Data Interpretation For Medical Students PDF

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Contents
Preface to second edition

Acknowledgements
Normal values
1. Haematology
2. Biochemistry
3. Endocrinology
4. Toxicology
5. Pleural and peritoneal fluid analysis
6. Microbiology
7. Neurology
8. Immunology
9. Imaging
10. Cardiology
11. Pathology
12. Genetics
13. Respiratory medicine
14. Interpreting bedside chart data
15. Miscellaneous
16. Complete clinical cases
Index
Preface to the second edition
The practice of medicine in the twenty-first century is centred on data interpretation. Never before have
so many tests been available to help diagnose disease and monitor patient progress. One difficulty facing
students and junior doctors is in choosing which tests to request. This is especially important in the
current financial climate where ordering a range of unnecessary tests will be very costly for the health
service. Once a test result is back, the investigator must be able to interpret the result confidently and
accurately. We encourage investigations to be assessed in a sequential manner, with their interpretation
dictating subsequent tests, rather than a ‘blunder-bus’ approach. This is professionally more satisfying and
more educational, and encourages thoughtful medicine and sensible use of resources.
We hope that the latest edition of this book will help you as you begin interpreting all forms of data for
your patients. All aspects of the book have been reviewed for the second edition. New sections have been
written to incorporate latest developments, difficult concepts have been further clarified, and more
example cases have been added to test your understanding. The imaging section has been extended in
keeping with the increasing influence that this plays in everyday clinical medicine.
The first edition has been more successful than we could have imagined; however, after 5 years a
refresher was much needed.
It is our hope that, in some small way, the care of patients will be improved from the use of this text.
Acknowledgements
We have included material that we feel represents common scenarios and that best illustrates the various
investigations in medicine. All material has received intensive feedback during the production process to
ensure that it is readable and usable. We both greatly value constructive criticism, and ideas to improve
this text further would be very welcome. Please e-mail us on
[email protected] if you have any suggestions.
A hugely influential contributor to this book must be mentioned first. Sandy Davey is a current medical
student in Queen’s University Belfast. His unique qualities, limitless enthusiasm and bravery to comment
have helped shape the final draft of this book. We both owe him a huge debt of gratitude.
A special mention must also be made of the contributions of Professor Patrick Bell who reviewed the
book critically.
We also owe our Commissioning Editor at Pastest, Elizabeth Kerr, our sincere thanks and apologies –
thanks for supporting us throughout this project and making valuable comments; apologies for having to
put up with our incessant demands, impatience and peculiarities.
Thanks are extended to Joel Rankin for assisting with the ECGs, Dr Barry Kelly for providing a selection
of radiographs, and Dr Ann Johnston for reviewing the neurology section.
PH would like to thank his parents and sister Kerry for their never-ending support and encouragement. He
also thanks Anna for her incredible patience during the writing process.
ICB would like to thank Haiza who, despite his spending hours putting this book together, still agreed to
marry him!
Like the world of medicine, our own lives has changed since the 1st edition in 2005. We have both
been blessed with beautiful daughters to whom we dedicate this 2nd edition.
Chloe and Nur Ayesha, you are the sunshine in your Daddy’s eyes.
Normal values
Haematology
Full blood picture
Haemoglobin (Hb)
Males 13.5–18 g/dl
Females 11.5–16 g/dl
Mean cell volume (MCV) 76–96 fl
Packed cell volume (PCV)
Males 0.4–0.54
Females 0.37–0.47
Red cell distribution width (RDW) 12–15%
White cell count (WCC) 4.0–11.0 × 109/l
Neutrophils 2.0–7.5 × 109/l
Lymphocytes 1.5–4.0 × 109/l
Eosinophils 0.04–0.4 × 109/l
Monocytes 0.2–0.8 × 109/l
Basophils 0.0–0.1 × 109/l
Platelets 150–400 × 109/l
Reticulocytes 0.5–2.5% of red blood cells
Erythrocyte sedimentation rate (ESR)
Males 0–15 mm/h
Females 0–22 mm/h
HBA1c (glycated haemoglobin) 3.8–6.4%
Tests of clotting
Activated partial thromboplastin
time (APTT) 35–45 s
Prothrombin time (PT) 12–16 s
Fibrinogen 2–4 g/l
Bleeding time 3–9 min
D-dimer <0.5 mg/l
Haematinics
Iron studies
Iron 11–32 mol/l
Total iron-binding capacity (TIBC) 42–80 mol/l
Ferritin 12–200 μg/l
Folate >2 μg/l
Vitamin B12 >150 ng/l
Biochemistry
Urea and electrolytes (U&Es)
Sodium (Na+) 135–145 mmol/l
Potassium (K+) 3.5–5.0 mmol/l
Urea 2.5–6.7 mmol/l
Creatinine 79–118 μmol/l
(dependent on muscle mass)
Chloride (Cl−) 95–105 mmol/l
Bicarbonate (HCO3−) 24–30 mmol/l
Liver function tests

Total bilirubin 3–17 μmol/l
Aspartate aminotransferase (AST) 5–35 IU/l
Alanine aminotransferase (ALT) 5–35 IU/l
Alkaline phosphatase (ALP) 30–150 U/l
γ-Glutamyl transpeptidase (GGT)
Male 11–58 IU/l
Female 7–33 IU/l
Albumin 35–50 g/l
Bone profile
Corrected calcium (Ca2+) (total) 2.10–2.65 mmol/l
Phosphate (PO43−) 0.8–1.45 mmol/l
Alkaline phosphatase (ALP) 30–150 U/l
Albumin 35–50 g/l
Poisoning
Alcohol Nil
Carboxyhaemoglobin <5% of total haemoglobin
Paracetamol Nil
Salicylates Nil
Tumour markers
α-Fetoprotein (AFP)
<50 years <10 kU/l
50–70 years <15 kU/l
70–90 years <20 kU/l
β Human chorionic gonadotrophin
(β-hCG) <5 U/l
CA-125 <35 U/ml
CA-19-9 <37 U/ml
Carcinoembryonic antigen (CEA) <10 ng/ml
Prostate-specific antigen (PSA; males)
40–49 years <2.5 ng/ml
Arterial blood gas analysis
pH 7.35–7.45
Arterial partial pressure of oxygen
breathing room air (PaO2) 11–13 kPa
Arterial partial pressure of carbon
dioxide breathing room air (PaCO2) 4.7–6.0 kPa
Bicarbonate 24–30 mmol/l
Base excess (BE) –2 to +2 mmol/l
Anion gap 12–16 mmol/l
Immunoglobulins
IgA 0.8–4.0 g/l
IgG 7.0–14.5 g/l
IgM 0.45–2.0 g/l
Other
Amylase 25–125 U/l
C-reactive protein (CRP) <10 mg/l
Creatine kinase (CK)
Male 25–195 IU/l
Female 25–170 IU/l
CK-MB <25 IU/l
Globulin 18–36 g/l
Glucose See page 152
Lactate 0.5–2.0 mmol/l
Lactate dehydrogenase (LDH) 70–250 IU/l
N-terminal pro-brain natriuretic
protein (NT-proBNP) <125 pmol/l
Osmolality (plasma) 280–300 mosmol/kg
pH 7.35–7.45
Total protein 60–80 g/l
Troponin I <0.1 μg/l
Troponin T <0.03 μg/l
Urate 0.15–0.50 mmol/l
Endocrinology
Cortisol
9am 200–700 nmol/l
10pm 50–250 nmol/l
Free thyroxine (T4) 7.6–19.7 pmol/l
Thyroid-stimulating hormone (TSH) 0.4–4.5 mU/l
Total thyroxine (T4) 70–140 nmol/l
Therapeutic drug levels

Digoxin (6 hours post-dose) 0.8–2.0 nmol/l
Lithium 0.5–1.5 mmol/l
Cerebrospinal fluid
Glucose 2.5–4.4 mmol/l
(two-thirds of plasma value)
Red cell count (RCC) 0/mm3
Total protein <0.45 g/l
White cell count (WCC) <5/mm3
Urine
Creatinine clearance
Male 85–125 ml/min
Female 75–115 ml/min
Metanephrines <5.5 μmol/day
Osmolality 250–1250 mosmol/kg
Protein <0.2 g/day
Sweat
Chloride <60 mmol/l
HAEMATOLOGY
One of the most frequently requested tests in medicine is the full blood picture (FBP). This contains a
wealth of information about the components of blood. The typical constituent parts of the FBP are as
shown in the box.
Abnormalities with red blood cells
Anaemia
Anaemia describes a low level of haemoglobin. It is usually defined by an arbitrary cut-off haemoglobin
concentration (eg 13 g/dl in men aged >15 years, 12 g/dl in non-pregnant women aged >15 years and 11
g/dl in pregnant women), below which a patient is deemed to be anaemic.
Before deciding on the particular subtype of anaemia present in a patient, it is worth looking at the other
cell types described on the full blood picture. If there are problems with red cells, white cells and
platelets, then the major problem is likely to be a disease of the bone marrow, and the test most likely to
give the diagnosis would be a bone marrow biopsy.
If the only problem on the full blood picture is low haemoglobin, the next stage is to check the reticulocyte
count. Reticulocytes are immature red blood cells, and will be found in increased amounts in patients who
are bleeding and in those in whom red cells are being destroyed (haemolysis). The history should
distinguish between these types. If the reticulocyte count is not elevated, the next step in diagnosis is to
look at the size of the red cells (erythrocytes).
Anaemia can be split into three big groups by looking at the size of the red blood cells. In microcytic
anaemia red cells are small, in normocytic anaemia they are normal size and in macrocytic anaemia they
are large. The mean cell volume (MCV) provides an average measurement of red cell size.
TYPE OF ANAEMIA SIZE OF ERYTHROCYTES

Microcytic Small
Normocytic Normal
Macrocytic Large
The diagram on page 5 shows the various causes based on this classification of anaemia.
Note that the MCV provides a measure of average cell size, and this is reliable in most instances. If,
however, a patient has two ongoing pathologies, such as iron deficiency and folate deficiency, the MCV
can be unreliable. They may have two populations of red cells, one with a low MCV and another with a
high MCV. When these measures are averaged, the MCV will be normal. For this reason, the red cell
distribution width (RDW) is sometimes measured. This gives an indication of the distribution of red cell
sizes. This measure will be raised if two red cell populations are present.
Fig 1.1: The various causes of the major classifications of anaemia.
Haematinics
Deficiencies in any of three key nutrients – iron, vitamin B12 and folate – can result in anaemia. These
nutrients are called haematinics. Iron deficiency is the most common cause of anaemia, and is commonly
found in association with blood loss.
DEFICIENCY TYPE OF ANAEMIA
Iron Microcytic
Vitamin B12 Macrocytic
Folate Macrocytic
Finding a haematinic deficiency is only the first part of establishing the cause of anaemia. Where
possible, the cause of the nutrient deficiency should also be sought. For example, iron deficiency is often
due to blood loss from the gastrointestinal tract, and endoscopy is often used to search for this.
Knowledge of exactly where haematinics are absorbed from the gastrointestinal tract can sometimes help
localise the pathology underlying anaemia. These sites are shown in the box below.
HAEMATINIC ABSORBED FROM

Iron Duodenum and jejunum
Vitamin B12 Terminal ileum
Folate Small bowel
Iron studies
A good understanding of how the body handles iron is required before iron studies can be interpreted.
Iron is best absorbed from the upper small bowel in the ferrous (Fe2+) state. Iron is transported across the
intestinal cell and into the plasma. Iron in the plasma is carried to developing red cells in the bone
marrow by a protein called transferrin. Iron is stored in the body as ferritin and haemosiderin. Red cells
have transferrin receptors (soluble transferrin receptors, sTfRs) which can be measured in plasma.
COMPONENTS OF AN IRON PROFILE

Serum iron
Serum total iron-binding capacity (serum TIBC)
Serum ferritin
Transferrin saturation
Serum soluble transferrin receptors
In iron deficiency states, iron studies are as follows:
IRON PARAMETER RESULT

Serum iron Reduced
Serum total iron-binding capacity Increased – the body tries hard to bind any iron around the system
Serum ferritin Reduced – since iron stores are low

Transferrin saturation Reduced
Serum sTfRs Increased – since red cells attempt to absorb any iron in the system
The serum ferritin level is the single best test for iron deficiency, with levels of below 15 μg/l being
suggestive.
To make matters a little more confusing, ferritin behaves as an acute phase reactant – its level increases
with active inflammation, in the same way as the erythrocyte sedimentation rate (ESR) and C-reactive
protein (CRP) (see pages 17 and 74). This means that, in states of iron deficiency associated with an
ongoing inflammatory process (eg an active infection), the serum ferritin level may be high. However, the
sTfR will reveal the true state of affairs.
Unfortunately sTfR is not routinely available, and often clinical judgement is required in such situations.
Sometimes, it can be difficult to be sure that a patient is iron deficient, and in such circumstances a trial of
iron treatment may be necessary. Once the diagnosis has been established, it is imperative that a reason
for the iron deficiency be sought.
In cases of diagnostic uncertainty, a bone marrow biopsy can be obtained and stained for the presence of
iron. In iron deficiency states, little or no iron will be seen in the marrow.
Iron studies are also abnormal in states of iron overload. This is commonly seen in haemochromatosis and
in haematological conditions that require frequent blood transfusions. In such cases, serum iron, ferritin
and transferrin saturation are raised. The total iron-binding capacity (TIBC) is usually low.
In anaemia of chronic disease, iron studies are commonly as follows:
IRON PARAMETER RESULT

Serum iron Normal or slightly reduced
Serum total iron-binding capacity Reduced
Serum ferritin May be raised as acute phase reactant
Transferrin saturation Reduced
Serum sTfR Normal – reflecting the true state of body iron levels
Goddard AG, James MW, McIntyre AS, et al. (2011) Guidelines for the management of iron deficiency anaemia. Gut
doi:10.1136/gut.2010.228874.
Vitamin B12
Vitamin B12 deficiency may result from inadequate intake, but the most common reason for deficiency
relates to poor absorption.
In health, vitamin B12 is bound to a protein called intrinsic factor secreted by gastric parietal cells. The
vitamin is then absorbed from the ileum. Poor absorption generally results from the absence of intrinsic
factor or disease of the ileum.
The most common disease causing vitamin B12 deficiency is pernicious anaemia, in which there is
defective intrinsic factor production. The disease is associated with autoantibodies against gastric
parietal cells and intrinsic factor (see Chapter 8).
Schilling test
The Schilling test may be used to distinguish between the various causes of vitamin B12 deficiency. In this
test, patients are given two doses of vitamin B12. One dose is radioactively labelled and given orally. The
other dose is given intramuscularly with the aim of flushing absorbed radiolabelled vitamin B12 into the
urine. The urine is collected over a period of 24 hours. Normally, a proportion of the oral vitamin B12
dose will be absorbed and excreted, so that more than 10% of the oral dose will be excreted in the urine.
With vitamin B12 malabsorption, this amount will be reduced. Unfortunately, despite the eloquence of the
Schilling test, it is being used with decreasing frequency, and in some areas is no longer available.
The test is repeated with an oral preparation of intrinsic factor being given at the same time as the oral
dose of vitamin B12. If the test results are now normal, one can assume that the patient’s problem lies with
inadequate intrinsic factor. If the test is still abnormal, the problem most likely lies in the ileum.
One possible cause of ileal disease is bacterial overgrowth. In order to test for this possibility, the patient
can be given a course of antibiotics. If the Schilling test returns to normal after this, the diagnosis of
bacterial overgrowth can be made. Alternatively, bacterial overgrowth can be diagnosed using a breath
test. The most commonly used test is the hydrogen breath test. A carbohydrate load is given orally.
Bacteria in the small bowel metabolise the carbohydrate, liberating hydrogen which is absorbed and
detected in exhaled air.
Folate
Folate analysis is simple. Serum folate levels are measured with a deficiency identified if levels are low.
Haemolytic anaemia
There are many causes of haemolytic anaemia, but in each case there is abnormal destruction of red blood
cells.
Evidence of haemolysis
When red blood cells are destroyed, haemoglobin is degraded, and bibirubin liberated. Bilirubin is
conjugated in the liver and passed into the bowel in the bile. Here, it is converted into urobilinogen. Some
of this is passed in the stools; some is reabsorbed, and excreted in the urine, where it can be detected
using a urinalysis strip. In cases of haemolysis, the plasma unconjugated bilirubin will rise, and increased
amounts of urobilinogen will be detected in the urine. The level of lactate dehydrogenase (LDH) will also
rise.
When red cells are destroyed inside blood vessels, haemoglobin is released. Haptoglobins bind to free
haemoglobin and escort it to the liver. However, haptoglobins can become saturated and in such
circumstances haemoglobin may be passed in the urine (haemoglobinuria), or converted to haemosiderin
which is then passed in the urine (haemosiderinuria). Alternatively, further reactions can occur which
result in the presence of methaemalbumin in the circulation.
INTRAVASCULAR HAEMOLYSIS IS SUGGESTED BY
• low haptoglobins
• haemosiderinuria
• methaemalbumin (detected in the Schumm test)

With excessive red cell destruction, the bone marrow works hard to replace the number of circulating
cells. The number of primitive red cells (reticulocytes) in the circulation therefore increases.
The causes of haemolytic anaemia are illustrated in the diagram on page 11.
Osmotic fragility test

Hereditary spherocytosis is a condition associated with an abnormal red blood cell membrane where red
cells become spherical in shape. The cells are less resilient to damage in this condition. This can be
assessed using an osmotic fragility test. Spherocytes have increased osmotic fragility.
Direct antiglobulin test

In autoimmune haemolytic anaemias, antibodies attack red cells and cause their destruction. The main
laboratory test for autoimmune haemolytic anaemia is the direct antiglobulin test (DAT or Coombs’ test).
In this test, antibodies to human immunoglobulin are added to a sample of red cells from the patient. If the
red cells are coated in antibodies (ie if the patient has an autoimmune haemolytic anaemia), they will
agglutinate.
World Health Organization (2008). Worldwide Prevalence of Anaemia, 1993–2005. Geneva: WHO.
Fig 1.2: The causes of haemolytic anaemia.

Polycythaemia
Polycythaemia is defined as a packed cell volume (PCV) greater than 0.51 in males or greater than 0.48 in
females.
POLYCYTHAEMIA
Males – PCV >0.51
Females – PCV >0.48
Red cell mass

In order to distinguish between true and apparent polycythaemia, the red cell mass must be measured. In
true polycythaemia, the red cell mass is raised. Apparent polycythaemia is due to a reduction in plasma
volume rather than an increase in red cell mass.
Red cell mass is measured by labelling red cells with a radioactive isotope. A predicted red cell mass
can be calcuated based on the patient’s height and weight. True polycythaemia is diagnosed if the red cell
mass is more than 25% higher than that predicted.
To distinguish between causes of true polycythaemia, further tests should be arranged. These usually
include:
• arterial blood gas analysis (to look for hypoxia)
• erythropoietin level (to detect inappropriately high levels)
an ultrasound of the abdomen (to detect structural renal or hepatic disease and to visualise the
•
spleen)
• further investigations depending on the most likely cause.
Haemoglobinopathies
Haemoglobin electrophoresis can be used to diagnose a variety of diseases in which the structure of
haemoglobin is abnormal. The most common diseases of this type are sickle cell disease and the
thalassaemias. In sickle cell disease, haemoglobin electrophoresis shows the presence of HbS.
Polycythaemia can be subdivided as shown in Fig 1.3.
Fig 1.3: Causes of polycythaemia.
Abnormalities with white blood cells
Abnormal white cell counts

Abnormalities in white blood cell counts are common. The most frequently occurring abnormalities are
listed in the boxes below with common causes.
COMMON CAUSES OF NEUTROPHILIA (NEUTROPHILS >7.5 × 109/l)
Bacterial infections Malignancy

Inflammation Myeloproliferative disorders
Necrosis, eg after myocardial infarction
Metabolic disorders, eg renal failure
Treatment with corticosteroids
COMMON CAUSES OF NEUTROPENIA (NEUTROPHILS <2.0 × 109/l)

Post-chemotherapy
Post-radiotherapy
Adverse drug reactions, eg clozapine, carbimazole
Viral infection
Felty syndrome
COMMON CAUSES OF LYMPHOCYTOSIS (LYMPHOCYTES >3.5 × 109/l)

Viral infections
Chronic infections, eg TB
Chronic lymphocytic leukaemia
Lymphomas
COMMON CAUSES OF EOSINOPHILIA (EOSINOPHILS >0.5 × 109/l)
Allergic disorders Skin diseases, eg eczema

Parasite infection Malignancy, eg Hodgkin disease
Hypereosinophilic syndrome Allergic bronchopulmonary aspergillosis
Abnormalities with platelets
Thrombocytosis
Thrombocytosis describes a high platelet count (>400 × 109/l). The common causes are shown in the box
below.
COMMON CAUSES OF THROMBOCYTOSIS

Primary haematological diseases: Reactive thrombocytosis secondary to:
• Essential thrombocythaemia and other myeloproliferative disorders • Infection
• Inflammation
• Chronic myeloid leukaemia • Malignancy
• Bleeding
• Myelodysplasia • Pregnancy
• Post-splenectomy
Thrombocytopenia
Thrombocytopenia describes a low platelet count (<150 × 109/l). The common causes are shown in the
box below.
CAUSES OF THROMBOCYTOPENIA
Reduced platelet production due to bone marrow failure:
• Infections (particularly viral, eg infectious mononucleosis)
• Drug induced, eg penicillamine
• Leukaemia
• Aplastic anaemia
• Myelofibrosis (later stages)
• Bone marrow replacement with tumour, eg myeloma or metastases
• Myelodysplasia
• Megaloblastic anaemia
Increased platelet destruction:
• Immune-mediated platelet destruction
• Autoimmune idiopathic thrombocytopenia purpura (AITP)
• Drug induced, particularly heparin-induced thrombocytopenia (HIT)
• Hypersplenism
• Thrombotic thrombocytopenic purpura/haemolytic uraemic syndrome
• Disseminated intravascular coagulation (DIC)
• After a massive blood transfusion
PLATELET CLUMPING
This is a relatively common cause for an apparently low platelet count. If a blood sample is sent to the laboratory in a tube containing
anticoagulant, clumping will not occur and the true platelet count will be apparent. It is therefore always worth sending a ‘citrated’ sample
for a platelet count if unexpected thrombocytopenia is found.
Pancytopenia
Pancytopenia is the term used to describe the pattern present when there are low levels of red blood cells,
white blood cells and platelets in the circulation. There are a wide variety of causes, the most common of
which are shown in the box.
COMMON CAUSES OF PANCYTOPENIA
• Aplastic anaemia
• Bone marrow infiltration, eg with tumour
• Hypersplenism
• Megaloblastic anaemia
• Sepsis
• Systemic lupus erythematosus (SLE)
Erythrocyte sedimentation rate
The erythrocyte sedimentation rate (ESR) measures how rapidly red blood cells form sediment when a
column of blood is kept upright for 1 hour. The further the red cells sink in the hour, the higher the ESR.
The ESR is a non-specific marker of disease. In inflammatory processes, raised levels of plasma proteins
result in red blood cells forming clumps called rouleaux. These clumps of cells sink more easily than
single cells, and thus, in the presence of such proteins, the ESR is high.
The ESR normally rises with advancing age, but levels of more than 35 mm/h should raise the suspicion
of a disease process in any age group. Causes of a raised ESR are myriad. Common examples are listed
in the box below.
COMMON CAUSES OF A RAISED ESR
• Infectious disease
• Neoplastic disease (particularly multiple myeloma)
• Connective tissue disease (particularly giant cell arteritis and polymyalgia rheumatica)
• Anaemia
• Renal disease
Blood film abnormalities
Examination of a peripheral blood film can aid or clinch a diagnosis in a range of clinical scenarios.
Correct identification of various cell types requires significant training, but knowledge of the different
terminology used can greatly aid interpretation of blood film reports. The following abnormal cell types
are among those most commonly seen.
Abnormal erythrocyte colour or shape

ABNORMALITY MEANING FOUND IN
Hypochromic cells Pale red cells Iron deficiency or defective haemoglobin synthesis
Microcytosis Small cells Iron deficiency or defective haemoglobin synthesis
Megaloblastic anaemia, high alcohol intake, liver

Macrocytosis Large cells
disease
Pencil cells Pencil-shaped cells Iron deficiency
Spherocytes Spherical cells Hereditary spherocytosis, haemolytic anaemia, burns
Hereditary elliptocytosis, thalassaemia major, iron

Elliptocytes Elliptical cells
deficiency
Abetalipoproteinaemia, post-splenectomy, liver

Acanthocytes Spiky-appearing cells
disease
Thalassaemia, iron deficiency, post-splenectomy, liver

Target cells Target-like cells
disease
Hereditary stomatocytosis, high alcohol intake, liver

Stomatocytes Cells with mouth-shaped area of pallor
disease
Also known as burr cells – less spiky

Ecchinocytes Post-splenectomy, liver disease, uraemia
than acanthocytes
Sickle cells Sickle shaped Sickle cell anaemia (homozygous HbS disease)
Microangiopathic haemolytic anaemia, haemolytic

uraemic syndrome, thrombotic thrombocytopenic
Fragmented cells Broken pieces of cell
purpura, mechanical heart valves, disseminated
intravascular coagulation
Myelofibrosis and other causes of extramedullary

Tear cells (dacryocytes) Tear-shaped cells
haematopoiesis
Poikilocytosis Abnormal shapes of red cells Iron deficiency
Anisochromia Varying shades of colour Iron deficiency
Abnormalities inside erythrocytes

ABNORMALITY FOUND IN
Heinz bodies Unstable haemoglobin states
Howell–Jolly bodies Hyposplenism, post-splenectomy
Pappenheimer bodies Post-splenectomy, haemolytic anaemia, sideroblastic anaemia
Basophilic stippling Lead poisoning, thalassaemia, myelodysplasia
Cabot rings Myelodysplasia, megaloblastic anaemia
Abnormal white blood cells
ABNORMALITY FOUND IN
Hypersegmented neutrophils Megaloblastic anaemias, chronic infections
Toxic granulation of neutrophils Bacterial infection, poisoning, burns, chemotherapy
Auer rods Acute myeloid leukaemia
Smear cells Chronic lymphocytic leukaemia
Leukoerythroblastic blood film

This is a term used to describe the overall appearance of a blood film in which immature red and white
blood cells are seen in peripheral blood. There are several causes.
CAUSES OF A LEUKOERYTHROBLASTIC BLOOD FILM
• Bone marrow infiltration, eg with tumour

• Idiopathic myelofibrosis
• Severe sepsis
• Haemolysis
Coagulation disorders
Haemostasis (the process of stopping bleeding) is a complex process. It involves the interplay of blood
vessel walls, platelets and clotting factors. The common tests used to assess coagulation are as follows:
COMMON TESTS OF COAGULATION
• Prothrombin time (PT)

• International normalised ratio (INR)
• Activated partial thromboplastin time (APTT)
• Bleeding time
Prothrombin time
The PT is dependent on clotting factors I, II, V, VII and X. In clinical practice, it is most commonly
measured to assess the synthetic function of the liver (eg in liver failure), or to monitor the effects of
warfarin therapy.
International normalised ratio

To allow comparison of coagulation results between laboratories, the PT is often converted to the INR,
by applying a correction factor. This takes into account differences in laboratory methods, and means that
the patient’s INR should be the same regardless of the laboratory used to measure it.
The INR is the parameter most commonly used to monitor the effects of warfarin. In a patient with normal
coagulation, the INR will be close to 1.0 before warfarin is commenced. As warfarin is introduced, the
INR rises. The higher the INR, the less coagulable the blood becomes (ie the more difficult it will be for
the blood to clot). Target INRs are set, and warfarin dosing must be adjusted to aim for these targets.
DISEASE TARGET INR

Deep venous thrombosis (DVT) 2.5
Pulmonary embolism (PE) 2.5
Atrial fibrillation 2.5
Mechanical prosthetic heart valve 2.5
Recurrent DVT/PE in a patient with a therapeutic INR 3.5
The essence of warfarin prescribing involves increasing the dose if the INR is too low, reducing the dose
if the INR is too high, and omitting it if the INR is dangerously high or the patient is bleeding. An example
of a warfarin prescribing chart is shown on page 486.
Activated partial thromboplastin time

The APTT depends on all clotting factors except factor VII. In clinical practice, the APTT is used most
commonly in patients receiving an infusion of heparin. The APTT is monitored frequently, and the rate of
the heparin infusion adjusted to achieve the desired level of anticoagulation. With the common prescribing
of low-molecular-weight heparin, in preference to unfractionated heparin, this process is now performed
infrequently. A frequent cause of concern relates to elevated APTTs in patients with central venous
catheters. The proximal end of such catheters are often filled with heparin to keep the lumina patent when
they are not being used. A spuriously high APTT will be obtained if blood is withdrawn from one such
lumen. If the APTT is tested on a sample of blood tested peripherally, the true value will be obtained.
Coagulation correction testing

In cases of deranged coagulation, laboratories will often perform a coagulation correction test. This is
performed to detect problems in coagulation arising because of a low level of a particular clotting factor.
Essentially, normal plasma (containing normal clotting factors) is mixed with the patient’s sample. If the
patient is deficient in clotting factors, a deranged coagulation profile would be expected to normalise.
There will be no change, however, if an inhibitor of coagulation is present. Specialised assays for
individual clotting factors are also available.
Bleeding time
Bleeding time is measured directly at the bedside. A sphygmomanometer cuff is inflated around the
patient’s arm to 40 mmHg. A specially designed blade is then used to make a small puncture in the arm.
Blood is removed from the area at fixed time intervals (eg 15 s) using a piece of filter paper to soak it up.
The time taken for bleeding to stop is recorded. Elevated bleeding times indicate defective platelet
function or low platelet numbers. This test should not be performed if the patient is known to have severe
thrombocytopenia.
Bear in mind that patients with abnormal numbers or deranged function of platelets may also have
abnormal bleeding. Patients with von Willebrand disease may have normal coagulation profiles.
DON’T FORGET
Patients with von Willebrand disease may have normal coagulation profiles.
Disseminated intravascular coagulation

Disseminated intravascular coagulation (DIC) is a disease of two apparently conflicting problems. On the
one hand, fibrin deposition in various organs results in areas of micro-infarction. On the other hand, the
body’s supplies of clotting factors become used up because of all the clotting, leaving the patient prone to
bleeding.
DISSEMINATED INTRAVASCULAR COAGULATION

A disease in which clotting and bleeding cause problems simultaneously.
Typical laboratory findings in DIC are as follows:

Raised PT and APTT Since clotting factors are reduced
Reduced fibrinogen Due to widespread fibrin formation
Raised D-dimer Due to the body’s attempt to break down the excess fibrin deposits
D-dimer
D-dimer is the most commonly measured fibrinogen/fibrin degeneration product. It is detected following
clot formation in the vasculature, as the body’s fibrinolytic system attempts to break the clot down. D-
dimer levels are often tested in cases of suspected deep venous thrombosis and pulmonary embolism, and
in the majority of cases will be raised. However, D-dimer levels are also raised in many other
conditions, and a raised level should always be interpreted in light of the clinical scenario.
Laboratory findings in bleeding disorders
PT APTT FIBRINOGEN
Warfarin treatment Increased Normal (or Increased) Normal
Heparin treatment Normal (or increased) Increased Normal
Haemophilia A or B Normal Increased Normal
Liver disease Increased Increased Normal
DIC Increased Increased Reduced
Plasma cell dyscrasias

Diseases of plasma cells are common, and their investigation is often a cause for confusion. They
represent a spectrum of disorders, with multiple myeloma being the most important at the undergraduate
level, and monoclonal gammopathy of unknown significance (MGUS) being the most common. The
hallmark of these conditions is that plasma cells secrete M protein in excess. The effects of multiple
myeloma can be far-reaching, and can lead to the following features:
• Anaemia
• Renal impairment
• Low levels of normal immunoglobulins with resultant infections
Bone involvement, causing bony pain, hypercalcaemia, lytic lesions and problems if bones
•
collapse
• Hyperviscosity of the blood.
The conditions should be suspected if any of the following abnormalities are present:
• Elevated ESR
• Hypercalcaemia
• Anaemia
• Renal impairment
• Abnormal M-protein detected on plasma protein electrophoresis
• Abnormal quantities of immunoglobulin light chains in the serum (with an abnormal κ:λ ratio)
• Low levels of immunoglobulins
• Lytic lesions on X-ray of bones
• Detection of Bence Jones protein in the urine (this represents immunoglobulin light chains)
• Abnormal plasma cells seen on bone marrow biopsy
• Elevated β2-microglobulin.
Case 1.1
A 48-year-old retired civil servant is concerned with her pale colour and feelings of faintness that have
occurred over the past 4 weeks. She had felt well before this and enjoyed regular trips to southern France.
Brief clinical examination reveals pallor. Her blood tests come to your attention.
1. How would you interpret these results?

