/L by term.
• lactation – peaks occur during episodes of breast-feeding with levels up to
5000 mU/L. Prolactin is essential for normal lactation.
• early morning collection — trough levels occur late morning.
• eating — small rises
Drugs
• psychotropics • cimetidine
• metoclopramide • tricyclic antidepressants
• methyldopa • opiates
• reserpine • haloperidol
• oestrogens, including oral contraceptives • androgens
Pathological
• pituitary adenomas and micro-adenomas
• other hypothalamic-pituitary disorders
• hypothyroidism
• renal failure
• seizures
• anorexia nervosa
• Addison’s disease
• hypoglycaemia
• idiopathic

Prostate cancer – histological grading
Prostate cancer is graded using the Gleason system based on the glandular pattern
seen microscopically. The predominant pattern is selected and given a grade of 1 to 5
and the second commonest pattern is also given a grade of 1 to 5. The two grades are
added to give a Gleason score of 2 to 10.
A Gleason score of 2-4 is a low grade tumour, 5-7 is intermediate grade, 8-10 is high
grade. Higher scores usually mean a more aggressive tumour.
The Gleason score and the clinical stage of the tumour are predictive of long-term
outcome.
Prostate specific antigen
see PSA (prostate specific antigen)
Prostatic acid phosphatase (PAP)
see Acid phosphatase, prostatic (PAP)
Protein electrophoresis

Protein C
ref. range: 70-120%
Deficiency of Protein C is an inherited cause of hypercoagulability (qv) and is found

in about 5% of cases of venous thromboembolism. The incidence of the deficiency is
1:5000 - 1:15,000. Approximately half of these will develop a thrombosis by the 6th
decade. Inherited deficiency is usually an indication for long term anticoagulation.
Severe homozygous deficiency is associated with purpura fulminans in neonates.
Acquired causes of Protein C deficiency are liver disease, warfarin therapy, vitamin K
deficiency.
Protein S
ref. range: 70-130%
Deficiency of Protein S, a cofactor for activated Protein C, is an inherited cause of

hypercoagulability (qv) and is found in up to 5% of patients with inherited thrombolic
disease. The lower end of the reference range is not well defined.
Acquired causes of Protein S deficiency are liver disease, warfarin therapy, vitamin K
deficiency, oral contraceptives, pregnancy.

Proteins, total, serum
specimen: serum
ref. range:
Age g/L
0-6 mths 45-75
6-12 mths 50-75
1-2 yrs 55-75
>2 yrs 60-84
total protein = albumin + total globulin
Total proteins, consisting of albumin and globulins, is a crude test, but a raised value
can be a pointer towards raised immunoglobulins; a low value can be due to reduced
albumin or globulins or both. Variations in protein concentration can be due to
dehydration, diuretics, fluid retention or diurnal changes. On changing from the
recumbent to the upright position, fluid is redistributed to tissues from the circulation
causing an increase of up to 10% in protein concentrations.
Protein-binding in serum Many serum constituents exist in two forms, a protein-

bound form, usually to an alpha or beta globulin or albumin; and a free form often a
tiny percentage of the total but this is the metabolically active form.
Examples of protein-bound constituents are thyroxine, tri-iodothyronine, cortisol,

testosterone, vitamin B12, iron, copper, calcium – and many drugs.
Proteins, urine (proteinuria)

specimen: 24-hour urine, no preservative
ref. range: <0.2 g/day – but see benign proteinuria below
Test methods

These depend on the clinical situation –
• Urine dipstick, as part of routine urinalysis

This is a semi-quantitative test with proteinurias divided into 4 categories.
g/L
trace 0.1-0.5
small 0.5-1.0
moderate 1.0-2.5
large >2.5
• Total protein concentration on spot urine – this gives a more accurate

measurement than a dip-stick and also detects non-albumin proteins such as
free light chains.
• Total protein concentration on spot urine – this gives a more accurate

measurement than a dip-stick and also detects non-albumin proteins such as
free light chains.
• 24-hour protein quantitation – this test is used as follow-up when a dip-stick

shows 1+ (or more) positive, or when monitoring known proteinuria.
• Urine microalbumin – a sensitive test measuring small quantities of albumin

in the range 0.01-0.20 g/L. The test is used as an early indication of diabetic
nephropathy.
see Microalbumin
• Electrophoresis of concentrated urine – used mainly in detection of free light

chains (Bence Jones protein).
Renal proteinuria
Causes include the whole differential diagnosis of renal disease.
Glomerular proteinuria is by far the most common and serious type. The protein is
predominantly albumin and when daily output >3 g/day, nephrotic syndrome

develops comprising oedema, albuminuria and hypoalbuminaemia. Serum lipids
become elevated.
In tubular proteinuria, electrophoresis shows a non-selective pattern with bands

representing the wide range of normal serum proteins normally reabsorbed by the
tubules. Causes include drugs, inherited disease (e.g. Wilson's disease), autoimmune
disease (e.g. SLE) or chronic infection.
Proteinuria of >1.0 g/day requires renal investigation including consideration of renal
biopsy.
Benign and non-renal proteinuria

40% of our routine urinalyses show a trace or more of protein and most of these are
benign.
Causes include:
• infection
• fever
• stress
• exercise
• heart failure
• orthostatic proteinuria, found particularly in young men, disappears when the
patient is recumbent. Protein is absent from a morning specimen collected on
first getting up.
• iodiopathic
24-hour protein in these is usually <0.5g/day. Levels of 0.2-0.5g/day (or even up to

1g/day) cannot be described as normal but often remain of unknown aetiology when
found as isolated abnormalities. Intensive follow-up is usually unrewarding.
Nevertheless, check on serum creatinine and urine culture and microscopy are
required and repeat 24-hr urine in 3-12 months unless other signs or symptoms
indicate need for earlier follow-up.

Proteus
Proteus species are gram-negative enteric bacilli causing urinary infections and a
variety of other infections, particularly in patients with impaired host defences.
Treatment is based on antibiotic susceptibility results. Recurrent urinary infections
with Proteus can be difficult to eradicate and should raise the possibility of the
presence of renal calculi.
Prothrombin mutation (20210G-A)
The prothrombin gene mutation 20210G-A, found in 1-3% of the population, is

associated with levels of prothrombin which exceed those in the normal population by
an average 30%.
Clinically the mutation is associated with

— thrombophilia
— 3-6 fold increase in VTE
— cerebral vein thrombosis
— myocardial ischaemia in patients age <50
Prothrombin ratio
see PR (prothrombin ratio) and INR
Protoporphyrins
see Porphyrias

PSA (prostate specific antigen)
specimen: serum
ref. range: <50 yrs <2.5 µg/L

50 - 60 <3.5
60 - 70 <4.5
>70 <6.5
PSA, an enzyme that liquefies the seminal coagulum, is found only in prostatic tissue
and is an excellent tumour marker for monitoring treatment and progress of prostatic
carcinoma.
Diagnostically it should always be requested when a patient presents with urinary

outflow obstruction or when DRE (digital rectal examination) shows a hard,
asymmetric or abnormally enlarged gland.
Controversy surrounds the use of PSA as a screening test, however, and the usual
recommendation outside the United States is that PSA should not be offered to
asymptomatic males unless they specifically request it – and if they do, they need to
understand the diagnostic and therapeutic implications of an elevated level.
Some centres measure the free fraction as well as total PSA, a higher free/total ratio,
e.g. >0.2, being more suggestive of benign enlargement.
PSA in benign prostatic conditions
In BPH (benign prostatic hypertrophy) the PSA is sometimes elevated but seldom
above 10 µg/L. The PSA velocity (annual rate of rise of PSA) is usually less than in
Ca prostate and a patient who chooses watchful waiting of a level below 10, may use
PSA velocity as a deciding factor before requesting prostatic biopsy. Allowance must
be made for a biological variation of 10-15% when observing serial PSA levels.

In prostatitis, the PSA can be elevated as high as 50 µg/L but will fall back to its
natural baseline after successful treatment.
DRE (digital rectal examination) may cause a 5% elevation, occasionally more,

falling back to the baseline over a few days.
PSA levels also rise for up to 24 hours after sex, especially in older men.
PSA in prostatic cancer
Up to 30% of patients with early Ca will have a PSA within the reference range.
Annual monitoring, as recommended by US urologists, would show a rising PSA in
this group.
A PSA above the upper reference limit but below 10 is in a zone of uncertainty where
only a biopsy will provide the diagnosis. Annual monitoring rather than biopsy will
be the chosen option for some patients.
When the PSA has risen above 10, the probability of carcinoma is rising steeply and
most patients proceed to biopsy.
The natural history of prostatic cancer
Prostatic Ca is usually an indolent tumour presenting in later life and most affected
males die with the tumour rather than of it.
It is a common tumour – 40% of males over the age of 75 are affected when
examined at autopsy.

It is the cause of death in 5% of males, the commonest male tumour after Ca lung; the
average age at death is 75.
Treatment of prostatic cancer
If treatment, whether radiotherapy or surgery, were easy and free of complications

there would be no controversy. The problem lies with the relatively high
complication rate and their unpleasant nature – incontinence and impotence – and this
is why some patients take the chance that their life will not be significantly shortened,
even without treatment.
Summary of indications for measuring PSA
• monitoring known prostatic Ca — PSA should be <1 after prostatectomy

• searching for a primary in disseminated malignancy
• symptoms of urinary tract obstruction
• abnormal prostate on DRE
• family history of Ca prostate
• the patient requests it and understands the implications. A patient above the
age of 75 should probably be discouraged from measuring his PSA as a
"check", especially if other significant chronic illness is present.
Pseudomonas aeruginosa
In general practice, Pseudomonas is encountered mainly in chronic otitis externa

where it usually responds to local toilet and topical polymyxin. The most commonly
used agent in the past, Chloromyxin, which contained polymyxin B, is no longer
available. Another ear preparation Colymycin S Otic, containing colistin which has
the same spectrum of antibacterial activity as polymyxin, is currently the most widely
used topical preparation for Pseudomonas otitis externa.

P. aeruginosa is often recovered from ulcer lesions on the lower limbs of the elderly.
It is frequently a coloniser rather than a pathogen in this situation. If, however, the
gram-stain reveals many WBC's with gram-negative bacilli and the ulcer has
deteriorated clinically Pseudomonas may be the cause of infection. In this instance
ciprofloxacin treatment may be indicated.
Pseudomonas can cause more serious infections in burns, in immuno-compromised

patients and in nosocomial infections. In these situations, early treatment with
carefully selected antibiotics is required because of the organism’s pathogenicity and
resistance to a variety of agents.
Psittacosis
see Chlamydia psittaci
PTH
see Parathyroid hormone (PTH)
Pus swabs
see Skin and wound swabs

Pyrophosphate
Calcium pyrophosphate is found in pseudogout either as crystals in synovial fluid or

as deposits resembling gouty tophi in periarticular tissues.
see also Synovial aspirate
Pyuria, sterile
infections)
Q Fever
specimen: serum
A rickettsial disease due to Coxiella burnetii, an obligate intracellular gram-negative

bacillus. It may present as an atypical pneumonia in someone who has had recent
contact with domestic animals overseas. Not present in New Zealand.

Antibody levels can detect current or recent infection.
Quinidine
see Antiarrhythmic drugs.
RA
see Rheumatoid arthritis (RA)
Rapid smears
Please contact Histology Department

RAST (Radioallergosorbent test)
specimen: serum
Individual allergens required must be listed. RAST screens for multiple allergens are
not done because of the high cost per test.
RAST tests use the patient’s serum to diagnose specific allergies by identifying the
presence of an IgE antibody against that allergen. They are used as a second-line
investigation, the first-line being the standard battery of skin tests (qv). Specific
indications for RAST tests are:
• severe skin disease

• non-reactive skin
• hyper-reactive skin (dermographism)
• skin test might be hazardous, e.g. penicillin, bee or wasp venom sensitivity
• very young children
• patients on antihistamines or sympathomimetics that cannot be stopped for
skin tests.
The list of specific allergen tests includes:
aspergillus grass mix

bee venom horse hair
blue mussel latex
cat dander mould mix
cheese peanut
cow's milk penicillin G
dog fur shrimp
dust mite soya bean
egg wasp venom
fish wheat
gluten yeast

RBC
= red blood cell
Reactive arthritis
see Arthritis, reactive
Reactive hypoglycaemia
see Hypoglycaemia
Red cell antibodies
specimen: serum
Indications:
• pregnancy - a screen test is followed by specific identification if the screen is

positive
see Bilirubin, total — haemolytic disease of the newborn
• autoimmune haemolytic anaemia
see also Coombs test

Red cell enzymes
specimen: blood (heparin)
Screening tests are available for:
• G6PD (glucose-6-phosphate dehydrogenase)

• pyruvate kinase
• pyrimidine-5-nucleotidase
Quantitative assays on these and other enzymes are available as follow-up.
Red cell mass (volume)
Used in the diagnosis of polycythaemia vera.

see Polycythaemia
Blood volume
Red cell osmotic fragility
see Osmotic fragility of red cells
Red cell survival
The patient's red cells are labelled with 51Cr and their survival in the circulation
determined.

This test is sometimes used in suspected haemolysis. If there is significant loss of
blood from the gastrointestinal tract, tagged red cells can be detected in the stools.
Reducing substances in faeces
specimen: fresh sample of faeces in small jar delivered to lab as soon as possible,
stored in fridge if delay is unavoidable.
The test is a simple qualitative test for reducing substances which include lactose,
glucose and fructose but not sucrose.
Acquired lactase deficiency, in which the disaccharide lactase is not digested,

presents as frothy diarrhoea with failure to thrive in infants after infectious diarrhoea.
The diagnosis can be confirmed by improvement after withdrawal of lactose from the
diet.
Reference ranges and the concept of normality
In the dawn of laboratory medicine, before 1969, before the invention of the
biochemistry Auto-Analyser or the flow-through haematology blood counter, we
believed a sharp line divided normal from abnormal results. This was always too
simplistic. Some results are almost certainly normal, others almost certainly
abnormal, and separating these is a broad grey zone where interpretation depends on
consideration of clinical history and findings and a host of other variables.
The term “normal range” was replaced by “reference range” (or “reference interval”)
to indicate that we make no judgement on whether a result is normal. We simply
provide a range that covers the values of 95% of a group (e.g. blood donors) who are

apparently disease-free and similar to the patients we are dealing with in terms of age,
gender, etc and we “refer” to that range when trying to decide whether our patient’s
result is indicative of, or consistent with, a particular diagnosis.
Most of the interpretative notes in this handbook are directed towards defining the
variables that influence this decision. Whenever there is doubt about the significance
of a result, the test should be repeated immediately if the clinical situation demands it
or in a week or a month or even a year if there is no urgency. The temporal pattern
provides an extra dimension by showing whether a result is increasing, decreasing or
staying the same, whilst at the same time the clinical picture has the opportunity to
move in one direction or the other.
Some reference ranges, such as those for cholesterol or uric acid, are not 95%
population ranges but "ideal" ranges that we should strive to attain.
see also introductory notes
Reiter's disease
see Arthritis, reactive
Renal calculi
Most calculi are of unknown origin but four aetiologies need to be remembered.
• hypercalcaemia – check serum calcium, vitamin D

• uric acid excess in urine
• cystinuria

• mixed "triple-phosphate" stones, often due to chronic, occult urine infections
with gram-negative bacteria such as Proteus.
The reason for analysing calculi is to detect pure uric acid (5-10% of all stones) or
cystine. In the case of uric acid stones, the causes of increased uric acid (qv)
excretion need to be looked for. Allopurinol is effective in preventing further stone
formation.
The remaining 90% of stones are composed of calcium oxalate or phosphate and in
half of these there is hypercalciuria due to increased intestinal absorption of calcium.
A 24-hr urine should be analysed for calcium, phosphate, urate and oxadate.
Renal glycosuria
see Glycosuria
Renal screen tests
a simple screen - serum creatinine

- urine for : microscopy
protein
culture
Creatinine clearance (qv) is not a useful screen test because of the inaccuracies
associated with 24-hour urine collections.
Renal tubular acidosis
Because of tubular defects, the kidney has impaired ability to secrete an acid urine.