2. How would you proceed with investigation?
Answer 1.1
This patient has a microcytic anaemia. Her iron profile is in keeping with iron deficiency with a
1. low iron, low ferritin and high TIBC. There is a mild thrombocytosis which may indicate active
bleeding.
The most common cause for these findings in young women is menorrhagia. In an older female or
male of any age, investigations should be carried out to exclude a sinister cause – in particular an
2. occult gastrointestinal tract malignancy. Investigations should begin with a thorough history and
clinical examination which should include rectal examination. The next line of investigation usually
involves gastrointestinal tract endoscopy.
Case 1.2
A 57-year-old woman attends her GP complaining of tiredness. The GP knows her medical history well
as she also suffers from Graves’ disease. A full blood count was analysed as well as haematinics.
1. Interpret these blood results.
Following these results the GP also requests another test shown below.
2. What is the diagnosis?

Answer 1.2
The haemoglobin is low with an elevated mean cell volume. This patient has a macrocytic anaemia.
1. Haematinics show a low vitamin B12 level. Iron studies and folate level are within normal limits.
The positive antibodies to gastric parietal cells and intrinsic factor indicate that the likely
underlying cause of the anaemia is pernicious anaemia. You will note that the patient was already
2.
known to have an autoimmune disease – Graves’ disease. Always remember that patients with one
autoimmune disease are prone to developing another.
A Schilling test would have been useful in this case. The initial test would show low levels of
radiolabelled vitamin B12 in the urine. Once the patient was given oral intrinsic factor, urine vitamin B12
excretion would be expected to return to normal.
Case 1.3
A 49-year-old woman with systemic sclerosis complains of malaise and palpitations. Her disease has
been quiescent for 2 years and she is not on any immunosuppressant medications. She has a balanced diet
and has had no previous surgery. Her rheumatologist requests the following tests:
1. What would you infer from these results?

2. What is the reason for performing a hydrogen breath test?
Answer 1.3
This patient has a macrocytic anaemia. Vitamin B12 is the only deficient haematinic, but the
autoantibodies for pernicious anaemia are negative. The history states that the diet is balanced and
no surgery has taken place on the bowel to interfere with the absorption of vitamin B12. The
1.
Schilling test is abnormal. Normally, at least 10% of the oral dose of radiolabelled vitamin B12 is
excreted in the urine. In this case, the excreted dose is low, and supplementation with intrinsic
factor makes no difference. The likely pathology is therefore in the ileum.
The abnormal hydrogen breath test result points to the cause of anaemia – small bowel bacterial
overgrowth. Patients with systemic sclerosis are prone to developing this condition. Definitive
2.
testing for bacterial overgrowth involves culturing small bowel contents. One would expect a
normal Schilling test after an adequate course of appropriate antibiotics.
Case 1.4
A 34-year-old accountant with a 15-year history of Crohn’s disease attends for outpatient review. He
feels reasonable, although has not yet been able to hold down full employment after numerous hospital
admissions and surgery over the past 10 years. His last surgery involved small bowel resection and
anastomosis after further failure of medical therapy. The doctor in the clinic requests the following tests.
What is your interpretation of these tests?

Answer 1.4
This man has a normocytic anaemia. He is deficient in iron, vitamin B12 and folate. The red cell
distribution width (RDW) is raised, indicating a wide variation in the size of circulating red cells. The
patient is likely to have a dimorphic blood picture, with small red cells resulting from iron deficiency,
and large cells resulting from deficiencies of vitamin B12 and folate. Crohn’s disease is an inflammatory
bowel disease involving the whole gastrointestinal tract so has the potential to cause deficiencies in all
three haematinics. In this case, multiple operations have left him with a very short small bowel (‘short gut
syndrome’).
Case 1.5
A 55-year-old woman with essential hypertension attends the medical clinic. Her blood pressure remains
elevated despite treatment with four drugs. Her consultant commences her on methyldopa. Four weeks
later she attends the accident and emergency department feeling generally unwell. The A&E doctor sends
off a variety of blood tests, which are shown here.
She is admitted to the medical unit, and several other tests are requested.
1. Interpret the results above

2. What is the likely diagnosis?
Answer 1.5
This patient has a normocytic anaemia. Her haematinics are normal. She has a raised blood
bilirubin level and urobilinogen in the urine which would be in keeping with haemoglobin
1. breakdown. Her blood film shows a reticulocytosis indicating that the bone marrow is working
hard to make new red blood cells. The direct antiglobulin test is positive indicating that the
patient’s red cells are coated with antibodies.
The patient has an autoimmune haemolytic anaemia, which is most likely to be an adverse effect of
2.
treatment with methyldopa.
Case 1.6
When on elective in Malawi, you are asked to see a patient. He is 35 years old and complains of anorexia
and abdominal discomfort. Examination is unremarkable. A full blood picture is requested.
What is the likely diagnosis?

Answer 1.6
This question is a little sneaky. The key to finding the answer is to remember that the total WCC is equal
to the sum of the component parts of the differential white cell count.
DON’T FORGET
Total white cell count = neutrophil count + lympocyte count + eosinophil count + monocyte count + basophil count
In this case, the neutrophil count and lympocyte count together cannot account for the total white cell count
((7.4 × 109/l) + (2.5 × 109/l) <13.2 × 109/l)). There must be a further type of white blood cell in elevated
numbers. It is impossible to tell for certain what this cell type might be. However, the likely diagnosis
here is helminthic (worm) infection. A full differential white cell count would reveal a raised level of
eosinophils.
Case 1.7
You see a 64-year-old woman in A&E. She has severe chronic obstructive pulmonary disease (COPD),
and has been an inpatient on several occasions in the past year. She appears short of breath, and
complains of a worsening cough productive of green sputum. This has become worse over the last 3 days.
Part of her admission blood tests are shown.
Outline the abnormalities shown, and discuss their most likely causes.
Answer 1.7
The first abnormality relates to the raised packed cell volume (PCV) indicating polycythaemia. The most
likely cause in this case is a true polycythaemia secondary to chronic hypoxia resulting from COPD.
Useful tests to confirm this would be an estimation of red cell mass to confirm true polycythaemia, and an
arterial blood gas sample to demonstrate hypoxaemia.
The second abnormality relates to the elevated white cell count. Note that the neutrophil count is markedly
elevated, and that the sum of the neutrophil and lymphocyte counts almost adds up to the total white cell
count. The small discrepancy is due to the presence of a small number of other white blood cells
(eosinophils, monocytes and basophils) in the circulation. The most likely cause for this picture is a
bacterial infection of the lower respiratory tract.
Case 1.8
A 74-year-old man presents to the A&E department after a 5 minute episode of loss of vision affecting the
right eye. Further questioning revealed that the patient had a similar episode 2 days previously. On each
occasion the vision was lost rapidly, ‘like a curtain being drawn’ over the visual field. Direct questioning
revealed that he had been lethargic for several weeks, and experienced some pain in his jaw on chewing.
Initial blood tests revealed the following:

2. What treatment would you prescribe immediately?
Answer 1.8
The episode of loss of vision is typical of amaurosis fugax. Taken together with the history of lethargy
and jaw pain on eating (jaw claudication), the clinical suspicion must be of temporal arteritis. Such
1. patients are at high risk of complications, including blindness. The extremely high ESR measured here
would support this diagnosis. Temporal arteritis is one of the few causes of an ESR greater than 100
mm/h.
Treatment should be given rapidly, and should comprise high-dose prednisolone (eg 60–80 mg orally
2.
immediately), followed by a reducing dose regimen.
Case 1.9
You are the junior doctor on the vascular surgical unit. One of your patients, a 75-year-old man with
peripheral vascular disease, is due to undergo bypass vascular surgery on his legs. You request a battery
of preoperative blood tests. The following results give the nursing staff some concern.
What should you do next?

Answer 1.9
This situation is a common cause for concern. The details omitted from the history above are that the
patient has chronic renal failure, and receives haemodialysis three times per week via his indwelling
central venous catheter. The raised urea and creatinine are a reflection of the chronic renal failure in this
case (see Chapter 2 for more information).
The cause of the deranged coagulation is most likely because blood has been drawn from the central
venous catheter, which is often flushed with a heparin solution. The next step should be to repeat the
coagulation profile using blood taken from a peripheral vein.
Case 1.10
A 58-year-old patient with immunodeficiency is admitted to the intensive care unit with severe
pneumonia. Despite aggressive antibiotic therapy, his condition does not improve. On his third day in the
unit, the nurses report that he is beginning to bleed around the sites of his indwelling venous lines. The
doctor in charge requests a coagulation profile. The blood is taken from a peripheral vein.

Answer 1.10
The PT and APTT are raised suggesting a tendency to bleed. The fibrinogen level is low indicating that
fibrinogen has been used up. The D-dimer level is markedly raised indicating that the body’s fibrinolytic
system is working hard to disperse clots.
This pattern of abnormalities is typical of DIC, a not uncommon complication in patients with critical
illness. Blood product support will be required, and the advice of a haematologist would be helpful.
Case 1.11
A 24-year-old woman from the Maldives is in Ireland on honeymoon. She attends the emergency
department after falling and spraining her wrist. The doctor is concerned about the results of her full
blood picture:
What is the most likely diagnosis and what test(s) would you arrange?
Answer 1.11
This patient has a microcytic anaemia. The striking abnormality on her FBP is that the MCV is extremely
low, whereas the haemoglobin concentration is only slightly below the reference range. She originates
from the Maldives – an area where thalassaemia is common. It is probable that this woman has
thalassaemia (most likely to be β-thalassaemia trait). Haemoglobin electrophoresis will confirm the
diagnosis. Concomitant iron deficiency is possible, so sending blood for iron studies would also seem
sensible.
Case 1.12
A 45-year-old man with a history of asthma is admitted with symptoms and signs in keeping with cardiac
failure. There are no risk factors for ischaemic heart disease. The cause for the cardiac failure remains
uncertain until a junior doctor reviews his FBP and suggests the correct diagnosis.
What is the rare disease that the junior doctor suspected?

Answer 1.12
The key to even thinking about the rare disease in this case starts with the basics in interpreting the
patient’s FBP. The neutrophil and lymphocyte counts do not account for the elevated total WCC. The
missing piece of information in the question is the eosinophil count which is highly abnormal in this case.
The diagnosis here is Churg–Strauss syndrome, a rare vasculitic disease associated with a peripheral
eosinophilia.
Case 1.13
An elderly patient is admitted to the rehabilitation ward 4 weeks after having surgery to repair a fractured
neck of femur. Her postoperative course was complicated by pneumonia and renal failure, both of which
have been treated successfully. She has not been out of bed since the operation. You review her recent full
blood pictures:
What is the major problem, and name one possible drug-induced cause?
Answer 1.13
On 1 July, the patient developed thrombocytopenia. This has worsened steadily and significantly since.
An extremely rare adverse drug reaction, ‘heparin-induced thrombocytopenia (HIT)’, can occur in
patients receiving unfractionated or low-molecular-weight heparin. It is likely that this patient was
receiving low-molecular-weight heparin in an attempt to prevent thromboembolic disease.
Case 1.14
A patient attends the emergency department because of a swollen leg on the right side. He has a history of
dementia, and is unsure for how long the leg has been swollen. On inspection, the right calf is 0.3 cm
larger than the left, there is no erythema and the calf is non-tender. You order a blood test to help with
management.
How would you proceed?

Answer 1.14
This patient gives an unconvincing history for deep venous thrombosis (DVT), and there is very little
clinical evidence for it. A normal D-dimer in this situation, when the pre-test probability for the condition
is low, is helpful in making DVT extremely unlikely in this man. The patient can be reassured that it is
extremely unlikely that he has a clot in his leg.
Case 1.15
A 62-year-old woman is admitted with septic arthritis of the knee. A D-dimer blood test is sent in error,
but comes back as follows:
Would you arrange investigations to test for thromboembolic disease?

Answer 1.15
D-dimer is an extremely helpful blood test when sent in the correct circumstances. In a patient with a
reasonable chance of having a blood clot, an elevated D-dimer would support the diagnosis. All too
often, however, D-dimer is measured in patients with no clinical suggestion of thromboembolic disease.
There are many causes for a raised D-dimer other than clot (eg commonly found in acutely unwell patients
malignancy, and following surgery or trauma), so, unless the patient has signs or symptoms in keeping
with thromboembolism, the test should generally not be ordered. No investigations for thromboembolic
disease are required in this woman in whom we are given no reason to suspect a blood clot.
BIOCHEMISTRY
Urea and electrolyte profile
A urea and electrolyte (U&E) profile is the most commonly requested biochemical blood test. U&Es, in
combination with a full blood picture (FBP), are performed for virtually all new hospital admissions. The
U&E profile incorporate measures of electrolytes (sodium and potassium), along with renal function (urea
and creatinine). U&Es are often used as a screening test in unwell patients, and frequently act as a
stimulus for further investigation.
Electrolyte abnormalities
Abnormalities in sodium and potassium occur when they are either too low (hyponatraemia – low sodium;
hypokalaemia – low potassium) or too high (hypernatraemia – high sodium; hyperkalaemia – high
potassium).
Hyponatraemia
Hyponatraemia is defined as a sodium concentration <135 mmol/l. The condition is a source of much
confusion among students and doctors alike. The first step in working out why a patient has hyponatraemia
is to investigate whether or not the low sodium is a true finding. This can be done by measuring serum
osmolality in the laboratory. In some circumstances (eg hyperglycaemia and hyperlipidaemia), a falsely
low sodium concentration can be reported. This is known as pseudo-hyponatraemia.
If the osmolality is low (and it will be in the vast majority of cases), it can be assumed that the
hyponatraemia is real. The next and most crucial step is to make a detailed assessment of the patient’s
volume status to decide if they are dehydrated (hypovolaemic), fluid overloaded (hypervolaemic) or
normally hydrated (isovolaemic). The likely cause of the hyponatraemia varies depending into which
group the patient falls. The diagnosis and potential causes of hyponatraemia are illustrated in the flow
diagram in Fig 2.1.
Fig 2.1: From GAIN. Hyponatraemia in Adults (on or after 16th birthday). GAIN, 2010. Available at: http://www.gain-
ni.org/Library/Guidelines/Hyponatraemia_guideline.pdf.
The syndrome of inappropriate antidiuretic hormone secretion (SIADH) is somewhat over-diagnosed as a

cause of hyponatraemia. It is in actual fact quite uncommon. SIADH is dealt with separately on page 149.
DON’T FORGET
Hyponatraemia does not mean SIADH!
Hypernatraemia
This is defined as a sodium concentration of more than 145 mmol/l. Hypernatraemia is a very strong
stimulus for thirst, so in normal circumstances (healthy patient with access to adequate fluid) it should not
develop.
CAUSES OF HYPERNATRAEMIA
Diabetes insipidus
Poor water intake, eg in frail elderly patients who are unable to access water freely, perhaps because they are bed-bound and unable to ask
Administration of excess sodium in intravenous fluids
Administration of drugs containing high concentrations of sodium
For further details on diabetes insipidus, see page 148.

Hypokalaemia
This is defined as a potassium concentration of less than 3.5 mmol/l.
CAUSES OF HYPOKALAEMIA
Drugs:
• diuretic therapy
Intestinal losses:
• excess vomiting (eg pyloric stenosis)
• profuse diarrhoea
• high stoma or fistula output
Renal tubular disease:
• renal tubular acidosis or drug-induced tubular damage
Endocrine causes (eg hyperaldosteronism)
Metabolic alkalosis
Hypokalaemia is associated with characteristic changes on the ECG. This is discussed on page 359.
Hyperkalaemia
This is defined as a potassium concentration of more than 4.5 mmol/l.
CAUSES OF HYPERKALAEMIA
Renal failure
Drugs:
• excess potassium supplementation
• potassium-sparing diuretics
• combination of drugs (eg angiotensin-converting enzyme [ACE] inhibitor and diuretic)
Rhabdomyolysis
Endocrine diseases (eg hypoadrenalism)
Diabetic ketoacidosis
Haemolysis of blood sample in transit (artefactual hyperkalaemia)
Hyperkalaemia is associated with characteristic changes on the ECG. This is discussed on page 359.
DON’T FORGET
Hyperkalaemia is a medical emergency with levels of potassium of more than 6.5 mmol/l requiring immediate attention and lesser levels
requiring immediate attention if the ECG is abnormal.
Renal function
The presence of a normal urea and creatinine level is not synonymous with normal renal function. A thin
elderly woman may have significant renal impairment despite her creatinine appearing within the
‘normal’ laboratory range. One must pay attention to the age, sex and muscle bulk of a patient when
interpreting the significance of a creatinine level.
For accurate measurement of renal function, estimation of the glomerular filtration rate (GFR) is required.
An estimated GFR (eGFR) is now routinely reported by many laboratories to highlight the importance of
small increases in creatinine. Rather than reporting precise estimations of GFR for all patients, often
laboratories have a cut-off value, so that, if a patient’s eGFR falls above the value, the eGFR is simply
reported as, for example, >60 ml/min per 1.73 m2.
DON’T FORGET
A normal GFR is considered to be approximately 100 ml/min per 1.73 m2.
ESTIMATING KIDNEY FUNCTION
As mentioned above, many laboratories will now report eGFR routinely. If you wish to learn more about the mathematics behind this
estimation, the following section explains the formula for calculating eGFR and also creatinine clearance.
ESTIMATED GFR
The eGFR is calculated using the serum creatinine and requires knowledge of the patient’s age, sex and race.
eGFR = 186 × (PCr/88.4)–1.154 × A–0.203

where PCr is plasma creatinine concentration (μmol/l) and A is age in years Correction factors for gender (0.742 female) and for race
(1.210 black) are needed
Computer programs are available for assistance with the mathematics.
EXAMPLE CALCULATION
For a 62-year-old black female patient with a plasma creatinine of 150 μmol/l the eGFR would be calculated as:
eGFR = 186 × (150/88.4)–1.154 × (62)–0.203 × 0.742 × 1.210 = 39.3 (in ml/min per 1.73 m2)
CREATININE CLEARANCE
’Creatinine clearance’ provides another useful indication of the GFR and can be measured in one of two ways.
Method 1
This requires a single blood creatinine value and a 24-h collection of urine.
where CLCr is the creatinine clearance (ml/min), UCr is the concentration of creatinine in the urine
(mmol/l), U is the urine flow rate (ml/min) and PCr is the concentration of creatinine in plasma
(mmol/l)
Difficulties in this method of calculation arise for two reasons:

1. The plasma creatinine is usually measured in μmol/l, not mmol/l as required by the formula.
Urine flow rate is usually measured in litres per 24 h, ie the amount of urine produced in one
2.
day (1440 min).
Hence a correction factor of 0.694 is required (1000/1440).
To account for this, use the following modified formula:
where V = 24-h urine volume (ml)

BCr = concentration of creatinine in plasma (μmol/l)
EXAMPLE CALCULATION
For a patient with a plasma creatinine of 150 μmol/l, a 24-h urine volume of 2 l and a urinary creatinine concentration of 10 mmol/l, the
creatinine clearance would be calculated as:
Method 2
This method requires knowledge of the patient’s age (A in years), mass (M in kg), sex and serum
creatinine concentration (PCr in mg/dl).
The formula generates an estimate of creatinine clearance for male patients. For females, the result of
this calculation should be multiplied by 0.85.
Difficulties in this method of calculation arise because plasma creatinine is usually measured in
μmol/l. To convert from μmol/l to mg/dl, divide by 88.4.
EXAMPLE CALCULATION
For a 66-year-old, 70-kg, female patient with a plasma creatinine of 150 μmol/l, the creatinine clearance would be calculated as:
Serum urea
The level of urea is reflective of both its production and elimination. Poor dietary intake can lead to a
low urea level. Elevations in urea levels occur in renal failure, but are also commonly seen following a
gastrointestinal bleed. Blood is effectively an excess protein load which is digested by the bowel.
Plasma osmolarity
Serum osmolarity can be calculated using the results of U&Es with the blood glucose level. Osmolarity is
determined by the concentration of osmotically active particles, of which sodium is the most influential. It
is calculated as follows.
Plasma osmolarity = 2 × (PNa + PK) + PUrea + PGlucose

where PNa is plasma sodium, PK plasma potassium, PUrea plasma urea and PGlucose is plasma glucose, all in mmol/l
Nutritional profile
A nutritional profile comprises measures of magnesium, calcium, phosphate and albumin. In patients with
poor nutrition, all these nutrients may be deficient. Commonly deficiencies are seen in patients with poor
oral diets (eg alcoholics, hunger strikers), or in patients with malabsorption. Further tests are available to
provide blood levels of trace metals such as selenium.
Re-feeding syndrome is the term used to describe the change in blood biochemistry that can occur in
patients who begin feeding after a period of starvation. Examples include hunger strikers who start to eat,
and patients who have been unable to swallow (eg after a stroke) and begin nasogastric feeding after a
period of starvation. Dangerous shifts in many electrolytes (eg phosphate, magnesium and calcium) can
occur in such individuals and this can cause problems. Electrolytes should be checked frequently and
replaced as necessary.
Urine in acute renal failure

Acute renal failure is a common problem in clinical practice. A common cause of this is renal
hypoperfusion. Urine is often analysed for electrolyte content in such patients to enable the differentiation
of prerenal uraemia from acute tubular necrosis. Patients with prerenal uraemia would be expected to
recover faster than those with acute tubular necrosis when appropriate therapy is initiated.
The key to correct interpretation of urinary electrolytes is understanding that, in prerenal uraemia, normal
renal regulatory mechanisms remain intact and attempt to maintain homeostasis. The juxtaglomerular
apparatus senses the reduction in renal blood flow and activates the renin–angiotensin–aldosterone
system. The end-product, aldosterone, acts to promote sodium reabsorption in the distal convoluted
tubule. This results in an increase in the circulating volume. Therefore, in prerenal uraemia, the urinary
sodium is low.
In acute tubular necrosis, the normal physiological mechanisms break down. Urinary sodium is therefore
high.
It is difficult to interpret urinary sodium levels when a patient is taking a diuretic.
The fractional sodium excretion (FENa) is sometimes measured in addition. This is simply a measure of
the proportion of sodium that is filtered at the glomerulus that ends up in the urine. The FENa will
therefore be low in prerenal uraemia and high in acute tubular necrosis.
The following table summarises the differences.
PRERENAL ACUTE TUBULAR

URAEMIA NECROSIS
Urinary sodium (mmol/l) <20 >40
FENa (%) <1 >1

Urine concentration Concentrated Relatively dilute
Bone profile
In health, bone undergoes a continuous process of remodelling by osteoclasts and osteoblasts. A bone
profile is a batch of biochemical blood tests grouped together as they are all relevant to bone disease. It
comprises calcium, phosphate and alkaline phosphatase (ALP). Albumin is also included for reasons
detailed below. Metabolic bone diseases are associated with characteristic abnormalities on the bone
profile. More specialised analyses, eg parathyroid hormone (PTH) or vitamin D levels, can be carried
out when clinically relevant.
COMPONENTS OF A BONE PROFILE

Calcium Alkaline phosphatase
Phosphate Albumin
Calcium homeostasis is under hormonal control with PTH being a key regulator. When calcium is low,
PTH is released. This acts to raise serum calcium levels by:
• increasing calcium reabsorption from bone
• increasing renal calcium reabsorption
• increasing renal excretion of phosphate
• indirectly increasing absorption of calcium from the gut via effects on vitamin D.
Major metabolic bone diseases

The major bone diseases that a student might be expected to identify from a bone profile are listed in the
box below.
MAJOR BONE DISEASES

Osteoporosis Bony metastases
Osteomalacia Hyperparathyroidism
Paget disease of bone
Typical patterns of results are shown in the following box.

DON’T FORGET
The bone profile is normal in osteoporosis.
Corrected calcium
It is important to appreciate that a high proportion of calcium is bound to protein (albumin). However, it
is the unbound calcium that is most important physiologically. For this reason when protein (albumin) is
low the total calcium level may be misleading and a correction calculation needs to be made. The
‘corrected calcium’ level refers to the calcium level corrected for the fact that the albumin is abnormal.
Corrected calcium can be calculated as follows:
where PCac (in mmol/l) is the corrected calcium level, PCa (in mmol/l) is the calcium level and Alb is the
albumin concentration (g/l).
EXAMPLE CALCULATION
CAUSES OF HYPERCALCAEMIA
Bone metastases
Multiple myeloma
Hyperparathyroidism
Excessive vitamin D intake
Liver function tests

Liver function tests (LFTs) comprise six measurements: bilirubin, aspartate aminotransferase (AST),
alanine aminotransferase (ALT), alkaline phosphatase (ALP), γ-glutamyl transpeptidase (GGT) and
albumin. Prothrombin time (PT) which is part of a coagulation screen is an important addition (see page
21).
COMPONENTS OF LIVER FUNCTION TESTS

Bilirubin
Aspartate aminotransferase
Alanine aminotransferase
Alkaline phosphatase
γ-Glutamyl transpeptidase
Albumin
Note that AST and ALP are not tests specific to the liver. AST is also released when muscle (including
cardiac muscle) is damaged. ALP is raised in a number of bone diseases, hence its presence in a bone
profile.
If these basic LFTs are abnormal, further specific tests may be performed to establish an underlying
cause.
TEST DISEASE EXPECTED RESULT

Anti-nuclear
Anti-smooth muscle
Autoimmune hepatitis
Anti-liver/kidney
microsomal-I
Autoantibody screen
Primary biliary cirrhosis Anti-mitochondrial
Coeliac disease Anti-transglutaminase
Iron profile Haemochromatosis High iron, ferritin and transferrin saturation Low TIBC
Low ceruloplasmin and elevated 24-hour urine copper

Copper studies Wilson’s disease
concentration suggestive
Viral hepatitis ‘screen’ Hepatitis Positive viral tests
α1-Antitrypsin
α1-Antitrypsin Low level
deficiency
α-Fetoprotein Hepatocellular carcinoma High level
Specific pattern of immunoglobulin rise can give a clue to

Immunoglobulins Several liver diseases
underlying disease but will not be diagnostic
Broadly speaking, disturbances of liver function may be classified into three patterns:
• Hepatitic (parenchymal)
• Cholestatic
• Mixed.
These patterns assist in narrowing the differential diagnosis of altered liver function. An understanding of
the different causes allows an appropriate sequence of investigation.
When hepatocellular damage occurs, hepatocytes ‘spill out’ transaminases (AST and ALT). A rise in
these indices alone may be termed a ‘transaminitis’.
When there is obstruction to the outflow of bile from the liver, a cholestatic pattern (elevated ALP and
GGT) will be seen. The bilirubin level would also be expected to be high.
Bilirubin is conjugated in the liver with the attachment of a glucuronide group. Measured bilirubin may be
conjugated (direct bilirubin) or unconjugated (indirect bilirubin). Total bilirubin is the sum of both types.
Confusion sometimes arises in cholestatic liver disease when the AST and ALT are also elevated. This
occurs because of back pressure on the liver. In such instances the elevation of ALP and GGT will be out
of proportion to that of the transaminases.
In cholestatic jaundice, conjugated bilirubin can be detected in the urine using urinalysis.
CAUSES OF HEPATITIC LFTs
• Viral hepatitis
• Autoimmune hepatitis
• Drugs and toxins
• Alcohol
• Metabolic disorders (eg Wilson’s disease)
• Fatty liver
• Malignancy (both primary and metastatic)
• Congestive cardiac failure
CAUSES OF CHOLESTATIC LFTs
Obstruction in the bile duct lumen

• Bile duct gallstone

An abnormal bile duct wall
• Bile duct stricture
• Cholangiocarcinoma

Compression of the bile duct by an extrinsic lesion
• Pancreatic carcinoma
• Nodes at the porta hepatis
• Ampullary carcinoma
One of the functions of the liver is protein synthesis. In a failing liver, synthetic function is often affected.
This will manifest as low albumin levels and a raised prothrombin time (since the liver manufactures
clotting factors).
C-reactive protein
C-reactive protein (CRP) is a protein produced in the liver. It is an acute phase reactant, being raised in
inflammation and infection. It is often thought of in a similar manner to the erythrocyte sedimentation rate
(ESR) (see page 17). The CRP and ESR are together termed inflammatory markers. There are a few
recognised conditions in which the ESR is raised, but the CRP is normal.
CAUSES OF A RAISED ESR WITH A NORMAL CRP

SLE
Multiple myeloma
The level of the CRP does not necessarily reflect the severity of a disease process.
Urate (uric acid)
Urate is produced during the metabolism of purines, and is excreted by the kidneys. High levels in the
blood (hyperuricaemia) can occur through two mechanisms:
• increased purine consumption or uric acid production
• impaired excretion of uric acid.
A modest amount of the body’s purines is ingested in food and drink. A patient with a raised urate level
may be asymptomatic or may be troubled with gout. It is common practice to measure serum urate levels
in any patient with an acute monoarthritis. High levels of urate support a diagnosis of gout. However,
urate levels can be normal during an acute attack of gout.
DON’T FORGET
Urate levels may be normal during an acute attack of gout.
Tumour markers
Tumour markers are a selection of blood tests that are commonly elevated in patients with neoplastic
disease. Most tumour markers are characteristically associated with a particular type of cancer, as shown
in the table.
TUMOUR MARKER ASSOCIATED TUMOURS

α-Fetoprotein (FP) Hepatocellular carcinoma; testicular teratoma
Human chorionic gonadotrophin (β-hCG) Testicular teratoma and seminoma Choriocarcinoma
Prostate-specific antigen (PSA) Prostate
CA-125 Ovarian
CA-19-9 Pancreatic
Carcinoembryonic antigen (CEA) Colorectal
However, with the exception of α-FP, β-hCG and PSA, tumour markers are fairly non-specific, and
several markers may be elevated with one underlying cancer. Tumour markers should therefore be
requested only when the significance of a positive result can be usefully interpreted.
Tumour markers have two chief roles in clinical practice. First, specific markers such as PSA can be used
in making a diagnosis. Second, serial measures of tumour markers can be used to monitor disease
progress and response to treatment.
DON’T FORGET
Tumour markers are isolated blood tests – interpret them in the context of clinical features and all allied investigations.
Sweat testing
Cystic fibrosis results from a mutation in the gene that encodes the cystic fibrosis transmembrane
conductance regulator (CFTR). CFTR is responsible for chloride ion transport across epithelial cells,
and abnormalities in its structure result in viscous secretions, particularly in the lung and pancreas.
Abnormal sweat gland function leads to high concentrations of sodium and chloride in the sweat. Indeed,
excessively salty tasting sweat was noted to be a clinical feature of cystic fibrosis long before the
genetics were fully understood. This feature underlies the diagnostic test for cystic fibrosis – the sweat
test.
In this test, sweating is stimulated, and sweat collected for analysis. Sufficient sweat (100 mg) must be
collected for the test to be reliable. The test is positive if more than 60 mmol/l chloride is present, and the
test should always be repeated before a conclusion is reached. Measurements of sweat sodium
concentration are less reliable, but a concentration of greater than 90 mmol/l is in keeping with cystic
fibrosis.
There are instances when a false-positive sweat test can occur. The most common of these are listed
below.
COMMON CAUSES OF A FALSE-POSITIVE SWEAT TEST

Adrenal insufficiency
Anorexia nervosa
Coeliac disease
Hypothyroidism
Case 2.1
A 49-year-old missionary is brought to your hospital by his wife. He has been vomiting for the past 24 h.
He is now very weak. He last ate 2 days previously and has struggled to keep down any liquids since. On
examination his mouth is dry, his abdomen is generally uncomfortable and he has reduced skin turgor.
After taking his routine blood tests, a 0.9% saline drip is erected before any results are checked. A short
time later the following result is available.
1. Outline the abnormalities on this blood result.
After noting the above results, his intravenous fluid prescription is changed to 1 litre of 0.9% saline
containing 40 mmol/l of potassium chloride, to be infused over 6 h.
Two hours later, his U&Es are repeated, and are shown below.
The ward doctor is concerned, and a further sample is taken.
2. How would you account for the discrepancy between these two blood tests?
Answer 2.1
1. Three abnormalities can be seen in the results above:

• Low sodium (hyponatraemia)
• Low potassium (hypokalaemia)
• High urea (uraemia).
The low sodium and low potassium are a consequence of a prolonged period of vomiting combined
with very limited oral intake. There has been a substantial loss of electrolytes without any means of

replacement until admission to hospital. The patient is clinically dehydrated and the raised urea is a
reflection of this.
Looking at the first repeat blood test, the sodium and potassium levels have both risen from the time
2. of admission a few hours previously. There has been a dramatic change in electrolyte levels. The
second repeat sample is very different again.
The explanation for these findings is that the first repeat blood sample has been taken from the arm
into which fluid is being infused. This is an erroneous sample.
The second repeat sample comes from a ‘non-drip’ arm, and shows the true state of affairs, ie

slowly improving electrolytes from the time of admission.
Case 2.2
A 22-year-old university student is trapped in her house during a fire and when rescued by firefighters has
developed substantial burns to the arms and chest. She is admitted to the burns unit. U&Es on her third
day are shown.
What is the main biochemical problem and name some of its causes?
Answer 2.2
Hypernatraemia is present. Other components of the U&Es are normal. A common cause for this
observation in hospital medicine is excessive use of 0.9% saline in those patients receiving intravenous
fluids. This is one reason why intravenous fluid prescribing should be considered carefully and regular
U&E samples checked. This is especially important in patients with excessive fluid losses, such as
patients with burns. In this patient, substantial fluid loss from her burns has led to a water deficit.
Consequentially, the sodium concentration has risen.
Other causes of hypernatraemia are listed on page 59.
Case 2.3
A 76-year-old woman is admitted unwell with vomiting and is found to have a low blood pressure. She
had recently been given diclofenac following a complaint of back pain. Her initial blood results included
U&Es.
1. What has happened to this patient?

2. What immediate treatment is indicated?
Answer 2.3
The urea and creatinine are both grossly elevated indicating that this patient has renal failure.
Comparison with previous blood tests would indicate whether this is acute or chronic. As a
consequence of the renal failure, serum potassium is dangerously elevated. The rising potassium is
1.
a reflection of the failing tubular function of the kidney. In this case it would appear that the use of a
non-steroidal anti-inflammatory drug (diclofenac) and vomiting are the causes of an acute
deterioration in renal function.
Hyperkalaemia can cause fatal dysrhythmias, including cardiac arrest. This requires immediate
treatment. Conventional treatment employs insulin and dextrose. Insulin drives potassium into the
2.
cells, while glucose prevents hypoglycaemia. Calcium gluconate should be given first to stabilise
the myocardium.
The ultimate treatment is to identify the cause of the renal failure and support the kidneys until

function is restored.
Case 2.4
A 46-year-old diplomat is transferred to your care following medical evacuation from Nigeria. In his
transfer correspondence it indicates that he has developed renal impairment which as yet has not been
investigated in depth.
His U&Es are shown, along with a 24-h urine collection for creatinine clearance.
Calculate his creatinine clearance.

Answer 2.4
Creatinine clearance can be calculated using the following equation:
where VCr is the concentration of creatinine in urine (in mmol/l), V is the 24-h urine volume (in ml) and
BCr is plasma creatinine in μmol/l
In this case:
The creatinine clearance is 12.4 ml/min. Bearing in mind that the normal creatinine clearance is
approximately 100 ml/min, it is clear that this man has significant renal impairment.
Case 2.5
A 34-year-old man is admitted with epigastric discomfort and a single episode of vomiting following a
week-long binge of alcohol. His vital signs are within the normal range. Blood tests were taken at the
time of admission.
Explain the elevated urea in the context of the other haematological results.
Answer 2.5
This man’s U&Es reveal an elevated urea. His creatinine is normal and his clinical history does not
suggest dehydration. His full blood count reveals information that helps in interpreting the significance of
the elevated urea. His haemoglobin, MCV, white cell count and platelets are all abnormal. The raised
MCV most likely represents chronic alcohol use.
During gastrointestinal bleeding, an increase in urea may occur. This is because urea is a breakdown
product of digested blood. Similarly during an active bleed, a rise in the white cell count and platelet
count may occur.
The combination of the following is suggestive of gastrointestinal bleeding:
• raised urea (with normal creatinine)
• low haemoglobin
• raised white cell count (in the absence of infection)
• raised platelets.
Case 2.6
A 39-year-old man with a history of Crohn’s disease and previous extensive small bowel resection is
admitted with anorexia and weight loss. His GP is very concerned that he now weighs only 39 kg and has
not been able to tolerate much in the way of oral foods for several months. In hospital, attempts were
made to start nasogastric feeding, but it could not be tolerated. Total parenteral nutrition (TPN) was
therefore commenced. The following table shows his U&Es and nutritional profile over several days
following commencement of parenteral feeding.
Comment on these results.

Answer 2.6
This scenario illustrates the issue of re-feeding in those patients who have been nutritionally depleted for
some time. When feeding is commenced, a rapid and precipitous drop often occurs, in particular, in
phosphate levels.
Case 2.7
A 72-year-old former engine driver attends his GP complaining of generalised aches and pains. During
the consultation you have to speak loudly to be understood. As part of your investigations you request a
bone profile. Liver function tests were normal.
On the basis of this test he received a course of treatment for several months. Following treatment his
bone profile is repeated and is as follows.
1. What bone disease does this patient have?

2. What treatment is he likely to have received to explain the change in his bone profile?
Answer 2.7
This elderly man has Paget’s disease of the bone. He has an isolated ALP rise, in the absence of any
liver disease. An ALP rise can occur for various reasons, including primary sclerosing cholangitis
1.
and bony metastases. However, in the context of this patient’s symptoms, with deafness, Paget
disease is most likely.
The repeat bone profile demonstrates lowering of the ALP after successful treatment. He is likely to
have received intravenous bisphosphonate therapy. Note that the majority of patients with Paget’s
2.
disease are asymptomatic and the disease is often diagnosed incidentally when tests are requested
for other reasons.
Case 2.8
A 69-year-old retired nurse complains of generalised aches and pains for the past 5 weeks, sometimes
preventing her from sleeping at night. Her past medical history includes hypothyroidism, hypertension and
a mastectomy 2 years ago for breast carcinoma. She is a very active member of the Women’s Institute and
feels less able to complete her daily tasks of late.
Blood tests included a bone profile. Liver function tests were normal.
Describe the findings on the bone profile and give an explanation.

Answer 2.8
The ALP is significantly raised. The rest of the bone profile is normal. ALP may be high in a number of
conditions. It is important to exclude liver disease, but we are told here that the rest of her liver function
tests were normal.
Bearing in mind the clinical history, a particular concern in this woman would be bony metastases from
breast carcinoma. This can occur a considerable time after treatment of the primary tumour. The calcium
may be normal or elevated in the presence of bony metastases.
Case 2.9
A 45-year-old teacher has been complaining of aches and pains for several months. Her colleagues have
said that she has not been herself recently, appearing ‘under the weather’ and sad. She is still menstruating
regularly. Among the blood tests requested by her GP was a bone profile.
A further blood test, of great importance in diagnosis, was sent the following day.
1. What is the additional test likely to be?
Answer 2.9
1. The additional test is for parathyroid hormone (PTH).

2. These findings are in keeping with primary hyperparathyroidism.
The excess PTH, most likely from a parathyroid adenoma, is causing excess bone resorption resulting in a
high calcium and ALP. Constitutional symptoms include bony aches, low mood and constipation, which
can arise due to the hypercalcaemia. Hence the patient with hyperparathyroidism can have problems with
‘bones, stones, moans and abdominal groans’.
Note that in primary hyperparathyroidism PTH is generally raised. However, a normal PTH level is also
abnormal in a patient with hypercalcaemia and may be indicative of hyperparathyroidism. This is because
PTH should normally be suppressed by negative feedback in the setting of hypercalcaemia.
Case 2.10
A 46-year-old office clerk attends a private health clinic complaining of aches in his bones and
tenderness over his muscles. This has been troubling him for some time and he is no longer able to walk
to work. He has suffered from coeliac disease for many years, but by his own confession finds it hard at
times to stick to his gluten-free diet. A ‘screen’ of tests is taken, some of which are shown below.

Answer 2.10
These findings are in keeping with a diagnosis of osteomalacia. Osteomalacia is a metabolic bone disease
in which there is a lack of calcium or phosphate (or both) for mineralisation of newly formed osteoid. As
a result, bone is ‘soft’ and unable to withstand the stresses and forces of normal bone. Parathyroid
hormone would need to be checked if there was any diagnostic doubt.
It is likely that this patient’s coeliac disease is contributing to the development of osteomalacia through
malabsorption of calcium.
Case 2.11
A 55-year-old woman is admitted with a fractured neck of femur after a minor trip in the car park of her
local supermarket. Looking back through her old records, the admitting doctor notices the following bone
profile taken 2 weeks previously.
What bone disease might you suspect?

Answer 2.11
You should suspect osteoporosis given the history of fracture after minimal trauma, and a previously
normal bone profile. Osteoporosis is the most common form of metabolic bone disease. It is
predominantly found in postmenopausal women and is considered a silent disease. First presentation is
often with a low trauma fracture as in this clinical scenario.
Diagnosis of osteoporosis is usually made using dual energy X-ray absorptiometry (DEXA) scan.
Case 2.12
A 47-year-old woman is referred to the regional hepatology outpatient clinic by her GP. She attended her
GP on several occasions complaining of tiredness, low mood, altered bowel habit and more recently of
itch. On examination a 4-cm smooth hepatomegaly is noted, with xanthelasmata around her eyes.
The referral letter contains the following LFTs:
A blood test taken at the clinic revealed the following:
1. Interpret these results.

2. Suggest a further investigation.
Answer 2.12
The only abnormality on the liver biochemistry is a raised ALP. ALP may be raised in bone as well
as liver disease (see page 70). An isolated ALP rise may be seen in both primary sclerosing
cholangitis (PSC) and early primary biliary cirrhosis (PBC). The normal albumin suggests that the
1. synthetic function of the liver remains intact. The immunological tests are the diagnostic key in this
case. A substantially raised anti-mitochondrial antibody (AMA) is observed. Ninety-five per cent of
patients with PBC will have a positive antibody for AMA-M2. In PSC the presence of
autoantibodies is uncommon.
2. The most useful investigation to confirm and assess the extent of disease would be a liver biopsy.
Case 2.13
A 68-year-old woman was admitted with itch, lethargy and discoloration of the skin over the past month.
On examination she is icteric and cachexic. There are no stigmata of chronic liver disease. Nursing staff
indicate that there is discoloration of her urine.
Her admission bloods include LFTs.
1. Outline the abnormalities seen on the liver function tests.

2. What would be your next choice of investigation?
3. What are the potential causes of these results?
Answer 2.13
1. The LFTs show an elevated bilirubin with cholestatic LFTs.

An ultrasound scan of the abdomen is the next most important investigation. This will confirm the
2. presence of obstruction and may identify the underlying cause. This can then act as a guide for
further investigations.
3. The causes of cholestatic jaundice are listed on page 73.
Case 2.14
A 34-year-old labourer is admitted with right upper quadrant discomfort, fever and sweats. He returned
from a project overseas 3 weeks earlier. On examination he is tender to palpitation over the right
hypochondrium making complete examination difficult. A spiking fever pattern is seen on his observation
chart. His LFTs are as follows.
What investigation does this patient need as soon as possible based on his clinical history and
1.
blood tests?
Answer 2.14
The bilirubin and transaminases are raised. The CRP is highly elevated. He requires an ultrasound
1.
scan of the abdomen to investigate an infective cause for his symptoms.
2. Viral hepatitis, a liver abscess or cholangitis are all potential causes.
Case 2.15
A 32-year-old man is recalled by his occupational health department following a recent ‘medical’ before
transfer to an overseas operation within the company. He is teetotal. He cannot understand what all the
fuss is about as he feels fine.
The blood results of concern are shown.
1. What pattern of LFTs is demonstrated?

2. What further blood tests may help in coming to a diagnosis?
Answer 2.15
1. This patient has a parenchymal LFT derangement. Both the ALT and AST are markedly elevated.
A set of ‘screening’ investigations should be performed next to further investigate the situation. See
2.
page 71 for details.
This patient had hepatitis C. Not infrequently hepatitis C is diagnosed incidentally when LFTs are
checked for some other reason.
Case 2.16
A 37-year-old manual worker is admitted with generalised abdominal discomfort, vomiting and
shakiness. On examination there is a 4-cm mildly tender hepatomegaly. He is sweaty to the touch. Some
blood tests are requested.
1. Outline the abnormalities on this set of blood results.

2. Explain the likely cause of the LFT abnormalities given the abnormalities in the other results.
Answer 2.16
1. The abnormalities seen include:

• a raised MCV, with a slightly low platelet count
• low values for urea, potassium, magnesium and, in particular, phosphate
• a raised GGT
• a low albumin.
The findings on these simple blood tests are classic for an individual who has consumed large
2.
quantities of alcohol for a significant time period.
Case 2.17
A 44-year-old woman with primary biliary cirrhosis has been attending hepatology outpatients for many
years. Over the past 18 months she has been feeling less well in herself and her frequency of attendance
for review has increased at the insistence of her physician. On examination she is jaundiced and her
abdomen is mildly distended with a 3-cm hepatomegaly.
Her recent blood results are shown.
Give a summary of the findings.

Answer 2.17
The course of primary biliary cirrhosis is variable. Patients may live with stable LFTs for a number of
years. Decompensation may occur at any time with deterioration in the liver’s synthetic function.
The chart shows LFTs over a period of 20 months. Initially only a moderately elevated ALP is seen in
April 2004. Over the ensuing months the ALP continues to rise, and with this the albumin falls reaching a
low of 28 g/l in December 2005.
The prothrombin time should also be checked. One would expect it to be raised indicating impaired
production of clotting factors by the failing liver.
Case 2.18
A patient is referred to a psychiatrist for investigation of bizarre thoughts. She has occasional involuntary
movements. The psychiatrist requests a series of blood tests as part of her initial screening tests, and the
following results are obtained.
What disease could account for the presentation and the blood test abnormalities? How would you
investigate it further?
Answer 2.18
The blood tests show very mild elevations in AST and ALT. These are very minor and non-specific
findings and could be caused by a variety of conditions, including viral hepatitis and drug-induced
hepatitis. The only condition that meaningfully links a psychiatric disorder with these abnormal liver
function tests is, however, Wilson’s disease – a condition associated with copper overload. Tests that
could be performed to investigate further include: serum copper level, serum ceruloplasmin level, slit-
lamp examination of the eyes to look for copper deposition, 24-hour urinary collection for copper
measurement and liver biopsy.
Case 2.19
A 38-year-old woman complains of a rash over her face and nose for several weeks and a recent problem
with pain and swelling in the joints of her hands. She is married but without children. A number of blood
tests were sent – some of which are shown below.
1. Summarise the results shown.

2. Using the clinical information what is the most likely diagnosis?
Answer 2.19
1. There are a number of abnormalities on this set of results:

• the haemoglobin is slightly low
• the platelet count is slightly below normal
• the WCC is low
• the ESR is raised, with a normal CRP
• protein is noted in the urine.
The CRP is normal. This would go against an infectious cause for a raised ESR and be more
suggestive of inflammation of some description. There are only a few conditions in which the ESR is
2.
elevated but the CRP remains normal. One such condition is systemic lupus erythematosus (SLE)
which this patient’s clinical features and blood test abnormalities are in keeping with.
Case 2.20
A 77-year-old patient with dementia was admitted generally unwell. No history was obtained. He was
pyrexic and appeared a little short of breath. Examination was difficult, although there was the impression
of reduced breath sounds at the right lung base. Urinalysis was normal. Blood tests were taken.
How do these tests help in the management of this patient?

Answer 2.20
Establishing a diagnosis in elderly people can be difficult by clinical assessment alone, especially when
no history is available. It is often necessary to place greater emphasis on investigations. Although, in this
case, the FBP and U&Es are normal, the CRP is significantly raised. In the presence of infection one might
expect the WCC to be raised too, but this is not always the case. An infection is likely to be the cause of
the patient’s illness. A urinary tract infection and pneumonia are the most common causes of these findings
in clinical practice. Given the normal urinalysis and abnormal examination findings in the chest,
pneumonia is the most likely diagnosis.
Case 2.21
A 34-year-old woman with acute lymphoblastic leukaemia (ALL) is receiving chemotherapy within the
haematology suite of the hospital. Several days into treatment she complains of an intensely sore right
knee. On examination there is an effusion and she is unable to extend the knee fully due to pain. She has no
pre-existing joint disease. Fluid was aspirated from the knee and sent for analysis along with blood
samples.
Interpret these results (see page 496 for details of synovial fluid analysis).
Answer 2.21
Hyperuricaemia may occur due to excess purine metabolism. This includes those suffering from
haematological malignancies in which there is increased cell turnover, especially following cell lysis
from chemotherapy.
The presence of negatively birefringent crystals from the joint aspiration confirms gout.
Case 2.22
A 32-year-old woman with diabetes is admitted for treatment of a large abscess. The patient is reluctant
to undergo surgical intervention and medical treatment is pursued initially. Four days into her care she
becomes more unwell and her treatment is changed. A further 3 days on, when her condition remains poor,
she agrees to surgical intervention. Below is a chart of her CRP throughout this period.
Try to explain the trend in the results.

Answer 2.22
Some of the most rewarding data to interpret are those collated over a period of time when trends can be
observed. This scenario illustrates the value of CRP in both supporting a clinical diagnosis and
monitoring its response to treatment. On admission this patient’s CRP is significantly raised, as one may
expect in the presence of an abscess. With the commencement of antibiotics, one might hope for the CRP
to improve as the abscess is treated. The worsening of her clinical state and the rising CRP suggest that
either the antibiotics are ineffective against the causative organism or they are unable to penetrate the
abscess. Day 4 sees a change in treatment, no doubt to an alternative antimicrobial. However, the CRP
remains stubbornly high. It is only in the days following surgical intervention that the CRP begins to
decrease, reflecting the successful treatment of the abscess.
Case 2.23
A 58-year-old man complains of an exquisitely tender great toe. It is red, swollen and impossible to
examine fully because of pain. No other joints are affected. He has a history of hypertension and a
previous myocardial infarction at 49 years of age. He drinks 14 units of alcohol a week. To his
knowledge he does not have any kidney problems. Blood tests are shown.
Does this man have gout? Justify your answer.

Answer 2.23
The clinical history is one of podagra (gout of the great toe). The elevated urate in the blood supports this
diagnosis. Definitive diagnosis of gout depends on the detection of crystals of sodium urate in synovial
fluid (see page 496). However, not all joints with acute gout are amenable to aspiration and one must rely
on a clinical impression and supportive blood tests. Remember that the serum urate level can be normal in
acute gout.
This patient may well be taking a thiazide diuretic for hypertension. This would place him at higher risk
for gout.
Case 2.24
A 67-year-old man attends outpatients with a complaint of constipation and vague abdominal discomfort.
Abdominal examination and proctoscopy were normal. Imaging investigations and endoscopy have been
arranged. CEA levels were also requested, along with routine blood tests.
What underlying diagnosis unites all the abnormalities observed?

Answer 2.24
The key findings on this patient’s blood tests are a microcytic anaemia (see page 4) and a raised CEA.
Given his symptoms, these results should arouse a great deal of suspicion of colorectal carcinoma.
Although proctoscopy was normal this visualises only a very small percentage of the large bowel and
further imaging is required. In this case the tumour marker merely adds weight to a clinical suspicion.
Case 2.25
A 55 year old with haemophilia attends her routine 6-monthly review at hepatology outpatients. She has
been attending for several years after contracting hepatitis C from a blood transfusion. The doctor notes
that she has not attended for 8 months, and requests a number of blood tests.
What would you infer from these results?

Answer 2.25
This patient most likely has liver cirrhosis secondary to hepatitis C. Her regular attendance at an
outpatient clinic is at least in part for surveillance for hepatocellular carcinoma. Her α-FP level is within
normal limits, indicating a low likelihood of this tumour being present. An annual surveillance ultrasound
of the liver will be used in conjunction with α-FP measurements to seek out a hepatocellular carcinoma. A
significant percentage of tumour markers are performed for monitoring so you should expect to interpret
some normal results.
Case 2.26
A 44-year-old reformed intravenous drug user with known hepatitis C is well known to the local
hepatologists. He has been attending on a regular basis and is enrolled in the hepatocellular carcinoma
surveillance programme. Below are an overview of his blood tests.
What may explain the pattern in these results?

Answer 2.26
One important role of α-AFP measurement is demonstrated well in this patient with hepatitis C. It is one
of the more specific tumour markers and can be used with some degree of confidence to monitor patients
with liver cirrhosis who have a substantially increased risk of developing hepatocellular carcinoma
(HCC). Identifying a patient who has developed HCC early may allow successful treatment to be
instigated. The level in January 2005 is higher than 6 months previously but is not dramatically elevated.
However, 6 months later it has increased substantially. This suggests the development of HCC, and
ultrasound and/or other cross-sectional imaging would be merited. The encouraging downward trend in
the following 6 months would indicate that the tumour has been successfully treated.
Case 2.27
A 55-year-old senior civil servant plucks up the courage to attend his GP after complaints of a poor
urinary stream, frequency and nocturia. He is concerned as his father had ‘prostate problems’, On rectal
examination an enlarged prostate was felt. Later that week his renal function and prostate-specific antigen
tests come back.
Does this patient have anything to worry about?

Answer 2.27
Of all the tumour markers available, probably the most commonly requested is the PSA. It is sometimes
used in an attempt to identify the presence of prostatic carcinoma, but more usefully in monitoring the
disease and treatment response. This patient has obstructive urinary symptoms and an enlarged prostate,
but this does not mean that he has prostate carcinoma. Likewise a normal PSA does not exclude the
presence of this tumour. However, this man most likely has benign prostatic hypertrophy. There are a
number of causes of a raised PSA, as shown below.
CAUSES OF RAISED PSA

Prostate carcinoma
Instrumentation of prostate (including urinary catheterisation)
Urinary tract infection
Recent ejaculation
Case 2.28
A 28-year-old media studies student attends A&E with a swollen left testicle. He is sexually active, with
multiple sexual partners in the last 6 months. The A&E officer is concerned, and arranges admission.
Ultrasound of the scrotum and blood tests were requested.
Can these results be explained by a diagnosis of epididymo-orchitis?

Answer 2.28
α-Fetoprotein is one of the few tumour markers with a good specificity for two different tumours –
hepatocellular carcinoma and testicular teratoma. Similarly testicular teratoma is unique in
characteristically causing high levels of two tumour markers – α-FP and β-hCG. Both tumour markers are
significantly elevated here indicating a high probability of testicular malignancy. Following treatment,
these markers should be checked again and should have decreased.
Case 2.29
A 55-year-old woman is admitted under the care of the surgical team with a distended abdomen. She
admits that it has become increasingly large over the past few weeks, but was scared to come to hospital.
She has no complaints of abdominal pain and her bowel habit is normal. The enthusiastic junior doctor
who admitted the patient included in the notes that she has sent blood for CEA, CA-125 and CA-19-9.
What do these blood results tell you?

Answer 2.29
It is not uncommon (though not particularly good practice), especially in puzzling clinical cases, to
request a host of blood tests. Tumour markers for intra-abdominal pathology are sometimes used in this
manner. However, due to the non-specific nature of these results, abnormal results can sometimes add to
the diagnostic conundrum. The abnormal marker in this case is CA-125. This is most closely associated
with ovarian malignancy. The clinical history is certainly in keeping with this, as the distended abdomen
may reflect both tumour bulk and/or the presence of malignant ascites.
ENDOCRINOLOGY
Endocrine disorders can be divided into primary and secondary disorders. In a primary endocrine gland
disorder, the problem lies within the endocrine gland itself. Thus, in primary hyperthyroidism, the
principal problem is an overactive thyroid gland. Secondary endocrine diseases arise when there is a
problem with the hormones controlling the activity of the target gland, such as the overproduction of a
hormone by the pituitary gland.
Thyroid hormones
Normally, thyrotrophin-releasing hormone (TRH) is released from the hypothalamus and stimulates the
pituitary gland to release thyroid-stimulating hormone (TSH). This hormone then acts on the thyroid gland
and results in the liberation of thyroxine (T4) and triiodothyronine (T3) into the circulation. These
hormones exert negative feedback on both the hypothalamus and pituitary, and result in a reduction in the
production of TRH and TSH. Most of the T3 and T4 in the body is carried by carrier proteins (principally
thyroxine-binding globulin, TBG). A small percentage is present in unbound form, and it is this that is
physiologically active. In clinical practice, the commonly measured hormones are TSH, free T4 and T3.
Total T4 (ie bound and unbound forms) is sometimes given.
Fig 3.1
Hyperthyroidism
In primary hyperthyroidism (eg with Graves’ disease), the thyroid gland autonomously produces thyroid
hormones. The levels of T3 and T4 therefore rise. Normal negative feedback continues, and the level of
TSH will be low. In T3 thyrotoxicosis, the T3 level may be elevated in isolation.
In secondary hyperthyroidism (eg due to a pituitary tumour secreting TSH), the levels of T3 and T4 will
again be high, but this time the TSH level will be inappropriately normal or high.
DON’T FORGET
The finding of a normal TSH level in the setting of raised T3 and T4 should raise suspicions of a pituitary lesion, since in normal
circumstances the TSH level will be suppressed.
Hypothyroidism
In primary hypothyroidism (eg with Hashimoto’s thyroiditis), the thyroid gland is defective. The levels of
T3 and T4 are low. As a result of reduced negative feedback, the TSH level will be high.
In secondary hypothyroidism (eg destructive pituitary tumour), the levels of T3 and T4 will again be low,
but this is because of low TSH levels.
Sick euthyroid syndrome

Caution should be taken when interpreting thyroid function tests in a patient with an acute illness. This is
because thyroid function tests are often abnormal during the acute phase of an illness, but normalise on its
resolution. This phenomenon is known as the sick euthyroid syndrome, indicating that the patient is
euthyroid (ie normal thyroid function), but that he or she has an intercurrent illness. The common picture
in sick euthyroid syndrome is one of low T3 and T4 with low or normal TSH.
DON’T FORGET
Be cautious when interpreting thyroid function tests in an acutely unwell patient.
Variations in thyroxine-binding globulin levels

Care must be taken when interpreting free and total T4 levels. This is because the level of TBG can vary
in various states. Always remember that it is the level of free hormone that is important physiologically.
Factors influencing the level of TBG are listed below.
INCREASE TBG DECREASE TBG

High oestrogen states, eg pregnancy, oral contraceptive pill use High corticosteroid levels
Protein deficiency states: low intake (malnutrition); low synthesis
(chronic liver disease); increased losses (nephrotic syndrome)
Hypothyroidism
Thyrotoxicosis
Adrenal hormones
Normally, corticotrophin-releasing hormone (CRH) is released from the hypothalamus and stimulates the
pituitary gland to release adrenocorticotrophic hormone (ACTH). This hormone then acts on the adrenal
cortex and results in the release of glucocorticoids. Glucocorticoids exert negative feedback on both the
hypothalamus and pituitary, and result in a reduction in the production of CRH and ACTH.
Fig 3.2
Cushing syndrome
Cushing syndrome results from glucocorticoid excess. It is seen most commonly in patients receiving
glucocorticoid treatment, eg for chronic severe asthma. Endogenous forms of Cushing syndrome have
several causes which are listed below.
ENDOGENOUS CAUSES OF CUSHING SYNDROME
Primary adrenal disease

• Adrenal tumour (adenoma or carcinoma)
ACTH excess
• From the pituitary gland (Cushing disease)
• From an ACTH-producing tumour
In primary adrenal disease causing Cushing syndrome, the adrenal gland autonomously produces adrenal
hormones. Normal negative feedback continues, and the level of ACTH will be low.
In instances of secondary hyperadrenalism (eg due to a pituitary tumour), the ACTH level will be normal
or high.
There are several methods for diagnosing Cushing syndrome:
Measure free cortisol in a 24-hour urine collection
1. An elevated level of free cortisol in the urine is in keeping with Cushing syndrome. An abnormal
test should be followed up by a repeat test in the first instance.
Measure cortisol in a late-night salivary sample
In people with a normal sleep pattern (sleeping through the night), the cortisol level should reach a
2. nadir at night. In patients with Cushing syndrome, cortisol levels may be elevated even at this time,
and elevated levels of cortisol can be measured in saliva. As with urinary free cortisol, an
abnormal test should be followed up by a repeat test in the first instance.
Perform a 1 mg overnight dexamethasone suppression test
In healthy individuals, taking 1 mg dexamethasone will have a negative feedback effect on the
3. pituitary gland, thereby decreasing ACTH and hence cortisol production. In patients with Cushing
syndrome, cortisol production will not be affected, and hence a cortisol test the morning after
dosing will reveal abnormally elevated cortisol levels.
Perform a 2 mg 48-hour dexamethasone suppression test (low-dose dexamethasone
suppression test)
4. The rationale for this test is similar to that for the overnight suppression test. For this test, however,
0.5 mg dexamethasone is given 6-hourly for 48 hours. A cortisol level taken 6 hours after the last
dose will reveal an abnormally elevated level in patients with Cushing syndrome.
Other more specialised tests can also be used to confirm the diagnosis and to help differentiate between
the causes of Cushing syndrome.
Nieman LK, Biller BM, Findling JW, et al. The diagnosis of Cushing’s syndrome. J Clin Endocrinol Metab 2008;93:1526–40.
Primary hyperaldosteronism
The measurement of aldosterone and renin levels is important in patients suspected of having primary
hyperaldosteronism. In this condition, aldosterone levels are elevated and renin levels are suppressed
(due to negative feedback mechanisms). Measuring these hormones is fraught with difficulty because the
levels vary depending on posture (lying or standing, for example), and can be affected by a variety of
drugs. The particular way in which the hormones are measured and the units of measurement vary
between laboratories, so take care when interpreting results that you understand what is being reported.
In order to screen carefully selected patients for the presence of primary hyperaldosteronism, increasing
emphasis is being placed on the ratio between aldosterone and renin levels (the aldosterone:renin ratio or
ARR). If plasma aldosterone concentration is given in nanograms/decilitre and plasma renin activity in
nanograms/millilitre per hour, then an accepted cut-off for an abnormal ARR is 30. If the ARR is above
this level, the patient may well have the condition and further investigations would be warranted.
There are several tests available to confirm or refute the diagnosis in patients with an abnormal ARR.
One test that is commonly used is the ‘saline suppression test’. The specifics of this test are beyond the
scope of this book, but, in principle, an infusion of saline should reduce blood aldosterone levels. Failure
of aldosterone levels to suppress after administration of saline makes the diagnosis of primary
hyperaldosteronism more likely.
If the diagnosis seems likely, imaging should be performed to visualise the adrenal glands. If unilateral
adrenal gland disease appears likely, blood can be sampled from the adrenal veins in an attempt to prove
that aldosterone is being produced in excess from an adrenal gland.
Funder JW, Carey RM, Fardella C, et al. Case detection, diagnosis, and treatment of patients with primary aldosteronism: An Endocrine
Society Clinical Practice Guideline. J Clin Endocrinol Metab 2010;93:3266–81.
Hypoadrenalism
In primary hypoadrenalism (eg Addison’s disease), the adrenal gland itself is defective. As a result of
reduced negative feedback, the ACTH level will be high.
In secondary hypoadrenalism, ACTH levels will be low.
Short Synacthen® test
Synacthen®, or SYNthetic ACTH, is used to stimulate the adrenal gland. Normally, an injection of
Synacthen® will result in an increase in circulating cortisol levels. If the patient has a primary adrenal
disease, the Synacthen® will not have its normal effect, and the rise in cortisol levels will be poor. A
cortisol level of less than 600 nmol/l 30 min after Synacthen® has been administered is in keeping with
failure of the adrenal gland. The Synacthen® test will be normal in cases of secondary hypoadrenalism.
Insulin tolerance test
This test is used in specialist centres to assess adrenal function as well as to assess for growth hormone
deficiency.
Several criteria must be met before this test can be attempted.
CRITERIA TO BE MET BEFORE PERFORMING AN INSULIN TOLERANCE TEST

Cortisol level >100 nmol/l
Normal thyroid function
No cardiovascular disease
No epilepsy or other seizure activity or blackouts
The essence of the test is to induce hypoglycaemia (blood glucose must fall to less than 2.2 mmol/l) in a
carefully controlled environment. In a normal patient, a stress response will occur with a rise in cortisol
and growth hormone levels. Normally, the cortisol level should rise to more than 550 nmol/l, and the
growth hormone level to more than 20 mU/l.
Phaeochromocytomas
These tumours are associated with excess circulating catecholamines. Diagnosis relies on the
demonstration of excessive amounts of catecholamine breakdown products in the plasma (free
metanephrines) or urine (fractional metanephrines).
If levels are extremely high, phaeochromocytoma is likely. If levels are only slightly high, a ‘clonidine
suppression test’ can be performed. Plasma free metanephrines are measured after dosing with clonidine,
and would be expected to be suppressed in people without a phaeochromocytoma.
If the diagnosis seems likely, an attempt should be made to visualise the tumour. This can be done using
MRI or CT. Alternatively, radionuclide scanning or positron emission tomography (PET) may be
necessary.
Lenders JW, Eisenhofer G, Mannelli M, Pacak K. Phaeochromocytoma. Lancet 2005;366:665–75.
The thirst axis
Psychogenic polydipsia and diabetes insipidus