The patient may present with renal calculi and show electrolyte disturbances
including low potassium, low bicarbonate, high chloride.
A useful screen test is to measure the pH of a spot urine on first rising. A pH <6.0
suggests normal acidification. An acid load test is used for follow-up.
Renin
Reptilase clotting time
Reptilase is a thrombin-like enzyme isolated from snake venom which is capable of

clotting fibrinogen. It is used to detect dysfibrinogenaemias.
Reticulin antibodies
specimen: serum
ref. range: not present
see Coeliac disease (gluten sensitive enteropathy) for interpretation
Reticulocyte count

ref. range: absolute count 10 – 100 x 109/L
percentage count 0.1–3.0% in non-anaemic subjects
Absolute counts are preferred to percentages because they are independent of

anaemia. Polychromasia is the morphological indicator of increased reticulocytes.
The reticulocyte count is increased in:
• chronic or acute blood loss

• haemolytic anaemias
• deficiency anaemias treated with iron, B12 or folate (treatment response).
• marrow infiltration
A reduced reticulocyte count suggests a hypoplastic basis for an anaemia.
Rhesus incompatibility
see Haemolytic disease of the newborn
Rheumatic fever
New Zealand still has a high incidence of acute rheumatic fever with Maori and
Pacific Islanders making up 84% of the total. 60% of cases are in the 5-14 age
group. It is a notifiable disease. Diagnosis is based on the revised Jones criteria:
major manifestations minor manifestations
carditis clinical
polyarthritis previous rheumatic fever

chorea or rheumatic heart disease
erythema margination or arthralgia
subcutaneous nodular fever
laboratory
raised ESR, or CRP, or WBC
ECG
prolonged P-R interval
evidence of streptococcal infection
— increased streptococcal antibodies

— positive throat culture for GpA streptococcus
— recent scarlet fever
The diagnosis requires:

• two major criteria
or
• one major and two minor criteria
plus evidence of streptococcal infection
Absence of evidence of streptococcal infection makes the diagnosis doubtful. A

serum sample should be collected for streptococcal antibodies whenever the diagnosis
of rheumatic fever is suspected and a second sample collected at least two weeks
later, looking for rising titres.
Rheumatoid arthritis (RA)
The commonest of the connective tissue diseases with an incidence of 1-2% in the
general population. The American Rheumatology Association (1982) recommends
that the diagnosis be applied to those who are positive for four of the following seven
criteria:

• rheumatoid factor (positive in 80%)
• morning stiffness
• arthritis of hand joints
• symmetric arthritis
• arthritis of 3 or more joint areas (of 14)
• rheumatoid nodules
• radiographic changes
Note that 20% of patients with rheumatoid arthritis are negative for rheumatoid
factor.
see also Rheumatoid factor (RF)
Rheumatoid factor (RF)
specimen: serum
ref. range: latex test <20 u/ml
Rose-Waaler <30 u/ml
Rheumatoid factor is an antibody, or rather a group of IgM, IgG and IgA antibodies,
directed againtst IgG. Most methods detect the same IgM rheumatoid factor but
specificities vary somewhat and for this reason a test that is positive in one laboratory
may be negative in another and the quantitations may differ.
2% of the healthy population are positive for RF, rising to 5-10% in the elderly.
In rheumatoid arthritis (RA) qv, RF is present in only 80% of cases. RF on its own
does not signify rheumatoid arthritis and conversely a clear clinical presentation of
RA does not require RF to establish the diagnosis. RF is often absent during the first

6 months of disease. Higher levels tend to be associated with more aggressive
disease.
Conditions, other than RA, with a high incidence of RF are:
• Sjogrens (90%)
• SLE (30%)
• other connective tissue disorders
• chronic inflammatory/infectious disorders
• malignancy
Ringworm
see Dermatophytes
Rochalimaea henselae
see Cat scratch disease
Rose-Waaler test
see Rheumatoid factor (RF)
Ross River fever

Although not contracted within NZ, this febrile illness, due to an arbovirus, may be
found in patients who have recently returned from Australia. Antibody tests can be
arranged.
Rotavirus
specimen: fresh faeces
Rotavirus is the commonest cause of diarrhoea in young children – 50% of children

under 5 hospitalised for gastroenteritis are infected with rotavirus. Essentially all
children are infected by the age of 3 with the peak incidence between 6 and 24
months. Adult infections are much less frequent. There is a clear winter peak.
Spread is by the faecal-oral route. It has a short incubation period, 24-72 hours.
Symptoms may be severe but usually settle within 7 days with oral fluid and
electrolyte replacement.
RPR (rapid plasma reagin) test
see Treponemal serology (STS, serological tests for syphilis)
Rubella
specimen: serum
tests: IgG for immune status
IgM for current infection
ref. ranges :

Units/ml
IgG <5 non-immune
5-11 equivocal
>11 immune
IgM detectable for about 3 months
during and immediately after
infection
Immune Status
MMR (measles/mumps/rubella) vaccine is recommended for all children as an SC

injection at one year followed by a booster at age 11.
The person with an IgG antibody level >10 µ/ml, can be assumed to have solid
immunity.
With levels between 5 and 10, immunity probably exists but a rubella vaccine booster
is recommended except in pregnancy when the booster should be delayed till after
delivery.
Below 5, immunity is either non-existent or slight and revaccination is indicated –

though as above, not in pregnancy.
It is essential that pregnant women found to be non-immune be vaccinated after

delivery. A big proportion of cases of congenital rubella occur in women who have
had previous pregnancies.
Infection during pregnancy
Because 85% of mothers infected during the 1st trimester give birth to infants with
congenital defects (eyes, ears, heart, brain), termination of pregnancy must always be
discussed when infection has been established.

The mother who has had contact with suspected rubella and whose immune status is
susceptible or unknown, should immediately have a blood collected for IgM and IgG
antibodies with at least one more specimen 3 weeks later.
If the woman develops signs or symptoms consistent with rubella, IgM antibodies
should be collected at weekly intervals for 3 or 4 weeks to check for presence of IgM
and subsequent rise in titre which will confirm infection.
Final confirmation is through detection of rubella RNA in a placental biopsy or foetal

blood.
S.
= serum
Salicylate
specimen: serum
ref. range: therapeutic 1.0-2.0 mmol/L
toxic >3.6 mmol/L

Salivary gland antibodies
specimen: serum
Positive in 50-70% of Sjogren’s syndrome, otherwise rare.
Salmonella antibodies (Widal Test)
specimen: serum
A test of limited value in the diagnosis of typhoid fever, blood culture being the
preferred diagnostic method.
Interpretation
O antigens titre >1:160 and rising sharply over 7-14 days suggests current
infection.
H antigen >1:160 suggests immunity
Vi antigen high titre sometimes indicates the carrier state.
Titres can be non-specifically elevated in diseases not caused by Salmonella and

vaccination can give positive titres.
Salmonella culture
specimen: faeces for diarrhoea
blood culture for suspected typhoid fever

Enterocolitis
Salmonella species make up 15% of the pathogens cultured from faeces in this
laboratory, the main reservoir being domestic animals (including poultry and eggs)
and infected humans, both symptomatic and carriers. Species causing enterocolitis
include S. typhimurium, S. choleraesuis and S. enteritidis. In healthy persons the
episode usually resolves in 2-3 days. Patients with impaired defences may require
antibiotic treatment, usually with cotrimoxazole, amoxycillin or ciprofloxacin. The
chronic carrier state can be treated with ciprofloxacin.
Salmonellosis is a notifiable disease.
Typhoid Fever
Only a few cases occur in Auckland each year, S. typhi being the usual cause or
occasionally S. paratyphi A or B.
During the early stages, diagnosis is by blood culture which should be done
repeatedly when clinical suspicion is strong. From the second week on, faeces
cultures may be positive.
Sarcoidosis
A systemic disorder of unknown cause characterised by non-caseating granulomata.

Diagnosis usually requires histological examination of lung, skin, lymph nodes or
liver.
Serum ACE (angiotensin converting enzyme) is elevated in 2/3 of patients but the test
is not specific enough to be of diagnostic value, nor does it have prognostic
significance.

Serum calcium may be elevated.
Saturation, iron
Scabies
Caused by the mite Scarcoptes scabiei and transmitted by direct skin to skin contact.
Transfer from clothes is possible but only if worn by infected people immediately
beforehand.
Incubation period 2-6 weeks without previous exposure but only 1-4 days in those
who have been infected before.
Burrows are characteristic in scabies. These consist of skin-covered ridges 0.5 - 1.0
cm in length, often with a small vesicle at the end.
The diagnosis is usually made clinically but where microscopic examination of

scrapings is required, this can be arranged. A few drops of paraffin oil are placed on
the affected area and the lesion scraped removing skin and the mite. Treatment is
usually with permethrin 5% cream. Gamma benzene hexachloride 1%, cream or
lotion, and crotamiton 10%, cream or lotion, are alternatives. Pruritis may persist for
some time after successful treatment.
Schilling test

The Schilling test used to be used more often in the investigation of vitamin B12
deficiency than it is now when pernicious anaemia can be diagnosed by simpler tests.
It measures the absorption of orally ingested labelled B12 with and without added
intrinsic factor. Normally >10% of the orally administered vitamin B12 is excreted in
the urine. An intramuscular loading dose of vitamin B12 is given to ensure that stores
are replete.
In either pernicious anaemia or malabsorption, <10% is excreted but in the case of

PA, the added intrinsic factor corrects the abnormality.
see also Pernicious anaemia

Vitamin B12
Schistosomiasis
specimens : — random faeces
— urine, full volume (not just an aliquot)
preferably collected between noon and 3pm when there is peak egg
excretion
— serum for antibody tests
Request examination for schistosome ova. Eggs may be found in urine and stool as
early as five weeks after infection. Patients with a low worm burden may have few or
no eggs in urine or stool.
Although over 200 million people in Africa, the Middle East, S. America and the
Caribbean are infected with these blood flukes, schistosomiasis is rare in travellers to
these areas. Infection requires skin contact with contaminated fresh water as in
swimming or wading bare-foot in paddy fields, water-holes, local streams, etc. The
infective form penetrates human skin, passes through a migratory phase in the lung
and liver and then moves to its final habitat in the portal venous system (S. mansoni)

or urinary bladder venous plexus (S. haematobium). Adult male and females live for
5-10 years.
Many New Zealanders have acquired infection in Lake Malawi in South East Africa.
It is stated in some travel guides that this lake is free of infection risk. This is not the
case and travellers should be advised against swimming in this lake.
The usual problem is the traveller who requires reassurance. Examination of faeces
for the highly characteristic ova; urine for ova and red cells; serum for serology, and
perhaps liver function tests, are adequate for this purpose.
Where more serious investigation is required, up to 6 specimens of urine and faeces

should be examined. Further investigation might include appropriate tissue biopsies
(rectum, bladder, liver).
Positive serology indicates present or past infection. Persons with negative stool
and/or urine tests but positive serology require treatment to avoid the uncommon but
catastrophic spinal cord complication of transverse myelitis.
Treatment with praziquantel and follow-up are best managed by those with
experience treating schistosomiasis.
Scleroderma, diffuse
Also called systemic sclerosis, this is a connective tissue disease characterised by

diffuse cutaneous and/or systemic fibrosis.
Raynaud's phenomenon is present in 95% of cases.

It has an incidence of about 1:50,000

Tests that are often positive include:
ANA (95%) usually with a nucleolar pattern.

RF (25%)
ENA anti Scl-70 (30%)
Scleroderma, limited
Previously called CREST syndrome:-
Calcinosis
Raynaud's phenonemon
Esophageal dysmotility
Sclerodactyly
Telangiectasia
Tests that are often positive include ANA (80%) usually centromere pattern.
Scoline (suxamethonium) sensitivity
This autosomal recessive disorder renders the carrier apnoeic for an abnormally long
period after administration of scoline. Family members of an infected individual
should be tested. The dibucaine number is an additional test used in identifying
carriers.
see Cholinesterase

Selenium
specimen: plasma or whole blood (heparin)

ref. range: plasma 630-990 nmol/L (50-80 µg/L)
Selenium is an antioxidant and is an essential trace element in humans and animals,

entering the food chain through plants. In the Keshan province of China, an endemic
cardiomyopathy has been attributed to the region's severe soil selenium deficiency.
It has been suggested that lesser degrees of deficiency contribute to health problems
in western countries including subfertility, cancer and heart disease. Although New
Zealand soils are low in selenium, documented human deficiency is rare except when
there is another cause such as prolonged parenteral nutrition.
Brazil nuts are a rich natural source of selenium.
Seminal fluid
A. Post-vasectomy specimens
This is a test for sperm count only, not motility. The specimen should be delivered to
the laboratory on the day of collection but without the urgency necessary for fertility
specimens.
Most post-vasectomy specimens have a zero sperm count but a small percentage have
a low count of non-motile spermatozoa even months after successful surgery. They
are believed to be sequestered spermatozoa stored in the recesses of seminal vesicles
or other parts of the male GU system.

B. Infertility specimens
The following written instructions can be given to the patient.
Instructions for the collection of semen for sperm count
1. The test is performed only on week days, not Saturday or Sunday.
2. The specimen should be delivered to the main laboratory within 2-3 hours of
collection and preferably before 3pm. Many people collect the specimen at home
at 7-8am and deliver the specimen before work.
3. You should refrain from sexual intercourse or ejaculation for 3 days before
collecting the sample.
4. The specimen should be obtained either by masturbation or by having intercourse

in the usual way (do not use a rubber sheath or other male contraceptive) and
withdrawing just before ejaculation. Ejaculate into the collection jar provided
which must be kept nearby and warm.
5. It is important that the whole of the specimen is collected. If some of the

specimen is lost at the time of collection, this should be noted.
Interpretation
normal doubtful probably

infertile
volume (ml) 2-6 1.5-2.0 <1.5
count (million/ml) 20-250 10-20 <10
motile sperm (%) >50 35-50 <35
Volume correlates least well with fertility. A high volume (>6ml) can be
associated with oligospermia or a low volume with normal fertility.

Count Even low counts do not absolutely exclude fertility.
Motility Reduced by exposure to temperatures above or below body

temperature. 24 hours at room temperature kills all motility.
Morphology Normally less than 20% are defective.
If an initial sample suggests sub-fertility, two further specimens should be collected

over a 2-3 week period with no intercourse or ejaculation for at least 3 days before
specimen collection.
Care should be taken in diagnosing “sub-fertility” on the basis of seminal fluid

analysis, particularly when the abnormalities are not marked.
Sensitivity/Specificity
As applied to a laboratory test, sensitivity refers to the ability of the test to detect a
condition or analyte. A test with a sensitivity of 97% will fail to detect the condition
in 3% of those who have it, i.e. there will be 3% false negatives.
Sensitivity tends to be achieved at the expense of specificity.
Specificity is the ability of a test to give a positive result only when the condition or
analyte being tested for is present. A test with a specificity of 97% will give a false
positive result in 3% of persons tested. A test must have a high degree of specificity
when searching for an important or uncommon condition in a large population, e.g.
when searching for HIV in a community.

Serotonin
In carcinoid tumours (qv) the plasma serotonin levels are elevated but 24-hr urinary
5-HIAA is the test used in diagnosis.
Sex hormone binding globulin
see SHBG (sex hormone binding globulin)
SGOT
the old name for AST
SGPT
the old name for ALT
SHBG (sex hormone binding globulin)
specimen: serum
ref. ranges: adult female 50-80 nmol/L
adult male 40-60 nmol/L
SHBG is a serum globulin that binds testosterone and, to a lesser extent oestradiol.
On its own, it has little diagnostic value but it is required when measuring the
biologically active free testosterone fraction as distinct from the 98% of total
testosterone which is bound and inactive.
SHBG is increased by: oestrogens, pregnancy, androgen deficiency, thyrotoxicosis,

cirrhosis.

It is decreased by: obesity, hypothyroidism, androgen excess, polycystic ovary
syndrome, hirsutism.
Shift to the left
see Neutrophils (polymorphs): neutrophilia
Shigella
specimen: fresh faeces
Shigella, the cause of “bacillary dysentery”, is predominantly found in third world

countries where it is transmitted by contaminated food and water. In this laboratory,
shigellae make up 4% of faecal pathogens. Children under 5 years are affected
particularly.
Mild cases are treated with oral rehydration alone but more severe infections may
require antibiotics – cotrimoxazole or ampicillin (not amoxycillin) or norfloxacin
(adults only) – and IV fluids. Shigellosis is a notifiable disease.
Shingles
see Varicella-zoster virus (VZV)

SI (systeme internationale) units
In 1975-77, New Zealand, Australian and UK laboratories switched from traditional

mass units (mg/100ml) to SI units (mmol/L). United States laboratories have mostly
retained mass units which may need to be converted when American patients present
in NZ with results from back home.
conversion
SI Unit mass unit factor
alcohol 1 mmol/L = 4.5 mg/100ml 0.22
bilirubin 1 µmol/L = .06 mg/100ml 17.1
calcium 1 mmol/L = 4 mg/100ml 0.25
cholesterol 1 mmol/L = 38.5 mg/100ml 0.026
creatinine 1 mmol/L = 11.4 mg/100ml 0.088
glucose 1 mmol/L = 17.9 mg/100ml 0.056
potassium 1 mmol/L = 1 meq/L 1.0
protein 1 g/L = .1 g/100ml 10.0
sodium 1 mmol/L = 1 meq/L 1.0
triglyceride 1 mmol/L = 91 mg/100ml 0.011
urate 1 mmol/L = 16.7 mg/100ml 0.060
urea 1 mmol/L = 5.9 mg/100ml 0.17
to convert mg/100 ml to mmol/L: multiply by conversion factor.

to convert mmol/L to mg/100 ml: divide by conversion factor.
An advantage of SI units is that osmolality (in mmol/L) of serum or urine can be

simply calculated by adding concentrations (in mmol/L) of the constituents, assuming
all the main ones have been measured.
SIADH (syndrome of inappropriate ADH)

Sickle cell test
specimen: blood (EDTA or heparin)
Sickle cell haemoglobinopathies are hereditary disorders due to HbS, found in blacks
of African descent. The homozygous state (sickle cell disease) causes a chronic
haemolytic anaemia and during crises, episodes of pain and multi-system organ
damage. Heterozygotes (sickle cell trait) are free of clinical disease and have normal
red cell indices but HbS can be demonstrated by appropriate tests including Hb
electrophoresis.
Sideroblastic anaemia
This is an acquired disorder of porphyrin metabolism seen in older patients and

associated with anaemia, either microcytic or dimorphic. It is a preleukaemic
condition and is part of the myelodysplastic (MDS) spectrum of disorders. The
hallmark is a marked increase in bone marrow iron, ring sideroblasts on Perl stain in
the bone marrow and an elevated ferritin. The disorder may be primary (in MDS) or
secondary to drugs, particularly antituberculous therapy.
Sjogren's syndrome
A connective tissue disease characterised by salivary and lacrimal gland involvement

resulting in dry mouth and dry eyes.
It may exist on its own or be associated with rheumatoid arthritis or other connective
tissue disease.