The combination of passing excessive volumes of urine (polyuria) with excessive thirst (polydipsia) is
common. The water deprivation test is used to differentiate between two major causes – psychogenic
polydipsia and diabetes insipidus (DI).
Patients with psychogenic polydipsia simply drink fluid in excess for psychological or psychiatric
reasons.
In DI, there is a problem with antidiuretic hormone (ADH). ADH normally acts on the collecting ducts in
the kidney to stimulate water reabsorption. If ADH does not function properly, too much urine is passed.
In turn the patient becomes relatively dehydrated and drinks to compensate for this.
MEMORY AID
Diuretic medications increase urine volume.
Therefore, antidiuretic hormone (ADH) does the opposite, and acts to
conserve water.
There are two forms of DI – cranial and nephrogenic. In cranial DI, there is a problem with the release of
ADH from the hypothalamus. Blood levels of ADH are low. In nephrogenic DI, there is sufficient ADH in
the system, but it fails to exert its effects on the kidney.
The water deprivation test restricts patients’ intake of water. If they have psychogenic polydipsia,
reducing water intake will solve their problem and they will gradually return to normal. However, with
DI, water restriction will result in a worsening state of dehydration.
The test involves forbidding the patient to drink after waking. Blood and urine osmolalities are tested
each hour for a period of 8 h. In health (or psychogenic polydipsia), one would expect the patient to retain
water and to pass concentrated urine (with a high urine osmolality). In DI, the urine osmolality does not
rise, and the patient becomes dehydrated with a rise in serum osmolality.
To differentiate between the two forms of DI, patients are then given a dose of a synthetic ADH compound
called desmopressin. This will correct the problem in cranial DI, but will have no effect in nephrogenic
DI.
Syndrome of inappropriate ADH secretion (SIADH)

In this condition, there is a state of excessive ADH production. SIADH has many causes, the most
common of which are listed in the table.
COMMON CAUSES OF SIADH
Intrathoracic causes:
• Infection
• Tumour
Intracranial causes:
• Infection
• Tumour
• Head injury
Medications:
• Carbamazepine
• Antipsychotics
SIADH is, in essence, the opposite of DI. Excessive ADH action results in retention of water, with the
subsequent development of dilute serum and concentrated urine.
For a person to be labelled with the diagnosis of SIADH the following criteria should be met:
1. Clinically isovolaemic
2. Normal renal function
3. Normal adrenal function
4. Normal thyroid function
5. Normal pituitary function
6. Absence of diuretic therapy
7. Low serum osmolality (<275 mosmol/kg)
8. Inappropriately concentrated urine (>100 mosmol/kg)
For a reference see the GAIN hyponatraemia document in page 58.
Hyperprolactinaemia
There are many causes of a raised serum prolactin level (see box below). Very high levels (>5000 mU/l)
strongly suggest a prolactin-secreting pituitary tumour.
COMMON CAUSES OF HYPERPROLACTINAEMIA
Physiological:
• Pregnancy
• Lactation
Prolactin-secreting pituitary tumour
Medications:
• Phenothiazine antipsychotics
• Most antiemetics
Polycystic ovarian syndrome
Following a seizure
Primary hypothyroidism
Hyperglycaemia
The diagnosis of diabetes mellitus and related hyperglycaemic states relies on accurate interpretation of
blood glucose readings. A patient’s glycaemic status can be classed as one of the following:
• Normal
• Impaired fasting glucose
• Impaired glucose tolerance
• Diabetes mellitus
• Gestational diabetes mellitus.
In some circumstances, diabetes will be suspected clinically, particularly if the patient is symptomatic
from hyperglycaemia. In other instances, hyperglycaemia will be detected incidentally when a blood
glucose level is checked. Typical symptoms are shown in the box below.
SYMPTOMS OF DIABETES MELLITUS

Polyuria
Polydipsia
Weight loss
Fatigue
Blurring of vision
Symptoms related to a complication of diabetes such as a cutaneous abscess
An oral glucose tolerance test (OGTT) is often used in differentiating between these various states. This
test involves giving the patient a 75 g glucose load by mouth, after they have been fasting. The plasma
glucose level is measured at baseline and after 2 h.
Diabetes mellitus may be diagnosed in a variety of ways. Any one of the following is sufficient:
1. A single random plasma glucose of more than 11.1 mmol/l in a patient with symptoms
Two separate random plasma glucose samples of more than 11.1 mmol/l in a patient without
2.
symptoms
3. A single fasting plasma glucose of more than 7.0 mmol/l in a patient with symptoms
Two separate fasting plasma glucose samples of more than 7.0 mmol/l in a patient without
4.
symptoms
A plasma glucose level of 11.1 mmol/l or more 2 h after a glucose load in an OGTT. An OGTT is
5.
generally performed only if borderline results are obtained on random or fasting samples.
DON’T FORGET
If a patient is asymptomatic, two blood tests are required before diabetes mellitus can be diagnosed.
Patients with normoglycaemia (ie definitely not diabetic) have a fasting plasma glucose of less than 6.1
mmol/l. Two hours following a glucose load in an OGTT, the plasma glucose will be less than 7.8
mmol/l.
’Impaired fasting glucose’ and ‘impaired glucose tolerance’ are terms used to describe states of
glycaemic control that lie somewhere between normal and frank diabetes mellitus. The terms are not
mutually exclusive. It is therefore possible for a patient to have both impaired fasting glucose and
impaired glucose tolerance. Alternatively, they may have one or other of the terms attached to them in
isolation. The significance of labelling a patient with one of these terms lies with the fact that such
patients have an increased risk of developing diabetes mellitus in the future. The diagnostic criteria are
shown in the table below.
Gestational diabetes mellitus describes diabetes that is of new onset in pregnancy, or that is first noted
during pregnancy. The principles of diagnosis are identical to those above. The term may be used if a
woman fits the criteria for impaired glucose tolerance or diabetes mellitus while pregnant. All such
women should have an OGTT at least 6 weeks after delivery, and be re-classified as necessary. The
significance of gestational diabetes mellitus again relates to the fact that such patients have a reasonable
chance of having a ‘large-for-dates’ foetus, and that they have a chance of developing diabetes mellitus in
later life.
Glycated haemoglobin
Random blood glucose measurements are useful for monitoring variations on a day-to-day basis,
however, the inevitable variation makes interpretation of long-term trends difficult. For this reason
measurement of glycated haemoglobin (HbA1 or HbA1c) is often used.
Glycated haemoglobin is the product of the reaction between glucose and haemoglobin A (the main type
of haemoglobin in most adults). The higher the average blood glucose level, the higher the glycated
haemoglobin level will be. As red blood cells have an average life-span of around 120 days, glycated
haemoglobin estimation provides information on the glycaemic control over this time period.
The Diabetes Control and Complications Trial (DCCT) provided evidence that well-controlled diabetes
was associated with fewer microvascular complications (N Engl J Med 1993; 329: 977–86). For most
patients, a target HbA1c of between 6.5 and 7.5% will be adequate. A slightly less ambitious target of
between 7 and 8% may prove adequate for some patients, and reduce the risk of hypoglycaemic attacks
when compared with a more intensive treatment regimen.
Glycated haemoglobin is reliable only when normal haemoglobin is present in red blood cells that have
normal life-spans. If a haemoglobin disorder is present, or in patients who have red cells with shortened
life-spans (eg haemolytic anaemia), measurement of fructosamine levels may be used instead to measure
glycaemic control. Fructosamine is a glycated plasma protein, and provides information on glucose levels
over the previous 1–3 weeks.
Hypoglycaemia
Hypoglycaemia describes a plasma glucose that is lower than normal (less than 3.5 mmol/l). The most
common cause is an imbalance between intake and insulin requirements in a patient with type 1 diabetes
mellitus (eg the patient who takes normal insulin without eating lunch). Other causes of hypoglycaemia are
listed in the box on page 154.
CAUSES OF HYPOGLYCAEMIA
Imbalance between insulin and calorie intake in type 1 diabetes
Excess exogenous insulin administration
As a side effect of anti-hyperglycaemic medication
Insulinoma
Liver failure
Alcohol ingestion
A fairly common clinical scenario is the patient who presents with hypoglycaemia of unknown cause.
Endogenous insulin (ie insulin derived from an insulinoma) can be differentiated easily from exogenous
insulin (ie a patient with Munchausen syndrome who administers insulin to themselves in an attempt to
seek medical attention) with a little knowledge of insulin physiology.
Normal physiological insulin is manufactured in the body from proinsulin which in turn is derived from
pre-proinsulin. Each protein precursor is cleaved to yield its product. This cleavage process generates a
‘waste’ chain of amino acids called C-peptide.
If hypoglycaemia is due to excess endogenous insulin from an insulinoma, one would expect high insulin
and C-peptide levels in a patient who is hypoglycaemic.
Exogenous insulin does not contain C-peptide. Therefore, a hypoglycaemic patient with raised levels of
insulin in the blood but normal/low levels of C-peptide is likely to have been given insulin.
Acromegaly
Acromegaly is associated with an elevated level of growth hormone (GH), usually due to a pituitary
tumour. Measuring the level is not a reliable method of making this diagnosis. Insulin-like growth factor I
(IGF-I) levels can be used as a marker of average GH levels and, if raised, is suggestive of acromegaly.
The definitive test for the diagnosis is a glucose tolerance test, exactly like that used in the investigation
of hyperglycaemia. The test is performed in the same manner, but GH levels are measured. Failure of the
GH level to fall below 1 mU/l is in keeping with a diagnosis of acromegaly.
DON’T FORGET
Acromegaly is diagnosed if the GH level is >1 mU/l during a glucose tolerance test.
Case 3.1
A 21-year-old woman is referred to the medical clinic because of abnormal thyroid function results noted
by her GP. There is no personal or family history of thyroid disease, and she is on no medication, but the
GP requested the test because the patient had been feeling generally unwell recently. Clinical examination
is unremarkable. The thyroid function tests are repeated and the following results are obtained.
1. How would you interpret these tests?

2. What two tests should be ordered?
Answer 3.1
Care should be taken when interpreting these results. Note that the TOTAL T4 level is given, not the
FREE T4 level. It is the free level that is important physiologically. It is impossible to make any
1.
further comments on these tests other than to say that the total T4 level is raised, and the TSH is
normal.
First, the free T4 level should be measured. In this case it was normal (result not shown), indicating
normal thyroid function. The patient therefore has an elevated total T4 level with a normal free T4
2. level. The reason for this is increased levels of TBG. The most likely reason for this is a high
oestrogen state (eg pregnancy or use of the oral contraceptive pill). Since the question states that the
patient is not on any medication, the most likely diagnosis here is pregnancy. The second test that
should be performed is therefore a pregnancy test.
Case 3.2
A 64-year-old woman is admitted with palpitations. She feels that these have been intermittent over the
last month. Examination reveals an anxious woman with an irregularly irregular pulse at 120 beats/min.
ECG confirms the suspicions of atrial fibrillation. As part of her initial investigations, the following
blood test is returned.
What is the underlying cause of the atrial fibrillation?

Answer 3.2
This woman has primary hyperthyroidism. Her overactive thyroid gland is producing thyroid hormones in
excess. Normal negative feedback mechanisms still function, however, so the TSH level is suppressed.
It is not uncommon for atrial fibrillation to be the only evidence of hyperthyroidism, so always remember
to check thyroid function in such patients.
Case 3.3
A patient is reviewed at the chest clinic. He was treated over 1 year ago for pulmonary tuberculosis. He
now complains of lethargy. Clinical examination reveals no chest abnormalities, but he is found to have
significant postural hypotension. A urea and electrolyte (U&E) blood test is sent and, on the basis of the
results, the following test is arranged.
1. What is the test, and what does it demonstrate in this case?

2. What were the likely abnormalities on the U&Es that raised suspicions of this disorder?
3. What is the likely underlying disease?
Answer 3.3
This is a short Synacthen® test. The cortisol level fails to rise to more than 600 nmol/l 30 min after
1. injection with Synacthen®. This indicates primary hypoadrenalism (ie a problem with the adrenal
gland itself).
A low sodium and raised potassium level are commonly found. The glucose level would also be
2.
expected to be low.
The underlying disease is primary hypoadrenalism, probably due to autoimmune adrenalitis or
3.
tuberculosis affecting the adrenal gland.
Case 3.4
A patient is referred to the endocrine clinic complaining of excess thirst and of passing excessive amounts
of urine. A random blood glucose level is 4.2 mmol/l. He is admitted to hospital and a water deprivation
test is arranged. The results are shown.
1. What is your interpretation of the blood glucose level?

Answer 3.4
The random blood glucose level is normal. The patient therefore does not have diabetes mellitus. It
1.
is important to exclude this diagnosis, since it can also present with polydipsia and polyuria.
The diagnosis is cranial diabetes insipidus. The patient has a problem producing ADH. When
deprived of water, he is unable to concentrate the urine. The plasma rapidly becomes more
2. concentrated. Following an injection of synthetic ADH (desmopressin), the urine osmolality
increases. This shows that the kidney is still sensitive to the effects of ADH, and excludes
nephrogenic diabetes insipidus as the diagnosis.
Case 3.5
A 57-year-old man is referred to the hypertension clinic. Two tests are performed in order to screen for
an endocrine cause of hypertension.
How would you interpret these results?

Answer 3.5
Three separate 24-h urine collections for urinary metanephrines have been taken. The metanephrine levels
are normal in each. This excludes phaeochromocytoma as a cause of the hypertension with some certainty.
The second test shows the results of an overnight dexamethasone suppression test. The morning cortisol
level is greater than 100 nmol/l, suggesting a diagnosis of Cushing syndrome.
Case 3.6
A patient is referred to the endocrine clinic after having been assessed in the eye A&E. The registrar
arranges for a glucose tolerance test to be carried out.
1. What two diagnoses can be made on the basis of this test?

2. Why do you think the patient was seen in the eye A&E?
Answer 3.6
1. The two diagnoses that can be made from this one test are: diabetes mellitus and acromegaly.
The glucose level before the start of the test is elevated in keeping with the label of impaired
fasting glucose. However, the abnormally high glucose level 2 h after the glucose load confirms the
diagnosis of diabetes mellitus.
The growth hormone level is greater than 2.0 μg/l at all stages of the test, allowing the diagnosis of

acromegaly to be made.
The most common cause of acromegaly is a pituitary tumour. This commonly extends in an upward
2. direction and can compress the optic chiasma, causing a bitemporal hemianopia. Loss of temporal
visual fields is the probable reason for presentation at the eye A&E.
TOXICOLOGY
Poisoning is one of the most common causes of admission to hospital. It is most often deliberate, but can
also be accidental, sometimes due to the accumulation of prescribed medications.
The management of a poisoned patient largely involves supportive care, allowing the body to excrete or
metabolise a drug naturally. In certain circumstances, antidotes may be necessary along with the use of
other methods designed to clear the drug more quickly from the body.
It is important that you are able to assimilate data of a variety of types when treating a poisoned patient.
Paracetamol
Paracetamol (called acetaminophen in the USA) is one of the most common drugs taken in overdose. This
reflects its ready availability and ubiquitous use. When taken in overdose, paracetamol depletes
antioxidant stores in hepatocytes and can result in liver damage. If a patient takes a significant quantity of
paracetamol and is delayed in their presentation to hospital, the following abnormalities may be apparent:
Elevated liver enzymes, particularly aspartate aminotransferase (AST) and alanine
1. aminotransferase (ALT). Bilirubin levels will also rise. These changes occur because of liver
cell damage. Further details on liver tests can be found on page 70.
Elevated prothrombin time (PT) (and international normalised ratio [INR], because this is
2. calculated from the PT). This occurs because of impaired liver synthesis of clotting factors.
Further details on PT and INR can be found on page 21.
Impaired kidney function (elevated urea and creatinine). This can arise secondary to liver
3. impairment (hepatorenal syndrome) or sometimes as a direct effect of paracetamol metabolites on
the kidney.
Metabolic acidosis mainly due to liver failure. This will be a high anion gap metabolic acidosis.
4.
For further details, refer to page 428.
Administration of an antidote, N-acetylcysteine, can help patients after a significant paracetamol
overdose. This agent replenishes liver antioxidant stores.
On most occasions in clinical practice, patients present to hospital within a few hours of taking an
overdose. Although N-acetylcysteine is a fairly safe and effective drug, anaphylaxis has been reported
after its administration. It is therefore routine practice to weigh up whether or not a patient requires
antidote administration. This is done by measuring blood paracetamol levels and using the nomogram in
Fig 4.1 (which can be found in the British National Formulary).
Fig 4.1
Timing of the overdose is critical because blood levels are interpretable only if the time of drug ingestion
is known. You will note that the lines on the nomogram start at 4 hours – blood levels taken within 4 hours
of ingestion are meaningless because absorption will be incomplete, and levels could rise if blood is re-
sampled later. Once timing has been established and the post-4-hour blood levels measured, plot the
patient’s data on the nomogram. Decide on whether the ‘normal’ or ‘high-risk’ treatment line should be
used (see below). If the patient’s level lies above the relevant line at the time point chosen, then they are
deemed to be at significant risk of liver injury, and the antidote should be administered. If their level is
below the treatment line, the risk of liver damage is small and treatment is not generally required.
As mentioned, knowledge of the time of ingestion is critical. It is, however, acknowledged that it is often
extremely difficult to be certain about this, because patients who have taken an overdose are often
intoxicated, drowsy or generally uncooperative. One should collect information from every available
source, and generally speaking one should have a low threshold for treatment if details are sketchy.
Another point of note is that the nomogram curves flatten considerably towards the right side of the chart.
The differences in blood levels between whom to treat and whom not to treat if presentation is delayed
are very small, and generally treatment should be instigated in all cases of delayed presentation. Patients
who have taken a potentially lethal quantity of paracetamol (>12 g in most circumstances) but who present
earlier than 4 hours should generally receive treatment, which can be stopped if their post-4-hour drug
level suggests that treatment is not required. In addition, patients who have taken a staggered overdose
should generally be treated regardless of the blood level.
DON’T FORGET
Always check plasma paracetamol levels at least 4 h after ingestion.
In routine circumstances, the ‘normal’ treatment line should be used. Some patients are deemed ‘high risk’
for liver damage, and for them the ‘high-risk treatment line’ should be used (see box for details). Such
patients are presumed to have lower than normal antioxidant stores.
PATIENTS AT HIGH RISK IN PARACETAMOL OVERDOSE

On hepatic enzyme-inducing drugs
(eg phenytoin, rifampicin, carbamazepine)
Alcoholics
Malnutrition (including anorexia nervosa)
Patients with AIDS
MEMORY AID
Always assess paracetamol overdose patients for high-risk status.
Salicylate
Salicylates (such as aspirin) are found in a wide variety of preparations commonly available in
households and are therefore taken reasonably commonly in overdose. Two main types of data can be
useful in salicylate poisoning:
Salicylate levels: the higher the level, the greater the likelihood of symptoms and organ damage,
and the more likely it will be that specific treatments will be required to increase clearance of
1.
salicylate from the body. The absorption of salicylates can be slow. It is therefore good practice
to repeat blood levels at intervals until they start to fall.
Abnormalities of acid–base balance: see Chapter 13 for detailed information about the
interpretation of acid–base abnormalities. Significant salicylate overdose produces a
characteristic pattern of acid– base disturbance. The respiratory centre in the brain is stimulated,
causing patients to hyperventilate and ‘blow off’ carbon dioxide. The levels of the acidic gas
2. carbon dioxide therefore fall, resulting in a respiratory alkalosis. At the same time, however, a
metabolic acidosis develops due to the production of a variety of acids. Levels of the alkaline
substance bicarbonate fall, and the pH becomes acidic. The overall effect on a particular patient
is hard to predict. Either alkalosis or acidosis can predominate, or alternatively the pH can
remain neutral due to opposing respiratory and metabolic effects.
Opiates
Significant opiate poisoning will have a variety of effects on the patient. From a data interpretation
perspective, however, the one piece of data that can provide a clue to the fact that opiates have been taken
is the respiratory rate. Opiates suppress respiratory drive, so, if a patient has taken a cocktail of unknown
drugs and the respiratory rate is slow, it would be reasonable to assume that they have taken an opiate and
to administer the antidote (naloxone).
Tricyclic antidepressants
Tricyclic antidepressants (TCAs) such as amitriptyline are extremely dangerous when taken in overdose.
The two major clinical complications that can arise are:
Cardiac toxicity – this can cause hypotension, arrhythmias and cardiac
1.
arrest
2. Seizures.
It would seem logical that one should measure blood levels of these drugs to predict which patients are
likely to develop problems. This is, however, not part of routine management, and the following two tests
are much more useful:
An electrocardiograph (ECG). Please see Chapter 10 for more information on ECG
1. interpretation. There are two major signs on the ECG that indicate that a significant TCA
overdose has been taken:
QRS broadening: the normal QRS width is <120 ms (three small squares on ECG paper). In
(a) the setting of TCA overdose, any QRS widening over 100 ms is significant. The broader the
QRS complex, the higher the risk of cardiac arrhythmia and seizure.
(b) Abnormally tall T wave in lead aVR, as shown in Fig 4.2.
Arterial blood gas analysis: see Chapter 13 for detailed information about the interpretation of
2. acid–base abnormalities. A metabolic acidosis can occur in significant TCA overdose and should
be treated with sodium bicarbonate. A respiratory acidosis may also occur.
Fig 4.2
Drugs with a low therapeutic ratio

The therapeutic ratio is the ratio between the dose of a drug needed to cause a toxic effect and the dose
required to produce the intended effect. Drugs with a low therapeutic ratio thus have a small difference
between helpful blood levels for treatment and toxic levels. The plasma levels of such medications can be
easily measured by a hospital laboratory. For details of antibiotic drug level interpretation, please refer to
page 219. For other drugs, an estimation of the steady-state drug level is most helpful, so blood is
generally sampled at a fixed time point following drug ingestion.
EXAMPLES OF DRUGS WITH NARROW THERAPEUTIC RATIOS

Digoxin
Theophylline
Lithium
Phenytoin
Antibiotics, eg gentamicin, vancomycin, tobramycin
From a data interpretation perspective, digoxin deserves special mention because of its effects on the
ECG. Ingestion of digoxin can cause down-sloping ST segment depression as shown in Fig 4.3 (see
Chapter 10 for further details on ECG interpretation). In addition, digoxin toxicity can cause virtually any
type of cardiac arrhythmia.
Fig 4.3
Urine testing for drug metabolites

A number of drugs can be detected in urine. A urine drug screen is often requested when a patient presents
with unusual symptoms and there is a suspicion of potential drug use.
TYPICAL COMPONENTS OF URINE ‘DRUGS’ SCREEN

Amphetamines, barbiturates, benzodiazepines, methadone,
cannabinoids, cocaine metabolites, LSD and opiates
Case 4.1
A 72-year-old woman is admitted complaining of poor appetite, nausea and vomiting. She also complains
of intermittent palpitations and visual disturbance. She had a stomach upset one week previously and had
been off her food and consumed little fluid. Her medical history includes hypertension, atrial fibrillation
and vertigo. She is unable to recall her medications. An ECG was reported as having ST-segment
abnormalities, but the house officer did not feel that this was significant.
Explain the full significance of these results.

Answer 4.1
This patient has been prescribed digoxin for atrial fibrillation, and has digoxin toxicity. Digoxin is a drug
with a narrow therapeutic ratio and a normal therapeutic range of 0.8–2.0 nmol/l. A level as high as 2.9
nmol/l is enough for the symptoms described in this elderly patient. Digoxin levels can accumulate
rapidly in patients with renal impairment. It is likely that this woman has become dehydrated following a
bout of gastroenteritis. Renal impairment has caused the rise in plasma digoxin resulting in toxicity.
Hypokalaemia is also present. This can exacerbate the symptoms of digoxin toxicity.
This iatrogenic problem is simply treated. Fluid resuscitation with the replacement of potassium
intravenously and the exclusion of digoxin is appropriate in this case. The ECG shows down-sloping ST-
segment depression (‘reverse tick’) often seen in patients on digoxin, and would have been a clue here
that the patient was taking this drug.
Case 4.2
A 20-year-old law student attends A&E feeling unwell after a car journey back to Belfast from Dublin,
having been to visit his girlfriend over the weekend. He has a headache and informs you that he had great
difficulty concentrating on the final part of his trip. He does admit to having a ‘big weekend’ while in
Dublin. On examination his pulse is bounding in character.
His various investigations are shown. The arterial blood gas was sampled with the patient breathing room
air.
Describe the abnormalities seen and explain the cause of this man’s symptoms.
Answer 4.2
On first inspection, one might suspect that illicit drug use could provide the explanation for this patient’s
symptoms. However, another diagnosis may be more likely – carbon monoxide poisoning. This student
developed symptoms following a car journey of several hours. Typically, students, elderly people and
socially deprived people are most susceptible to exposure to carbon monoxide from poorly maintained
fires and motor cars. Carbon monoxide poisoning can be diagnosed by measuring carboxyhaemoglobin in
an arterial blood gas sample. This patient’s carboxyhaemoglobin is elevated, in keeping with the clinical
suspicion. It is entirely appropriate that a urine drug screen has been performed, although the patient
should be informed if this is being sent. A trace of cannabinoids suggests recent use of cannabis. This is,
however, unlikely to be the explanation for this recent onset of symptoms.
Case 4.3
A 25-year-old shop assistant is brought to hospital by her colleague at 16:30 hours after she admitted to
taking an overdose of paracetamol. She regrets the incident and is able to tell you clearly that she has
taken one packet of 16 tablets during her lunch break between 12:00 and 12:30 hours. She feels fine and
wishes to go home. No other medications or alcohol was taken. She has no health problems and is on no
prescribed medications except the oral contraceptive pill. Blood tests taken on arrival at the hospital are
shown.
Would you treat this patient? Detail the logic for your decision.
Answer 4.3
The three most important pieces of information to ascertain from a paracetamol overdose patient are:
• How much has been taken?
• When was it taken?
Does the patient have any factors to make them ‘high
•
risk’?
Further questions to ascertain the psychiatric state and suicide risk are also clearly important.
In this case:
• How much?
16 tablets. Paracetamol tablets are normally500 mg. Thus total dose = 16 × 500 mg = 8000 mg = 8 g.
• Timing?
4 h post-ingestion.
• Risk?
No high-risk features from history
The 4 h level in this patient is 155 mg/l.
Using the graph illustrated earlier, one can interpret a paracetamol level of 155 mg/l at 4 h as not high
enough to warrant treatment. Note, however, that if this patient were deemed to be ‘high risk’, treatment
would have been necessary. The cut-off difference between the normal and high-risk groups at 4 h is
substantial – 200 mg/l and 100 mg/l.
Case 4.4
A 33-year-old single mother attends A&E with her neighbour who found that she had taken an overdose
when she came round to visit. The patient is a difficult historian but does indicate that she took about 30–
50 tablets from the cupboard during the midday news. It is now 19:15 hours. The neighbour indicates that
the woman has a history of epilepsy and she is on medication for this. Blood tests were taken on arrival.
State what treatment this woman might need and justify your answer.
Answer 4.4
This overdose case is more difficult, although perhaps more typical. The patient is only admitting to
taking ‘tablets’, although the quantity, type and timing are more uncertain. At the time of presentation to
hospital it is over 7 h since ingestion. To complicate matters further she is also on an unspecified
anticonvulsant medication. This patient has taken alcohol with the tablets, has a raised paracetamol level
and a mildly raised salicylate level. The patient also has mild impairment of her liver function tests.
On first glance 80 mg/l of paracetamol doesn’t appear that remarkable. However, if the exact drug history
cannot quickly be ascertained, one must assume that this patient is on hepatic enzyme-inducing
antiepileptic medication. When this is transferred to the nomogram, one can see that a level of 80 mg/l is
well above the treatment line in high-risk groups. Instigation of an infusion of N-acetylcysteine must
commence immediately.
Case 4.5
A 41-year-old patient with bipolar disorder presents to A&E indicating that she has taken an overdose of
her prescribed lithium. She is subdued and states that she had been feeling low at the time. Her
examination is normal and she does not have any direct complaints. Blood tests are shown.
Explain the treatment options in lithium overdose with specific reference to this patient.
Answer 4.5
One must be particularly mindful in psychiatric patients of the accuracy of information conveyed and
compliance with medication. Lithium is a commonly used drug in bipolar affective disorder, but has one
major drawback – overdose. It has a narrow therapeutic ratio. Patients on long-term lithium can become
unwell due to toxicity even without deliberate overdose. Overdoses of lithium can be fatal. The normal
range is 0.4–1.5 mmol/l with levels above 2.0 mmol/l requiring treatment that may include haemodialysis.
Levels between 1.5 and 2.0 mmol/l, as in this case, may require only fluid resuscitation and supportive
treatment, along with temporary discontinuation of the drug.
PLEURAL AND
PERITONEAL FLUID
ANALYSIS

In health, only a small volume of fluid surrounds the pleural lining of the lung. In various pathological
states, excess fluid can accumulate forming a pleural effusion. When a significant volume has collected it
may be detected on clinical examination or on a chest radiograph (see page 265 for further details).
Approximately 300 ml of fluid must be present before a pleural effusion is apparent on a chest
radiograph. Pleural fluid is not the only fluid that can collect within the pleural cavity. Blood in the
pleural space is termed a haemothorax, lymph a chylothorax, and pus an empyema.
Analysis of this fluid may help determine the cause of the effusion. If significant volumes of fluid are
removed there can also be symptomatic benefit to the patient. Fluid is collected by performing pleural
aspiration (‘a pleural tap’) which should be performed under imaging guidance.
A number of key parameters are analysed routinely, with many additional tests being possible on request.
The first fundamental point to establish is whether the effusion is unilateral or bilateral. Unilateral
effusions are more likely to be ‘exudates’ and bilateral effusions are more likely to be ‘transudates’, but
this is not always the case. The protein concentration of the pleural fluid is a good starting point for fluid
analysis.
DON’T FORGET
Unilateral pleural effusions are more likely to be exudates.
For pleural effusions

Exudate ≥30 g/l of protein
Transudate <30 g/l of protein
Reliance on the fluid protein concentration is most useful when there is a clear clinical suspicion of either
exudate or transudate, and when the protein concentration of the fluid is either much higher or much lower
than 30 g/l. Occasionally, reliance on the protein concentration can result in misclassifying an exudate as
a transudate, or vice versa. For this reason, the ‘Light’s criteria’ can be used to make the distinction with
greater certainty. This requires knowledge of pleural fluid and serum protein levels, as well as lactate
dehydrogenase (LDH) levels.
THE ‘LIGHT’S CRITERIA’
A pleural effusion is likely to be an exudate if one or more of the following conditions are met:
• Pleural fluid:serum protein ratio >0.5
Pleural fluid LDH >200 IU/l (commonly taken as more than two-thirds of the upper limit of
•
normal for blood)
• Pleural fluid:serum LDH ratio >0.6
Light RW, MacGregor MI, Luchsinger PC, et al. Pleural effusions: the diagnostic separation of transudates and exudates. Ann Intern Med
1972;77:507–13.
COMMON PARAMETERS
REASON FOR ANALYSIS
ANALYSED IN PLEURAL FLUID
Total protein Differentiate exudate and transudate
Lactate dehydrogenase (LDH) Differentiate exudate and transudate
Microbiology (microscopy, cell count,

Identify an infection
Gram stain and culture)
Low in empyema. If pH <7.2, chest drain insertion should be

pH
strongly considered
Cytological examination To identify and characterise malignant cells
ADDITIONAL PARAMETERS
INTERPRETATION
ANALYSED IN PLEURAL FLUID
Glucose Low in rheumatoid disease
Rheumatoid factor High in rheumatoid disease
Amylase High in pancreatitis
Ziehl–Neelsen stain and culture To diagnose tuberculosis
Haematocrit High in haemothorax
COMMON CAUSES OF A TRANSUDATE PLEURAL EFFUSION

Cardiac failure
Liver failure
Nephrotic syndrome (think ‘renal failure’ for ease of memory)
Hypoalbuminaemia (‘nutritional failure’)
Hypothyroidism (‘thyroid failure’)
Hooper C, Lee YC, Maskell N. Investigation of a unilateral pleural effusion in adults: British Thoracic Society pleural disease guideline 2010.
Thorax 2010;65(suppl 2): ii4–17.