Tests that are usually positive include:
ANA usually with a speckled pattern

RF (90%)
ENA (60%) anti SSA (Ro) or SSB (La)
Skin and wound swabs
When collecting the swab, aim to get pus or exudate from the base of an actively
inflamed lesion. Remove scab if present and open infected blisters. Avoid getting
bacteria from normal skin. 80% of skin/wound/pus swabs in the Auckland
community grow Staph. aureus. Strep. pyogenes makes up most of the remainder.
The latter is the usual pathogen in impetigo and cellulitis.
% susceptibilities
fluclox amox-clav cefaclor pen eryth cotrim cipro tet
S.aureus¹ 93 93 93 12 85 99 100² 97
S. pyogenes 100 100 100 100 99 99 — 83
1. There has been an increase in MRSA in Auckland from 0.2% in 1990, 0.7% in 1993.
to 7% in 1998. MRSA is more common in South Auckland than in other areas of the region.
2. Quinolones are not recommended for treating S. aureus infection because the MIC's are
close to the cutoff for susceptibility and the common emergence of resistance.
Chronic leg and foot ulcers are commonly associated with vascular insufficiency,
and, in the diabetic foot, with loss of pain and touch sensation. Swabs usually show a
mixed growth of gram-positive cocci and gram-negative bacilli. Cellulitis confined to
the rim of the ulcer can be treated with an oral agent such as amoxycillin-clavulanate
but a spreading cellulitis, particularly in a diabetic foot, needs urgent admission for
parenteral antibiotics.
All chronic ulcers require careful daily cleansing with warm saline and debridement
of dead tissue down to a healthy base.

Skin biopsy
A. Method
1. Excisional skin biopsy
This technique should be used for:

• atypical pigmented lesions
• deep dermal/subcutaneous nodules
• where evaluation of margins is important
• where panniculitis (inflammation of subcutaneous fat) is
suspected
2. Punch biopsy
This technique is useful for:
• inflammatory dermatoses
• suspected basal or squamous cell carcinomas prior to definitive
treatment
Excisional biopsy should be performed rather than punch biopsy if

malignant melanoma is suspected. The punch biopsy should include
subcutaneous fat. Crush artefact, when forceps are used to extract the
biopsy, should be avoided. The specimen should be immediately
placed in 10% formalin.
3. Shave biopsy
This usually results in epidermis only or epidermis and superficial
dermis. Shave biopsy should not be used if there is any suspicion of
malignant melanoma. In acral sites (soles of feet, palms of hands)
usually only keratin is obtained in a shave biopsy.

4. Curettage
This is the least satisfactory form of skin biopsy as the tissue may not
be satisfactory for histology.
B. Site selection
This is of critical importance particularly in:
• Inflammatory dermatoses — biopsy should be from a fully developed
lesion and if the lesions are in different stages of evolution, multiple
biopsies should be taken. Treated areas should be avoided.atypical
pigmented lesions
• Vesiculobullous lesions, ulcers, pustules — biopsies should be taken
from very early lesions and should include normal skin.
C. Direct immunofluoresence microscopy

Biopsies should be submitted to the laboratory fresh on damp saline-soaked
gauze in a specimen container packed in ice. The specimen needs to be snap
frozen in the laboratory within 2 hours of the specimen being taken.
The pathologist should be contacted 24 hours prior to taking the biopsy to

ensure rapid handling.
Skin scrapings for mycology
see Dermatophytes
Skin tests for allergy
These tests require an appointment. A set of tests takes about 30 minutes.

Indications
For identifying trigger allergens in asthma, allergic rhinitis and contact eczema.
Where skin tests are not feasible, serum RAST (qv) tests for specific allergens can be
used.
Preparation
The patient must discontinue antihistamines or sympathomimetics for three days.
Steroids and cromoglycate can be continued.
Method
A drop of dilute allergen is placed on the skin; a needle prick through the drop
introduces a minute amount of allergen into the dermis; if it encounters specific IgE
antibodies bound to mast cells, histamines are released and a wheal and flare develop.
Allergens 16 allergen solutions and 2 controls are used.
• house dust mite 1 (D. • plantain

pteronyssinus)
• house dust mite 2 (D. farinae) • mixed tree pollen
• cat hair • privet
• dog hair • milk
• horse hair • egg-white
• feathers • peanut
• mixed moulds • wheat
• mixed grass pollens • +ve control (histamine)
• perennial rye • -ve control (suspension
fluid)
Interpretation

• A positive result does not always mean the patient will suffer an allergic
illness when exposed to that allergen.
• A negative result does not entirely exclude sensitivity – these false negatives
are more common in children under the age of 5.
• The food tests are the least reliable – a negative result does not exclude
sensitivity.
• The mould mixture can give false negatives as it is not possible to include the
full range of allergic moulds in the mixture.
• Privet is often blamed for allergies but positive tests are uncommon. More
often a grass pollen is the cause of "privet allergy".
• If all results are positive, including the negative control, the patient has
dermatographism which is not due to allergy.
• If the positive control (histamine) is negative, the patient is probably taking
antihistamines.
• If all tests are negative (except the positive control), the patient is unlikely to
have atopic disease
see also Bee and wasp venom allergy

Food allergy
Penicillin allergy
SLE (systemic lupus erythematosus)
A relatively common (1:1000) connective tissue disease which can affect a wide
variety of systems and is characterised by auto-antibodies directed against nuclear
components.
There is no single specific test but rather a list of diagnostic criteria. The American
Rheumatology Association (1982) recommend that if four of the following criteria
are positive, the diagnosis can be made:
• ANA positive (95%)

• anti- DNA, or ENA Sm, or biological false positive VDRL

• haemolytic anaemia, or leukopenia, or thrombocytopenia
• nephropathy (proteinuria >0.5 g/day)
• arthritis
• pleuritis or pericarditis
• malar rash
• CNS involvement (psychosis, seizures)
During active SLE, complement (C3 & C4) are reduced and the ESR is raised.
see also: ANA (antinuclear antibodies)

DNA antibodies (anti-double-stranded DNA)
Smear cells
These are lymphocytes which rupture in a blood film presenting a smeared

appearance. They are typically found in large numbers in chronic lymphatic
leukaemia.
Smooth muscle antibodies (SMA)
specimen: serum
SMA are present in high titre in 80-90% of autoimmune hepatitis, usually in

association with positive ANA and raised total IgG. Transient low titre SMA
elevations occur in other liver diseases and viral illnesses.
see also Hepatitis, autoimmune

Sodium (Na+), serum
specimen: serum
ref. range: 135-148 mmol/L
Decreased sodium – hyponatraemia
Values in the range 130-134 are common and sometimes difficult to explain. Below
130, an explanation must be sought.
• fluid or electrolyte loss with inadequate electrolyte replacement –

diarrhoea, vomiting, excessive sweating, post-operative losses, fistulae,
parenteral fluid replacement with saline <0.9%.
• drugs – diuretics (particularly thiazides), ACE inhibitors, NSAIDs,
carbamazepine, imipramine, amitriptyline, lithium, – and others
• oedematous states – cardiac, hepatic, renal
• renal tubular disease – salt-losing syndromes
• Legionnaire's disease and other chest infections
• pseudo-hyponatraemia – hyperlipidaemias and paraproteinaemias
• endocrine diseases — diabetes, hypothyroidism, Addison's disease,
hypopituitarism
SIADH – syndrome of inappropriate ADH, a common cause of hyponatraemia,

including those where the sodium is very low (<125). Causes of SIADH include:
– carcinoma, particularly of lung

– pulmonary infections
– CNS disorders
– drugs
The cause of the low serum sodium is water retention due to inappropriate secretion
of ADH in the face of a serum osmolality below 270 mosmol/L.

The correct physiological response in this situation is inhibition of ADH secretion
with formation of a dilute urine of osmolality <100 mosmol/L but in SIADH, urine
osmolality is >100 and urine Na+ concentration is typically >20 mmol/L.
Diagnosis is based on exclusion of known causes of hyponatraemia and measurement

of urine osmolality and Na+ concentration. Reducing water intake will usually
correct the hyponatraemia.
Sodium, urine
ref. range: 40-220 mmol/day
In a well person, urine sodium output reflects dietary intake. A low output, <20
mmol/day, may be an indicator of a total body sodium deficit but interpretation
requires consideration of all fluid and electrolyte parameters.
Somatomedin C
see IGF-1 (insulin-like growth factor-1, somatomedin C)
Somatotropin
Specific gravity, urine

ref. ranges: random urine 1.002-1.030
24-hr urine 1.015-1.025
after 12-hr fluid restriction >1.025
This outdated measure of urine concentration has been replaced by urine osmolality
(qv).
Specificity
see Sensitivity/Specificity
Sperm antibodies
specimen: seminal fluid
Antibodies in seminal fluid are a marker for immunological male infertility.
Spermogram
see Seminal fluid
Spherocytes

Spherocytosis is associated with haemolysis:
• congenital spherocytosis
• autoimmune haemolytic anaemia
• microangiopathic haemolysis
• severe burns
• after splenectomy
Splenectomy specimens
Pack in ice without fixative and forward to lab as soon as possible.
Sputum culture
Sputum is examined in three clinical situations:
Suspected TB Where infectious TB is a possibility, ZN stain and culture are

essential. see Tuberculosis (TB) for more detail.
Pneumonia If the patient can produce sputum – often a problem – the examination
is worthwhile provided it is collected before antibiotics are commenced.
Acute on chronic bronchitis A sputum examination is seldom useful though the

matter is debated. In exacerbations of chronic bronchitis the important organisms are
Strep. pneumoniae and Haemophilus influenzae. Moraxella (formerly Branhamella)
catarrhalis may also be involved.

% susceptible
amox tetra cotr cefaclor amox-clav eryth pen
H. influenzae 81 99 91 100 100 0¹ —
S. pneumoniae —² 71 67 —² —² 100 68
M. catarrhalis 3 98 98 100 100 98 3
1. The newer macrolides roxithromycin and to a greater extent

clarithromycin have activity against H. influenzae.
2. While pneumococci with reduced susceptibility to penicillin
are also less susceptible to other B-lactam agents they usually
respond to amoxycillin treatment for lung infections. Recent
New Zealand data indicates that approximately 93% of
pneumococci are susceptible to amoxycillin or augmentin.
Sputum cytology
Early morning deep cough specimens should be collected on 3 separate days and each
one delivered to the laboratory that day to prevent the cell deterioration that occurs if
specimens are stored for more than a few hours. Refrigeration at 4°C slows
deterioration. 65% of lung tumours are picked up by three good specimens and 85%
by five specimens.
SST (serum separator tube)
Staphylococci

These organisms are divided into two groups according to whether they produce
coagulase, an enzyme-like protein that bestows invasive potential.
Coagulase-positive staphylococci
Staph. aureus The common pyogenic organism of skin and wound infections and a
variety of serious systemic infections. About 30% of normal people carry Staph.
aureus in their anterior nares.
% susceptibilities
fluclox amox-clav cef cotrim eryth pen
staph. aureus 93¹ 93 93 99 86 9
1. There has been a significant increase in the prevalence of MRSA in
Auckland in recent years.
2. Quinolones are not recommended for treating S. aureus infection
because the MIC's are close to the cutoff for susceptibility and
the common emergence of resistance.
MRSA – methicillin resistant Staph. aureus
MRSA are always resistant to methicillin/oxacillin, penicillin, amoxycillin,

amoxycillin-clavulanate, and all cephalosporins.
With regard to other sensitivities, it is important to distinguish between two different

forms of MRSA:
• multi-resistant MRSA Until 1995 these were the only variety known. They
are resistant not only to penicillin and cephalosporins but also alternative oral
agents such as erythromycin, tetracycline and cotrimoxazole. They are found
infrequently but when identified require action:
– isolate the patient

– minimise staff contact
– screen staff if there is evidence of cross-infection
– treat infection

– consider eradication therapy for those who are colonised
– consult Infection Control Officer
• non multi-resistant MRSA In 1995 new strains of MRSA were identified

that were seldom resistant to erythromycin, tetracycline or cotrimoxazole.
Because they were believed to have originated in Western Samoa, they have
been designated WSPP strains and they now represent more than 90% of all
MRSA isolates in Auckland. They do not require the expensive infection
control procedures listed above but should be treated with standard
precautions as for other S. aureus.
MRSA Screening
This is done on patients coming from outside New Zealand for surgery or from parts
of New Zealand where there is known to be an MRSA problem.
A minimum of two swabs is required:
• nostrils – one swab inserted into each nostril in turn

• perineum – swab close to the groin
• skin lesions if present must also be swabbed – these include furuncles, eczema
and psoriasis. The swab should be moistened with transport medium first.
Results are available in 2 or 3 days, depending on speed of growth of the organisms.

Where clearance is required for urgent surgery or admission, please provide a phone
number.
Coagulase-negative staphylococci
Staph. saprophyticus A relatively non-pathogenic organism. It is of clinical interest

mainly as a cause of urinary tract infections, particularly in young women where it is
second in frequency to E. coli.

% susceptibilities
amox-clav amox nitrof trim
Staph. saprophyticus 100 98 100 94
Staph. epidermidis A universal skin commensal, non-pathogenic except where host

defences are seriously compromised or when introduced by instruments or prostheses.
S. epidermidis is not infrequently grown from an MSU but is of doubtful

pathogenicity. If accompanied by pyuria, treatment could be considered bearing in
mind the other causes of pyuria.
STD (sexually transmitted disease)
The two main pathogens causing urethral or vaginal discharge and pain are Neisseria
gonorrhoeae and Chlamydia trachomatis. Collection of specimens is described under
Neisseria and Chlamydia. The list of sexually transmitted organisms includes:
• Candida species
• Chlamydia trachomatis
• Gardnerella vaginalis
• hepatitis B
• herpes simplex virus
• HIV
• HPV
• Neisseria gonorrhoeae
• syphilis (Treponema pallidum)
• Trichomonas vaginalis
It is essential that the sexual partner(s) be investigated and treated as well as the
person who presents with symptoms.

Steatorrhoea
see Faecal fat

Malabsorption
Sterile pyuria
infections): white cells
Steroid estimations
Steroid hormones are described under individual headings including: aldosterone,

androstenedione, cortisol, DHEAS, 17-hydroxyprogesterone, oestradiol,
progesterone, testosterone.
Stippling of red cells
This classical sign of lead poisoning (qv) is also a non-specific finding in other
haemopoietic disorders including aplastic anaemia, thalassaemia, myelodysplasia and
megaloblastosis.
Streptococcal antibodies (ASK, ASOT, ADNAse)

specimen: serum

ASK = antistreptokinase
ASOT = antistreptolysin O titre
ADNAse = antiDNAse
ref. ranges:
ASK ASOT ADNAse

probably no infection 0-640 0-250 0-200
equivocal 640-2560 250-400 200-350
probable recent infection >2560 >400 >350
The figures above are interchangeably described as "titres" or "units".
These tests are used when searching for evidence of recent streptococcal infection in
suspected post-streptococcal glomerulonephritis (PSGN) or rheumatic fever (RF).
Serial tests should be done, looking for rising titres. A high level is more likely to be
significant and sustained levels may indicate persisting infection. PSGN or RF can
easily be over-diagnosed when an isolated, equivocal, titre is used as evidence.
Time-course after streptococcal infection

ASOT and ASK start to rise a few days after infection commences. ADNAse tends to
rise somewhat later. In uncomplicated infections, titres return to baseline levels in 2-
3 months. Average baseline levels in adults are half those in children due to the
frequent streptococcal throat infections in the latter. ASOT does not usually rise in
streptococcal skin infections whereas ADNAse does.
see also Rheumatic fever

Streptococci
Streptococci cause a wide spectrum of common diseases. Three species or groups are
commonly isolated.
1. Streptococcus pyogenes
Also known as beta-haemolytic group A streptococcus, this organism is the

common cause of bacterial pharyngitis. It also causes 20% of skin and wound
infections, particularly cellulitis and impetigo where it is the most frequent
pathogen. There are a wide variety of other less common sites of infection.
% susceptible
pen amox-clav cef eryth tetra
Strep. pyogenes 100 100 100 99 80
Strep. pyogenes pharyngitis is responsible for the post-strepococcal immune

disorders rheumatic fever and post-streptococcal glomerulonephritis hence the
importance of recognising and treating the infections, particularly in children.
see also Streptococcal antibodies (ASK, ASOT, ADNAse), Throat swabs.
2. Streptococcus pneumoniae
Often called the pneumococcus, a common commensal in our upper

respiratory tract, with up to 60% of people carrying it. It is a gram-positive
diplococcous which causes α -haemolysis on blood agar (greening of the agar
due to partial haemolysis of the red blood cells) and often has a capsule
conferring resistance to host defences. More than 80 different serotypes are
known but most disease is caused by a limited number of serotypes.
Transmission is from person to person by droplet spread.

It causes a wide range of infections : pneumonia with or without bacteraemia,
otitis media, sinusitis , meningitis, and other types of invasive disease. It does
not cause pharyngitis or tonsillitis. 30-50% of community acquired
pneumonia is due to pneumococci and around 10% of nosocomial pneumonia.
There are about 80 cases of pneumococcal bacteraemia a year in Auckland.
Several conditions are associated with more frequent and severe

pneumococcal pneumonia: alcoholism, diabetes, chronic renal disease, heart
failure and some malignancies.
% susceptibilities
pen eryth tetra cotri chlor
Strep. pneumoniae 71 80 81 52 96
While pneumococci with reduced susceptibility to penicillin are also

less susceptible to other B-lactam agents they usually respond to
amoxycillin treatment for lung infections. Recent New Zealand
data indicate that approximately 93% of pneumococci are
susceptible to amoxycillin.
In the eye, S. pneumoniae is susceptible to chloramphenicol ointment but is

intrinsically resistant to neomycin.
Pneumococcal vaccine
Splenectomised patients are at significant risk for invasive pneumococcal disease and
should receive vaccine.
Pneumococcal vaccine contains 23 of the most common serotypes and covers 90% of
strains causing invasive diseases. 90% of adults respond to a single dose. The
vaccine is also recommended for persons >65 years, persons at increased risk of
complications such as those mentioned above, immunocompromised patients,
including those with HIV. It is ineffective in children under the age of 2 years. The
vaccine is under utilised. Greater use will probably require a change in its funding.

3. Viridans streptococci
Universally present in the throat as a commensal. It can cause sub-acute

bacterial endocarditis when it settles on damaged heart valves during transient
bacteraemia.
Streptococcus bovis is a member of the viridans streptococci which is

important through its association with colonic neoplasia. 20% of patients with
S. bovis bacteraemia have an underlying colonic adenocarcinoma and they
also need evaluation for endocarditis.
4. Streptococcus faecalis (Group D streptococcus)
see Enterococcus
Strongyloidiasis
Intestinal infestation with Strongyloides stercoralis is found world-wide in tropical

regions, particularly SE Asia and Central America. Clinically it can present with
abdominal discomfort, diarrhoea or malabsorption. A life-threatening disseminated
hyperinfection occurs in immunocompromised patients. Diagnosis relies on finding
larvae in faeces or, in disseminated disease, respiratory secretions. It tends to be less
easy to eradicate than hookworm, which is a related nematode. Treatment of choice
is now ivermectin, 200 µg/kg/day once daily for two days. Treatment of infection in
immunocompromised patients requires specialist advice. Follow-up tests are
recommended 4-6 weeks after treatment.
STS (serological tests for syphilis)

Subacute thyroiditis
see Thyroid disease — diagnosis and monitoring, paragraph D
Sulphaemoglobin
see Haemoglobin pigments
Sweat electrolytes
specimens: an appointment is necessary

ref. ranges:
-
interpretation sweat Na+ or Cl
normal <40 mmol/L
doubtful 40-50 mmol/L
cystic fibrosis >50 mmol/L
In the absence of DNA testing, this is the definitive test for cystic fibrosis (qv).
Sodium and chloride levels in the range 80-190 mmol/L are consistent with the
diagnosis.
The sweat specimen is collected into a patch of blotting paper taped to an area of skin
to which a weak electric current is applied. Sodium and chloride are present in sweat
in approximately equal concentrations. The test turns positive in affected infants at
age 3-5 weeks.

Synacthen stimulation test
specimens: serum
– collect baseline specimen
– inject 0.25 mg Synacthen (synthetic ACTH) IM
– collect specimens ½ hr and 1 hr after Synacthen injection. The peak level is
usually reached at 1 hr rather than ½hr.
Indications:
Used in suspected Addison's disease or for assessment of adrenal reserve after long-
term steroid therapy.
Interpretation:
The criterion for adequate adernal reserve or Synacthen testing is a peak level of 700
nmol/L or more. The degree of rise is not useful to confirm or refute an adequatre
response.
A basal level >500 nmol/L almost always indicates adequate adrenal reserve unless
the patient is on steroid treatement or under severe stress.
In the rare situation where there is pituitary disease of recent onset, the Synacthen test
may be normal, becoming abnormal later as the adrenal atrophies.
Synovial aspirate
specimens: collect into a plain tube. If sufficient fluid is available, collect a

citrate (blue top) tube as well.
Synovial fluid examination provides definitive diagnosis of septic arthritis, gout and
pseudogout, and places other effusions into the broad categories of non-inflammatory

lesions (trauma, osteoarthritis, etc.) and inflammatory non-infective disease
(rheumatoid arthritis, etc.).
Examination covers the following:
• gross appearance: clear, cloudy, purulent, blood-stained (trauma)
• volume
• white cell count - normal <200/cmm

non-inflammatory 200-2000/cmm
inflammatory non-infective 2000-60,000/cmm
septic arthritis >60,000/cmm
• white cell differential — polymorphs predominate in septic arthritis, gout, pseudo-

gout and sometimes in rheumatoid arthritis; mononuclear cells usually predominate
in the inflammatory non-infective disorders.
• Gram stain
• crystals — polarised light is used to look for the urate crystals of gout or the
pyrophosphate crystals of pseudogout.
• culture — aerobes, gonococci and anaerobes
Other examinations will be performed on request. Synovial fluid rheumatoid factor is

not a useful test.
Syphilis
Syphilis is uncommon in New Zealand and most genital ulcers have other aetiologies.
Where there is a possibility of syphilis, serological tests (see Treponemal serology
(STS, serological tests for syphilis)) should be performed. If a lesion is strongly

suspicious of syphilis with the typical painless indurated ulcer, direct fluorescent stain
can be arranged with the microbiologist.
see also Treponemal serology (STS, serological tests for syphilis)
Systemic lupus erythematosus
T3, free (tri-iodothyronine)

specimen: serum
ref. range:
pmol/L
< 10 yrs 3.0 - 10.0
> 10 yrs 2.5 - 5.5
pregnancy 1st trimester 3.0 - 7.6
2nd 2.8 - 7.2
3rd 2.6 - 6.4

T3 is the active thyroid hormone with T4 being effectively a "prohormone". 80% of
T3 is formed from T4 in the tissues, the remainder being directly secreted by the
thyroid.
Like T4, T3 is protein-bound in the blood and protein-binding abnormalities can

elevate both free and total T3 without causing hyperthyroidism.
Elevated by:
• hyperthyroidism, including T3 thyrotoxicosis

• T3 (Tertroxin) therapy — because T3 has a short half-life, levels fluctuate up
to 30% depending on time of last dose.
• subacute thyroiditis – early stage
see Thyroid disease — diagnosis and monitoring, paragraph D6
• Hashimoto's thyroiditis – occasionally in early stage see Thyroid disease —
diagnosis and monitoring, paragraph C4
• heterophilic antibodies, protein-binding abnormality
see Thyroid disease — diagnosis and monitoring, paragraph D2
Lowered by:
• hypothyroidism – but is a poor test for this
• T4 therapy — though T3 is usually within the reference range when T4 dose
is appropriate
• non-thyroidal illness see Thyroid disease — diagnosis and monitoring,
paragraph D1
• drugs : amiodarone (qv), propranolol, steroids,
• lithium, iodine in tonics or contrast medium
• hypopituitarism (secondary hypothyroidism)
see Thyroid disease — diagnosis and monitoring, for more detail.

T4, free (thyroxine)
specimen: serum
ref. ranges:
pmol/L
4 - 7 days 16 - 40
1 - 4 wks 15 - 35
1 - 12 mths 11 - 32
Over 1 year 10 - 24
pregnancy 1st trimester 10 - 23
2nd 10 - 19
3rd 8 - 19
Although T4 is the principal thyroid hormone, it is converted to T3 in the tissues. It

is the preferred thyroid replacement therapy in hypothyroidism.
Elevated by:
• hyperthyroidism
• T4 (Eltroxin) therapy — because the half-life is long, time of sampling for
monitoring is unimportant.
• non-thyroidal illness see Thyroid disease — diagnosis and monitoring,
paragraph D1
• drugs: amiodarone, NSAIDS, propranolol, steroids, iodine-containing contrast
medium, heparin
• heterophilic antibodies, protein-binding abnormalities see Thyroid disease —
diagnosis and monitoring, paragraph D2
• sub-acute thyroiditis – early stage see Thyroid disease — diagnosis and
monitoring, paragraph D4
• Hashimoto's thyroiditis – early stage see Thyroid disease — diagnosis and
monitoring, paragraph C4
• self-administration of T4 e.g. for attempted weight reduction
Lowered by:

• primary hypothyroidism
• non-thyroidal illness (uncommon)
• hypopituitarism (secondary hypothyroidism)
• Hashimoto's thyroiditis
• sub-acute thyroiditis (recovery stage)
• drugs: T3 (Tertroxin), phenytoin, lithium, carbamazepine
Target cells
These are cells with a "target" appearance due to a stained centre within the normal
hypochromic zone. They are seen in liver disease, thalassaemia, after splenectomy
and in severe iron deficiency.
TB
TCT
see Thrombin clotting time (TCT)
TDM (therapeutic drug monitoring)
see Drugs, therapeutic monitoring (TDM) (TDM) individual drug listings

Tegretol (carbamazepine)
see Anticonvulsants
Telopeptide
see N-telopeptide
Testosterone
specimen: serum
ref. ranges:
free testosterone total testosterone

pmol/L nmol/L
adult female 8 - 58 0.5 - 2.5
adult male 380-1200 11.0 - 35.0
Note :
• These are peak values measured at 7-9 am. Late afternoon and evening values
can be substantially (20-30%) lower, especially in young men.
• The lower ends of these ranges are not well-defined. A total testosterone of
say 9 or 10 in a male may be transient or may be normal for that person.
• Acute illness lowers testosterone levels which should be measured only in

well patients.

Free and total testosterone
Free testosterone, the biologically active fraction, is derived from total testosterone
using the value for SHBG which is the serum binding protein. Where the increase in
testosterone is small, as in minor degrees of hirsutism in the polycystic ovary
syndrome, it may be found that only the free testosterone is above its reference limit.
Age changes in males
The male embryo has high levels of testosterone falling to female levels at time of
birth but with a second peak during the first few months of life. Throughout
childhood male levels are not much higher than in females until at about age 11 the
pubertal rise commences, reaching adult levels at about age 17. Levels decline
slowly from about age 40 on, the decline being more marked in free testosterone than
total testosterone which is partially sustained by a rise in SHBG.
About 50% of males aged over 60 have free testosterone levels below the young male
reference limit. Level of sexual activity and libido are not usually correlated with
testosterone levels until total testosterone falls below 8.

Increased levels
• hirsutism (50% of cases)
• adrenal tumours
• drugs
– some testosterone supplements
– oestrogens in low dose
– anticonvulsants (free level is often low)
• exercise
Decreased levels
• obesity
• alcoholism
• debilitating disease
• primary hypogonadism - LH is elevated
• secondary hypogonadism - hypopituitarism (qv)
• hyperprolactinaemia
• hypothyroidism
• haemochromatosis
• hepatic insufficiency
• drugs
– synthetic androgens
– steroid therapy
– high dose oestrogens
– phenothiazines and others
– oral contraceptives
Thalassaemias
The thalassaemias are common hereditary conditions in which there is a reduction in

the synthesis of one or more of the four globin chains of the haemoglobin molecule.
Adult haemoglobin, HbA, which makes up >96% of normal Hb, contains two a and
two ß globin subunits and these define the two main groups of disorders, the a
thalassaemias and the ß thalassaemias.

The genes for thalassaemia are found commonly in Asians, Polynesians, Africans and
Mediterranean peoples. Clinically, the thalassaemias range from the clinically
undetectable heterozygous state, through mild microcytic, hypochromic anaemias,
(thalassaemia minor) to severe transfusion-dependent anaemias or foetal death
(thalassaemia major).
Clinical presentation
The major thalassaemia syndromes usually come under specialist care early in life
with moderate or severe haemolytic anaemias.
The thalassaemia trait disorders, which are usually asymptomatic, will for the most
part be discovered incidentally on a routine blood film:
— anaemia, usually mild, sometimes moderate, sometimes lower end of the

reference range
— microcytic, hypochromic blood film, resembling an iron deficiency anaemia but

with an MCV which is disproportionately low compared with the anaemia
— normal ferritin, s. iron, iron-binding capacity
— the blood film may show other suspicious abnormalities; and the histogram of
red cell size distribution may show a pattern typical of thalassaemia.
When iron deficiency coexists with thalassaemia, the diagnosis may not become
apparent until iron replacement has been achieved.
Diagnosing the type of thalassaemia
The thalassaemias are complex and diverse and under certain circumstances may
require specialised DNA and globin chain analyses to characterise them fully. In

ordinary clinical practice, once the diagnosis of thalassaemia has been suspected
because of microcytosis in the absence of iron deficiency, a group of tests is applied
to broadly separate a from ß thalassaemias. These tests are:
• HbH inclusion bodies (a)

• Hb electrophoresis
• HbA2 % (ß)
• HbF % (ß)
• Kleihauer stain (ß)
Alpha Thalassaemias
Each parent contributes two a genes giving a total of four. Alpha thalassaemia
results from deletion of 1 or more of these 4 genes.
deletion Hb MCV HbH bodies clinical

-a /aa single gene N N absent 'silent carrier'
a
- /- a two gene (trans) N N (usually) very occas. Polynesian type
--/aa two gene (cis) ± occas. more severe than trans.Asian type
--/-a three gene numerous HbH disease
--/-- four gene - - - intrauterine death
Beta thalassaemias
Beta thalassaemias arise from point mutations in the coding genes rather than
deletions and more than 300 mutations have been identified. The first thalassaemia to
be described, by Cooley in 1925, was severe ß thalassaemia found in a patient of
Mediterranean descent, thalassa being the Greek for sea.
a and ß thalassaemias occur with roughly equal frequency.

Clinical implications of thalassaemia
Once a thalassaemia has been identified it is essential that the patient be told of the
diagnosis and that they should not be given iron unless there is coexisting iron
deficiency.
Testing of a partner and genetic counselling may be required for a woman planning a
family.
Theophylline (Nuelin)
specimen: serum
therapeutic range: 55-110 µmol/L
The therapeutic range refers to peak levels. The specimen is collected 4-6 hours after
the last dose for long-acting preparations, 2 hrs after those that are short-acting.
Thirst
see Polydipsia/polyuria
Threadworms
see Enterobius vermicularis (pinworm)

Throat swabs
Swabs are taken from the tonsillar area for a sore throat, or the posterior pharyngeal
wall for sinus trouble so as to collect post-nasal discharge.
The most common indication for a throat swab is to detect Group A streptococcus (S.
pyogenes). Culture results take 1-2 days to be reported.
Rapid streptococcal antigen tests are not performed in the laboratory. Their general
use increases the cost of testing as it is commonly recommended that all patients with
a negative rapid antigen test require a culture.
Streptococcus pyogenes (qv), which is 100% sensitive to penicillin, is by far the

commonest bacterial pathogen in pharyngitis in immune competent patients.
Occasional pathogens include Arcanobacterium haemolyticum (qv), Bordetella,
gonococci, groups C and G streptococci, diphtheria, and anaerobic organisms in
quinsy.
Thrombin clotting time (TCT)

ref. range: 10-18 seconds
The thrombin clotting time is prolonged by hypofibrinogenaemia,

dysfibrinogenaemias, FDPs and heparin.

Thrombocytopenia
9
A reduction in platelets below 150 x 10 /L. The lower the platelet count, the stronger
the possibility of spontaneous bleeding.
80-150 bleeding very unlikely

40-80 bleeding unusual
20-40 bleeding becomes increasingly common but is certainly not invariable
0-20 severe thrombocytopenia which can be life-threatening.
Should always be referred to a haematologist.
Bleeding is not directly proportional to the degree of thrombocytopenia.
Thrombocytopenia in pregnancy can put the foetus at risk and should be referred for a
specialist opinion.
Causes of thrombocytopenia:
· acute infection transient, often marked, thrombocytopenia may be seen

in association with acute viral illnesses in children. In
this setting, platelet levels often recover rapidly. Post-
viral thrombocytopenia in adults may persist at mild to
moderate levels and is assumed to have an immune-
mediated mechanism. Acute HIV infection may be a
cause of thrombocytopenia.
· drugs a long list including salicylates, sulphonamides,

trimethoprim, penicillins, cephalosporins, methyldopa,
chlorthiazide, frusemide, tolbutamide, heparin,
phenytoin, phenobarbitone, carbamazepine,
phenothiazines, phenylbutazone, gold, penicillamine –
and others.