DON’T FORGET
Transudates are usually associated with FAILURE.
COMMON CAUSES OF AN EXUDATE PLEURAL EFFUSION
Cancer
Pneumonia (parapneumonic effusion)
Pulmonary embolus/infarction
Tuberculosis
Connective tissue disease (eg rheumatoid disease)
Acute pancreatitis
DON’T FORGET
An exudate exudes (pumps out) protein so the protein content is normally high.
The colour of the fluid aspirated from a pleural effusion also gives useful information as to the potential
cause.

COLOUR OF FLUID DIAGNOSIS

Straw Normal
Yellow Infected
Blood stained Traumatic, malignancy
Frank blood Mesothelioma, trauma, other malignancy
Pus Empyema
Food debris Oesophageal rupture
Peritoneal fluid analysis

In health, peritoneal fluid is present only in small volumes. In illness it may collect in vast quantities, in
which case it should be detected on clinical examination. Smaller volumes may be detected on imaging.
An abnormal collection of peritoneal fluid is termed ‘ascites’.
Paracentesis (often termed ‘peritoneal tap’) may be undertaken for diagnostic purposes. Alternatively,
large volumes of fluid can be removed to provide symptomatic benefit to the patient.
Analysis of peritoneal fluid has two main purposes:
To characterise the disease causing
•
ascites
• To detect infection.
Characterising the disease causing ascites

The most common cause of ascites by far is portal hypertension secondary to liver cirrhosis. However,
there are a great many other causes. It is important to be able to distinguish between these. In a method
analogous to pleural fluid analysis, the causes of ascites can be divided into whether they cause an
exudate or a transudate. The total protein content is used to differentiate between the two, with a cut-off
level of 25 g/l.

FOR ASCITES
Exudate ≥25 g/l of protein
Transudate <25 g/l of protein
CAUSES OF TRANSUDATE ASCITES

Cirrhosis
Cardiac failure
Hypoalbuminaemia
Nephrotic syndrome
CAUSES OF EXUDATE ASCITES

Intraperitoneal malignancy (primary or secondary)
Intraperitoneal infection including tuberculosis
Pancreatitis
Hypothyroidism
Chylous ascites
Characterising ascites is, however, notoriously unreliable. Accuracy can be improved by comparing the
albumin content of the ascitic fluid with its level in the serum. This yields a serum–ascites albumin
gradient (SAAG) as shown in the box.
Serum–ascites albumin gradient

SAAG (g/l) = Serum albumin (g/l) – Ascites albumin (g/l)
If the SAAG is ≥11 g/l, one can say that the patient is very likely to have portal hypertension. Bear in
mind, however, that a patient may have portal hypertension alongside another cause of ascites. Other
causes listed in the ‘Transudate’ box are possibilities. If the SAAG is <11 g/l, the causes listed in the
‘Exudate’ box are more likely.
Detecting infection
The detection of infection in ascitic fluid is extremely important. The WCC of the ascites is increased in
peritonitis. In most patients with ascites associated with cirrhosis, peritonitis is a primary problem, and is
termed ‘spontaneous bacterial peritonitis’ (SBP). Occasionally another cause of peritonitis, such as a
subphrenic abscess or perforated bowel, can be mistaken for SBP.
The diagnosis of SBP can be made when bacteria are identified after culturing ascitic fluid. However, this
process takes some time, so the ascites white cell count is usually used to guide treatment. This result
should be available within a matter of hours. An ascites neutrophil count ≥250 cells/mm3 (0.25 × 109/l) is
in keeping with SBP. If the clinical setting fits with this diagnosis, treatment with an appropriate antibiotic
should be commenced.
DON’T FORGET
Ascites neutrophil count of ≥250 cells/mm3 is in keeping with SBP.
An alternative cause for peritonitis (eg perforated bowel) should be suspected when multiple organisms
are seen on Gram staining.
The parameters shown in the box may be analysed. Those marked with an asterisk should be requested
only when clinically indicated.
PARAMETER PURPOSE
WCC (including differential) To detect infection
Total protein content and albumin To distinguish exudates and transudates To calculate the serum–ascites albumin gradient
Microscopy including Gram stain To visualise bacteria
Culture To identify bacteria
Glucose* Low in malignant ascites
Cytology* To detect malignant cells
Amylase* Raised in ascites associated with pancreatitis

Case 5.1
A 36-year-old man is admitted with shortness of breath and a cough productive of green sputum. He is
feverish and complains of left-sided pleuritic chest discomfort. He has led a perfectly healthy life to date.
He is a smoker of 10 pack-years. On examination a pleural effusion is noted on the left side to the mid-
zone. This finding is confirmed on chest radiography.
The effusion is aspirated at ward level and sent for analysis.
Describe the findings and the likely cause of the pleural effusion.
Answer 5.1
This patient has symptoms suggestive of a bacterial pneumonia. He is otherwise healthy and there is little
to suspect an underlying sinister or chronic disease. A proportion of bacterial pneumonias will present
with a pleural effusion. Pleural fluid is produced in excess in reaction to the local irritation of the pleura
from the surrounding infection.
The findings from the simple pleural fluid analysis are in keeping with this clinical suspicion. It is an
exudate (total protein >30 g/l) and the lactate dehydrogenase level is high.
This patient has a parapneumonic pleural effusion. Treatment consists of antibiotics for the pneumonia,
with the effusion expected to resolve over several weeks. The patient should have a repeat chest
radiograph 6 weeks after treatment to ensure resolution of the effusion. If the patient’s condition were to
deteriorate one would have to consider the development of an empyema (pus collection in the pleural
space).
Case 5.2
A 65-year-old retired headmaster presents with progressive shortness of breath and swelling of the feet.
Nine years ago he sustained an anterior myocardial infarction and has had subsequent problems with
angina requiring coronary artery stenting. He also suffers from hypertension and gout. Following a recent
flare of gout his GP prescribed a short course of ibuprofen. Examination reveals pitting oedema to the
mid-calves bilaterally and a jugular venous pulse (JVP) raised by 3 cmH2O. The bases of both lungs are
dull to percussion. Breath sounds are reduced and vocal resonance is decreased over these areas.
After some initial treatment these examination findings remain and a decision is made to carry out pleural
aspiration: 30 ml was aspirated from the right hemithorax and sent for analysis.
Describe the findings and likely cause.

Answer 5.2
The clinical features of this patient suggest a diagnosis of congestive cardiac failure (CCF). The
prescription of a non-steroidal anti-inflammatory drug (NSAID) for acute gout has caused fluid retention,
leading to worsening of the underlying cardiac failure. The effusions are bilateral, which suggests that
they are likely to be transudative. The pleural fluid sample confirms this suspicion with a total protein
content of only 21 g/l and an LDH of 140 IU/l. Of all the causes of transudate pleural effusions, cardiac
failure best fits in this case.
Case 5.3
As the medical junior doctor on-call you are asked by your surgical colleagues to see a 45-year-old
overweight housewife. She was admitted with abdominal pain 2 days ago and an ultrasound scan of the
abdomen showed gallstones with extrahepatic bile duct dilatation. Bowel gas obscured visualisation of
the pancreas. Your opinion is sought as the patient is short of breath and complains of left-sided pleuritic
chest discomfort. On examination you detect a left-sided pleural effusion which is confirmed on chest
radiography. You decide to perform a diagnostic pleural aspiration.
What is your interpretation of this result?

Answer 5.3
Pleural effusions can be found in acute pancreatitis. It is most typical for this to be unilateral; however,
bilateral effusions are recognised. The key to diagnosis is the amylase level within the aspirated fluid.
Case 5.4
A 33-year-old secretary presents with malaise, joint discomfort and by her own admission generally
feeling ‘out of sorts’. She was diagnosed with Graves’ disease 3 years ago and has been rendered
euthyroid (normal thyroid function). She has also suffered from coeliac disease since her teens. She has
no respiratory complaints. As part of her investigative work-up a chest radiograph is taken, which to the
medical team’s surprise shows a right-sided pleural effusion of moderate size.
Pleural aspiration is performed.
What is the cause of her effusion?

Answer 5.4
Pleural effusion is an uncommon but well-documented finding in rheumatoid disease. This is a systemic
disease and a number of manifestations occur in the chest. Among these are: pleural effusion, pulmonary
nodules, interstitial fibrosis, pleural thickening and bronchiolitis obliterans. This patient has a number of
autoimmune diseases so it would not be unreasonable for her to be diagnosed with rheumatoid disease.
The pleural effusion is an exudate. The rheumatoid factor level is hugely elevated at 556 IU/ml. In
addition the glucose is low at 2.2 mmol/l in the effusion, further supporting the diagnosis.
Case 5.5
A 42-year-old salesman with established alcoholic liver cirrhosis is a known patient to the ward. He has
been admitted on multiple previous occasions and continues to drink heavily. On this admission he is a
little confused and tremulous. On examination, ascites is present along with small bilateral pleural
effusions. His abdomen is mildly tender throughout. Bowel sounds are present.
The on-call doctor performs a diagnostic peritoneal aspiration. One hour later, the laboratory technician
phones with the report below.
His blood albumin level is 29 g/l.

What is the diagnosis, and how should the patient be treated?
Answer 5.5
His ascites white cell count shows a neutrophilia, with more than 250 cells/mm3.
The albumin content is less than 25 g/l indicating a transudate.
The SAAG is 13 g/l (29 g/l – 16 g/l). This is in keeping with portal hypertension.
Gram staining shows the most typical finding in SBP – Gram-negative bacilli. In time, one might expect
culture to yield Escherichia coli or Klebsiella species.
This man has spontaneous bacterial peritonitis, on a background of hepatic cirrhosis caused by alcohol.
His clinical features are typical with general abdominal discomfort, often accompanied by pyrexia. This
infection has also made him mildly encephalopathic, hence the confusion.
In a patient with a history of alcohol dependency, abdominal distension and pain, pancreatitis is a further
differential diagnosis. However, this would cause an exudate, and one would expect the amylase level to
be raised significantly.
Case 5.6
A frail 88-year-old nursing home resident is brought to hospital because of abdominal pain. Her nurse is
also concerned about the progressive increase in her abdominal girth over the past 6 weeks. She has a
history of vascular dementia. On examination there is a grossly distended abdomen, with shifting dullness
and a fluid thrill. A CT scan of the abdomen and pelvis demonstrated a massive mixed solid–cystic lesion
in the pelvis and gross ascites.
Peritoneal aspiration was performed for diagnostic purposes and symptomatic benefit: 9500 ml was
drained and sent for analysis. The results are shown.
Her blood albumin level is 29 g/l.

Provide a diagnosis and explain your reasoning.
Answer 5.6
The WCC is not significantly raised.

The albumin level is greater than 25 g/l, indicating an exudate.
The SAAG is 1 g/l (29 g/l – 28 g/l), indicating a low probability of portal hypertension.
The diagnosis is seen on cytology.
This patient has an advanced intraperitoneal malignancy. The specific primary origin is unknown. The
cells present may originate from a primary intraperitoneal malignancy or be due to intraperitoneal
metastatic disease. A large volume of ascites in an elderly patient without known liver disease should
always arouse the suspicion of malignancy. The CT findings are in keeping with a primary pelvic
malignancy of likely ovarian origin.
Case 5.7
A 36-year-old banker attends A&E complaining of recurrent bouts of intense abdominal discomfort. He
has been reluctant to present previously for fear of admission. He admits to being a heavy drinker, but his
family and colleagues are not aware of his problem. On examination there is distension of the abdomen
with ascites present, tenderness in the upper abdomen and a faint upper midline incision.
You are concerned about his level of abdominal pain. He agrees to peritoneal aspiration, but does not
wish to be admitted.
The patient’s blood albumin level is 32 g/l.

Give a diagnosis and list useful further investigations.
Answer 5.7
The ascites is an exudate, and there is no evidence of infection.

The SAAG is 3 g/l (32 g/l – 29 g/l), indicating a low probability of portal hypertension.
The amylase is elevated at 894 U/l, in keeping with acute pancreatitis.
Every effort should be made to persuade this man of the need to stay in hospital for further investigation
and treatment of his pancreatitis.
MICROBIOLOGY
Infections account for a wide spectrum of human illness. Bacteria and viruses predominate in clinical
medicine in the UK, but one should bear in mind that other organisms (eg fungi, protozoa, helminths and
arthropods) can all cause problems. Infections that are rare in clinical practice in the UK should be borne
in mind when patients have been travelling or are from endemic regions. In addition, patients who are
immunocompromised are prone to infections that are not normally seen in individuals with healthy
immune systems.
If treatment is required for an infection, a drug must be chosen that has activity against the pathogen
causing the problem. Often, a ‘best guess’ at treatment is made. For example, an antibiotic called
trimethoprim is often given to patients with symptoms of a urinary tract infection because the bacteria that
are responsible for most urinary tract infections are likely to be targeted by this drug. In many cases,
however, it is appropriate to collect samples from the patient so that an attempt can be made to accurately
identify the organism that is causing the infection. It is the results from the analysis of such samples that
are considered further here.
To have the best chance of identifying a causative organism, samples should normally be taken from the
body site that is affected. Common samples include sputum, urine, faeces, synovial fluid, swabs from
mouth, skin or genitals, pus from any site, cerebrospinal fluid and biopsy samples. On occasion,
organisms can move from the site of origin into the bloodstream causing septicaemia. Thus, blood is often
cultured in addition to material from the likely focus of infection.
Infections with bacteria

Infections with bacteria tend to predominate in undergraduate assessments because they are the infections
that most commonly cause serious disease in the UK. Once a sample containing bacteria has been
collected, there are two basic methods for identifying the organism. First, the sample can be examined
using light microscopy with a stain applied. The stain normally used first is the Gram stain. Organisms
that stain blue are termed ‘Gram positive’ and those that stain pink are termed ‘Gram negative’. Bacteria
can then be described using their shape. ‘Bacilli’ are rod shaped whereas ‘cocci’ are spherical. Thus,
very quickly one can have a fair idea of the likely organism contained in a sample. Common organisms
characterised by staining characteristics and shape are listed in the box on page 216. ‘Aerobes’ grow best
in oxygen-rich environments, whereas ‘anaerobes’ grow best in oxygen-poor environments. This will
become apparent during culture. Another staining technique, Ziehl–Neelsen staining, can be used to detect
mycobacteria (responsible for tuberculosis).
EXAMPLES OF COMMON ORGANISMS

Staphylococcus aureus
Streptococcus pyogenes
Gram-positive cocci
Streptococcus pneumoniae
Enterococcus faecalis
Listeria monocytogenes
Gram-positive bacilli
Aerobes Bacillus anthracis
Gram-negative cocci Moraxella catarrhalis
Neisseria meningitidis
Escherichia coli
Gram-negative bacilli
Pseudomonas aeruginosa
Peptococci
Cocci
Peptostreptococci
Anaerobes
Bacteroides fragilis
Bacilli
Clostridium difficile
The second method for organism identification is culture. Samples are placed on growth media and given
time for the organisms to multiply. After multiplication has taken place, microbiologists use a range of
techniques for identifying the particular type of bacteria present. This takes time – several days for most
bacteria. The identification of tuberculosis can take weeks, however. The payoff for waiting is that the
exact species of organism can usually be identified after culturing. Once a bacterium is cultured, its
sensitivity to a batch of suitable common antimicrobial agents is tested. There are three outcomes to this
testing: sensitive (S), intermediately sensitive (I) and resistant (R). A typical culture and antibiotic
sensitivity report might look like this:
In this example, the patient’s urinary tract infection appears to have been caused by the Gram-negative
bacillus Proteus species. If treatment is deemed necessary, it would be most appropriate to prescribe one
of the drugs shown as sensitive (S), because this would be expected to have the highest likelihood of
killing the micro-organism in question.
MINIMAL INHIBITORY CONCENTRATION (MIC) AND MINIMUM BACTERICIDAL

CONCENTRATION (MBC) TESTING
Occasionally it is desirable to have more information about an organism’s sensitivity to a particular antimicrobial agent rather than a simple
yes/no answer. This is commonly the case for infections that are difficult to treat or that require prolonged courses of antibiotics, eg
infective endocarditis. In such circumstances detailed testing can be performed to work out the minimum concentration of antibiotic
necessary to stop bacterial growth (MIc) and the minimum concentration of antibiotic necessary to kill the bacteria (MBc). These data can
then be translated into the most appropriate dose and duration for drug prescription purposes.
Staphylococcus aureus requires special mention for two reasons:

If resistant to meticillin, it is deemed meticillin-resistant Staphylococcus aureus (MRSA). This is
1.
highly important because different antibiotics are required to treat this particular type of bacterium.
It is a reasonably common finding to isolate ‘coagulase-negative’ Staphylococcus aureus on blood
cultures. Laboratories often test staphylococci for their production of coagulase. Staphylococci that
2.
normally colonise skin (such as S. epidermidis) do not produce coagulase. The identification of
these organisms on blood cultures usually reflects the fact that the skin surface was inadequately
sterilised before blood was drawn.
Other methods are available for detecting certain bacteria, but the clinician must actually have the
knowledge to suspect a likely organism and request the appropriate test. In patients presenting with
pneumonia, for example, urine is often tested for the presence of antigens to Streptococcus pneumoniae
and Legionella species. In patients with diarrhoea, faecal samples are often tested for the presence of
Clostridium difficile toxin. Genetic testing can also be carried out to look for the presence of bacterial
DNA or RNA in a sample. Polymerase chain reaction (PCR) techniques can be used to assist in this
process.
Finally, it is possible to perform serological tests to detect antibodies to various organisms in a patient’s
blood. Immunoglobulin type M (IgM) levels tend to rise early in a disease course, with IgG levels rising
later. If IgM is detected to a particular bacterium, it is likely that this is the cause of the illness. The IgG
level is more difficult to interpret, however, because the IgG antibody level would be expected to be
elevated if a patient has either had a particular illness previously or been immunised against it. It is thus
difficult to distinguish between current infection and previous exposure based on a single measure of IgG
level. The best use of serological testing is in the measurement of acute and convalescent levels of IgG, ie
measure the level during the acute illness and again once the patient has recovered. If there has been a
significant rise in the antibody levels to a particular microorganism during the patient’s recovery, it is
probable that the organism suspected was the likely pathogen. The disadvantage with serological tests is
the inevitable time lag in making the diagnosis, and the fact that treatment decisions must therefore be
made without confirmation of the pathogen.
Infections with other organisms

The principles for the detection of other microorganisms are similar to those used for bacteria. Light
microscopy can be useful in detecting fungi (eg in skin scrapings samples), parasites (eg in faecal
samples) and protozoa (eg malaria in blood). Electron microscopy can be used to identify certain viruses.
Pathogen antigen testing can be attempted with certain organisms also (eg hepatitis B surface antigen).
Genetic testing employing PCR techniques is being increasingly used for the rapid detection of viruses.
An example would be the rapid testing of cerebrospinal fluid for herpes simplex virus in patients with
suspected encephalitis (viral brain infection). Fungi can be cultured similarly to bacteria, but culture of
viruses and other organisms is time-consuming and difficult because they must be grown in cell or tissue
preparations. Serological testing is the method most useful in clinical practice for confirming infection
with a virus.
It should be apparent that the difficulty with microbiological investigations for a clinician lies
with knowing which test to request. Thanks to the efforts of highly skilled laboratory
technicians, the interpretation of test results is generally relatively straightforward.
Interpretation of drug levels

Drug treatment of patients with infections sometimes requires the use of drugs with ‘narrow therapeutic
ratios’. This means that there is a small difference between the dose of a drug required to produce a
therapeutic effect and the dose required to cause toxicity. Use too low a dose, and the infection may not be
adequately treated. Use too high a dose, and you will put the patient at risk of an adverse drug reaction.
Drugs for which levels are commonly tested include aminoglycoside agents (eg gentamicin) and
glycopeptides (eg vancomycin). It is possible to measure a peak drug level in the blood (sample taken
shortly after drug administration) or a trough level (taken just before the next dose being administered).
Target ranges for peak and/or trough levels are listed in drug formularies. Generally, if levels are lower
than required, dosing is increased. If levels are too high, the drug is omitted until the level returns to a
safe level before a modified dosing regimen is re-started.
Bedside testing for urinary tract infection

Urine samples can be quickly analysed at ward level using a reagent strip that is dipped into the urine.
Typical strips allow for the estimation of a range of substances in the urine (see page 9 for urinalysis in
haemolysis and page 72 for its use in cholestatic jaundice). Operators wait for a set time period and then
compare a colour change with each reagent to a standard set of results. The colour change seen will
depend on the amount of a particular substance in the urine. Substances that are useful in the detection of
urinary tract infection (UTI) include leukocyte esterase, nitrites, protein and blood. Urinalysis can only at
best point towards the diagnosis of UTI – culture is necessary for a definitive diagnosis. The sensitivity
and specificity of abnormalities in each of the parameters mentioned have been published with regard to
diagnosing a UTI, but a good rule of thumb is to say that, if urinalysis is totally normal, then a UTI is
unlikely. If it is abnormal in any way, a UTI is a possibility and culture should be performed if there is
clinical suspicion.
Simerville JA, Maxted WC, Pahira JJ. Urinalysis: a comprehensive review. Am Fam Physician 2005;71:1153–62.
Interpretation of microbiological data is found within Chapter 16.
NEUROLOGICAL INVESTIGATIONS
There are three main groups of tests used to investigate neurological disease. Cerebrospinal fluid analysis
and neurophysiological investigations are dealt with in this chapter. Imaging is touched upon in Chapter 9.
It is the combination of findings from these tests, rather than one in isolation, that frequently enables a
diagnosis to be made
Cerebrospinal fluid analysis

Cerebrosinal fluid (CSF) is obtained by performing a lumbar puncture. A wide variety of tests can be
performed on CSF as detailed below. This box details the components of a routine CSF analysis.
COMPONENTS OF A ROUTINE CSF ANALYSIS

Opening pressure
Total protein
Appearance
Glucose
(Gram stain + culture if infection
Microscopy for cell counts
suspected)
Bedside tests
Important information on a patient’s condition can be gleaned at the bedside during the process of lumbar
puncture, even before fluid is sent for analysis.
Opening pressure
Once a needle has been passed and CSF is draining, a manometer can be attached to measure the ‘opening
pressure’. This is meaningful only if the patient is in the ‘standard’ lateral decubitus position (lying on
their side) at the time of puncture. If lumbar puncture is performed with the patient upright, the opening
pressure will be artificially elevated. Normal values for opening pressure are variably quoted between
texts, but a pressure of between 8 and 20 cmCSF is probably normal.
CAUSES OF ABNORMAL OPENING PRESSURE

Abnormally low Abnormally high
Meningitis
CSF leak Tumour
Recent lumbar puncture Intracranial haemorrhage
Idiopathic intracranial hypertension (‘benign intracranial hypertension’)
CSF appearance
The gross appearance of CSF can give an early indication of fluid composition. Textbooks list many
subtle colour variations of CSF, which are quite difficult to appreciate unless you are experienced in this
area. The most abnormal CSF appearances are listed in the box below.
CHARACTERISTIC CSF APPEARANCE
Appearance Characteristic of
Normality
Clear
Meningitis
Cloudy or purulent
Traumatic tap or subarachnoid
Bloody
haemorrhage
The inadvertent puncture of a blood vessel during the process of lumbar puncture will result in blood-
stained fluid being drained. The operator will not know with any certainty, however, that a blood vessel
has been hit, and one must therefore be able to distinguish between CSF that is truly blood stained and
CSF that appears blood stained only because of the puncture of a vessel. One simple method for doing
this at the bedside involves collecting three separate CSF samples. If the fluid remains blood stained to
the same degree in all samples, it is likely that the CSF is truly blood stained. If, however, the fluid
becomes less blood stained with time, it is more likely that the lumbar puncture has been a traumatic tap.
Laboratory testing of the CSF for the presence of xanthochromia provides another method of
distinguishing between these two possibilities and is discussed below.
Laboratory tests
Microscopy
CSF microscopy permits the estimation of cell counting in the fluid. An elevated red cell count is most
commonly seen as a result of the lumbar puncture needle puncturing a blood vessel en route to the
subarachnoid space. It will also be seen in cases of intracranial haemorrhage. However, a measure of the
red cell count in three consecutively collected specimens of CSF can help differentiate between these two
possibilities, similar to the bedside test described above.
An elevated white cell count (>5 cells/mm3) suggests central nervous system infection (ie meningitis or
encephalitis), but can also be found in other conditions such as inflammatory diseases and cancer. If
puncture of a small blood vessel has occurred during lumbar puncture, the white cell count will also be
elevated falsely due to the presence of these cells in the blood. The particular type of white cells present
can also be informative. A predominance of neutrophils suggests bacterial meningitis. Lymphocytes
predominate in other infective causes of meningitis (eg viral, tuberculosis or fungal).
Microbiological testing
Microscopy after Gram staining (for bacterial infection), Ziehl–Neelsen staining (for tuberculosis),
culture and genetic techniques (eg polymerase chain reaction [PCR] techniques to detect bacterial or viral
DNA) can all be useful in the analysis of CSF when infection is suspected. Refer to Chapter 6 for further
details. It is worth bearing in mind that, as it is imperative that antimicrobial treatment should be
administered as soon as possible in patients with suspected bacterial meningitis, lumbar puncture is often
(rightly) performed after treatment has been started. This can change the CSF constituents such that
‘textbook’ patterns may not be seen, and a high index of suspicion is necessary. More specialised
microbiological testing can be performed if an unusual organism (eg syphilis, cryptocococci, human
immunodeficiency virus [HIV]) is suspected.
Protein measurement
Normal CSF contains between 0.15 and 0.45 g/l of protein approximately, but the precise reference range
varies depending on the laboratory used. Abnormally elevated CSF protein is a good pointer that some
pathological process is active in the central nervous system, but it is impossible to be sure about causality
using the protein measure alone. The box on page 226 lists some of the more common conditions that are
associated with elevated CSF protein, but this list is by no means exhaustive.
CAUSES OF RAISED CSF PROTEIN
Meningitis Neoplastic disease

Brain abscess Guillain–Barré syndrome
Intracerebral haemorrhage Multiple sclerosis
Glucose measurement
Interpretation of the CSF glucose concentration in isolation is meaningless – it must be interpreted in
relation to the blood glucose concentration. A blood sample for glucose measurement must always be sent
at the time of lumbar puncture.
DON’T FORGET
always interpret CSF glucose results in the context of blood glucose levels.
CSF glucose should be around 40–60% that of the level in blood. An abnormally high glucose level will
be seen with simultaneous high blood sugar level (ie in poorly controlled diabetes) and is not a pointer to
CSF pathology. An abnormally low CSF glucose level is, however, highly important and is suggestive of,
but not limited to, bacterial, fungal or tuberculous infection. Viral infections of the CNS do not
characteristically lower the CSF glucose concentration.
Other tests
There are a multitude of specialised tests that can be performed on CSF in certain circumstances. The
most commonly requested of these are detailed below.
Xanthochromia
The term ‘xanthochromia’ describes a yellow discoloration of CSF. This can sometimes be detected by
inspecting CSF, but is more reliably quantified in a laboratory using spectrophotometry. A positive test
indicates that bilirubin is present in the fluid, and will therefore be found in patients with significant
jaundice. Assuming that the patient does not have jaundice, xanthochromia is tested for most commonly in
patients who are suspected to have had a subarachnoid haemorrhage (SAH), because blood in the CSF
breaks down to form bilirubin. CT scanning of the head should be performed first, with lumbar puncture
being performed if SAH is suspected but no evidence of it is seen on the scan. It is routine to wait at least
12 hours after the onset of symptoms to ensure that any blood in the CSF has had time to break down into
bilirubin.
The presence of xanthochromia in a sample can also be helpful in distinguishing blood-stained CSF from
a traumatic tap in addition to the methods used above. In a traumatic tap, blood will only have entered the
CSF at the time of lumbar puncture, and will not have had time to break down into bilirubin. Testing for
xanthochromia will therefore be negative in these circumstances.
Oligoclonal bands
The presence of oligoclonal bands in CSF is often tested for in patients who are suspected of having
multiple sclerosis (MS). Oligoclonal bands are due to the presence of immunoglobulins in the CSF and
are detected when CSF is tested using electrophoresis. Although characteristic of MS, the finding of
oligoclonal bands is not diagnostic, because they can be found in a variety of rare neurological diseases.
Cytological examination
Cytological examination of the CSF can be helpful in the diagnosis of neurological malignancy. The
specifics of the tests used are beyond the scope of this text, but a cytological report normally incorporates
a cytologist’s overall impression and is therefore relatively easy to interpret.
Neurophysiological investigations
Neurophysiology is a specialist domain within neurology. Only a brief understanding of the common
investigations is necessary for an undergraduate. Likewise, knowledge of the key findings in classic
conditions will suffice. It is unlikely that one would be expected to interpret neurophysiological
investigations.
The main investigations to be aware of are nerve conduction studies and electromyography. Visually
evoked responses and electroencephalography are further aids to diagnosis.
NEUROPHYSIOLOGICAL INVESTIGATIONS
Nerve conduction studies
Electromyography
Visually evoked responses
Electroencephalography
Nerve conduction studies

Nerve conduction studies (NCSs) measure how well individual nerves transmit electrical signals. The
nerve of interest is stimulated, usually electrically, with surface electrodes placed on the skin. One
electrode stimulates the nerve and the resulting electrical activity is recorded by the other electrodes. The
distance between electrodes and the time taken for electrical impulses to travel between electrodes are
used to calculate the nerve conduction velocity.
The most common reason for NCSs to be requested is for suspected carpal tunnel syndrome. In this
condition, the median nerve is entrapped within the confines of the carpal tunnel.
Electromyography
Surface or needle electrodes are used to detect muscle action potentials following controlled electrical
stimulation. The electrical stimulation provokes action potentials within the nerves which in turn stimulate
a magnified response in muscles.
Electromyography (EMG) may be modified for some indications. The most important to know is single-
fibre EMG and EMG with repetitive stimulation used when myasthenia gravis is clinically suspected.
Visually evoked responses

In this test, the eye is stimulated in order to evoke a response within the occipital cortex. It is performed
by placing a series of electrodes over the scalp in the occipital area while asking the patient to observe a
series of visual patterns. The response is recorded via the electrodes. Two indices are noted:
1. The speed of response of the nerve (termed ‘P100 latencies’)
2. The height of the waveform obtained.
This test is usually performed in patients in whom multiple sclerosis is suspected. In multiple sclerosis,
the waveform will be preserved, but the speed of response will be delayed because of optic nerve
demyelination.
Electroencephalography
Electroencephalography (EEG) is the recording of electrical activity from the brain using a series of
scalp electrodes. Usually, recordings over a period of several minutes are taken. Broadly speaking, EEG
can be used to diagnose epilepsy and diffuse brain disease. In epilepsy, it is most valuable if a recording
takes place during a seizure since it is not unusual to obtain a normal recording between seizures.
In difficult cases, EEG recording can take place over several hours or days in a supervised room in
hospital with video recording. EEG may also be invaluable in diagnosing non-convulsive status
epilepticus and distinguishing true seizures from pseudoseizures. In non-convulsive status epilepticus, a
patient is having ongoing seizures, despite these not manifesting themselves clinically. Prompt diagnosis
by EEG may prevent a permanent neurological deficit.
Classic neurophysiological disease associations
TEST RESULT DISEASE

EEG Spike and wave Primary generalised epilepsy
EEG Periodic complexes Creutzfeldt–Jakob disease
Short polyphasic motor potentials

EMG Sometimes spontaneous fibrillation and high-frequency repetitive Polymyositis
discharges
EMG (single fibre) Fatiguability following repetitive stimulation Myasthenia gravis
Repetitive single motor unit potentials all low amplitude. Short duration
EMG Myotonic dystrophy
polyphasic motor unit potentials
EMG Spontaneous fibrillations Motor neuron disease
Carpal tunnel syndrome

NCS Delay in conduction of median nerve
(entrapment neuropathy)
Visually evoked
Delayed P100 latencies, without amplitude loss Multiple sclerosis
responses (VERs)
Case 7.1
A 19-year-old university student complains of a headache of 8 h duration accompanied by a dislike for
lights. She has vomited twice. She is sweaty to the touch. No rash is apparent. The A&E officer was
concerned enough to request a CT scan of the brain which was reported as normal. She proceeds to
lumbar puncture. The CSF pressure was normal at the time of lumbar puncture.
Describe the CSF, and state the most likely diagnosis.