· alcohol and liver disease
· ITP (qv) idiopathic immune thrombocytopenic purpura
· leukaemias
· marrow infiltration malignancy, myelofibrosis
· other hypersplenism, SLE, B12 or folate deficiency, DIC, post-

transfusion, post-partum
· pregnancy ITP, dilutional or gestational thrombocytopenia, GPH

syndromes
Thrombocytosis
Refers to an increase in the platelet count above 450 x 109/L.
Transient reactive thrombocytoses up to about 800 x 109/L are common. Causes are:
• blood loss
• surgery, trauma
• infection, including viral infection
• other inflammatory disorders
• malignancy – an important cause of persistent thrombocytosis
• essential thrombocythaemias
• polycythaemia vera
• myelofibrosis
• myelodysplasia

Thromboembolic disease
Venous thromboembolism (VTE)
Thrombophilia
Thrombophilia, an increased tendency to thrombosis, either inherited or acquired or

both, is described under hypercoagulability.
Thyroglobulin
specimen: serum
Used for monitoring treatment of thyroid carcinoma
Thyroglobulin antibodies
see Thyroid antibodies

Thyroid antibodies
specimen: serum
ref. range: not present
Graves' disease and primary hypothyroidism are both autoimmune diseases and are
associated with a variety of antibodies.
Antimicrosomal and anti-thyroglobulin antibodies
These are the standard "thyroid antibodies" requested and they give the same
information; when only one is elevated, it is more likely to be anti-microsomal.
Elevated in:
· Hashimoto's thyroiditis – antibodies in high titre will differentiate non-toxic

goitre from Hashimoto's
· primary hypothyroidism – antibodies present in 90%, often in high titre
· thyrotoxicosis – 90% have antibodies, usually in low titre
· autoimmune disease marker – there is an association with diabetes and

pernicious anaemia.
· euthyroid normals – 10% have antibodies usually in low titre. Annual follow up
will show progression to thyroid disease in some, indicating that these elevations
can be a marker for an early autoimmune state.
Thyroid Stimulating antibody (TSab, also called TSH receptor ab)
This IgG antibody, formerly known as LATS, is the marker for autoimmune
thyrotoxicosis (Graves' disease).

Thyroid disease — diagnosis and monitoring
A. Choice of test
TSH is the one-test screen for patients with non-specific symptoms such as
tiredness. A level between 0.4 and 4 mU/L gives 99% exclusion of hyper- or
hypothyroidism.
T4 is added:
• when there are more specific symptoms of thyroid disease such as

tachycardia, atrial fibrillation, weight loss, cold or heat intolerance etc.
• when monitoring thyroid therapy
• suspected hypopituitarism
T3 is added when thyrotoxicosis is suspected.
The combination of clinical and laboratory features will indicate probable status
as hyperthyroid, hypothyroid or euthyroid.
B. Hyperthyroid states
1. Aetiology of thyrotoxicosis
There are three main causes of thyrotoxicosis:-
• Graves' disease (65%) diffuse hyperplasia associated with

autoimmune TSH receptor antibodies and often with
ophthalmopathy. Graves' disease is 10x commoner in women and
has a peak incidence in middle life. Treatment with carbimazole is
associated with remission in 50%.

• Toxic multinodular goitre (25%) – the incidence steadily increases
with age. This is not an autoimmune condition and there is no
ophthalmopathy. Because remission is infrequent, treatment is
typically with I131.
• Toxic uninodular goitre (<10%) – defined by radionuclide scan.

Treatment is by surgery or I131ablation.
2. Lab results in thyrotoxicosis
Thyroid tests
The clear-cut case has a T4 above 40, a T3 above 12 and an

undetectable TSH (<0.03). Borderline abnormalities in a
clinically euthyroid person suggest that hyperthyroidism, if
present, is of mild degree.
Over a period of time, mild hyperthyroidism can either progress

to more obvious disease or revert to normal, hence the
importance of monitoring levels at intervals of 1-6 months.
T3 thyrotoxicosis (normal or low T4, TSH, <.03, raised T3) will

be missed if T3 is not measured in all patients with undetectable
TSH, particularly if they are clinically hyperthyroid. T3
thyrotoxicosis is more frequent in the elderly.
Non-thyroid tests
Other abnormalities that may be found are:
– elevated ALP of bony origin

– elevated calcium
– elevated ferritin
– elevated liver enzymes
– normocytic anaemia
– macrocytosis due to associated pernicious anaemia
– neutropenia
3. Monitoring carbimazole therapy

Because of the possibility of agranulocytosis, a blood count is part of
the pre- and post-treatment laboratory profile along with T4 and
TSH. With the usual starting dose of about 15mg carbimazole twice
daily, many patients will be clinically and biochemically euthyroid
within 4 weeks though biochemical abnormalities may lag behind
clinical changes and later overshoot into hypothyroidism. The aim is
to adjust the carbimazole dose, usually downwards, and monitor the
T4 and TSH at about 8-week intervals so as to keep them normal
over a 12-24 month period after which withdrawal can be observed
to see if remission has been obtained.
4. Hashimoto's thyroiditis and subacute thyroiditis (see below) can

both pass through transient hyperthyroidism in their early stages.
5. Factitious thyrotoxicosis due to taking of T4 or T3 tablets must

always be kept in mind.
C. Hypothyroid states
1. Primary hypothyroidism
This is an autoimmune disorder, more common in women and with

advancing age, reaching a prevalence of around 10% above the age
of 60. Because its presenting symptoms resemble those of normal
aging, the diagnosis can easily be missed if a screening TSH is
omitted. The term subclinical hypothyroidism describes clinically
euthyroid patients with a TSH between 5 and 10 and a T4 in the 8-16
range. There is debate whether they need to be treated withthyroxine
but early treatment is favoured in the younger age group (40-60 yrs),
and those, with high levels of thyroid antibodies or
hypercholesterolaemia. If not treated, these patients should be
monitored at least annually
2. Lab results in primary hypothyroidism
• Thyroid tests

The diagnosis rests on the elevation of TSH, usually above 20,
and often over 100 which makes it one of the easiest diagnoses
in laboratory medicine. T4 is variably reduced but may still be
within the population reference range. T3 levels are a poor
predictor of hypothyroidism.
• Non-thyroid tests
Abnormalities that may be found include:
– elevated cholesterol
– elevated triglyceride
– elevated CK due to myopathy
– elevated liver enzymes
– normocytic or macrocytic anaemia due to direct effect on
erythropoiesis
– macrocytosis due to associated pernicious anaemia
– iron-deficiency anaemia due to associated menorrhagia
– elevated creatinine
3. Thyroxine therapy in hypothyroidism
The aims of therapy are:
• reduce TSH to within the reference range

• eliminate symptoms of hypothyroidism
• avoid induction of cardiac ischaemia or arrhythmias in those
with coronary artery disease or in the elderly.
• reduce cholesterol and triglyceride to their euthyroid levels
The dose range for thyroxine is usually in the range 0.05-0.15 mg/day,
depending on body weight. A healthy younger person weighing 70 kg
could start at 0.10 mg/day.
After two months to allow hormone levels to reach their new

equilibrium (the TSH can be slow to change), T4 and TSH are re-
measured. Depending on whether the TSH is above or below the
range 0.4-4.0, the thyroxine dose will be increased or decreased by
0.025 mg/day with further laboratory check in two months.

In the older person or those with coronary artery disease, the starting
dose is 0.025 mg/day, increasing by 0.025 every 8 weeks until TSH
has fallen or cardiac symptoms call a halt to further increases.
Thyroxine therapy, once stabilised, will continue for life with
monitoring of TSH every 6-12 months or more frequently if the
patient's clinical status changes.
4. Hashimoto's thyroiditis Like primary hypothyroidism, this is an

auto-immune destruction but instead of gland atrophy there is
infiltration with lymphocytes and exudate causing goitre. In theearly
stages, release of T4 and T3 into the blood stream can cause mild
thyrotoxicosis but this leads to permanent hypothyroidism.
5. Secondary hypothyroidism due to hypopituitarism is very much less

common than other aetiologies but must always be considered in the
puzzling situation where T4 and T3 are low and the TSH is normal
or low instead of showing the expected elevation. The finding of a
normal TSH in these hypothyroid patients is due to detection of
physiologically inactive TSH by the assay.
see also Hypopituitarism
6. Congenital hypothyroidism – see neonatal screening
D. Euthyroid states with abnormal thyroid tests
1. Non-thyroidal illness (sick euthyroid syndrome) Any intercurrent

illness, particularly when severe, can cause transient depressions in
TSH, T3 or T4 levels. Sometimes the T4 is elevated and the TSH
may rise briefly during the recovery phase.
2. Thyroid autonomy/subclinical hyperthyroidism with normal T4

and T3 but low TSH
The situtation where a suppressed TSH is found in a healthy,

clinically euthyroid patient has a prevalence of up to 15% in older
patients. The term thyroid autonomy describes the situation where
thyroid hormone secretion is suppressing pituitary TSH partially or

completely but without lifting T4 or T3 levels above their reference
ranges and without clinically detectable hyperthyroidism.
Euthyroid suppression of TSH is more common in women, in the
elderly, and in patients with multi-nodular goitre. Because a small
percentage of these patients progress to overt hyperthyroidism,
monitoring is indicated, perhaps annually, particularly in those
where TSH remains persistently undetectable.\
3. Pregnancy
Because hCG has some thyroid stimulating activity, TSH may be

suppressed during the first trimester.
4. Thyroid-binding protein abnormalities and assay artefact
Sometimes T4 and/or T3, and occasionally TSH as well, are

markedly elevated (e.g. a T4 of 50-100 pmol/L) in a person who is
clinically euthyroid. This is due to presence of clinicallyirrelevant
heterophilic or autoantibodies in serum or else to abnormal thyroid-
binding serum proteins.
5. Subacute thyroiditis
A not uncommon condition due to viral infection of the gland

which is swollen and tender – the thyroid equivalent of mumps. As
in Hashimoto's there can be a thyrotoxic picture in the early
destructive stage but return to normal is usual, sometimes with a
hypothyroid swing during the recovery stage.
Thyroid stimulating hormone (TSH)

specimen: serum
ref. range:

mU/L
cord blood 3 - 20
age 1 day 10 - 100
2 - 3 days 1 - 20
4 days - 1 yr 1.0 - 8.0
children & adults 0.4 - 4.0
TSH is the thyroid screen test of choice – a level between 0.4 and 5 mU/L gives 99%
exclusion of hyper- or hypothyroidism.
The third generation assays now in common use measures down to 0.03 mU/L. A
level below this, described as an undetectable TSH, is strongly supportive of a
diagnosis of thyrotoxicosis.
Abnormal TSH levels, whether high in hypothyroidism or low in hyperthyroidism,

respond slowly to appropriate therapy with the new equilibrium level not reached for
2-8 weeks.
TSH is elevated by
• primary hypothyroidism, subclinical or clinical — see Thyroid disease —

diagnosis and monitoring paragraph C1
• Hashimoto's thyroiditis — see Thyroid disease — diagnosis and monitoring

paragraph C4
• subacute thyroiditis, recovery phase — see Thyroid disease — diagnosis and

monitoring paragraph D5
• non-thyroidal illness – occasionally during recovery phase — see Thyroid

disease — diagnosis and monitoring paragraph D1
• ectopic TSH from tumours of lung, breast etc.
• drugs: lithium, metoclopramide, clomiphene, domperidone, iodides: kelp tabs,

amiodarone, contrast medium

• TSH release is pulsatile – minor elevations may simply be detecting the transient
peak of a pulse.
TSH is decreased by:
• hyperthyroidism – usually the TSH is <0.03 in clinical thyrotoxicosis —

see Thyroid disease — diagnosis and monitoring paragraph B2
• thyroid autonomy /sub-clinical hyperthyroidism — see Thyroid disease —

diagnosis and monitoring paragraph D2
• patients on supra-optimal T4 or T3 therapy — see Thyroid disease —

diagnosis and monitoring paragraph C3
• drugs: steroids, L-dopa, bromocriptine, heparin.
• non-thyroidal illness — see Thyroid disease — diagnosis and monitoring

paragraph D1
Thyroiditis, sub-acute
see Thyroid disease — diagnosis and monitoring — paragraph D5
Thyrotropin
see TSH

Thyrotropin releasing hormone
see TRH (thyrotropin releasing hormone) stimulation test
Thyroxine
see T4, free (thyroxine)
TIBC (total iron binding capacity)
Tinea
see Dermatophytes
Tobramycin
see Aminoglycoside, serum levels
TORCH(es) antibodies

This is an acronym derived from infections causing intra-uterine growth retardation
or death : Toxoplasma, Other, Rubella, CMV, Herpes (and Syphilis).
"TORCH antibodies" is no longer regarded as an appropriate block of tests –

individual tests should be requested according to indications.
Torulopsis glabrata (Candida glabrata)
A yeast which closely resembles Candida albicans (q.v.) in both symptoms and
treatment.
Total CO2
see Bicarbonate
Total protein
see Proteins, total, serum
Toxic granulation
see Neutrophils (polymorphs), neutrophilia

Toxocara canis (and cati)
An ascarid worm found in dogs and passed on to young children who ingest egg-
contaminated dust and soil. Eggs passed in dog faeces are not infective and require 2-
5 weeks under favourable conditions to mature. Ingested mature eggs hatch,
releasing larvae which traverse gut mucosa and may migrate to any organ, in
particular eye and lung. Antibodies to Toxocara are common throughout the world
but clinical infections (visceral larva migrans) are rare. Eosinophilia, often marked,
may be present. A limited serology study in New Zealand revealed <5% of adults
and teenagers were seropositive.
Treatment is of unknown value.
Toxoplasma
specimen: serum
ref. range : IgM antibodies reported as; negative

borderline
positive
IgG antibodies 0 - 6 µ/ml -ve
>6 µ/ml +ve
IgM antibodies become detectable 5 days after infection and remain for months or
occasionally years. A positive IgM result does not separate current from past
infection except when a rising titre can be demonstrated. Approximately 2% of
women tested antenatally are +ve for IgM but most do not have active infection.
IgG antibodies become positive 1-2 weeks after infection and remain positive for
life. A strongly rising titre over a 3-week interval is good evidence of current
infection. 30 - 60% of the population have IgG antibodies.
Life-cycle & clinical disease

Toxoplasma gondii is an intracellular protozoan found in cats, humans, sheep, pigs
and other mammals. Cats are the primary hosts spreading cysts in their faeces to be
accidentally ingested by cat-lovers and grass-eating animals. In the secondary host –
man’ domestic animals – the infection is usually subclinical but with
lymphadenopathy, variant lymphocytes in the blood film and a lymphocytosis.
Viable parasites in the tissues of domestic animals cause infection when their meat is
eaten undercooked. In the immunocompromised human, quiescent lesions can be
reactivated causing serious disseminated infections.
Toxoplasmosis in pregnancy
About one third of women acquiring toxoplasmosis during pregnancy will transmit
the parasite to the foetus. In the first trimester the incidence of infection is about 10%
but with a high risk of serious or fatal disease in the foetus. In the second and third
trimesters the foetal infection rate rises to 30% and 60%, respectively, but with less
serious effects in the foetus where the disease may not be apparent until later in
childhood with CNS impairment or chorioretinitis.
If antibodies were known to be present at least one month before conception, the
foetus will be safe.
Because infection, whether in or out of pregnancy, is usually subclinical, the

diagnosis is often made only when an affected foetus or child is encountered.
Sometimes a mother will ask for toxoplasma tests during pregnancy and about 2% of
these will test +ve for IgM antibodies, most of them derived from pre-pregnancy
infections.
If a mononucleosis-like illness occurs in pregnancy, or if there is any other reason to

suspect acute maternal infection, serial testing of antibodies is obligatory followed by
toxoplasma DNA testing of amniotic fluid or foetal blood. DNA testing of amniotic
fluid at around 18 weeks of pregnancy is highly predictive for the presence or absence
of foetal infection. Discussion with a microbiologist is recommended when
toxoplasmosis in pregnancy is suspected.

TPHA
Transferrin
specimen: serum
Transferrin is the serum iron-binding transport protein which is measured by "iron-

binding capacity" and is described under that heading.
As an approximation, transferrin = IBC ÷ 20.
Trephine biopsy
A trephine biopsy of iliac bone is taken by haematologists as part of a bone marrow

examination.
Treponemal serology (STS, serological tests for

syphilis)
specimen: serum

ref. range: non-reactive
1. Screen test
The initial enzyme-immunoassay test is a screen for both non-treponemaland

treponemal antibodies. A positive screen test will be followed by the RPR
(rapid plasma reagin), TPHA (treponema pallidum haemagglutination) and
FTA (fluorescent treponemal antibody).
2. Non-treponemal (reagin) tests, RPR and VDRL
The RPR and VDRL (venereal disease research lab) are the most widely used
of the older, non-specific reagin tests. They can be transiently positive in a
wide range of viral and autoimmune diseases as well as syphilis and yaws.
After successful treatment of syphilis, the RPR/VDRL titre declines and may
become negative.
The RPR/VDRL is used as a screening test for syphilis and for monitoring
response to treatment. A positive result may be due to:
• current infection – rare in New Zealand. The titre will nearly always be
>1:16
• past, inactive, treponemal infection – the titre is usually <1:16, often 1:1 or
1:2.
• SLE – the "biological false positive RPR" is found in 10-20% of SLE and
is one of the serological markers
• other autoimmune diseases, including antiphospholipid syndrome
• viral infections, malaria and Mycoplasma pneumonia infections – positive

for < 6 months
• parenteral drugs
• aging

• pregnancy is sometimes listed as an infrequent cause of a low titre false
positive RPR
3. Treponemal tests TPHA and FTA
The TPHA and FTA are much more specific for treponemal infections but
unexplained, weakly reactive, false positives of one or both tests are sometimes
found.
After a treponemal infection, the TPHA and FTA stay positive indefinitely
without indicating whether disease is current or past.
In true treponemal infections, all three tests, VDRL or RPR, TPHA and FTA,
will usually be clearly reactive.
Antibody tests cannot distinguish between yaws and syphilis infections which
are both due to Treponema pallidum species.
WHO attempted to eradicate yaws from the Pacific Islands in 1961 but without
success, there having been numerous new outbreaks since then.
TRH (thyrotropin releasing hormone)

stimulation test
Formerly used as a test for borderline hyperthyroidism but now replaced by sensitive
TSH estimation. In hyperthyroidism, the TSH response to TRH is reduced.
Trichinosis
An intestinal and muscular infection caused by the nematode Trichinella spiralis.

Pigs are the main reservoir, and eating under-cooked pork the principal mode of
infection. Although T. spiralis is common world wide, particularly in North America
and Europe, cases in New Zealand are most likely to be in persons who have acquired

the disease overseas. New Zealand and Australia are considered essentially free of
infection though a focus was detected in a pig farm in the North Island in May 1997.
Infected pigs probably still exist. It is likely that rats and wild cats serve as a
reservoir.
Diagnostic tests include eosinophil count, CK, serological tests and muscle biopsy.
Trichophyton
see Dermatophytes
Tricyclic antidepressants
see Antidepressant drugs, tricyclic
Triglyceride
specimen: serum
ref. range: <2.0 mmol/L (fasting)
Non-fasting specimens: After eating, dietary triglyceride is found in chylomicrons

and smaller "remnant" products. However, 90% of normal people have a non-fasting
triglyceride of <1.8 mmol/L which excludes hypertriglyceridaemia and can make the
inconvenience of fasting unnecessary.
Fasting specimens (>8 hours after food): The above comment not withstanding, it is
usual to measure triglyceride in the fasting state and with abstention from alcohol for
the previous 24 hours.

Triglyceride in the fasting state comes from the liver in VLDL particles and their
smaller IDL products. When triglyceride metabolism is markedly impaired,
chylomicrons can be present in the fasting state. If the fasting triglyceride is above 5
mmol/L, the specimen will appear cloudy due to raised VLDL and/or chylomicrons
which rise to form a creamy layer on standing.
Elevated fasting triglyceride:
1. Primary • familial combined hyperlipidaemia

• familial hypertriglyceridaemia
• type III ("remnant removal disease") hyperlipoproteinaemia
2. Secondary • obesity
• alcohol
• diabetes
• hypothyroidism
• liver disease, particularly obstructive
• pancreatitis
• pregnancy
• significant illness
• drugs: oestrogen, oral contraceptives, beta blockers, corticosteroids,
thiazides, retinoic acid, anti-viral agents, valproic acid
Very high triglycerides
A patient with a triglyceride above 10.0 mmol/L is at risk for acute pancreatitis and
requires immediate restriction of dietary fat and alcohol, treatment of any other
underlying cause such as diabetes, and addition of a triglyceride-lowering drug such
as a fibrate if other measures fail.
With massive hypertriglyceridaemias, serum can have the appearance and consistency
of cream. Often there is more than one aetiology, e.g. diabetes and alcohol.

Triglyceride levels can rise and fall very quickly. Above a level of 6.0 mmol/L,
lipoprotein lipase clearance mechanisms are saturated which means that dietary fat
can rapidly raise triglyceride to surprising levels. Dietary restrictions may cause it to
fall equally quickly.
see also Lipid disorders
Tri-iodothyronine
see T3, free (tri-iodothyronine)
Trophoblastic disease
Troponin I (TnI) and Troponin T (TnT)
specimen: serum
ref. ranges: Troponin I <2.0 µg/L
Troponin T <0.1 µg/L
Elevation of one of the cardiac troponins, which are almost identical in their clinical
usage, is more sensitive and specific for myocardial infarction than CKMB.
Concentrations rise within 4 - 12 hours of commencement of cardiac pain and remain
elevated for 7 days in the case of TnI or 10 days for TnT.

Unstable angina can also cause elevations due to minimal myocardial damage not
detected by CKMB. It is important to recognise that angina without myocardial
necrosis will not elevate troponins.
If the specimen was obtained less than 12 hours after commencement of chest pain, a
follow up should be collected 6-12 hours after the first.
TnT can be elevated in chronic renal failure in the absence of known myocardial
damage whereas TnI is largely unaffected.
Absence of rise doesn't exclude ischaemic cause for chest pain — may warrant
specialist follow-up.
see also Myocardial markers for infarction (MI) and ischaemia
Trypsin, blood
see Cystic fibrosis

Neonatal screening
Trypsin, faeces
An old and unsatisfactory test for cystic fibrosis in infants, now replaced by the blood
test
see Cystic fibrosis

Neonatal screening
Faecal chymotrypsin is sometimes used as a test of pancreatic function.

Tryptase
specimen: serum
Tryptase, an enzyme found in mast cells, is released after an anaphylactic reaction,

reaching a peak after 1 hour and falling back to baseline over the next 8 hours. It can
be used to differentiate true anaphylaxis from non-immunological reactions such as a
vaso-vagal attack.
Tryptase may also be used in the diagnosis of mastocytosis.
TSH
see Thyroid stimulating hormone (TSH)
Tuberculin test (Mantoux test)
Indications
• patients with a clinical illness consistent with TB

• people who have been in contact with a case of proven TB.
• assessing immune status in a person expecting to work in contact with TB,
e.g. a hospital service dealing with TB or someone working in a country
where TB is endemic.
Method

The standard Mantoux test consists of an intradermal injection of 5 units of tuberculin
(PPD - purified protein derivative) contained in 0.1 ml of solution. The injection is
made into the anterior aspect of the forearm and read 3 days later (2-4 days are the
outer limits if 3 days is impracticable).
When reading the test, the arm is palpated to define an area of induration and the
diameter of this induration, if present, is measured in mm transverse to the long axis
of the forearm.
An area of surrounding erythema (redness), or erythema alone, is ignored.
If vesiculation (blistering) or necrosis (darkening or ulceration) of the indurated skin

is present, these must be described as an important part of the result.
Interpreting results
A diameter of induration >10 mm is described as positive and is consistent with

current or past TB infection.
A strong positive in a person with active TB disease may be >15 mm with

vesiculation and necrosis.
Previous BCG vaccination is associated with induration up to 15 mm though usually

<5mm.
In children under age 5 years, an induration >5 mm is read as positive.
In immuno-compromised persons, the tuberculin reaction may be reduced or

suppressed, even in the presence of proven infection.

False positive Mantoux results
These are usually due to operator error, particularly reading errors where the area of
erythema rather than induration has been read.
False negative Mantoux results
Although a -ve Mantoux usually indicates that person has never been exposed to TB,
there are important exceptions.
• the person has had TB in the past but the immune response has faded.
• overwhelming infection or illness of any type, including overwhelming TB.
• patients with immune suppression – HIV, immunosuppressive drugs,
sarcoidosis, renal failure, malignancy, malnutrition.
• acute viral infections, recent live virus vaccinations.
• neonates.
• operator error, improperly stored PPD.
Positive predictive value of tuberculin testing
The positive predictive value is the % of people with a positive tuberculin reaction
who are actually infected with TB.
Figures are not available for New Zealand, but the Canadian figures below are
indicative. They are for young adults vaccinated with BCG after age 5.

Positive
prevalence predictive value
(%) (%)
Mantoux result > 5 mm > 10 mm > 5 mm > 10 mm
Clinical situation
Screening, Canadian born 6 4 17 17
Casual contact of smear-positive case 10 10 26 31
Household contact of smear-
positive case 50 50 63 70
Recent immigrant from tuberculosis
endemic country 80 70 73 78
Note that despite BCG vaccination, only 6% of Canadian-born subjects had a

Mantoux >5 mm. Of these, 17% had TB.
The test has much stronger predictive power in recent immigrants from a TB endemic
country. In these, the prevalence of past or present TB infection was 50-60%.
see also MOH Guidelines for Tuberculosis Control in New Zealand, 1996.
Tuberculosis (TB)
One third of the world's population is infected with TB, the majority of them in the
developing world.
High risk groups are those who have arrived from Asia or the Pacific Islands in the
past few years and those with other family members who have been infected.
Infection is by inhalation of droplet nuclei. Local replication leads to acute disease in

about 5% of those infected. It is higher in infants and those more than 60 years old.
About 10% of infected people reactivate during their lifetime. This is more common
over the age of 50 and in men than women.

Diagnosis
Specific diagnosis requires isolation of bacilli from an appropriate specimen. The

tuberculin test (qv) can be useful provided its limitations are recognised.
Specimens
Urines The whole of an early morning specimen should be collected on 3

different days. A special collection jar is provided and each should be
returned to the lab on the day of collection.
Sputum ZN stain and culture of sputum is the most effective test for diagnosing
infectious TB. Three specimens should be examined, preferably early
morning on separate days. Automated liquid-based culture methods
grow TB from most smear-positive specimens within a week.
Bronchial washings Collect into a sterile container
Aspirated fluid Collect into a citrate bottle
Tissue Specimens for culture must be placed in sterile saline or water,

not in formalin.
Treatment
M. tuberculosis remains the predominant cause of mycobacterial disease in New

Zealand. The incidence is highest in SE Asian immigrants, Polynesian Pacific
Islanders and Maori. Resistance to antituberculous antibiotics is uncommon but
highest in immigrants. When tuberculosis is suspected seek specialist advice.

Principal drugs
– Isoniazid (INH) is an oral agent coming in 100mg tablets. Side effects

include hepatoxicity and peripheral neuropathy (prevented by routinely
taking pyridoxine 10mg daily). The usual dose is 300 mg/day for adults.
– Rifampicin is also an oral agent but there is an IV preparation. It causes red

or orange discolouration of all body secretions (urine, tears, saliva) and may
stain soft contact lenses. Fever, rash and hepatotoxicity are other side effects.
Usual dose is 600mg daily, commonly combined with INH 300mg daily
(Rifanah '300' or '150' tablets).
– Pyrazinamide is now the most commonly used third initial drug. Tablets are
500 mg and common doses are 1500mg - 2000mg. Hepatotoxicity,
gastrointestinal tract disturbance and skin rash are seen.
– Ethambutol was the most usual oral third drug but has now been relegated.
Usual dosing is 15 mg/kg/day and tablets are 400mg and 100mg. At higher
doses it causes retrobulbar neuritis.
– other agents, e.g. amikacin, ethionamide, new macrolides, new quinolones

and capreomycin may be used for drug resistant tuberculosis.
see also Tuberculin test (Mantoux test)
Tubes for blood collects
Blood consists of two fractions:
• cells – red cells, white cells and platelets

• plasma – fibrinogen plus serum

If blood is left to stand in a plain glass or SST tube, the fibrinogen precipitates
forming clot which contracts leaving the straw-coloured serum to be poured off the
clot.
Haematologists, when doing blood counts, are interested in the cellular components
and therefore add an anticoagulant, usually EDTA, to prevent clotting.
Biochemists and immunologists are interested in serum components and use clotted
specimens. Sometimes, however, plasma is the preferred specimen rather than serum
and a heparin anticoagulant is used.
A further point is that blood cells are a living tissue and continue to live in the tube.
As the specimen stands at room temperature, red cells consume energy, converting
glucose to lactic acid thus reducing the blood glucose. These processes are slowed
but not prevented, by storage in a refrigerator. After a few hours, the red cells
become increasingly sick, releasing their potassium, haemoglobin, phosphate and
enzymes into the surrounding serum or plasma.
Types of tube
The colour of the stopper denotes the preservative or anticoagulant within the
vacutainer. Recently the trend has been to smaller volumes (10 or 7ml tubes
changing to 5ml) and from glass tubes with rubber stoppers to all-plastic. As
analytical systems evolve, the tubes change but currently, the tubes in use are:
Plain tube bright red plastic top
Provides a clotted specimen from which serum can be poured. Used mainly for
immunology tests where antibodies are to be measured. It can be used for
biochemistry tests but the SST is preferred because of its superior qualities of
separation.

SST tube yellow plastic top
Used for most biochemistry tests.

SST stands for Serum Separator Tube. It contains a 1cm glug of material which
promotes clotting and separation of serum from clot.
EDTA tube purple top
Used for most haematology including haemoglobin, white count, differential,

platelets, film and ESR. Also for HbA1c, blood lead and other biochemical tests
where the analyte is inside the red cell. EDTA is an anticoagulant which acts by
removing calcium.
Citrate tube blue top (also called sodium citrate or buffered citrate)
Used for INRs and other coagulation tests. The tube must be allowed to fill
completely to achieve optimum citrate:blood ratio.
Fluoride tube grey top
Used only for glucose. The SST or plain tube can be used for glucose provided the
specimen is analysed within 2 or at the most 4, hours. Fluoride is an enzyme poison
which blocks red cell metabolism and thus prevents the consumption of glucose.
Heparin tube green top
Used for blood gases and some hormone assays.
CPD tube yellow top
Used for tissue-typing, DNA and cell marker studies.

CPD is citrate phosphate dextrose.
Tumour markers
Because of their low specificity, most tumour markers are not used as screening tests
– there are just too many false positives.
Their main use is in monitoring treatment and progress in established disease but they
are also used when a particular malignancy is suspected on clinical grounds or when
the site of the primary lesion is unknown in disseminated malignancy.
marker most common tumour type

AFP (alpha foeto protein) primary liver, gonad
Bence Jones Protein in urine myeloma
CA 15-3 breast
CA 19-9 pancreas
CA 72-4 gastrointestinal malignancies
CA 125 ovary
calcitonin medullary thyroid carcinoma
catecholamines phaeochromocytoma
CEA (carcino-embryonic antigen) colon (various)
hCG (human chorionic gonadotropin) testis, placenta
HIAA carcinoid tumour
immunoglobulins in serum EPP myeloma, macroglobulinaemia
PSA (prostate specific antigen) prostate
thyroglobulin thyroid carcinoma

Turner's syndrome
In Turner's syndrome, phenotypic females have only one X chromosome rather than
the usual two. Clinical features include short stature, sexual infantilism and primary
amenorrhoea. Gonadal dysgenesis is indicated by raised FSH and LH and low
oestradiol.
Diagnosis is based on demonstration of the abnormal karyotype by the cytogenetics

laboratory.
Typhoid
see Salmonella antibodies (Widal Test) typhi
Ulcer scrapings for cytology
These are collected particularly from lesions in the oral cavity suspected of
malignancy. Scrape the surface firmly with a wooden spatula or cytobrush. Fix at
least one slide with Cytofix as for a cervical smear. Another slide should be left to
air-dry if lymphoid neoplasia is suspected.

Unconjugated bilirubin
Units
see SI (systeme internationale) units
Urate, serum
specimen: serum
ref. range: adult female 0.14 - 0.36 mmol/L

adult male 0.20 - 0.42 mmol/L
children 0.10 - 0-.30 mmol/L
0.42 mmol/L has been chosen as the upper end of the male range because this is the
level above which the risk of gout begins to rise from 1 in 1000 below 0.42 to 1in 20
at a level above 0.54. About 20% of Auckland males have a urate above 0.42.
0.36 mmol/L is used for women because on average their levels, before the
menopause, are 0.06 mmol/L lower than men. After menopause, levels in women
approach those in men and their risk of gout increases.
Polynesians have higher levels than Caucasians.

Urate is a breakdown product of cell nuclei, one third from the diet, two thirds from
endogenous tissue catabolism. 20% of urate is excreted by the kidney, the remainder
in the gut.
Elevated urate
Like cholesterol, baseline serum urate levels are genetically determined but elevated
by secondary factors:
• high purine diet – liver, kidney, shellfish, fish roe, kina

• alcohol
• renal insufficiency
• drugs : diuretics, salicylates in low dose, steroids, chemotherapeutic agents,
niacin, ethambutol, pyrazinamide
• polycythaemia vera
• malignancies, particularly leukaemias or lymphomas being lysed by
chemotherapy
• hypothyroidism
• rare enzyme defects – can present as gout or urate nephropathy in children,
young adults or pre-menopausal women
• Down’s syndrome
• metabolic syndrome – hypertension, dyslipidaemia, diabetes, obesity
• pregnancy – compared with the non-pregnant base-line, levels are 20% lower
1st trimester and 20% higher in the 3rd. Levels above 0.35 mmol/L in the 3rd
trimester associated with hypertension are a perinatal risk factor.
• gout – an acute inflammatory arthritis precipitated by urate deposition in
synovial tissue and occurring mainly in middle-aged and older men and in
post-menopausal women.
Demonstration of urate crystals in aspirated synovial fluid establishes the

diagnosis beyond doubt.
Raised serum urate levels are contributory but not diagnostic. During an acute
attack of gout, serum urate may actually fall below the levels that will be
found between attacks.