Answer 7.1
Several features in the history should set off alarm bells for bacterial meningitis. The patient is young and
in an institutional environment, and has an acute headache with photophobia. In addition, the CSF is
cloudy with a raised WCC and a low CSF:plasma glucose ratio.
Three important points can be learned from this case:

If the leukocyte count is raised, analysis of the differential leukocyte count will help in
1.
distinguishing the cause.
A patient may have bacterial meningitis without any organisms being seen on microscopy. Don’t be
2.
put off by this.
3. In bacterial meningitis, CT of the brain can be normal even when the CSF is highly abnormal.
This patient has bacterial meningitis and requires immediate treatment with intravenous antibiotics.
THE CLASSIC CSF FINDINGS IN BACTERIAL MENINGITIS

A cloudy appearance Raised (but only mild–moderate)
Organisms seen in CSF total protein
Raised WCC Significantly reduced CSF glucose
(with >95% neutrophils) Reduced CSF:plasma glucose ratio
Red cell count (RCC) normal (to less than two-thirds)
Case 7.2
A 21-year-old soldier complains of a headache for the past 2 days and a dislike of light. He is feverish.
He has recently returned from deployment in Germany. Examination did not reveal any focal neurological
signs or signs suggestive of raised intracranial pressure. The CSF opening pressure at the time of lumbar
puncture was normal (17cmCSF). Lumbar puncture is performed, and the following result obtained.
Interpret this CSF sample and give a differential diagnosis of the cause.
Answer 7.2
This history is not dissimilar to Case 7.1. However, the CSF analysis is significantly different. The WCC
is raised – although less so than in the example of bacterial meningitis. The differential WCC is also
different – lymphocytes being the predominant cell type here. The plasma glucose is a little abnormal, as
is the CSF:plasma glucose ratio. Total protein is elevated – but only marginally. In summary many of the
parameters are abnormal, but not markedly so.
CAUSES OF LYMPHOCYTE-PREDOMINANT LEUKOCYTOSIS IN CSF

Viral meningitis Tuberculous meningitis
Mumps meningoencephalitis Partially treated bacterial meningitis
The most common cause for these findings is viral meningitis – the virus itself may never be identified.
Polymerase chain reaction analysis of CSF can be performed to test for a number of viruses, including
herpes simplex. The treatment and outcome of viral meningitis are markedly different to those of partially
treated bacterial meningitis, and if any diagnostic doubt exists treatment should continue for bacterial
meningitis. The reason for partial treatment may have been the commencement of an antibiotic by a GP.
Case 7.3
A 39-year-old man is admitted to the neurology ward following a short illness. He is unable to move his
legs. He was previously well, although he did have a short bout of diarrhoea a week ago after his return
from holiday in Turkey.
Lumbar puncture was performed. The CSF opening pressure at the time of lumbar puncture was 18
cmCSF.
1. What are the significant findings and what condition could cause this appearance?
2. What other test might help in coming to a diagnosis?
Answer 7.3
The history is short and the symptoms significant. However, the only significant abnormality on the
CSF sample is the elevated level of protein within the CSF. The plasma total protein is normal. The
CSF protein is raised to a greater degree than one would usually expect for a viral or bacterial
meningitis/encephalitis. Note that the WCC and the CSF:plasma glucose ratio are also not in
1. keeping with an infective pathology. The differential diagnosis is therefore of a high CSF protein.
When interpreted in the context of the history of leg weakness after an episode of infectious
diarrhoea, the diagnosis is most likely to be Guillain– Barré syndrome (an acute inflammatory
polyneuropathy).
Nerve conduction studies (NCS) would help diagnosis (see Neurophysiological investigations on
2.
page 228 for further details).
Case 7.4
A 29-year-old bank clerk has become known to local neurologists over the past year following several
presentations to both the hospital and the outpatient clinic with a variable constellation of neurological
symptoms. Initially a complaint of numbness over the lateral aspect of the left leg was mentioned. This
resolved. Of late, she has had an episode of loss of vision in the right eye lasting 4 weeks. Examination
reveals global hyperreflexia and a mild cerebellar gait.
The patient attends the ward for a series of tests including lumbar puncture. The CSF opening pressure
was 17cmCSF.

Answer 7.4
This CSF sample shows essentially normal values for all the common indices. Additional analyses have
been performed, including oligoclonal bands which are present.
These bands represent immunoglobulin G (IgG). The presence of this has been noted in a number of
conditions – it is therefore of poor specificity in isolation. However, it is found in over 80% of patients
with multiple sclerosis (MS). MS is the most common cause for its presence on CSF analysis. It is a
supportive feature rather than a diagnostic feature of the disease, since MS is a clinical diagnosis defined
as ‘two episodes of neurological deficit disseminated in time and place’.
CAUSES OF OLIGOCLONAL BANDS IN CSF

Multiple sclerosis
Subacute sclerosing panencephalitis
Guillain–Barré syndrome
Neurosyphilis
Lyme disease
Neurosarcoidosis
IMMUNOLOGY
Interpretation of autoantibodies is often difficult. This is because of the degree of overlap in the presence
of antibodies between various disease states. For example, rheumatoid factor can be found in well over a
dozen diseases. Furthermore, certain autoantibodies may be found in healthy people, and the absence of
an autoantibody may not rule out a particular disease. Therefore, always bear in mind that the presence of
an autoantibody does not necessarily mean that a patient has a particular disease.
DON’T FORGET
A disease may be present without the typical autoantibody profile.
For the purpose of undergraduate examinations, the classic autoantibody associations will be tested.
These are listed in the box below. Those tested commonly in examinations are in bold type.
DISEASE AUTOANTIBODIES
Addison’s disease Anti-21-hydroxylase
Anti-cardiolipin
Anti-phospholipid syndrome
Lupus anticoagulant antibodies
Red blood cell autoantibodies (this disease can be classified into

Autoimmune haemolytic anaemia warm and cold, depending on the temperature at which the
antibodies best attach to red cells)
Anti-nuclear
Anti-smooth muscle
Autoimmune hepatitis Anti-liver/kidney microsomal-I
Myeloperoxidase anti-nuclear cytoplasmic antibody (MPO-ANCA),
also called perinuclear A NCA (pANCA)
Churg–Strauss syndrome MPO-ANCA
Anti-endomysial
Anti-tissue transglutaminase
Coeliac disease
Anti-reticulin
Anti-gliadin
Rheumatoid factor
Anti-nuclear
Diffuse cutaneous scleroderma
Anti-SCL-70
Polymerase 1, 2 and 3
Goodpasture syndrome Anti-glomerular basement membrane
Anti-TSH receptor
Graves’ disease
Anti-peroxidase
TSH-receptor-blocking antibodies
Hashimoto’s thyroiditis
Anti-peroxidase
Lambert–Eaton myasthenic syndrome Anti-P/Q-type voltage-gated calcium channels

Rheumatoid factor
Limited cutaneous scleroderma Anti-nuclear
Anti-centromere
Mixed connective tissue disease (overlap syndrome) Anti-U1-RNP
Anti-nuclear
Myasthenia gravis Anti-acetylcholine
receptor antibodies
Anti-YO
Anti-Hu
Anti-Ri
Paraneoplastic conditions
Anti-MA
Anti-CV2/CRMP5
Anti-amphiphysin
Anti-parietal cell
Pernicious anaemia
Anti-intrinsic factor
Polyarteritis nodosa MPO-ANCA
Anti-nuclear
Polymyositis/dermatomyositis Rheumatoid factor
Anti-Jo-1
Anti-mitochondrial (more particularly against pyruvate

Primary biliary cirrhosis
dehydrogenase complex type E2- and/or E3-binding protein)
Rheumatoid factor
Rheumatoid disease Anti-nuclear
Anti-CCP
Rheumatoid factor
Anti-nuclear
Sjögren syndrome
Anti-Ro (SS-A)
Anti-La (SS-B)
Double-stranded DNA
Rheumatoid factor
Anti-nuclear
Systemic lupus erythematosus Anti-Ro (SS-A)
Anti-Sm
Anti-U1-RNP
Anti-cardiolipin
Proteinase 3 anti-nuclear cytoplasmic antibody (PR3-ANCA),

Wegener syndrome
also called cytoplasmic ANCA (cANCA)
IMAGING
The interpretation of imaging investigations is a comprehensive topic that forms a specialty in its own
right. Its influence and remit in contemporary medicine are vast forming huge amounts of ‘digital data’ for
interpretation. It is essential that medical students and trainee doctors have a sound basic understanding of
plain radiographs (X-rays), in particular chest and abdominal radiographs. Likewise an appreciation and
insight into the more advanced imaging investigations at their disposal is increasingly important, in
particular the ever popular and influential computed tomography (CT). A good professional relationship
with the radiology department, including thoughtful and selective referral, can hugely aid patient care.
This chapter does not aim to be a concise undergraduate textbook on radiology. Nor will it be an
exhaustive description of characteristic radiological findings in common diseases or a gallery of images.
It is a guide to approaching the interpretation of common X-rays and the basics of CT of the head. In the
clinical cases featured the emphasis will be on inpatient films – these are X-rays that one might be
expected to interpret during work on general medical and surgical wards or the accident and emergency
department. Films are presented in a symptom-based manner to best reflect everyday practice and to
provide instruction on how interpretation may immediately assist your diagnostic pathway and therefore
your management decisions. No film will be viewed in isolation without clinical information. As with all
the data interpretation considered in this book, investigations should be assessed in the light of the
clinical scenario and laboratory results. This should also be the gold standard to aspire to in clinical
practice.
Imaging studies may feature in both written and clinical examinations, offering the chance to assess a
broad knowledge base.

DON’T FORGET
Always interpret X-ray findings in a clinical context.
Compare the images with old films if available.
Interpreting the chest X-ray

The chest X-ray (CXR) is the single most requested imaging investigation and is also the most likely film
to feature in daily practice or an undergraduate exam. It is the perfect prompt for questioning other aspects
of a patient’s condition and to explore management strategies. To be able to comment confidently on the
film’s findings, and have an understanding of how to approach interpretation, an appreciation of normality
is required. Don’t forget that a CXR is a two-dimensional representation of a three-dimensional structure.
Fig 9.1: A normal chest X-ray.
Fig 9.2: Normal anatomy on CXR.
One may think of a CXR as a picture that contains five ‘shades’ on a black-and-white scale. These shades
represent four different natural ‘tissues’ and one for artefacts.
These are:
1. Bone is WHITE
2. Gas is BLACK.
3. Soft tissue is GREY
4. Fat is DARKER GREY.
5. Most man-made things on the film are BRIGHT WHITE.
Film specifics and technical factors

Before proceeding to interpret a CXR, always comment on film specifics and technical factors as shown
in the boxes below.
FILM SPECIFICS (DETAILS)
Name of patient
Age and date of birth
Location of patient
Date taken
Film number (if applicable)
FILM TECHNICAL FACTORS

Type of projection (see box below)
Markings regarding any special techniques used (eg taken in expiration)
Rotation
Inspiration
Penetration
TYPES OF PROJECTION
Posteroanterior (PA): the X-ray tube is behind the patient and film against the chest. The GOLD standard projection
Anteroposterior (AP): the X-ray tube is in front of the patient and film against the back
Supine: the patient is lying on his or her back
Erect: the patient is upright
Semi-erect: the patient is partially upright
Mobile: the X-ray has been taken with a mobile X-ray unit. VERY SICK patients ONLY (on the ITU/HDU/CCU usually)
These descriptions may be combined. For example, an acutely unwell patient who has a CXR taken on an
intensive therapy unit (ITU) may have a mobile, semi-erect AP film.
You might think of this part of the interpretation, like the safety announcement on an airplane, as one you
have heard many times: necessary to acknowledge, but tedious and of little consequence. However, this
could not be further from the truth. Changes in these parameters can give the impression of abnormalities
in the structures visualised. For example, a widened mediastinum, on an AP chest X-ray may provoke the
impression of a thoracic dissection or a pneumothorax may be overlooked if one does not appreciate that
the chest X-ray is supine rather than erect.
Assess the film in detail

A structured systematic approach is needed for thorough interpretation, just as one would approach a
clinical system examination in a methodical manner.
It is good practice to mention a clear-cut abnormality at the outset. A reasonable way to say this would be,
‘The technical quality of the film is satisfactory. The most striking abnormality on initial assessment is
…’.
The examiner will then expect the candidate to demonstrate an organised approach to looking at the rest of
the film. Do not stop when one abnormality has been noted (termed ‘the satisfaction of search’) – there
may be more to see.
DON’T FORGET
Keep looking – multiple findings may give the definitive diagnosis.
The structures below need to be assessed in the interpretation of the CXR. It is fair to assume that, if one
major abnormality is clearly ‘spotted’ at the beginning, this structure or system should be commented on
first.
Structures to assess on CXR

• Heart and major vessels
• Lungs and pleura
Mediastinum (including
•
hila)
• Bones and soft tissues.
Be particularly careful not to miss the following REVIEW areas. They should be specifically checked as
abnormalities in these areas may be easily overlooked.
Review areas
• Costophrenic angles (1)
• Apices (2)
• Behind the heart (3)
• Below the diaphragms (4)
• Breast shadows (in females) (5).
Fig 9.3: Review areas on a chest X-ray assessment.
Heart and major vessels

Assess:
• Size of the heart
• Size of individual chambers of the heart
• Size of pulmonary vessels
• Evidence of stents, clips, wires, valves, pacemakers
Outline of aorta, inferior (IVC) and superior (SVC) vena
•
cava.
DON’T FORGET
Do not comment on heart size on an AP chest X-ray because it is magnified.
Lungs
Assess:
• Size
• Intrapulmonary pathology
Bronchovascular lung
•
markings.
Pleura
Assess:
• Thickness or calcification
Fluid or air in the pleural
•
space.
Mediastinum (including hila)

Assess:
• Width of the mediastinum
• Contour of the mediastinum
• Size and density of the hila
Level and symmetry of the
•
hila.
Bones and soft tissues

Assess:
• Diffuse or focal bony abnormalities
• Surgical emphysema
Breast presence/absence and
• symmetry.
Interpreting the abdominal X-ray
Abdominal X-ray
The abdominal X-ray (AXR) has more limited value in diagnosis than a CXR. Its chief value is in the
diagnosis of bowel obstruction and renal tract calculi, although other pathology may be identified. Even in
these cases, the abdominal X-ray is often just a ‘stepping stone’ to further imaging with ultrasonography
or CT. Indiscriminate requesting of the abdominal X-ray is discouraged.
The radiation exposure of an AXR compared with a CXR is also considerably higher. One AXR is
equivalent to 35 CXRs.
As with a CXR, an appreciation of normality is vital in order to make a correct interpretation.
Fig 9.4: A normal AXR
Fig 9.5: Normal anatomy on AXR
Film specifics and technical factors

The initial assessment of an AXR is similar to for a CXR.
FILM SPECIFICS FILM TECHNICAL FACTORS

Name of patient
Age of patient Type of projection (supine is standard)
Location of patient Markings of any special techniques used
Date taken Adequate anatomical coverage
Film number (if applicable)
Assess the film in detail

A simple guide to interpretation is shown below. Working through these headings, one covers ‘black bits’,
‘white bits’, ‘grey bits’ and ‘bright white bits’ in turn. Alternatively one may take an anatomical approach
to interpretation.
’Black bits’
Intraluminal gas
Intraluminal gas can be normal. Extraluminal gas is abnormal. However, intraluminal gas can be abnormal
if it is in the wrong place or if too much is seen.
The maximum normal diameter of the large bowel is 5.5 cm. Small bowel should be no more than 3.5 cm
in diameter. The natural presence of gas within the bowel allows assessment of calibre, although the
amount varies between individuals. The caecum is not considered to be dilated unless wider than 8.0 cm
in diameter.
Large and small bowel may be distinguished by looking at bowel wall markings.
DON’T FORGET
The haustra of the large bowel extend only a third of the way across the diameter
of the large bowel from each side. The valvulae conniventes of the small bowel
traverse the whole diameter.
It is usual to see small volumes of gas throughout the gastrointestinal (GI) tract and the absence in one
region may in itself represent pathology. For example, if gas is seen to the level of the splenic flexure and
nothing is apparent distal to this, a site of the obstruction at this site – a ‘cut-off’ point – is assumed.
Extraluminal gas
When a bowel or any other gas-containing structure perforates, its contained gas becomes extraluminal.
Extraluminal gas is never normal, but it may be seen following intra-abdominal surgery or laparoscopy.
CAUSES OF EXTRALUMINAL GAS

Post-abdominal surgery/laparoscopy
Perforation of viscus (eg bowel, stomach)
Abscess/Collection
DON’T FORGET
An erect CXR (not AXR) is the best projection to diagnose a
pneumoperitoneum (gas in the peritoneal cavity).
’White bits’
Calcification
Calcified structures are often seen on an AXR. The main question is: ’Does their presence have any
important implications?’ Calcification can be broadly divided into three types:
Calcification that is an abnormal structure, eg gallstones, renal calculi, calcified splenic
1.
artery aneurysm.
Calcification that is within a normal structure, but represents pathology, eg pancreatic ductal
2.
calcification.
Calcification that is within a normal structure, but is not clinically significant, eg lymph node
3.
calcification or a calcified pelvic phlebolith.
Bones are normal ‘white’ structures. On the AXR they comprise mainly those of the thoracolumbar spine
and pelvis. Findings are often incidental.
’Grey bits’
Soft tissues
Soft tissues represent most of the contents of the abdomen and feature prominently in the AXR. However,
these tissues are poorly visualised and delineated when compared with other imaging techniques such as
ultrasonography, CT or MRI.
The outlines of the kidneys, spleen, liver and bladder (if filled) can be seen in addition to psoas muscle
shadows. An abdominal X-ray, however, should not be requested to specifically look at these structures.
’Bright white bits’

Foreign bodies
Foreign bodies represent an interesting final observation. These may have been purposely placed in or on
the body, for example, an aortic stent, an inferior vena cava filter or abdominal drains. Sterilisation clips
and an intrauterine device are common findings in women. Other objects that may be seen include
ingested and rectal foreign bodies, as well as items in the path of the X-ray beam, such as belt buckles,
dress buttons and umbilical jewellery.
Other imaging modalities

There is a range of other imaging modalities in regular use – the majority of which do not feature
significantly in undergraduate exams. Knowledge of their importance in diagnosis should be sufficient, in
particular which investigation should be requested for different common clinical scenarios.
IONISING RADIATION TECHNIQUES

Contrast/fluoroscopic studies (mostly barium) Positron emission tomography (PET)
Computed tomography (CT) Nuclear (radionuclide) imaging
NON-IONISING RADIATION TECHNIQUES

Ultrasonography
Magnetic resonance imaging (MRI)
Computed tomography (CT) and MRI play a diverse and pivotal role in contemporary clinical care.
These cross-sectional imaging modalities have a hugely influential position in the diagnostic process.
Fig 9.6: CT Pulmonary angiography: saddle pulmonary embolus.
Fig 9.7: MRCP: CBD stones

CT of the head
In the last decade the use of computed tomography (CT) has exploded, with clinicians increasingly
becoming familiar with its value and undertaking self-review of images within their specialty areas. This
is particularly true for CT of the head. With this there is a growing expectation of familiarity and
knowledge of key pathologies.
The most commonly requested CT scan, all hours of the day and night, is a head CT. Quick and
inexpensive to acquire, and fast to report, an ever-growing number of clinicians view CT of the head
independently. For this reason an introduction to CT of the head is included and key pathologies are
featured in the clinical cases.
Specific NICE (National Institute for Health and Clinical Excellence) guidelines have been written with
respect to the indications for head CT after trauma. These include:
• Glasgow Coma Scale (GCS) <13 when first assessed or GCS <15 2 hours after injury
• Suspected open or depressed skull fracture
• Signs of base of skull fracture
• Post-traumatic seizure
• Focal neurological deficit
More than one episode of vomiting (SIGN [Scottish Intercollegiate Guidelines Network]
•
guidance suggests two distinct episodes of vomiting)
• Coagulopathy + any amnesia or loss of consciousness since injury
• More than 30 minutes of amnesia of events before impact.
DON’T FORGET
If there is concern over intracranial haemorrhage, the scan must be performed
unenhanced. Acute blood and contrast look the same!
Approach to assessment of a head CT

A brief outline of how to approach reviewing a head CT study is outlined below, starting with an
understanding of the major anatomical structures.
The normal appearances of key structures in the supra- and infratentorial brain are shown in Figs
9.8–9.12.
Fig 9.8
Fig 9.9
Fig 9.10
Fig 9.11
Fig 9.12
Head CT: key basic facts

CT demonstrates a wide-ranging grey scale, referred to as attenuation. In the brain this is often stated to
be hypo-, iso- or hyperdense in relation to the brain normal parenchyma:
• CSF in the brain will appear black
• The bone of the skull will appear white
Grey and white matter within the brain have different attenuations; the densely packed nerve
• cell bodies of the grey matter have a higher attenuation than the nerve axons of the white
matter, meaning that surprisingly white matter is darker than grey matter on CT
Blood contains protein, making it dense, and areas of acute haemorrhage appear high
•
attenuation (white) on a CT scan
Areas of dead or damaged brain tissue (encephalomalacia or ischaemic brain) will become
•
less dense, meaning that they will appear darker than the surrounding brain (low attenuation)
Intravenous contrast on CT highlights blood vessels or vascular areas of the brain. It is also
• useful for identifying areas of high cell turnover, such as tumours and infection. Aneurysms,
tumours and abscesses all become brighter after contrast administration.
Assessment of the CT head

• Is the ventricular system the appropriate size?
Is there any acute blood present? If so, is it intraparenchymal, subarachnoid or an extra-axial
•
collection?
• Is there any evidence of ischaemia? If so is it focal or territorial in nature?
• Is there normal differentiation between the grey and white matter of the brain?
• Is there space around the cord at the level of the foramen magnum?
• Are the sulci effaced or the ventricles displaced suggesting mass effect?
Check the bony skull (on bone window settings) to look for a fracture or other bony
•
abnormality.
Check the review areas to finish:
• Anything in the ventricular system, eg blood in the occipital horns?
• Are the visualised orbits normal?
Is there any abnormality in the mastoid air cells or paranasal
•
sinuses?
Scenarios presenting with shortness of breath
Case 9.1
This 23-year-old university student presents to A&E acutely short of breath.
1. Describe your findings on the chest X-ray.

List five conditions that predispose to this
2.
condition.
Answer 9.1
The left hemithorax is translucent with absent pulmonary markings. The collapsed left lung is
1.
apparent centrally. No evidence of mediastinal shift.
The appearances are consistent with a large left-sided pneumothorax.
Numerous chronic pulmonary diseases predispose to pneumothoraces. These include: chronic
obstructive pulmonary disease (COPD), asthma, pulmonary fibrosis and cystic fibrosis. Other
2.
important causes of pneumothorax include: trauma, congenital pulmonary blebs and iatrogenic
reasons (eg central venous line insertion, mechanical ventilation).
Case 9.2
This 46-year-old retired hairdresser has become increasingly short of breath over the past 6 months. She
complains of a dry cough. Pulmonary function tests and CXR were requested.
1. How would you describe the lungs on this CXR?

2. What are the possible causes for these findings?
What are her pulmonary function tests likely to
3.
demonstrate?
Answer 9.2
Diffuse reticulonodular (‘lines and dots’) shadowing is evident in both lungs. This has lower
1.
zone predominance.
The appearances of this CXR are of pulmonary (interstitial) fibrosis.
The causes may be divided according to whether the fibrosis predominantly affects the upper
2.
or lower zones.
MEMORY AID
Upper lobe fibrosis
(mnemonic = BREAST)
Berylliosis (uncommon)
Radiation fibrosis
Extrinsic allergic alveolitis
Ankylosing spondylitis
Sarcoidosis
Tuberculosis
Lower lobe fibrosis
Cryptogenic fibrosing alveolitis
Drug induced (eg amiodarone, methotrexate)
Asbestosis
Connective tissue diseases
(eg rheumatoid diseases)
Spirometry would demonstrate a restrictive pattern (see page 429 for further
3.
details).
Case 9.3
This 55-year-old man attended his local hospital feeling increasingly short of breath over the past week.
He has lost 1 stone in weight recently. He is a smoker of 60 pack-years. His CXR is shown.
1. Describe the appearances on the CXR.

List the causes of this finding, and state the most likely cause in this
2.
patient.
3. What other simple test may assist in forming a diagnosis?
Answer 9.3
There is an area of increased radio-opacity in the lower left hemithorax. The edge can be seen to
1. taper at the lateral aspect of the chest, forming a meniscus. There is no shift of mediastinal structures.
This is a moderately sized left-sided pleural effusion.
2. For unilateral pleural effusions, the causes are mostly exudates. These include:
• malignant tumours (both primary and metastatic disease)
• parapneumonic
• pulmonary embolus or infarction
• rheumatoid disease.
A malignant effusion would be most likely in this patient because of his weight loss and smoking

history.
A diagnostic pleural aspiration could be performed. This will help distinguish whether the effusion is
3.
an exudate or transudate based on the protein content (see page 191 for details).
In this case, malignant cells may be identified when the pleural fluid is examined cytologically.
Case 9.4
This 45-year-old smoker of 30 pack-years attends his GP with increasing shortness of breath over the past
2 weeks.
1. Describe the abnormality on this chest X-ray.

What is your concern regarding these appearances and what would you
2.
recommend?
Answer 9.4
A triangular density is present in the left retrocardiac position, which is separate from the left heart
1. border. The medial aspect is difficult to delineate, but the abnormality has a ‘sail-like’ appearance.
The left hilum is inferiorly displaced and there is volume loss within the left hemithorax.
The appearances are consistent with a ‘tight’ left lower lobe collapse.
The nature of further investigation depends on the clinical scenario. The three most common causes of
2.
a left lower lobe collapse are:
(a) a central hilar or endobronchial mass
(b) an endobronchial foreign body
(c) an endobronchial mucus plug.
In children a foreign body is most likely and, in a postoperative or ITU patient, a mucus plug; both
can be dealt with by bronchoscopy. In adults, especially smokers, left lower lobe collapse must

always be viewed with suspicion for an underlying tumour. Bronchoscopy and CT of the chest are
indicated, after clinical assessment by a respiratory team.
Case 9.5
This 21-year-old patient, well known to the local hospital, attends A&E with acute-on-chronic shortness
of breath.
1. Describe the appearances on this chest X-ray.

Give a short summary of the underlying
2.
condition.
Answer 9.5
Throughout both lungs there are increased interstitial markings, most pronounced in the upper lobes,
1. consistent with fibrosis. At the right lung apex, the lung edge is apparent with no lung markings
peripheral to this, consistent with a small apical pneumothorax.
Given the patient’s young age this would be compatible with a pneumothorax on a background of

cystic fibrosis.
Cystic fibrosis is the most common lethal inherited disease in white individuals. It is an autosomal
recessive disorder, for which most carriers of the gene are asymptomatic. It is caused by defects in
the CFTR gene, which encodes for a protein that functions as a chloride channel, and also regulates
2. the flow of other ions across the apical surface of epithelial cells. It is a disease of exocrine gland
function that involves multiple organ systems, albeit most commonly associated with pulmonary
manifestations. Pancreatic insufficiency is also a common element of the disease. The median
survival is now 36 years of age.
Scenarios presenting with chest pain
Case 9.6
This 62-year-old patient presented to A&E with chest pain and shortness of breath.
1. Describe the appearance on this chest X-ray.

What conditions may cause these appearances with a normal-sized
2.
heart?
Answer 9.6
This AP erect film demonstrates evidence of bilateral perihilar consolidation (‘bat’s wings’). The
1. remainders of both lungs are plethoric. The AP projection indicates an ill patient; however, it does
limit the assessment of cardiac size.
The appearances are in keeping with acute pulmonary oedema.
The most common cause of pulmonary oedema is cardiac failure, which is typically associated with
2. cardiomegaly. However, pulmonary oedema can occur in a number of situations where the heart is
normal in size. These include:
(a) in acute renal failure – so-called ‘flash’ pulmonary oedema
(b) non-cardiogenic pulmonary oedema in adult respiratory distress syndrome (ARDS)
(c) after aggressive fluid resuscitation
(d) with a massive acute myocardial infarction/valve rupture
(e) in association with a subarachnoid haemorrhage.
Case 9.7
This 34-year-old woman attends A&E with chest pain. She is known to the departmental staff from
previous admissions.
1. Describe the appearances on this chest X-ray, especially the cardiac outline.
What else might you consider doing to establish the exact cause of these
2.
appearances?
Answer 9.7
The heart is severely enlarged with a globular configuration, suggesting a diffuse cardiac abnormality
1.
rather than individual chamber enlargement. There is no evidence of cardiac failure.
The differential diagnosis for these appearances includes congenital cardiac disease, cardiomyopathy

and a pericardial effusion.
2. Important aspects that may help establish the exact cause include:
(a) a full clinical history, including childhood illness and a family history of cardiac disease
a review of previous radiological investigations, eg old films may indicate that the cardiomegaly
(b)
is longstanding and therefore unlikely to be due to a pericardial effusion
(c) an echocardiogram.
Case 9.8
This 80-year-old woman is brought to A&E by her daughter due to a short history of chest pain.
1. Outline the features on the chest X-ray that suggest mitral valve disease.
If this patient presented with cardiac failure due to her underlying condition, what signs
2.
might be present on a chest X-ray?
Answer 9.8
The heart is moderately enlarged, with prominence of the left atrial appendage. A double right heart
1. border is evident, indicating enlargement of the left atrium. The subcarinal angle is normal; however,
the other features all point towards a diagnosis of left atrial enlargement (a ‘mitral heart’).
2. The following are all features of cardiac failure on chest X-ray:
(a) cardiomegaly
(b) pleural effusions
(c) perihilar consolidation (‘bat’s wings’)
(d) upper lobe venous distension
(e) interlobular septal lines (‘Kerley B lines’).
Scenarios presenting with weight loss
Case 9.9
This 67-year-old lady was admitted with shortness of breath and weight loss. A large lung mass was seen
on her CXR. Other investigations confirmed that the lesion was a bronchial carcinoma at the left lung
apex. 1. What other findings might be seen on CXR in a patient with bronchial carcinoma?
What other findings might be seen on CXR in a patient with bronchial

1.
carcinoma?
2. What else could cause the appearance of a mass like this on a CXR?
3. What other imaging investigation would be helpful?
Answer 9.9
A lung mass on a CXR in a smoker over 50 years of age should be regarded as a bronchial carcinoma
1.
until proven otherwise. Other features that may be seen on CXR with bronchial carcinoma include:
• pleural effusion
• lung collapse (due to endobronchial tumour)
• pulmonary metastases
• bony metastases (and pathological fracture)
• secondary pneumonia
• lymphangitis carcinomatosis
• enlarged lymph nodes (hilar and paratracheal).
2. Causes of a lung mass on CXR include:
• bronchial carcinoma
• pulmonary metastasis
• round pneumonia
• lung hamartoma
• encysted pleural effusion
• rheumatoid nodule
• lung abscess (usually cavitating).
Computed tomography of the chest would image the mass in greater detail. It will also help in the
3.
assessment of lymphadenopathy and provide evidence of local or metastatic spread
Case 9.10
This 52-year-old man attends his GP complaining of non-intentional weight loss of 8 kg.
Describe the appearances on the chest X-

1.
ray.
2. Provide a short differential diagnosis.
Answer 9.10
The inferior aspect of the right hilum is dense and enlarged. The left hilum and paratracheal regions
1.
are normal. The lungs are clear. Further investigation advised.
2. The differential diagnosis for unilateral hilar enlargement includes:
(a) bronchial carcinoma
(b) tuberculosis
(c) lymphoma
(d) metastatic mediastinal lymph node disease
(e) atypical sarcoidosis
(f) vascular anomaly.
Case 9.11
This 34-year-old man is admitted with weight loss, shortness of breath and fever.
1. Describe the findings on this CXR.

What are the potential causes of such an
2.
appearance?
Answer 9.11
There is dense consolidation in the right upper lobe with an area of cavitation within. There is an air–
1.
fluid level within the cavity.
2. The differential diagnosis for a cavitating lung lesion is:
• bronchial carcinoma (especially squamous cell carcinoma)
• pulmonary metastasis
• tuberculosis
• cavitating pneumonia
• lung abscess
• vasculitic disease (eg Wegener’s granulomatosis)
• lung infarction
• rheumatoid nodule.
Case 9.12
This 67-year-old ex-coal miner presents with a history of weight loss over the past month, now
accompanied by shortness of breath.
1. Describe the appearances on the chest X-ray.

What further investigations are required and
2.
why?
Answer 9.12
The left hemithorax is opacified in a ‘veil-like’ manner. There is the impression of a dense and
1.
enlarged left hilum. The right lung is clear.
The appearances are in keeping with a left upper lobe collapse, with a strong suspicion of an

underlying hilar mass.
The chest X-ray appearances are highly suspicious for a central (hilar) bronchial carcinoma, which
has resulted in a left upper lobe collapse due to obstruction of the left upper lobe bronchus. This
merits urgent referral to the lung cancer multidisciplinary team (MDT) meeting for work-up and
2.
discussion. This will entail CT of the chest and upper abdomen and bronchoscopy. With a central
tumour, bronchoscopic biopsy is likely to be performed to confirm the histology and so plan for
treatment.
Scenarios presenting feeling generally unwell
Case 9.13
A 32-year-old man attends A&E complaining of shortness of breath and the development of a rash on his
shins.
A CXR was requested.
1. Outline any abnormal findings seen on this film.

Give a differential diagnosis for this
2.
appearance.
Answer 9.13
The mediastinal contour is abnormal. There is bilateral hilar enlargement. When bilateral
hilar enlargement is observed the three important potential diagnoses are sarcoidosis,
1. lymphoma (enlarged nodes) and pulmonary hypertension (enlarged pulmonary vessels). You
should therefore pay special attention to the lungs to assess for the presence of other signs that
might point to one of these diagnoses.
DISEASE SUPPORTING FEATURES

Sarcoidosis Interstitial fibrotic change
Lymphoma Enlargement of other nodes (para-tracheal)
Peripheral pruning
Pulmonary hypertension
Chronic lung disease (cause of secondary pulmonary hypertension)
2. Causes of bilateral hilar enlargement include:

• sarcoidosis
• lymphoma
• pulmonary hypertension (primary and secondary)
• metastatic nodal disease.
Case 9.14
This 30-year-old man presents with fatigue, for which a chest X-ray is among numerous investigations.
1. Describe the appearances on this chest X-ray.

Give a short differential diagnosis and how you might establish the exact
2.
diagnosis.
Answer 9.14
Large, predominantly right-sided, anterior mediastinal mass. This is causing displacement of

1.
the trachea to the left. The heart and lungs are normal in appearance.
The main differential diagnoses for an anterior mediastinal mass are: thyroid enlargement,
thymoma, teratoma and lymphoma. CT of the chest will assist in identifying the extent of the
2.
mass and may also point towards a diagnosis, such as internal calcification in the case of a
teratoma. Histological confirmation can be ascertained by CT-guided biopsy.
Case 9.15
This 61-year-old woman complains of non-specific symptoms, including malaise and anorexia.
1. Succinctly describe the appearances on this film and the likely diagnosis.
Which primary tumour types are most likely to result in these
2.
appearances?
Answer 9.15
Multiple masses in both lungs of variable size, measuring up to 4 cm, consistent with pulmonary
1. metastases. The appearances are those of ‘cannon-ball’ metastases and identification of the primary
tumour is recommended, with CT of the chest, abdomen and pelvis.
The most likely primary tumour to cause cannon-ball metastases is renal cell carcinoma. Others
2.
include testicular malignancy and choriocarcinoma.
Scenarios presenting with fever
Case 9.16
This 39-year-old woman attends A&E with a high fever, following a recent holiday overseas.

What follow-up imaging is necessary, how long after treatment should this be performed
2.
and why is it performed?
Answer 9.16
Dense consolidation is evident in the right upper and mid-zones, clearly delineated inferiorly by the
horizontal fissure. This, combined with the right heart border remaining distinct, implies that the
1.
consolidation is in the right upper lobe The left hilum cannot be clearly visualised in its entirety.
The right lung is clear.
The appearances are in keeping with right upper lobe pneumonia.
A follow-up chest X-ray is indicated with a dense lobar pneumonia, especially a case like this,
where the hilum cannot be properly assessed. A lobar pneumonia may be the presentation of
something more sinister underlying it, such as a central bronchial carcinoma, which has resulted in
2. a distal ‘obstructive’ pneumonia. A follow-up film should be performed 6 weeks after antibiotic
treatment. For every decade of life after 60 years of age, an additional week should be added.
Radiological resolution may lag behind clinical resolution. The follow-up film enables assessment
for resolution of the pneumonia for any underlying mass.
Scenarios presenting with incidental findings
Case 9.17
This 55-year-old retiree has a chest X-ray as part of a medical insurance assessment.
Report the chest X-ray including what previous surgery has been
1.
performed.
2. List five indications for the surgery performed.
Answer 9.17
Dual lead pacemaker. Median sternotomy, aortic and mitral valve replacements. The heart is mildly
1.
enlarged, but there is no evidence of cardiac failure. The lungs are clear.
Cardiac valve replacement may be with a tissue or metallic valve. Only the latter will be visible on
chest X-ray. Most commonly a single valve is replaced. The most common valve replacements are
2.
those of the ‘left side of the heart’ – the mitral and aortic valves. Indications for valve replacement
include:
(i) endocarditis
(ii) rheumatic heart disease (usually mitral valve)
(iii) congenital valve disease (eg a biscupid aortic valve)
(iv) severe acquired valve incompetence or stenosis
(v) acute valvular rupture.
Case 9.18
This 57-year-old woman is attending a follow-up clinic after previous surgery.

Name the other review areas when examining a chest X-
2.
ray.
Answer 9.18
The right breast shadow is absent in keeping with a mastectomy. No evidence of recurrent disease in
1.
the lungs. Normal bony skeleton.
2. There are five key areas to review on chest X-ray:
(i) costophrenic angles
(ii) apices
(iii) behind the heart
(iv) below the diaphragms
(v) breast shadows (in females)
Scenarios presenting with a distended abdomen
Case 9.19
This 63-year-old man attends A&E complaining of a short history of abdominal distension.
1. Describe the appearance on this abdominal X-ray.

What investigation should be performed next and how will it be
2.
useful?
Answer 9.19
The large bowel is gas filled and dilated up to 6 cm in diameter down to the left side of the pelvis,
1. where there is an abrupt cut-off. The rectum is nondistended and the small bowel collapsed. The
appearances are consistent with a large bowel obstruction at the level of the sigmoid colon.
A CT of the abdomen is indicated to investigate further, before probable surgical intervention. This
2.
will enable the following:
(a) confirmation of the site of obstruction
establishment of the cause of obstruction; a sigmoid tumour is most likely, although other causes
(b)
include a diverticular stricture or hernia
(c) identification of whether a perforation has occurred
in the case of the cause being a tumour, identification of any local, regional or distal metastatic
(d)
disease.
Case 9.20
A 55-year-old man was admitted with acute abdominal pain and a CXR was performed.
1. What abnormality is seen on this film?

2. What projection has been used?
3. List some causes of this finding.
Answer 9.20
1. A radiolucent linear abnormality is noted inferior to the diaphragm bilaterally.

Remember that gas on a plain X-ray is black so this must be gas in the abdomen.
It is outside the bowel lumen – an abnormal finding. This is called a pneumoperitoneum.
This is an ERECT CXR. An erect film is invariably requested to assess for free gas within the
2.
abdomen (pneumoperitoneum).
3. The causes of pneumoperitoneum are listed on page 254 (see table ‘Causes of extraluminal gas’).
Case 9.21
This 69-year-old woman was admitted to the surgical ward with malodorous vomiting and a distended
abdomen.
An AXR was taken while she was in A&E.
1. Describe the findings on the AXR.

What are the causes of this
2.
abnormality?
Answer 9.21
Multiple dilated small bowel loops. The bowel measures 4 cm in diameter and is located in the
1. centre of the film. Multiple loops suggest that the obstruction lies in the distal small bowel. These
findings are in keeping with a diagnosis of small bowel obstruction.
FEATURES OF SMALL BOWEL OBSTRUCTION

Bowel lies in centre of the film
Markings seen across the bowel wall (valvulae conniventes)
Several loops (more loops the lower the obstruction)
2. Causes of small bowel obstruction include (most common first):

• adhesions
• hernia
• extraluminal causes more common than intraluminal (obstructing mass)
• intussuception.
Case 9.22
This 77-year-old nursing home resident is brought to hospital because her carers are concerned about an
enlarged abdomen over the last 24 hours.
1. Describe the appearances on the AXR.

What are the treatment options for this
2.
condition?
Answer 9.22
A large distended featureless loop of bowel arises from the pelvis into the mid/upper abdomen,
1. with a ‘coffee-bean’ configuration. Proximal to this there is distended large bowel consistent with
obstruction. The small bowel is collapsed. Appearances are consistent with a sigmoid volvulus.
The usual treatment for sigmoid volvulus is insertion of a flatus tube. A plain film is usually
sufficient for diagnosis and a management decision. On occasion the volvulus might result in a
2. section of ischaemic bowel requiring surgical resection. Sigmoid volvulus is commonly recurrent,
which in itself may merit surgery. Of the three types of volvulus of the gastrointestinal tract,
sigmoid is the most common followed by caecal and gastric.
Case 9.23
This 38-year-old woman attends A&E with abdominal distension and discomfort lasting the previous 12
hours.
Describe the findings on the AXR and provide a

1.
diagnosis.
2. Which group of patients typically get this condition?
Answer 9.23
A large, distended, gas-filled, featureless viscus is sited in the right upper abdomen, which is
separate from the collapsed stomach. The caecum is not apparent in the right iliac fossa. The small
1.
bowel is dilated. The appearances are consistent with a caecal volvulus with a resultant small
bowel obstruction
Caecal volvulus typically occurs in young/middle-aged women with ‘virgin’ abdomens in
2. comparison to sigmoid volvuli, which tend to cluster in the elderly population. Treatment is with
surgery, requiring a caecopexy.
Scenarios presenting with abdominal pain
Case 9.24
This 35-year-old man is a regular attendee at the hospital with severe upper abdominal pain.
1. Give a brief report of your findings on this AXR.

List the potential complications after acute
2.
pancreatitis.
Answer 9.24
Extensive punctate calcification is evident in the upper abdomen, extending across the midline,
1.
conforming to the shape of the pancreas, in keeping with chronic pancreatitis.
Numerous complications may follow acute pancreatitis, which can be identified on imaging, in
2.
particular CT. Complications may be acute, subacute or chronic in nature, including the following:
(a) pancreatic necrosis
(b) pancreatic haemorrhage
(c) pancreatic or peripancreatic abscess
(d) pancreatic pseudocyst
(e) pseudoaneurysm formation
(f) thrombosis of adjacent vessels, eg the superior mesenteric vein
pancreatic calcification, which occurs in the chronic phase of pancreatitis and may involve the
(g)
parenchyma or ductal components of the pancreas.
Case 9.25
This 43-year-old man complains of left-sided flank pain.
1. Describe any abnormalities present on this AXR.

Which other imaging modality is best for imaging renal stone
2.
disease?
Answer 9.25
Multiple calcific densities project over the lower pole of the left kidney in keeping with renal
1. calculi. An additional similar density projects between the left L3 and L4 transverse process, in
keeping with a calculus within the left mid-ureter.
CT KUB (kidneys, ureters and bladder) is the gold standard imaging investigation for the
assessment of renal calculi, with over 99% sensitivity for calculi as small as 1 mm. This is
performed without contrast with 1-mm (thin) slice acquisition. Renal calculi and the level of
2. obstruction are identified. In addition perinephric/periureteric inflammatory change and fluid are
visualised. Complications, such as hydronephrosis or pyonephrosis, can be seen. Pyonephrosis due
to renal stone disease is a urological emergency and is an indication for percutaneous nephrostomy
insertion.
Scenarios presenting with an abdominal mass
Case 9.26
This 25-year-old man presented with upper abdominal discomfort. An AXR was performed because the
admitting doctor was concerned about bowel obstruction.
Describe the appearances on the abdominal

1.
radiograph.
2. List some potential causes.
Answer 9.26
A large soft-tissue mass is present in the left upper quadrant extending inferomedially into the
1. lower abdomen and upper pelvis. This is displacing both large and small bowel, consistent with
being located within the peritoneal cavity. The findings are consistent with splenomegaly.
2. Potential causes of splenomegaly include: sickle cell disease, myelofibrosis and lymphoma.
Note the bilateral hip abnormalities (much more pronounced on the right) of sclerosis and collapse
consistent with avascular necrosis. The unifying diagnosis is sickle cell disease. Later in the
disease process the spleen may become small due to infarction.
Case 9.27
This 75-year-old man complains of an ongoing aching pain in the centre abdomen.
1. Describe your findings on this AXR

What additional imaging investigation is
2.
recommended?
Answer 9.27
A large, left, paraspinal, soft tissue abnormality is present in the mid-abdomen with a curvilinear
1. lateral aspect, which contains a rim of calcification. The psoas shadow is separate from this.
Appearances are consistent with a large abdominal aortic aneurysm.
Although both ultrasonography and CT can be used to assess the aorta, in this instance CT is the
best choice. Ultrasonography is used for surveillance of aneurysm size. This aneurysm is large
2.
enough to warrant elective surgery and therefore full assessment with CT is merited. CT is the
investigation of choice in the acute setting to assess for rupture.
Case 9.28
This 37-year-old woman complains of lower abdominal pain and early bladder fullness.
1. Describe the abnormality present on the AXR.

Give a differential diagnosis and suggest an additional imaging technique to assess
2.
further.
Answer 9.28
A large soft-tissue mass arises from the pelvis extending to the level of the umbilicus. This is well
1. defined superiorly and is displacing the bowel into the upper abdomen. Appearances are in keeping
with a pelvic mass, most likely gynaecological in origin.
The differential diagnosis for these appearances includes: ovarian cyst, dermoid cyst, pelvic
abscess/collection and an enlarged fibroid uterus. In the first instance assessment with
2.
ultrasonography is recommended. Depending on this further cross-sectional imaging may also be
required.
Scenarios presenting with headache
Case 9.29
This 37-year-old woman attended A&E complaining of a severe sudden headache.
1. Describe the appearances on the head CT.

What other imaging investigation(s) would be helpful in the patient’s management
2.
plan?
Answer 9.29
Extensive high-attenuation material consistent with acute blood is present within the suprasellar
1. cistern and sulci of the brain in keeping with subarachnoid haemorrhage. The temporal horns of the
lateral ventricles are dilated in keeping with early hydrocephalus.
Spontaneous subarachnoid haemorrhage is commonly associated with an underlying vascular
abnormality, most commonly a cerebral (‘berry’) aneurysm. Imaging is focused on trying to identify
an aneurysm, which will permit definitive treatment, such as a coil embolisation or less commonly
2.
now surgical clipping. This usually involves CT angiography of the circle of Willis, although
catheter angiography may be performed alone or in addition to CT, especially if endoluminal
treatment is to be performed.
Case 9.30
This 39-year-old man was brought to A&E by his wife, because he has developed a progressively
worsening headache over the past 2 weeks, particularly severe first thing in the morning.

2. List potential causes for these appearances.
Answer 9.30
The ventricular system of the brain is dilated, in particular on the single image provided, note that the
lateral ventricles (frontal and temporal horns) are dilated as is the third ventricle, which is also
1. uncharacteristically round. Periventricular low attenuation is evident around the frontal horns, in
keeping with transependymal oedema, which typically occurs in acute hydrocephalus (the CSF leaks
across the ependymal lining of the ventricle due to high pressure within).
Hydrocephalus may be obstructive or non-obstructive. It may involve individual ventricles or the
2.
whole ventricular system. Causes include:
(a) an obstructive malignant mass, such as a tumour; potential tumours include an ependymoma
(b) an obstructive non-malignant mass, such as a third ventricular colloid cyst
(c) obstruction due to intraventricular debris, such as blood post-subarachnoid haemorrhage.
Case 9.31
This 69-year-old man developed a severe headache while attending a local football match.

What is the most likely cause for these
2.
appearances?
Answer 9.31
A moderate-sized, well-defined, high-attenuation focus is present in the right thalamus, in keeping

1. with a thalamic haemorrhage. This is an intraparenchymal haematoma, and there is a little reactive
surrounding oedema.
Thalamic haemorrhage is typically due to hypertension. This would be classed as a haemorrhagic
2. stroke, which accounts for 15% of all strokes, most being due to infarction. Other typical locations
for hypertensive haemorrhage include the basal ganglia and dentate nucleus of the cerebellum.
With large intraparenchymal haemorrhages there may be intraventricular extension. A small

proportion of infarcts may undergo haemorrhagic transformation.
Scenarios presenting with confusion
Case 9.32
This 55-year-old woman was brought to A&E by her relatives who state that she has been confused over
the past 24 hours. She had a mastectomy for breast cancer 2 years ago.
1. Describe the appearances on the CT head.

If this was the patient’s first presentation, what is the potential differential
2.
diagnosis?
Answer 9.32
This CT has been performed following contrast administration. An approximately 3-cm rim-
enhancing mass lies within the right frontoparietal region, with significant surrounding perilesional
1. oedema. This is causing a mass effect, as demonstrated by sulcal effacement and mild displacement of
the body of the right lateral ventricle. In the context of the clinical history a cerebral metastasis is the
most likely diagnosis.
2. The differential diagnosis for a single rim-enhancing intraparenchymal mass includes:
(a) cerebral metastasis
(b) primary brain malignancy
(c) cerebral abscess
(d) tumefactive multiple sclerosis (mass like in appearance).
Case 9.33
This 24-year-old intravenous drug user is accompanied to A&E by his friend who states that he has been
‘really muddled’ over the last 3 days and has a fever.

Name some other complications that commonly occur in those using intravenous
2.
drugs.
Answer 9.33
This scan has been performed following contrast administration. Adjacent to the frontal horn of the
left lateral ventricle is an avidly rim-enhancing lesion, with a low attenuation centre. There is a
1. moderate amount of perilesional oedema. Although there is a wide differential for a rim-enhancing
solitary cerebral lesion (see Case 9.32), correlation with the clinical history makes a cerebral
abscess by far the most likely cause.
Although not necessarily unique to those taking intravenous drugs, there are a number of conditions
2.
that occur much more commonly in this patient subgroup, including:
(a) infective endocarditis
(b) cerebral abscesses
(c) groin pseudoaneurysms, which may also become infected
(d) septic pulmonary emboli.
Scenarios presenting with reduced GCS score
Case 9.34
This 18 year old was involved in a skiing accident 2 hours previously. His GCS on arrival at A&E is
9/15.

What is normally associated with this finding on CT and which vessel is typically
2.
damaged?
Answer 9.34
A high-attenuation, lens-shaped (biconvex), extra-axial abnormality is present in the left parietal

1. region, which is causing a mass effect in the form of sulcal effacement, along with both
compression and displacement of the left lateral ventricle.
The appearances are consistent with an acute extradural haematoma.
Ninety-five per cent of extradural haematomas are associated with a skull fracture. The middle
2. meningeal artery is usually the vessel damaged and is responsible for the haematoma. This differs
from subdural haematomas, which are usually due to tears of the bridging veins.
Case 9.35
This 77-year-old widow is found at home by her neighbour. On arrival at A&E her GCS is 12/15.

There is no history of severe head trauma. How might this haematoma have
2.
arisen?
Answer 9.35
Blood of variable age is present within the left subdural space, in keeping with a moderate-sized
subdural haematoma. Most of the haematoma content is isodense, with the brain parenchyma
1. indicating subacute blood with some high-attenuation material within, consistent with more acute
blood. The haematoma is causing significant mass effect, with displacement of the frontal horn of
the left lateral ventricle and subfalcine herniation.
Subdural haematomas are not uncommonly found after relatively low-impact head trauma. Often, if
questioned directly, patients might recall a slight blow to the head or a fall before presentation –
2.
which is often considered too trivial to be mentioned. This history may not be given, however, due
to the presence of confusion.
Case 9.36
This 35 year old was found on the street late at night. She was intubated at the scene for a GCS of 3/15.

2. What is the likely cause?
Answer 9.36
Throughout the visualised brain (on the single slice provided) there is diffuse loss of grey–white
1. material differentiation of the brain parenchyma. In addition to this the basal cisterns are
completely effaced. The sulci of the brain are also non-apparent.
The appearances of the CT are consistent with cerebral anoxia. When the brain is deprived of
sufficient oxygenation for a prolonged period of time, eg during a cardiac arrest in the community
2.
with a long period of lost cardiac output, anoxia occurs. This results in the loss of grey–white
matter differentiation and cytotoxic oedema.
Scenario presenting with neurological deficit
Case 9.37
This 66-year-old man gives a 3-hour history of right-sided weakness. Examination confirms a right
hemiparesis.

Explain the concept of ‘time is brain’ in the modern management of
2.
stroke.
Answer 9.37
Extensive low attenuation is present throughout the left temporoparietal region with sparing of the
head of caudate and lentiform nucleus (basal ganglia). These appearances are consistent with a left
1.
middle cerebral artery (MCA) territory infarction. No evidence of haemorrhagic transformation.
No visible intra-arterial thrombus.
‘Time is brain’ refers to the urgency with which acute stroke should be treated, where appropriate,
with intravenous thrombolysis. Those patients who present to hospital within a specified time
window with the clinical diagnosis of stroke, and who fill a number of pre-agreed criteria, should
2. receive intravenous thrombolysis. The concept is that ischaemic, but not yet dead, brain (ischaemic
penumbra) is reperfused and saved, resulting in a reduction in neurological deficit. At present the
time window that is adopted in many centres is 4.5 hours from the onset of symptoms. The patient
must receive a CT of the head before treatment to exclude intracranial haemorrhage.
Case 9.38
This 78-year-old woman has developed progressive right-sided weakness in recent days.

Name three primary brain tumours that occur in the supra- and infratentorial
2.
brain.
Answer 9.38
This post-contrast scan outlines a large heterogeneous enhancing mass in the right cerebral
1. hemisphere bulging into and compressing the right lateral ventricle. The most likely cause for these
appearances is a glioma. At present there is no evidence of hydrocephalus.
In adults, primary brain tumours are more common in the supratentorial than the infratentorial brain.
The reverse is true in children. Potential supratentorial tumours include: glioblastoma multiforme,
astrocytoma, meningioma, oligodendroglioma, neurofibroma and craniopharyngioma. Infratentorial
2.
(or posterior fossa) tumours include: ependymoma, pilocytic astrocytoma, brain-stem glioma,
cerebellar haemangioblastoma and medulloblastoma, some of which are essentially unique to
children.
Case 9.39
This 62-year-old man developed a left-sided visual deficit 3 months previously. On this occasion CT was
performed after head trauma.
1. Describe the appearances on this CT of the brain.

2. List a few factors that predispose to stroke.
Case 9.39
There is a focal area of low attenuation in the left occipital lobe. The appearances are consistent with
1. an established posterior cerebral artery stroke involving the left occipital lobe. No acute findings to
suggest an injury following trauma.
2. There are a number of factors that predispose to stroke. These include:
• hypertension
• atrial fibrillation
• cardiovascular disease elsewhere (‘arteriopath’ status)
• diabetes mellitus
• smoking
• hyperlipidaemia
• family history of cardiovascular disease
• atheromatous plaques in the carotid or vertebrobasilar arteries
• infective endocarditis – resulting in septic emboli
• vasculitis
• dissection of the carotid or vertebrobasilar arteries (especially in stroke of young people)
• procoagulant states, such as polycythaemia.
CARDIOLOGY
Electrocardiography
The electrocardiogram (ECG) is one of the most important commonly requested tests in medical practice.
DON’T FORGET
If possible, always compare ECGs with previous tracings.
Components of an ECG tracing

A standard ECG comprises 12 individual tracings (called leads). An ECG machine produces these
tracings by comparing electrical signals from 10 sensors. Six are placed on the chest and one on each of
the four limbs. By convention, the tracings are given standard names, with each representing an electrical
signal from a particular part of the heart. V1, V2, V3, V4, V5 and V6 ‘look at’ the heart in a horizontal
plane. Each of these tracings represents the electrical signal detected at one of the chest sensors; aVL,
aVF, aVR, I, II and III look at the heart in a vertical plane.
LEAD LOOKS AT
V1, V2, V3 and V4 Anterior surface (right ventricle and septum)
V5, V6, aVL and I Lateral surface (left ventricle)
II, III and aVF Inferior surface
aVR Right atrium
In a patient having an acute myocardial infarction, it is therefore possible to determine which part of the
heart is affected by assessing which leads show changes.
If any individual lead is examined in detail, various peaks and troughs will be noted. These represent
electrical activity at various times in the cardiac cycle. It is sometimes difficult to see every detail on
each tracing. Names are attached to particular parts of the tracing as follows.
Fig 10.1: The P wave.
The first bump in a tracing is called a ‘P wave’. This represents the electrical activity associated with
depolarisation of the atria. There is a further electrical signal associated with atrial repolarisation, but
this cannot usually be seen on an ECG, since the small electrical signal is overshadowed by the much
more powerful ventricular activity.
Fig 10.2: The Q wave.
Following along from the P wave, a downward dip in the tracing is known as a Q wave. This may or may
not be present.
Fig 10.3: The R wave.
The first upward peak after the P wave is known as an R wave.
Fig 10.4: The S wave.
Any dip below the baseline following an R wave is called an S wave.

The Q, R and S waves are known collectively as the QRS complex. This represents ventricular
depolarisation.
Fig 10.5: The T wave.
Following the QRS complex, an upward deflection in the tracing is known as a T wave. This represents
ventricular repolarisation. T waves are followed by P waves, and the cycle is complete.
Interpreting an ECG
The following aspects should be addressed when interpreting an ECG:
Heart rate QRS complexes

Heart rhythm ST segment
Cardiac axis Q–T interval
P waves T waves
Heart rate
ECGs are printed on squared paper. This paper usually runs through the ECG machine at a standard rate
(25 mm/s). If, for some reason, the machine is set to run at a different speed, interpretation is more
difficult.
DON’T FORGET
Always check that the paper speed is at 25 mm per second.
At this speed, on a horizontal axis, each small square represents 0.04 second, and each large square
(which is five small squares wide) represents 0.2 second.
Fig 10.6: Standard squared paper used when recording ECGs.
The ventricular rate is calculated by looking at the distance between consecutive QRS complexes.
Usually the distance between R waves is analysed.
When there are a number of large squares between each R wave, the ventricular rate is most easily
calculated by counting the number of large squares between each R wave and dividing this number into
300.
Fig 10.7: Measuring the R–R interval.
In the ECG shown, there are approximately five large squares between each R wave. The ventricular rate
is therefore 300 ÷ 5 = 60 beats/min.
When the ventricular rhythm is more rapid, counting large squares can prove difficult. In such instances,
the number of small squares between consecutive R waves is counted, and this number divided into 1500.
Fig 10.8: Measuring the R–R interval with a faster heart rate.
In the example, there are 12 small squares between each R wave. The ventricular rate is therefore 1500 ÷
12 = 125 beats/min.
Ventricular rate (beats per minute) = 300 ÷ number of large squares between R waves
OR
Ventricular rate (beats per minute) = 1500 ÷ number of small squares between
R waves
Both approaches give the same answer, but the second approach tends to be easier if the heart rate is rapid.
A heart rate of less than 60 beats/min is termed bradycardia. A rate of greater than 100 beats/min is
tachycardia.
If the heart rhythm is irregular, calculate the rate using the number of squares between several R waves.
Divide the answer to obtain an average R–R interval.
For example, if there are 40 large squares between the first and the eleventh R wave, the average R–R
interval is 4 large squares and the heart rate is approximately 300 ÷ 4 = 75 beats/min.
Heart rhythm
There are several heart rhythms that you will be expected to recognise. To assess rhythm, look for P
waves and their relationship to QRS complexes. Remember that normally one P wave should be followed
by one QRS complex. Good leads for assessing P waves are leads II, V1 and V2.
Sinus rhythm
Sinus rhythm describes a normal heart rhythm in which electrical signals begin in the sinus node. A P
wave should precede each QRS complex, and be at a normal, fixed interval from it. The P–R interval is
used to measure the interval between P waves and QRS complexes. It is measured by counting the number
of squares between the start of the P wave and the start of the QRS complex. This distance should be
between three and five small squares.
Fig 10.9: Normal sinus rhythm illustrating the P–R interval.
• Sinus tachycardia describes sinus rhythm at a rate of over 100 beats/min.

• Sinus bradycardia describes sinus rhythm at less than 60 beats/min.
Sinus arrhythmia is the term used to describe the normal variation in heart rate with respiration.
•
Normally, the heart rate increases on inspiration.
In sinus arrhythmia, the heart rate INcreases on INspiration.
SINUS RHYTHM CHECKS

To diagnose sinus rhythm, all of the following criteria should be met:
1. P wave preceding every QRS complex
2. P–R interval is normal
3. P–R interval is constant
Atrial fibrillation
This is the term used to describe erratic electrical activity in the atria. In this condition, no P waves are
seen, and the ECG baseline commonly shows irregularity. QRS complexes occur irregularly.
Fig 10.10: Atrial fibrillation.
This tracing fails sinus rhythm check 1, as no P waves are visible.
Atrial flutter
This condition is similar to atrial fibrillation in many ways. However, the ECG shows the presence of F
waves (flutter waves). The baseline of the ECG therefore adopts a ‘saw-toothed’ appearance. Atrial
flutter may occur with a fixed degree of atrioventricular block, eg three-to-one block. This means that, for
every three flutter waves, there would be one QRS complex. Alternatively, the rhythm may have variable
block, where the number of flutter waves preceding each QRS complex varies from beat to beat.
Fig 10.11: Atrial flutter.
This tracing fails sinus rhythm check 1, as no P waves are visible. You should be able to instantly
recognise atrial flutter on account of its distinctive appearance.
Heart block
Heart block describes a problem with conduction between the atria and ventricles. There are various
types.
First-degree heart block

In first-degree heart block, a P wave precedes each QRS complex, but the P–R interval is prolonged
(more than five small squares). The P–R interval remains constant from beat to beat.
In simple terms, imagine first-degree heart block as a condition in which the wiring of the heart is still
intact, but is a little slow. It therefore takes longer than normal for electrical signals to travel from the
atria to the ventricles.
Fig 10.12: First-degree heart block.
You will appreciate that this example is not sinus rhythm because, although there is a P wave before every
QRS complex (check 1), the P–R interval is prolonged (six small squares).
Second-degree heart block

Second-degree heart block Second-degree heart block describes the spectrum of conduction problems that
are more severe than first-degree, but less severe than third-degree, heart block.
There are three main types:
Mobitz type I (Wenckebach phenomenon)
This rhythm runs in cycles, and will be identified if the tests for sinus rhythm are checked. The first
P–R interval in a cycle is often normal. With each successive heart beat, the P–R interval lengthens.
Eventually, there will be a P wave with no following QRS complex. The cycle then begins again.
1.
Fig 10.13: Mobitz type I heart block.
Mobitz type II
Again, you will diagnose this rhythm if you check the requirements for sinus rhythm. In this rhythm,
the P–R interval is constant. Its duration may be normal or prolonged. However, periodically there
will be no conduction between the atria and ventricles, and there will be a P wave with no associated
QRS complex.
2.
Fig 10.14: Mobitz type II heart block.
Fixed degrees of atrioventricular block

These rhythms are described as two-to-one, three-to-one, four-to-one block, etc. In two-to-one block,
for example, two P waves are found for every QRS complex.
3.
Fig 10.15: Two-to-one atrioventricular block.
Third-degree heart block

In this condition, there is no functioning electrical connection between the atria and ventricles. You may
like to think of this as a state in which the ‘wires’ between atria and ventricles have been ‘cut’. P waves
and QRS complexes will be seen, but these will have no constant relationship to each other. If you suspect
this rhythm, take a sheet of paper and lay it alongside the ECG in question. Mark on the paper the position
of the P waves. Next, move your paper so that the first mark you have made lines up with the first QRS
complex. You will see that the P waves and QRS complexes are completely dissociated. The QRS
complex arises because of intrinsic pacemaker activity below the atrioventricular node.
Note that QRS complexes can be normal in width or wide (see below).
Fig 10.16: Third-degree heart block.
Cardiac axis
The cardiac axis is an arbitrary concept used to describe the average direction of electrical activity in the
heart. Normally, the average flow of electrical energy is from the upper right heart border towards the
apex. In various disease states, the cardiac axis can shift.
There are several methods for assessing axis, but students often find this a difficult exercise. One method
relies on looking at leads I, II and III, and determining whether the QRS complexes are predominantly
upgoing or downgoing. QRS complexes in a particular lead are upgoing if average electrical flow (axis)
is towards that lead, and downgoing if it is away from the lead (see Fig 10.17).
A good rule of thumb is to assess the QRS complexes in leads I and II and, if both are predominantly
upgoing, the axis is normal as shown in Fig 10.19. In right axis deviation, the axis shifts clockwise and, as
a result lead I becomes downgoing because average electrical flow is away from it. In left axis deviation,
the axis shifts anti-clockwise, and as a result, leads II and III become downgoing. Figure 10.18 illustrates
the standard convention for quantifying the cardiac axis. Figure 10.19 illustrates all three scenarios.
Fig 10.17: Upgoing and downgoing QRS complexes.
Fig 10.18
AXIS LEAD I LEAD II LEAD III

Normal Upgoing Upgoing Upgoing (or downgoing)
Right axis deviation Downgoing Upgoing Upgoing
Left axis deviation Upgoing Downgoing Downgoing

Fig 10.19: Leads I, II and III showing a normal axis, right axis deviation and left axis deviation.
P waves
Look at leads II, V1 and V2 for the best views of P waves. Assess their size and shape. P waves should
not exceed the maximum dimensions shown in Fig 10.20. Always make sure that an ECG has been
correctly calibrated before commenting on the heights of peaks. The standard calibration is 10 mm = 1
mV.
DON’T FORGET
Always check that an ECG is calibrated to 10 mm = 1 mV.
Fig 10.20: Normal P-wave dimensions.
P pulmonale describes tall, peaked P waves. These occur in conditions when the right atrium
•
becomes enlarged.
P mitrale describes wide P waves that are often bifid. This may be seen in patients with mitral
•
stenosis.
Fig 10.21: P pulmonale and P mitrale.
MEMORY AID
In P Pulmonale, the P waves are Peaked.
In P Mitrale, the P waves are bifid and look like the letter M.
QRS complexes
Q waves
Look at the location and size of Q waves. The maximum dimensions of Q waves should not exceed those
shown in Fig 10.22.
Fig 10.22: Q-wave maximum dimensions.
Because of the direction taken by electrical signals in the heart, small Q waves may normally be seen in
leads looking at the lateral aspect of the heart (V5, V6, aVL and I). Large Q waves or Q waves in other
locations are abnormal, and indicate the presence of scar tissue in the heart (eg after a myocardial
infarction).
Height of R and S waves

Much information can be gleaned by looking at the height of R and S waves. The most common
abnormality detected is left ventricular hypertrophy. There are many ECG criteria for predicting whether
hypertrophy is present. One method involves finding the sum of the height of the S wave in V1 (in mm)
and the height of the R wave in V6 (in mm). If greater than 35 mm, it is probable that left ventricular
hypertrophy is present. An echocardiogram is necessary to confirm hypertrophy.
There are several causes of very small complexes, the most common being pericardial effusions,
pericarditis and emphysematous lungs.
QRS duration
A normal QRS complex should be less than three small squares wide.
Fig 10.23: Normal maximum QRS complex duration.
Wide complexes indicate abnormal conduction through the ventricles. Normally, electrical signals are
carried through the ventricular muscle in specialised conducting tissue – the bundle of His and its left and
right branches. Problems in this conducting tissue result in electrical impulses being carried more slowly
through non-specialised cardiac tissue. This results in widening of the QRS complex. You should be able
to recognise the typical ECG features of both problems in both the left and right bundle branches (named
left and right bundle-branch block). Problems with QRS duration and other ECG abnormalities can be
seen in tricyclic antidepressant toxicity – see page 173 for details.
In right bundle-branch block (RBBB), two upward deflections (ie two R waves) are seen in the QRS
complex in V1. This is known as an RSR pattern. A deep S wave is normally seen in V6.
Fig 10.24: Right bundle-branch block.
In left bundle-branch block (LBBB), the ECG is typically highly bizarre in appearance. An RSR pattern
may be seen in V6. Conduction is so disordered in LBBB that many of the normal morphological features
of an ECG are not distinguishable. After establishing heart rate, rhythm, axis and that LBBB is present,
analysis of the ECG should stop. Confusion often arises in practice when students attempt to comment on
what appear to be highly abnormal ST segments and T waves. It is important to be able to identify LBBB,
because, if it develops in a patient, it can be a sign of myocardial infarction.
Do not attempt to comment on the ST segment when LBBB is present.
Fig 10.25: Left bundle-branch block.