Urate, urine
specimen: 24-hr urine without preservative

ref. range: 1.5-4.5 mmol/day when on average diet
Increased levels are due to high purine diet or endogenous over-production of urate.
Low levels can be due to reduced renal excretion of urate.
Urea
specimen: serum
ref. range: < 4 yrs 1.4 – 5.4 mmol/L
> 4 yrs 2.6 – 7.7 mmol/L
Elevated by:
renal impairment but s. creatinine is a better test being less subject to

other interferences
high protein diet an important determinant
catabolic states any acute serious illness, particularly sepsis
dehydration at low urine flow, there is increased tubular

reabsorption of urea

bleeding into GI tract can give elevations up to 15 mmol/L
prostatic hypertrophy or other post-renal obstruction
drugs steroids, diuretics
As a routine measure of renal function, creatinine has almost entirely replaced urea.
Nephrologists, however, measure urea as well as creatinine in dialysis patients, the
preferred urea level being below 20-30 mmol/L.
An unexpected fall can be due to loss of albumin in dialysis fluid.
Unexpected rises in dialysis patients can be due to:
– dietary non-compliance, too much protein

– sepsis
– dehydration or catabolic illness
– steroid dose too high
Urethral swabs
Male
Where there is a discharge, swabs for Chlamydia (qv) and gonococci (qv) should be
collected by the doctor at the time of examination. Alternatively, a specimen can be
collected by a male nurse or microbiologist at the laboratory – or, as a last resort, the
patient can be given swabs in one of our other rooms and asked to collect the
specimen himself. Our female nurses do not collect urethral specimens from males.

In the absence of a discharge, urethral swabs are unlikely to grow a pathogen. A first
catch (not mid-stream) urine specimen is a better test for Chlamydia than a swab,
particularly when there is no discharge.
Female
The urethra should be swabbed for gonococci and Chlamydia when looking for STD.
Uric acid
see Urate, serum
Urinalysis (routine biochemistry and

microbiology) and UTIs (urinary tract infections)
specimens: MSU (mid-stream urine), CSU (catheter-stream urine) or casual.

Store specimen in fridge while awaiting transport.
Urinary catheter tips are not suitable for culture because results do not predict the
presence of bacteruria. They should not be sent.
A. Component tests
• bacterial count
• culture
• Microscopy – performed when an abnormality is detected by dipstick or

when specifically requested (e.g. when searching for casts in suspected
renal disease). We use phase contrast microscopy and look for

squamous epithelial cells, white cells, red cells and red cell ghosts,
bacteria, casts and crystals.
• dipstick analysis
— protein
— red cells/Hb
— white cells as shown by leucocyte esterase activity
— gram-negative infection as shown by nitrite activity which
has excellent specificity but only 40-80% sensitivity for
infection
— glucose
— ketones
— bilirubin/urobilinogen
B. Interpretation
1. Bacterial count A count of >105/ml (>108/L) in the presence of a

growth of a single organism is virtually pathognomonic of urinary tract
infection.
A count of <102/ml is most unlikely to be associated with infection.
This leaves the range 102-105/ml as a grey area where interpretation

requires consideration of the whole clinical picture including
symptoms, past history, age and sex. For example a sexually active
young woman with dysuria and frequency should usually be treated in
the presence of pyuria, even if her bacterial count is only 103/ml.
2. Culture A pure culture of a single organism usually indicates

infection whereas a mixed growth is usually due to contaminants. The
rule is by no means invariable and in a person with recurrent infections
and predisposing factors, a mixed growth may be significant.

Organism % susceptible
(% of total isolated) amox-clav amox trimeth cefaclor nitrof norflox
E. coli (74) 95 44 78 98 99 100
Proteus mirabilis (5) 97 81 84 97 res 99
Staph. saprophyticus (4) 99 65 92 98 100 99
Strep. Gp B (4) 100 100 100 99 100 98
Enterococci (4) 100 99 53 res 98 79
Pseudomonas (3) res res res res res 88
Kleb. pneumoniae (3) 96 0 87 97 89 98
Staph. epidermidis (1) 97 29 71 85 97 91
Staph. aureus (1) 99 17 96 97 100 95
% Sens. for all organisms 93 48 75 90 92 98
3. White cells A count of up to 10 white cells/cmm is accepted as normal.
The commonest cause of pyuria (increased white cells) is bacterial infection

which will show up in the bacterial count and culture. The infection can be at
any level in the urinary tract — urethra, prostate, bladder, kidney.
Sterile pyuria describes the finding of increased white cells but with no
bacterial growth on routine media.
Causes include:
• resolving urinary tract infection on antibiotics — a test for anti-bacterial

substances (ABS) will be positive.
• gonococcal urethritis – standard urine culture media do not grow

gonococci which require a urethral swab for STD
• chlamydial urethritis – see Chlamydia trachomatis
• renal TB – uncommon but important; consider TB culture
• urinary tract tumour – urine cytology may help
• calculi
• trauma, including recent instrumentation

• prostatitis
• viral or Mycoplasma infection
• age: elderly men and women may have pyuria, 20-40 WBC/cmm, and
sterile urine
Collection of a mid-stream specimen helps to identify urethritis and prostatitis

where the white cells are concentrated in a first-catch specimen.
4. Haematuria — red cells and/or free Hb have been detected in the urine.
Normal urine has less than 10 x 106 red cells/L which is approximately at
the limit of detection of a urine dipstick.
Dipsticks give a positive test for blood with:
• intact red cells

• free Hb
• myoglobin
When the dipstick is positive for blood we do a red cell count using phase
contrast microscopy. There are 8 possible results : nil, 10, 25, 50, 100,
250, 500, >500. At about the 500 level, blood just becomes visible to the
naked eye. Results below this, detectable only by dipstick or microscope,
are termed microhaematuria.
40% of our routine urinalyses test positive for blood. Most of these are
microhaematuria and most are transient and benign. Sometimes the
dipstick is positive but the red cell count nil. On very rare occasions this is
due to haemoglobinuria (qv) or myoglobinuria but for practical purposes it
can be treated as if it were microhaematuria with red cells present.
When considering diagnostic implications, haematurias can be divided into

two groups;
a. Benign or relatively benign transient haematuria
These include the haematurias that have an identifiable benign cause, e.g. UTI
and which disappear with elimination of the cause.

• UTI – a very common cause of haematuria. White cells are almost
invariably present as well.
• menstrual contamination – also very common. Presence of epithelial

cells indicates contamination
• vigorous exercise
• benign renal microhaematuria – a somewhat nebulous entity, diagnosed

by exclusion. There is no hypertension or proteinuria and serum
creatinine is normal. Phase contrast microscopy of freshurine shows
that the red cells are entirely dysmorphic (see below) indicating their
glomerular origin.
• contaminants such as hypochlorite
• medications, e.g. vitamin C, anticoagulants
• transient haematuria of unknown origin – the blood has vanished when a

follow-up specimen is examined. This group includes the unexplained
transient dip-stick-only haematuria with no red cells seen on microscopy.
b. Persistent pathological haematurias
A persistant haematuria always requires investigation. Causes include:
• urinary tract tumours

• urinary tract stones
• urinary tract trauma
• renal pathology – glomerulopathy, etc.
• bleeding disorders
• intravascular haemolysis causing haemoglobinuria
• myoglobinuria
c. Red cell morphology in haematuria
Some workers recommend examination of a fresh urine (less than 1 hour old)
under phase-contrast microscopy to allow distinction of dysmorphic (distorted)
red cells, which are entirely of glomerular origin, from eumorphic (normal-
looking) red cells which can originate anywhere in the urinary tract. Presence

of eumorphic red cells in urine is an indication to consider further investigation
such as cystoscopy and imaging. If the red cells are entirely dysmorphic and
there is no clinical or other evidence of renal disease, the diagnosis of benign
renal microhaematuria can be applied and follow-up confined to repeat urine in
3-12 months.
5. Proteins The dipstick, which is only semi-quantitative, turns positive at a

protein concentration of about 100-300 mg/L. A trace or 1+ can be due to an
infection, particularly one involving the kidney rather than just the bladder. A
test registering 2+ or greater raises the possibility of glomerular disease. If
proteinuria persists, 24-hour urine protein output should be measured.
The dipstick detects mainly albumin and may entirely miss other proteins such
as free light chains.
see Proteins, urine (proteinuria) for more detail
6. Casts Hyaline protein casts are found relatively frequently and are not
regarded as significant. Granular (white cell) and red cell casts on the other
hand are strong indicators for renal disease, particularly glomerular disease.
7. Glucose Positives indicate diabetes or renal glycosuria (qv) and require blood
glucose estimations as follow-up.
8. Bilirubin & urobilinogen Positives require serum bilirubin and liver

enzymes for interpretation.If the blood tests are normal, a positive
urobilinogen can be ignored.
9. Crystals Cystinuria is sometimes detected by finding cystine crystals.
Urine cytology
A series of three mid-morning, randomly-voided urine samples from a well-hydrated

ambulant patient gives the best results. A 2-3 hour output, (at least 50mls), is
required. Urine specimens should be forwarded to the laboratory as quickly as
possible and refrigerated (not frozen) if there is any delay. Adequate diagnostic
results can be achieved with samples kept cool for up to 48 hours prior to processing

but the best yields require refrigeration of under 4 hours. Catheter specimens, bladder
wash, and ureteric specimens are treated similarly.
Urine free cortisol
see Cortisol, urine free
Urine, pigmented
Causes include:
Red urine
• haematuria
• phenolphthalein – containing purgatives, which are red when alkaline. Fresh
urine is acid but turns alkaline on standing
• diet – beetroot, rhubarb turn red on standing, particularly with coexisting iron
deficiency
• some porphyrias – turn red/brown on standing
• haemoglobinuria (qv)
• myoglobinuria (qv)
Orange/brown urine
Concentrated urine in febrile states is sometimes described as abnormal by patients.

• bilirubin, or urobilinogen which turns brown on standing
• drugs, e.g. methyldopa, de Witts pills, chloroquine, rifampicin, quinine,
metronidazole, nitrofurantoin, riboflavin
• some porphyrias turn brown on standing
• melanin in disseminated melanoma
• alkaptonuria, turns brown on standing
• tyrosinaemia
Yellow urine
• vitamin B complex, multivitamins
Blue/green urine
• drugs, e.g. amitriptyline, NSAIDs, triamterene

• biliverdin
Milky urine
• infection
• chyluria (qv)
• oxaluria
Factitious additives (something the patient has added) are another source of
pigmentation.

Urine, preservatives
Urine specimens should always be kept in the refrigerator to prevent growth of

bacteria.
Some tests require special preservatives, the commonest being 10mls of concentrated
acid. It is absolutely essential that the patient be warned that any apparently
innoccuous-looking fluid in the bottom of the bottle may be dangerous and corrosive.
The fluid must not be touched and children must not be allowed to get near the bottle.
Tests which require acid preservatives are:
Catecholamines (for phaeochromocytoma)

HMMA (VMA)
5HIAA (for carcinoid syndrome)
arsenic
copper
lead
No preservative is required for:
creatinine (and creatinine clearance)

free cortisol
protein
cystine
amylase

Urine for TB
specimen: 3 early morning urines
Urobilinogen in urine
Urobilinogen is sometimes reported positive on routine urinalysis by dipstick. Viral
hepatitis and haemolytic disease should be excluded by checking liver enzymes,
reticulocyte count and haptoglobins. If these are normal, the positive urobilinogen
can be ignored.
Uroporphyrins
see Porphyrias
URTI (upper respiratory tract infection)
see Throat swabs

Ear swabs & infections
UTI (urinary tract infection)
infections)

V
Vaginal discharge
specimen: routine swab collected from 5 cm inside the vagina and placed in
transport medium.
The normal flora of the vagina is an abundant growth of gram-positive lactobacilli.
Undesirable organisms are of three main types:
Trichomonas detected by microscopic examination of a smear taken from the swab.
Candida often obvious clinically as a curd-like growth, it is easily cultured.
Bacterial vaginosis a growth of predominantly anaerobic organisms associated with a lack of

normal lactobacilli. Clue cells are a feature and Gardnerella vaginalis may be
present.
Metronidazole provides effective treatment for both bacterial vaginosis and

Trichomonas infections.

Where an STD is suspected as cause of a discharge, cervical and urethral swabs
should be collected. Vaginal swabs seldom grow gonococci or test positive for
Chlamydia.
Valproic acid (Epilim)
specimen: serum
Serum levels are generally unhelpful and should not be done except to check
compliance. There is no accepted therapeutic range though levels below 300 µg/L
are said to be more likely to be associated with poor seizure control and levels above
700 more likely to be associated with hepatotoxicity.
Vanillyl mandelic acid (VMA)
Variant lymphocytes
see Lymphocytes
Variation
= variance

When a test is repeated day after day on the same person, results will not be identical.
The term variation or variance describes the extent of these day-to-day and week-to-
week changes. Consideration of variation is essential when trying to decide whether
a patient is getting better or worse. For example, someone's cholesterol is 6.8. They
go on a diet. A month later the result is 7.2. Does this mean the diet is making the
situation worse?
There are two components to variation.
Analytical variation
This is the "noise" in a method, the sum of the technical imperfections that prevent it
producing a perfect result every time. Modern methods are vastly better than those in
use 20, or even 10, years ago and analytical variation is generally overshadowed by
biological variation.
Biological variation
Serum concentrations in the body are controlled by physiological mechanisms which
are, not surprisingly, never perfect. This biological variation is typically about twice
as large numerically as analytical variation though this varies from test to test.
Here are some indicative examples of biological variation for results within the
reference range:
• sodium ± 4 mmol/L
• cholesterol will vary about ± 0.5 mmol over a period of weeks.
• iron commonly is 30% lower in the afternoon than the

morning.
• albumin varies 10% according to position (recumbent or

upright), time of day, state of hydration. Medication,
such as a morning diuretic, will add further variation.

Concentrations of protein-bound constituents will vary
along with the changes in protein level.
• TSH release of this and many other hormones is pulsatile

and the level will vary according to whether the sample
is collected at the peak of a pulse or near the trough.
TSH, with a reference range of 0.4-4.0 units, can vary
by up to 2 units. A change from 0.4 to 2.0 units may
not be significant.
It should be noted that reference ranges are made wide enough to allow for variation
and that is one reason they are such crude indicators of what is "normal".
Coefficient of variation (CV) The CV is the commonly used method for expressing
the analytical or biological variation of a test.
s tan dard deviation

CV = x100%
mean
For a good method, e.g. sodium, the analytical CV might be 1-2% and the biological
variation 2-4%. Mathematically this gives a combined variation of 2.2-4.5%.
The mathematical application of a measured CV tends to give a wider variation than

most people expect. As an example, consider a serum sample with an actual Ca++
level of 2.40 mmol/L. The analytical CV is 2%.
If the serum is tested 100 times, 95% of the analyses will lie in the range
2.40 ± 2cv
= 2.40 ± 2x2%
= 2.40 ± 4%
= 2.40 ± 0.10 mmol/L
= 2.30 – 2.50 mmol/L

In practice, few clinicians actually use these figures. Most assess a result intuitively
using a mixture of experience, clinical assessment and theoretical knowledge to
decide on the significance of a result and what action to take.
Varicella-zoster virus (VZV)
specimen: air-dried smear from base of fresh vesicle
The same virus is responsible for both chicken-pox (varicella) and shingles (herpes
zoster) the latter being a reactivation of dormant virus acquired during a childhood
attack of chickenpox.
Diagnosis is clinically obvious in most cases but the virus can be identified by a
fluorescent antibody applied to a suitable smear.
To collect the specimen, open a fresh vesicle, scrape the base with a spatula, smear on
a slide, air-dry and send to the lab in a labelled envelope.
Although varicella-zoster takes several weeks to grow, culture can be attempted. Use
the special viral transport swab (Virocult).
Antibody tests, preferably applied to paired sera, are also available.
VDRL

Venom
see Bee and wasp venom allergy
Venous thromboembolism (VTE)
In hospital practice venous thromboembolism is thought to contribute to 10% of

deaths. In the community, incidence varies, depending on age, between 0.1 and
1/1000 per year.
Objective diagnoses of DVT (deep vein thrombosis) and PE (pulmonmary

embolism) are important for three reasons – managing the current event, identifying
and managing recurrent disease, and managing prophylaxis in high-risk situations
such as pregnancy or surgery. The initial objective tests are ultrasound for DVT and
lung scanning or helical CT for PE. A normal D-dimer level is a useful negative
predictor for VTE.
Primary heparin therapy is essential for VTE and until recently this was administered
by continuous intravenous infusion in hospital followed by outpatient warfarin. Low
molecular weight heparins (qv) are now available which enable many patients with
both DVT and PE to be treated on an outpatient basis. The low molecular weight
heparin (LMWH) with dose adjusted for body-weight, is given subcutaneously once
or twice each day for a minimum period of five days followed by warfarin. Using
this approach more than 75% of patients will not require admission to hospital.
The duration of warfarin therapy depends on a variety of factors including extent and
site of DVT (above or below the knee), and whether there is a temporary precipitating
risk factor such as surgery, immobilisation or pregnancy:
calf vein thrombosis: – 6 weeks if associated with transient risk factor

– 3 months for idiopathic disease

proximal DVT – 3 months if associated with transient risk factor
– 6 months for more extensive or idiopathic disease
see also Hypercoagulability
Vibrio alginolyticus
An organism found in sea-water where it can cause significant infections of the

external ear or wounds. It has been found, for example, on rope-burns in yachties or
chronic ulcers in elderly people who bathe in sea-water. It is usually susceptible to
amoxycillin-clavulanate and doxycycline.
Vibrio cholerae
The causative organism of cholera. Occasionally found in Asian immigrants and on
rare occasions in visitors to endemic areas. Fluid replacement is paramount.
Treatment shortens the illness, reduces the volume of stools and fluid requirements,
and decreases organism secretion. Treatment options are ciprofloxacin, 1g as a single
dose; norfloxacin, 400mg 12-hourly for 3 days; or doxycycline, 300mg as a single
dose.
Vibrio parahaemolyticus
Found in New Zealand and Japan in shell fish which, when eaten raw, can cause food
poisoning. Treatment is fluid replacement. Most infections are self-limiting. Severe
disease may benefit from treatment, using a cholera regime, but the benefit is likely to
be small.

Virilism
see Hirsutism/virilism
Virology
Despite the vast spectrum of disease caused by viruses, they are less often
investigated by the laboratory than bacteria. They are harder to grow, harder to treat
and the trivial viral infections tend to be self-limiting.
Specific tests are described under the alphabetic entry for each disease.
As with bacteria, identification is by growth of the organism, by detection of viral

antigen, or by detection of antibodies.
Virus or its antigen Specimens can be faeces, throat swab, serum, vesicle fluid or
CSF.
Antibodies IgM antibodies usually indicate current infection. IgG antibodies indicate
past or present infection.
Diagnosis is established by an increase in titre of 4-fold or more on paired sera, the

first collected as early as possible in the disease, the second after 2-3 weeks of illness.
Enquiries about specific tests can be directed to a clinical microbiologist.
Non-specific features of some viral compared with bacterial illnesses

Viral Bacterial
neutrophil count decreased increased
lymphocyte count increased unchanged
or unchanged
blood film atypical (variant) shift to left in
lymphocytes neutrophil series
Viscosity
Blood viscosity is increased in polycythaemia vera, macroglobulinaemia and in the
late stages of myeloma. The test is not much used now.
Vitamin B12
specimen: serum
ref range: 160-600 pmol/L
140-160 pmol/L, borderline low
Normal absorption of B12 requires a non-vegetarian dietary source, a normal stomach

to produce intrinsic factor, and a normal terminal ileum to absorb the B12/IF
complex. A healthy person with replete body stores has enough B12 to last 3-6 years
if no more is ingested.
Low B12 levels
Causes include:
• vegetarian diet

• drugs – oral contraceptives
– metformin
– other : methotrexate, colchicine, slow K, anticonvulsants, cimetidine,
triamterene
• pregnancy — B12 levels are often low without tissue deficiency
• low B12 binding protein, transcobalamin I, which can be measured, but the
expense is seldom warranted
• pernicious anaemia (qv)
• malabsorption
• inflammatory bowel disease: Crohn's disease, or ulcerative colitis in the terminal
ileum
• previous gastrectomy or ileectomy
• primary folate deficiency
• Diphyllobothrium fish tapeworm infestation
Further investigation and treatment of low B12
If haematological abnormalities are present – raised MCV, anaemia, neutropenia,

thrombocytopenia, oval macrocytes and hypersegmented neutrophils in the blood film
– the underlying cause must be identified
If there are no haematological abnormalities and the patient seems healthy, there is
less urgency. The level may be normal for that person or it may indicate early
deficiency. It is a matter of clinical judgement and patient choice whether to
investigate further at once; or follow-up in 6 months or so; or, for the person who
believes in vitamin supplements, start a course of oral vitamin B12 or multivitamin
supplements. There is also the group of patients who have unshakeable faith in B12
by injection.
The elderly often have low B12 and folate levels and may benefit from supplements.

Elevated B12 levels
• oral or parenteral vitamin B12 supplement

• haematological disorders: myeloproliferative disorders, leukaemias, high
white cell counts
• liver disease
Vitamin C
see Ascorbic acid (Vitamin C)
Vitamin D
specimen: serum
ref. range: 25-hydroxy-cholecalciferol 14-76
µg/L
1a, 25-dihydroxy-cholecalciferol 18-62
ng/L
When "vitamin D" is requested, the 25-hydroxy-cholecalciferol is measured.
Vitamin D levels decline with advancing age and many very elderly people,
particularly women living in rest-homes, have levels low enough to contribute
significantly to decrease in bone density.
There is debate whether vitamin D levels should be measured routinely in this group.
Most will have low levels and it is probably more cost-effective to provide the
cheaper forms of vitamin D supplement with calcium.

In general usage, "vitamin D" is loosely applied to the physiologically active
hormone, calcitriol, and its precursors.
(in vivo) 7-dehydro-cholesterol
(dietary) ergocalciferol (vitamin D2)
(sunlight on skin)
cholecalciferol (vitamin D3)
(in liver)
25-hydroxy-cholecalciferol
(in kidney)
(physiologically active) 1α, 25-dihydroxy-cholecalciferol (calcitriol)
see also Osteoporosis/Osteomalacia
Vitamin K
Vitamin K is a fat-soluble vitamin which is essential for hepatic formation of

functionally active prothrombin (Factor II) and coagulation Factors VII, IX and X.
Although vitamin K is found in the diet, particularly green vegetables, the more
important source is the normal bacterial flora of the bowel which synthesises the
vitamin. Body stores last only 1-2 weeks if absorption stops.
Deficiencies of vitamin K and Factors II, VII, IX and X can be due to pre-hepatic or
hepatic causes.

pre-hepatic intestinal malabsorption – coeliac disease,
pancreatic disease, biliary obstruction
broad spectrum antibiotics altering the normal flora
warfarin therapy
neonates
hepatic advanced cirrhosis
severe hepatitis
The Echis ratio (qv) helps distinguish between pre-hepatic and hepatic causes.
The prothrombin ratio (PR) and its standardised presentation, INR, are used to
monitor vitamin K-dependent factor deficiencies and the anticoagulant effect of
warfarin.
Vitamin K injections correct factor deficiencies due to lack of absorption or

availability and are also used to correct a prolonged INR due to excess warfarin
action.
VLDL (very low density lipoproteins)

In the fasting state, VLDL particles contain most of the plasma triglyceride and 10-
15% of total cholesterol.
see also Lipoproteins

Triglyceride
Cholesterol

VMA (vanillyl mandelic acid)
VTE
see Venous thromboembolism (VTE)
von Willebrand's disease (vWD)
vWD, discovered in 1926 and the commonest inherited bleeding disorder, is due to a
defect in the plasma von Willebrand factor (vWF) causing a secondary abnormality of
platelet adhesion.
vWF, like fibrinogen and fibronectin, is an adhesive protein important in platelet

attachment to subendothelial surfaces and in platelet-platelet interactions at sites of
vessel injury. vWF also plays an important role in the stabilisation and protection of
coagulant FVIII:C in plasma.
The most commonly encountered type of vWD is transmitted as an autosomal

dominant trait. These patients usually have mild bleeding symptoms and mild to
moderate abnormalities in the relevant laboratory tests (type I heterozygous vWD).
Testing for vWD
FVIII:C The coagulant activity of the FVIII : C protein.
von Willebrand Factor (vWF) Measured as the von Willebrand factor antigen
(vWF:Ag). This large glycoprotein normally stabilises factor VIIIC and is variably
reduced in vWD. vWF is essential for normal adhesion of platelets and therefore for
a normal bleeding time.

von Willebrand factor activity (vWF:Activity) This is a functional activity which
measures the vWF's ability to bind to the Glycoprotein 1b platelet binding site
responsible for normal adhesion.
Collagen binding assay (CBA) The functional assay which measures the vWF's
ability to bind to collagen. A discrepancy between the vWF antigen and the CBA
suggests a variant form of vWD.
Ristocetin-induced platelet aggregation The functional activity of vWF measured as

the ability of plasma vWF to agglutinate platelets in the presence of ristocetin. The
assay is relatively sensitive and specific for vWD.
In the initial laboratory evaluation of patients suspected of having vWD, the

following should be performed:
• Bleeding time
• Platelet count
• APTT
• FVIII : C
• FVIII : C
• vWF Activity
• CBA
• Blood group
• Ristocetin platelet aggregation (not routinely performed in all patients)
One or more of these tests are usually abnormal in patients who have vWD but the
results may vary in the same patient with repeat testing. It is essential that the
patient not be taking drugs which could affect the bleeding time. Most frequent
offending agents are aspirin or other NSAIDs. Many conditions such as pregnancy,
hypo- or hyperthyroidism, uraemia, recent exercise, infection or diabetes can affect
the FVIII:C activity and vWF antigen levels. Individuals with blood group O have
significantly reduced levels of the vWF:Ag and vWF activity compared with blood
groups A, B or AB.

Patterns of Factor VIII results in vWD:
FVIII:c vWF:Ag vWF:Activity CBA Ag/CBA ratio
Normal Ν Ν Ν Ν Ν
Type 1 vWD Ν−↓ ↓ ↓ ↓ Ν
Type 3 vWD Absent Absent Absent Absent —
Type 2A vWD Ν−↓ Ν−↓ Ν−↓ ↓↓↓ ↑↑↑

Type 2B vWD Ν−↓ Ν−↓ Ν−↓ ↓ ↑
Type 2M vWD Ν−↓ Ν−↓ ↓↓ Ν−↓ Ν
Type N vWD ↓↓↓ Ν Ν Ν Ν
Notes: Type 1 is the usual heterozygous form of vWD

Type 3 is very rare and presents like severe haemophilia
Type 2 forms are the known variant forms of vWD. These are uncommon.
Warfarin anticoagulant therapy


Wasp venom
see Bee and wasp venom allergy
WBC (white blood cell count)

see Blood count
Weight loss
Consider:
• thyrotoxicosis
• diabetes
• eating disorder
• malignancy
• HIV
White blood cell antibodies
see Lymphocyte antibodies
White blood cell count and differential

see Blood count

Whooping cough (pertussis)
Widal test
see Salmonella antibodies (Widal Test)
Wound swabs
see Skin and wound swabs.
Where clinical details indicate a deep-seated infection, anaerobic cultures will be set
up.
WR (Wasserman Reaction)
replaced by VDRL/RPR
Wuchereria bancrofti
see Filariasis

X
X-match
see Crossmatch
d-Xylose test
A test formerly used for malabsorption but now discontinued because of lack of
specificity and sensitivity.

Yaws
All STS (serological tests for syphilis: RPR/VDRL, TPHA FTA) are positive in those
who have had yaws which is endemic in the Pacific, and positive STS in a Pacific
Islander are often due to yaws.
Yeasts
Yeasts grow readily from ordinary bacterial swabs and cultures. Candida albicans
(qv), the principle human pathogen, is a member of the normal flora of the gut. Other
species of Candida are also common and may cause clinical infection.
Yersinia enterocolitica
A pathogen which is being isolated with increasing frequency from cases of

infectious diarrhoea - currently about 10% of the total.
Yersinia spp. are frequently present in the intestinal tract of wild and domesticated
clinically healthy birds and animals. In New Zealand, Y. enterocolitica has been
recovered from pigs, cattle and dogs. Processed meat ready for sale has only rarely
be shown to be contaminated with Yersinia. The source of most cases of Yersinia
infection is unknown.
Some patients develop an abdominal pain syndrome which may last for weeks. The
most likely cause for this is intra-abdominal lymphadenopathy.

Y. enterocolitica is susceptible to cotrimoxazole, tetracycline and fluoroquinolone but
antibiotics do not shorten the diarrhoea which usually settles spontaneously in 3-10
days.
Infections tend to be sporadic rather than epidemic and are found world-wide. It can
cause terminal ileitis which mimics acute appendicitis presenting as right lower
quadrant pain, fever and leucocytosis. Some patients develop a reactive arthritis.
Yersinia has been transmitted by blood donated by asymptomatic donors. Patients

who have Yersinia-associated diarrhoea should inform the blood collection service if
they donate blood over the next six months.
Zarontin (ethosuxiamide)
see Anticonvulsants
Zinc, plasma
specimen: blood, trace metal tube, patient must be fasting
ref. range: 12 - 20 - µmol/L
Plasma levels are an indifferent measure of body stores.

Zinc deficiency in New Zealand can occur in patients on renal dialysis or parenteral
nutrition and in conditions involving chronic loss of protein and electrolytes. Some
drugs, including steroids, diuretics and anticonvulsants, may reduce zinc levels. The
rare recessive condition acrodermatitis enteropathica is associated with an isolated
malabsorption of zinc.
Reported possible symptoms of deficiency include loss of appetite, poor taste,

dermatitis, abdominal pain, diarrhoea, decreased growth and sexual development, and
infertility.
Health food shops sell zinc supplements to boost the immune system and cure colds
and topical preparations may promote healing of wounds and ulcers. Plasma levels
do not give useful information in these situations - better to try the products and see if
they work.
More serious levels of zinc deficiency are found in developing countries where the
high phytate content of cereal diets binds zinc. In 1961a group of anaemic clay-
eating Iranian dwarfs with rough dry skin and absent secondary sex characteristics
were shown to be zinc deficient and their troubles corrected by oral zinc sulphate.
Zinc toxicity has been described in welders inhaling zinc oxide fumes causing metal-
fume fever or brass chills.

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Diagnostic Handbook

The Interpretation of Laboratory Tests

PREFACE TO THE THIRD EDTION

biochemistry Mike Gill

cytology/histology Tony Bierre

haematology Paul Ockelford

immunology Mike Gill

microbiology Arthur Morris

see also — Reference ranges and the concept of normality

S.I. units are used throughout.

Abiotrophia defectiva and A. adjacens

Nutritionally variant streptococci which need growth factors to support growth. An

see Blood grouping

see Antibacterial substance (ABS)

© 2000 Diagnostic Medlab View Terms of Use Page 7

see Needlestick injuries

ACE (angiotensin converting enzyme)

see Paracetamol (acetaminophen)

see Blood gases & pH

© 2000 Diagnostic Medlab View Terms of Use Page 8

see Tuberculosis (TB)

Acid phosphatase, prostatic (PAP)

A gram-negative bacillus commonly present in soil and water. In the hospital

© 2000 Diagnostic Medlab View Terms of Use Page 9

ref. range: 2 – 11 pmol/L at 0700 – 1000 hrs

ACTH is elevated in primary adrenal insufficiency (Addison's disease).

An anaerobic gram-positive filamentous bacillus found as a normal commensal in the

The most common form of infection is cervicofacial infection characteristically

Actinomyces species also grow in association with IUCDs (intrauterine contraceptive

© 2000 Diagnostic Medlab View Terms of Use Page 10

Activated partial thromboplastin time

see APTT (activated partial thromboplastin time)

Activated protein C resistance (APCr)

see also Factor V Leiden (FVQ506)

© 2000 Diagnostic Medlab View Terms of Use Page 11

Acute lymphoblastic leukaemias (ALL)

The more common childhood leukaemia. Prognosis is relatively good in children

Acute myeloid leukaemia (AML)

The M3 subtype, acute promyelocytic leukaemia (APML), is treated with ATRA (a

© 2000 Diagnostic Medlab View Terms of Use Page 12

Following inflammation or tissue destruction there is an increase in the so-called

analyte rise response time adult ref range

see Adrenocortical insufficiency

© 2000 Diagnostic Medlab View Terms of Use Page 13

In suspected SIADH (syndrome of inappropriate ADH), urine osmolality, which

Where there is difficulty separating pituitary-hypothalamic diabetes insipidus from

see also Osmolality, SIADH (syndrome of inappropriate ADH), Diabetes mellitus

Adrenal antibodies are present in 80% of autoimmune Addison's disease.

Adrenal medullary hormones

© 2000 Diagnostic Medlab View Terms of Use Page 14

Addison's disease (primary insufficiency)

Tests: • 0900 hrs cortisol (but 20-30% of Addison's have

Secondary insufficiency: • hypopituitarism

© 2000 Diagnostic Medlab View Terms of Use Page 15

see Cushing's syndrome

see ACTH (adreno-corticotrophic hormone)

Human infections include:

© 2000 Diagnostic Medlab View Terms of Use Page 16

AFP (alpha foetoprotein)

AFP has two uses:

AGA (antigliadin antibodies)

see Gliadin (gluten) antibodies (AGA)

© 2000 Diagnostic Medlab View Terms of Use Page 17