ST segment
The ST segment is that part of a tracing that lies between the QRS complex and the T wave.
Fig 10.26: The ST segment.
Normally, the ST segment should be horizontal and isoelectric (ie lying on the baseline of the tracing).
Abnormalities include elevation and depression.
The ST segment may be elevated. The most common causes for this are myocardial infarction (where ST
elevation occurs in the heart leads ‘looking at’ damaged parts of the heart) and pericarditis (where ST
elevation occurs in most or all ECG leads). The ST elevation associated with myocardial infarction is
typically convex upwards, whereas it is concave (saddle-shaped) in pericarditis.
Fig 10.27: Convex and concave ST elevation (exaggerated for clarity).
ACUTE MYOCARDIAL INFARCTION REQUIRING URGENT REPERFUSION

1. ST segment elevation (convex upwards) in keeping with acute myocardial infarction, or
2. New LBBB: in a patient with typical chest pain
ST elevation that persists over weeks and months after a myocardial infarction commonly signifies the
presence of a ventricular aneurysm.
Horizontal ST depression can represent cardiac ischaemia, and may be seen during episodes of angina
pectoris. ST depression may also indicate a non-ST elevation myocardial infarction (NSTEMI), which
can be distinguished from ischaemia only by measuring biochemical markers of cardiomyocyte damage
(see page 366 for details).
Fig 10.28: Horizontal ST depression.
When ST depression in lateral chest leads is seen alongside features in keeping with left ventricular
hypertrophy, this is called a strain pattern, and is a feature of marked left ventricular hypertrophy. It can
be difficult to differentiate from changes associated with ischaemia.
Down-sloping ST depression (often called ‘reverse tick’ ST depression) is seen in patients on digoxin.
Fig 10.29: Down-sloping ST depression.
Q–T interval
The Q–T interval is the distance from the start of the QRS complex to the end of the T wave. Long Q–T
intervals predispose to cardiac dysrhythmias. The Q–T interval varies with heart rate, but should in
general not be more than two large squares in duration.
Fig 10.30: Prolonged Q–T interval.
To make matters a little more complicated, the Q–T interval increases as the heart rate slows. Thus
bradycardia can be associated with an apparently long Q–T interval. To correct for this, the Bazett
correction is applied to the Q–T interval to take the heart rate into account. The corrected Q–T interval
(Q–Tc) is calculated as follows:
where R–R is the number of seconds between consecutive R waves.

This value should generally be less than 0.45 second.
T wave
The final stage in ECG interpretation should be to look at the T waves. T waves may be upright or
inverted (upside down). They are generally less than two-thirds of the height of their neighbouring R
wave, and should not be more than two large squares tall.
Inverted T waves are normally seen in leads aVR and III. They may also be seen in lead V1 ± V2, but not
V2 alone. T-wave inversion in other leads may be of little consequence, but is often a sign of cardiac
ischaemia, or of NSTEMI.
Fig 10.31: 12-lead ECG with T-wave inversion in the lateral chest leads.
T-wave changes often accompany changes in the serum potassium level. Typical findings are shown in the
table.
HYPERKALAEMIA HYPOKALAEMIA
Tall, tented T waves Flat, broad T waves
Loss of P waves ST depression
QRS complex broadening Long Q–T interval
Sine-wave-shaped ECG Ventricular dysrhythmias
Cardiac arrest rhythms
Fig 10.32: T waves in hyperkalaemia.

Fig 10.33: T waves in hypokalaemia.
Summary
When interpreting an ECG, always use the following headings:
Heart rate QRS complexes
Heart rhythm ST segment
Cardiac axis Q–T interval
P waves T waves
Cardiac arrest rhythms

When a patient has a cardiac arrest, the heart stops pumping blood around the body. The electrical activity
in the heart does not always stop immediately, however, and the immediate advanced management of
patients with cardiac arrest is largely determined by exactly what is happening to the heart rhythm. It is
imperative that you are able to identify each of the following rhythms.
‘Shockable’ rhythms
If one of these rhythms is identified, the priority in treatment is to deliver electricity to the heart using a
defibrillator.
Ventricular fibrillation (VF)

This is identified by the erratic nature of the electrical activity. It is random and unpredictable. It is
sometimes classified as being fine or coarse depending on whether the electrical activity is of small (fine)
or large (coarse) amplitude.
Fig 10.34
Ventricular tachycardia (VT)

This is a broad QRS complex tachycardia that has a very distinctive appearance on an ECG monitor. It is
not always associated with cardiac arrest, but is always a significant arrhythmia.
Fig 10.35
‘Non-shockable’ rhythms
Defibrillation will not be helpful to patients with one of these rhythms. Cardiopulmonary resuscitation
should be administered and attempts made to reverse the cause of the cardiac arrest.
Pulseless electrical activity (PEA) (also known as electromechanical dissociation or EMD)

The heart rhythm is indistinguishable from a heart rhythm normally compatible with life.
Fig 10.36
Asystole
There is no identifiable cardiac electrical activity. It is important to adjust the gain on the ECG monitor to
ensure that ‘fine’ ventricular fibrillation is not missed.
Fig 10.37
P-wave asystole
In this rhythm, only P waves are seen. There is no ventricular activity. This rhythm may respond to cardiac
pacing.
Fig 10.38
Cardiac imaging
Echocardiography
It is unlikely that you will be required to have detailed knowledge of echocardiography at undergraduate
level. However, it is important that you are familiar with echocardiographic reports and understand how
to interpret them.
You may find it helpful to use the following headings when reading echocardiographic reports. Common
abnormalities and points to bear in mind are also listed.
COMPONENT OF REPORT COMMENT

The normal maximum diameter of the left atrium is 4.5 cm. Enlargement of the left
atrium is particularly significant in patients with atrial fibrillation. The normal maximum
Size of heart chambers (atria and ventricles)
diameter of the left ventricle in diastole is 5.5 cm – this will be increased in abnormally
enlarged left ventricles, eg with dilated cardiomyopathy
This should be less than 1.2 cm. A thickened septum should raise suspicions of
Ventricular septal thickness
hypertrophic obstructive cardiomyopathy (HOCM)
Hypokinesis refers to walls that contract poorly. Akinesis refers to walls that do not
Left ventricular function
appear to contract at all. The left ventricular ejection fraction is normally around 65%
Stenotic or regurgitant valves will often be described in terms of severity as trace, mild,
moderate or severe. Often pressure gradients across valves and valve areas are
Details about each valve documented. For the aortic valve, severe stenosis is present if there is a pressure
gradient of more than 50 mmHg across the valve, or if the valve area is less than 1 cm2
Bear in mind that a small vegetation may be missed with transthoracic echocardiography.
Vegetations or tumours
Transoesophageal echocardiography is more reliable
A pressure >35 mmHg suggests pulmonary hypertension. Note that this is an estimated
Estimated pulmonary artery pressure
pressure reading only
Pericardial effusion Present or absent
Other imaging modalities

Increasingly, computed tomography (CT) and magnetic resonance imaging (MRI) of the heart are being
performed in patients with suspected cardiac disease. CT assessment of the coronary arteries, including
an assessment of calcification (calcium scoring), is likely to be used increasingly in the noninvasive
assessment of patients with chest pain. MRI of the heart can provide detailed information on many aspects
of cardiac structure and function. Interpretation of such images is in the territory of a specialist
cardiologist and is certainly beyond the scope of this book. Thankfully the written reports from such
imaging investigations are usually self-explanatory.
Dynamic tests in cardiology
Dynamic heart testing is commonly used to investigate chest pain and known ischaemic heart disease. In
the resting state, a patient with significant coronary artery atherosclerosis may have a normal ECG.
However, when the heart is put under stress by increasing its rate, its energy requirements increase. If
sufficient blood cannot be supplied to the myocardium under such circumstances, the tissue becomes
ischaemic and the ECG will change.
Features that would be in keeping with ischaemic heart disease include horizontal or down-sloping ST
segment depression or elevation, particularly if these are associated with angina or a reduction in blood
pressure.
Other dynamic tests are used to assess cardiac function in particular patient groups. In patients who are
unable to exercise, pharmacological agents (eg dobutamine) can be administered to increase the heart rate
and put the heart under stress. Cardiac function can then be assessed by performing echocardiography or
by nuclear imaging techniques which look at the uptake of isotopes by cardiac muscle. By so doing, areas
of the heart that pump defectively or have inadequate blood supply can be identified.
Cardiac biomarkers
Testing for the presence of the cardiac contractile protein troponin (type I or T) is currently the test most
commonly performed to assess for myocardial cell damage. Troponin is normally involved in cardiac
muscle cell contraction, and is released systemically when cardiac muscle cells are damaged. Troponin
may be elevated after 2 hours, and can stay elevated for up to 7 days. Levels are generally measured 12
hours after the onset of symptoms. A fairly recent development in this area is in the use of ‘high-
sensitivity’ troponin, which rises more quickly than standard troponin. Unfortunately, elevated troponin
levels are not specific to myocardial infarction, and may be found in conditions such as those listed in the
box:
CAUSES OF RAISED TROPONIN

• Myocardial infarction
• Heart failure
• Myocarditis
• Pulmonary embolism
• Renal failure
• Severe sepsis
• Supraventricular tachycardia
Aside from troponin measurement, a range of enzymes rises in concentration after heart damage. These
vary in the time taken to peak and to be cleared from the blood after a cardiac event. Differences in the
tests are shown in the table below.
TIME TO DURATION OF ELEVATED

TEST PEAK BLOOD LEVEL AFTER
(h) CARDIAC EVENT
Creatine kinase (CK) 24 48
AST 30 60
Lactate dehydrogenase (LDH) 72 240
Creatine kinase is also released from damaged skeletal muscle. Its level will therefore rise in several
instances other than myocardial damage, such as trauma, polymyositis/dermatomyositis (when muscle is
inflamed) and rhabdomyolysis (when muscle breaks down). To aid differentiation between these
conditions, isoenzymes (different types) of CK can be measured. The isoenzyme released mainly from
cardiac muscle is called CK-MB, and a high level of this enzyme should raise suspicions of cardiac
damage.
B-type natriuretic peptide (BNP)

In heart failure, heart chambers are stretched more than normal. In such circumstances, substances are
released that cause increased sodium excretion (natriuresis) in an attempt to improve the situation for the
failing heart. One such substance is BNP. BNP, and its inactive cleavage fragment (N-terminal pro-BNP),
tend to be elevated in patients with heart failure to such an extent that, if the level of these hormones is
normal, then heart failure is an unlikely diagnosis. The extremely low likelihood of heart failure in a
patient who has the combination of a normal ECG and a normal BNP or N-terminal pro-BNP level makes
this approach a very effective screening test for this condition.
Case 10.1
A 50-year-old manager presents to the accident and emergency department complaining of chest pain. He
is very worried that he may be having a heart attack, since his brother had one last year. He has no other
risk factors for cardiac disease. On further questioning, he describes doing heavy work in his garden on
the previous day. Examination reveals an anxious man with tenderness on either side of the sternum. An
ECG is performed.
What is your interpretation?

Answer 10.1
Heart rate
There are 12 small squares between consecutive R waves. The ventricular rate is therefore 1500 ÷ 12 =
125 beats/min.
Heart rhythm
A P wave precedes each QRS complex. The P–R interval is normal (four small squares) and does not
vary from beat to beat. The rhythm is sinus rhythm.
Cardiac axis
Leads I and II are upgoing. Lead III is downgoing. The axis is normal.
P waves
P waves are of normal size and shape.
QRS complexes
There are no abnormal Q waves. The R and S waves are of normal height. The QRS complex is of normal
duration (two small squares).
ST segment
The ST segment is horizontal and isoelectric.
Q–T interval
The Q–T interval is normal (1.5 large squares).
T waves
T waves are normal in size and shape.
Conclusion – sinus tachycardia. The most likely cause of this is anxiety. Sinus tachycardia is the most
common ECG finding in patients with a pulmonary embolism, so this diagnosis should be considered.
However, in this case, history and examination point to the true cause of this man’s chest pain – muscular
strain.
Case 10.2
A 70-year-old woman with a history of a myocardial infarction presents with palpitations that are of
recent onset. Her ECG is shown.
How would you interpret it?

Answer 10.2
Heart rate
There are nine small squares between the first two consecutive R waves in lead I. The ventricular rate is
therefore 1500 ÷ 9 = 167 beats/min. However, since the rhythm is clearly irregular, a more accurate
assessment of heart rate can be made by measuring the distance between the first and eleventh R waves
and dividing this distance by 10 to find the average R–R interval.
By this method, there are approximately 20.5 large squares between the first and eleventh R waves. The
average R–R interval is therefore 2.05 large squares. The heart rate is 300 ÷ 2.05 = 146 beats/min.
Heart rhythm
No P waves are visible. The baseline is erratic. QRS complexes occur irregularly. The rhythm is atrial
fibrillation.
Cardiac axis
Leads I and II are upgoing. Lead III is downgoing. The axis is normal.
P waves
No P waves are visible.
QRS complexes
There are abnormal Q waves in leads III and aVF, indicating a previous inferior myocardial infarction.
The R and S waves are of normal height. The QRS complex is of normal duration (two small squares).
ST segment
The ST segment is horizontal and isoelectric in leads II, III, aVR, aVF, V1, V2 and V3. There is slight
downsloping ST depression in the other leads, most marked in I and V6.
Q–T interval
The Q–T interval is normal (seven small squares).
T waves
T waves are normal in size. There is T-wave inversion in leads I, aVL, V5 and V6.
Conclusion – atrial fibrillation with a ventricular rate of 146 beats/min. Inferior Q waves. There is
downsloping ST elevation and T-wave inversion in the leads looking at the lateral aspect of the heart. The
patient may be on digoxin, but the T-wave changes probably indicate ischaemia. This may be related to
the rapid heart rate, and may disappear if the rate is slowed. This woman’s palpitations are due to a
sudden onset of atrial fibrillation.
Case 10.3
A 74-year-old man is admitted complaining of dizziness. He has had several myocardial infarctions in the
past. Clinical examination reveals a pulse rate of 30 beats/min, and a blood pressure of 62/46 mmHg. An
ECG is performed.
What does it show?

Answer 10.3
Heart rate
There are 10 big squares between consecutive R waves. The ventricular rate is therefore 300 ÷ 10 = 30
beats/min.
Heart rhythm
P waves are seen, but these show no consistent relationship with the QRS complexes. The P waves and
QRS complexes are completely dissociated. The rhythm is third-degree heart block.
Cardiac axis
Leads I, II and III are all upgoing. The axis is normal.
P waves
P waves are of normal size and shape. One P wave is difficult to see because it is obscured by a
simultaneous QRS complex.
QRS complexes
There are no abnormal Q waves. The QRS complexes are narrow (two small squares). This indicates that
the electrical signal to the ventricles is originating in specialised conducting tissue. The R and S waves
are of normal height.
ST segment
The ST segment is horizontal and isoelectric.
Q–T interval
The Q–T interval is prolonged (three large squares). The Bazett correction is therefore required. Three
large squares= 3 × 0.2 second = 0.6 second. The R–R interval is 10 large squares = 10 × 0.2 second = 2
seconds. The Q–Tc is therefore:
T waves
T waves are normal in size and shape.
Conclusion – third-degree heart block with a ventricular rate of 30 beats/min. This rhythm is resulting in
symptomatic hypotension. Consideration should be given to an emergency pacing procedure, followed by
the placement of a permanent pacemaker.
The patient eventually had a permanent pacemaker inserted. An ECG was performed to check its function,
and is shown below. Note the presence of pacing spikes, which indicate that the pacemaker is
discharging. When a pacemaker stimulates the ventricles directly, the QRS complexes will be wide and
bizarre. It is impossible to interpret anything else from the ECG in such circumstances, other than that an
artificial pacemaker is present.
Case 10.4
A 52-year-old male shop assistant presents as an emergency to his general practitioner complaining of
central chest pain. This has been present for 30 minutes. He is sweaty and short of breath, and complains
of nausea. His risk factors for ischaemic heart disease include smoking and hypertension.
His ECG is shown. How would you interpret it?

Answer 10.4
Heart rate
There are 4.2 big squares between consecutive R waves. The ventricular rate is therefore 300 ÷ 4.2 = 71
beats/min.
Heart rhythm
A P wave precedes each QRS complex. The P–R interval is normal (four small squares) and does not
vary from beat to beat. The rhythm is sinus rhythm.
Cardiac axis
Lead I is upgoing. Lead III is downgoing. Lead II is neither upgoing nor downgoing. The axis is
approaching that of left axis deviation.
P waves
P waves are of normal size and shape.
QRS complexes
There are no abnormal Q waves. The R and S waves are of normal height. The QRS complex is of normal
duration (two small squares).
ST segment
The ST segment is elevated, in a convex shape, in leads I, aVL, V2, V3, V4 and V5. The ST segment is
depressed and horizontal in leads II, III, aVR and aVF. When ST depression accompanies ST elevation, it
is known as reciprocal ST depression.
Q–T interval
The Q–T interval is normal (1.5 large squares).
T waves
The T waves appear large, but are difficult to interpret on account of the ST segment changes.
Conclusion – anterolateral ST elevation myocardial infarction or STEMI (ie affecting the anterior and
lateral surfaces of the heart). Reciprocal ST depression in some of the limb leads.
Case 10.5
An 80-year-old female nursing home resident presents with acute confusion. No other history is available.
On examination, she is tachypnoeic, with oxygen saturations of 83% on 85% oxygen. She is peripherally
cyanosed. Blood pressure is 74/32 mmHg. On auscultating her lungs, she has medium inspiratory
crepitations to her midzones.
Interpret the ECG

Answer 10.5
Heart rate
There are 11 small squares between the first two consecutive R waves in lead I. The ventricular rate is
therefore 1500 ÷ 11 = 136 beats/min. However, since the rhythm is irregular, a more accurate assessment
of heart rate can be made by measuring the distance between the first and eleventh R waves and dividing
this distance by 10 to find the average R–R interval.
By this method, there are 24 large squares between the first and eleventh R waves. The average R–R
interval is therefore 2.4 large squares. The heart rate is 300 ÷ 2.4 = 125 beats/min.
Heart rhythm
No P waves are visible. The baseline is erratic. QRS complexes occur irregularly. The rhythm is atrial
fibrillation.
Cardiac axis
Lead I is upgoing. Leads II and III are downgoing. There is left axis deviation.
P waves
No P waves are visible.
QRS complexes
The QRS complexes are abnormally wide. The complex in V1 has a ‘W’ shape, and that in V6 is ‘M’
shaped. This is left bundle-branch block.
ST segment
The ST segment is difficult to visualise.
Q–T interval
The Q–T interval is difficult to measure.
T waves
T waves appear grossly abnormal in size and shape.
Conclusion – atrial fibrillation at 125 beats/min with left bundle-branch block. When this pattern is
present, it is impossible to make any further comments about an ECG (ie ST segment changes or T-wave
abnormalities). Left bundle-branch block that is of new onset would be in keeping with an acute
myocardial infarction. Old ECGs should be reviewed to determine whether this ECG finding is new.
Case 10.6
You are called to a cardiac arrest. Nursing staff have attached ECG electrodes, and the following rhythm
is noted on the monitor. What is the rhythm?
Answer 10.6
It is entirely possible to approach the interpretation of this rhythm as with all the ECGs above. However,
for practical purposes, this rhythm should be instantly recognised as ventricular fibrillation (VF) by its
erratic nature, and appropriate treatment given. This involves cardiac defibrillation.
After delivering three shocks, the rhythm on the monitor changes to that shown below. A pulse is
still not present. What is the rhythm now?
Again, this strip can be analysed in detail, but it should be instantly recognised by its shape as ventricular
tachycardia (VT). The ECG shows a tachycardia with wide QRS complexes. This rhythm can be
associated with a cardiac output, so it would be imperative to check for the presence of a pulse. Cardiac
arrest associated with VT is treated with defibrillation.
Case 10.7
A 67-year-old woman is reviewed in the cardiology clinic 2 months after a myocardial infarction. She
complains of shortness of breath on walking 100 metres on the flat, which she did not have before her
heart attack. On further questioning, she reports having to sleep on five pillows to prevent shortness of
breath. An echocardiogram is requested.
How would you explain this woman’s symptoms?

Answer 10.7
The important points to take away from the echocardiographic report are as follows:
Size of heart chambers (atria and ventricles) Normal
Ventricular septal thickness Normal
Severe left ventricular wall hypokinesis. Markedly reduced left
Left ventricular function
ventricular ejection fraction
Details about each valve Only a trace of aortic and mitral regurgitation
Vegetations or tumours None seen
Estimated pulmonary artery pressure Normal
Pericardial effusion None
This woman has symptoms (dyspnoea and orthopnoea) of left ventricular failure. Her echocardiogram
demonstrates the poor residual function of her left ventricle following her myocardial infarction.
Case 10.8
You assess a patient after a short-lived episode of central chest pain. His medical history includes chronic
kidney disease, not requiring dialysis at present. A 12-lead ECG is normal. Blood is sampled 12 hours
after the onset of pain.
Has the patient suffered a myocardial infarction?

Answer 10.8
It is difficult to be sure whether or not the patient has had a myocardial infarction (MI) based on the
information given. The chest pain was short-lived, and the ECG normal which points away from MI.
Although the troponin T level is quite markedly raised over normal, there is an alternative explanation for
this other than MI, namely renal failure. A reasonable course of action in this case would be to repeat an
ECG and repeat the troponin T level after several more hours. If the patient has really had an MI, one
would expect the ECG to change and/or the troponin level to change.
Case 10.9
You assess an elderly man who complains of shortness of breath on exertion. He has fine crepitations on
auscultation of both lung bases, and you suspect cardiac failure as a possible diagnosis. On review of his
blood tests, you note that a colleague requested the following test 1 month ago.
Should you order an echocardiogram?

Answer 10.9
The finding of a normal N-terminal pro-BNP level in this man makes the diagnosis of cardiac failure
extremely unlikely. Another cause for his breathlessness and crepitations should be found. A chest X-ray
would seem like a useful first test.
Case 10.10
A 55-year-old man who smokes and has a strong family history of coronary heart disease presents 14 h
after a 30-min episode of central crushing chest pain. He was afraid to come to hospital at the time. He is
currently pain free, and his ECG was normal. The A&E officer requests the following test:
Where should this patient be managed?

Answer 10.10
This patient has a significantly elevated troponin I indicating a significant amount of cardiac damage. The
clinical information is consistent with myocardial infarction. The patient is at significant risk of cardiac
arrhythmias and should be managed in a coronary care unit.
PATHOLOGY
This chapter lists typical pathological findings for a range of disease states. It is not by any means
comprehensive, but includes most of the classic abnormalities that are commonly tested in general
medical examinations. Further reading will be required when preparing for pathology examinations.
DISEASE TYPICAL PATHOLOGICAL CHANGES

Gastroenterology
Lower oesophageal epithelium undergoes metaplasia to become gastric or intestinal-type

Barrett’s oesophagus
epithelium
Total or subtotal villous atrophy in the small bowel Crypt hyperplasia with inflammatory cells in
Coeliac disease
the mucosa
Can affect any part of the gastrointestinal tract Macroscopically: skip lesions (ie lengths of
Crohn’s disease normal bowel between diseased segments); cobblestone appearance with fissured ulcers
Microscopically: thickened wall with transmural inflammation; granulomas
Affects large bowel only

Ulcerative colitis Affects mucosa and submucosa only
Crypt abscesses and superficial ulcers
Chronic cholecystitis Chronic inflammatory changes Rokitansky–Aschoff sinuses
Hepatology
Acute viral hepatitis Swelling of hepatocytes with spotty necrosis Councilman bodies
Alcoholic hepatitis Fatty accumulation in cytoplasmic vacuoles, necrosis, Mallory hyaline material
Chronic active hepatitis Piecemeal necrosis
Autoimmune hepatitis Interface hepatitis, portal plasma cell infiltration
Excessive hepatic iron

Haemochromatosis
(shows up blue on Perl’s stain)
Portal hepatitis and granulomatous destruction of bile ducts. Later, periportal hepatitis and bile
Primary biliary cirrhosis
duct proliferation
Macroscopically: macronodular or micronodular Microscopically: fibrous tissue (shows up red

Liver cirrhosis
on von Gieson stain)
Respiratory
Diffuse alveolar damage (DAD) which

can lead to adult respiratory distress Alveolar hyaline membranes and thickened alveolar walls
syndrome (ARDS)
Previous asbestos exposure Asbestos bodies in lung
Pulmonary fibrosis Proliferation of type II pneumocytes with thickening of the alveolar walls
Nephrology
Malignant hypertension Renal arteriole fibrinoid necrosis
Kimmelstiel–Wilson nodules, thickened capillary basement membranes with hyalinisation of

Diabetic glomerulosclerosis
arterioles
Haematology
Reed–Sternberg cells
Hodgkin’s disease Abnormal lymph node architecture
Nodular sclerosing type has fibrous tissue
Myelofibrosis Bone marrow fibrosis secondary to fibroblast proliferation
Multiple myeloma Plasma cell proliferation in bone marrow
Rheumatology
Temporal artery biopsy may be normal Alternatively, plasma cells, lymphocytes and
Temporal arteritis
multinucleate giant cells can be present
Polymyositis Muscle fibre necrosis Lymphocyte infiltration
Endocrinology
Acromegaly is associated with acidophil macroadenomas (somatotroph adenomas)

Pituitary tumours Hyperprolactinaemia is associated with chromophobe adenomas ACTH excess is associated
with basophil microadenomas (corticotroph adenomas)
Neurology
Macroscopically: thinning of gyri

Alzheimer’s disease
Microscopically: neurofibrillary tangles; plaques
Parkinson’s disease and dementia with

Lewy bodies (inclusions inside neurons)
Lewy bodies
Obstetrics and gynaecology
Ovarian endometriosis Macroscopically: chocolate cyst

GENETICS
Family trees
In clinical practice, family trees are often recorded when there is a suspicion that a disease may have a
familial element.
To the untrained eye, interpretation of family trees can seem like a daunting process, and many students
resort to guessing what the inheritance pattern might be. However, if a few simple rules are borne in
mind, interpretation can be made fairly simple. Being able to work out the expected inheritance patterns
for the common mendelian disorders from first principles is a good way to check that your answer is
correct.
Work through the various inheritance patterns for the common mendelian disorders below, and attempt to
reproduce the information for yourself. This will be much easier to remember than if you simply learn off
a list of rules.
The two main classes of conditions that are inherited in a mendelian manner are:
• autosomal conditions (affecting the autosomes, ie chromosomes 1 to 22)
• sex chromosomal conditions (affecting the sex chromosomes, ie X and Y).
Genotype refers to the genetic code.

Phenotype refers to the actual manifestation of the genetic code.
Autosomal conditions
Autosomal dominant inheritance
There are usually two copies of each chromosome in each cell, each carrying copies of the same genes. In
autosomal dominant conditions, inheritance of one faulty gene is sufficient to give rise to the disorder.
Thus one chromosome in the pair will be normal; the other will carry the faulty gene.
In the following diagram, the letter ‘a’ is used to denote a normal chromosome. The capital letter ‘A’
represents a chromosome with an abnormal gene. Thus an individual with two ‘a’ chromosomes will be
normal. Someone with one ‘a’ chromosome and one ‘a’ chromosome will have the disorder, since only
one faulty gene is needed for the condition to be manifest. If both parents are affected, it would also be
possible for offspring to have two ‘a’ chromosomes.
Since 50% of the offspring’s genetic code comes from one parent and 50% from the other, there is a 50%
chance that either chromosome will be passed on.
In the example, the father has an autosomal dominant condition, and therefore has one normal chromosome
(a) and one abnormal chromosome (A). The mother has two normal chromosomes. There are four
possible ways that the genes can be passed on to the offspring (aa, aa, Aa and Aa).
Thus for autosomal dominant conditions:
• both males and females can be affected
• if one parent is affected, there will be a 50% chance that a child will also be affected.
Autosomal recessive inheritance

For an autosomal recessive disorder to be manifest, both chromosomes in a pair must carry the abnormal
gene. One abnormal gene must therefore be passed on from each parent.
If a person has one normal and one abnormal chromosome, he or she is a termed ‘a carrier’ and does not
exhibit any features of the disorder, and therefore will appear normal (ie normal phenotype).
The inheritance pattern for one carrier parent and one normal parent will be as follows (remember ‘a’ is
the normal chromosome, and ‘A’ the abnormal).
For autosomal recessive conditions with one carrier parent:

• both male and female offspring can be carriers
• 50% of the offspring will be carriers.
The inheritance pattern for two carrier parents will be as follows.
For autosomal recessive conditions with two carrier parents:

• both male and female offspring can be carriers or be affected
• 50% of the offspring will be carriers
• 25% of the offspring will be normal (ie not carriers)
• 25% of the offspring will have the condition.
The inheritance pattern for one affected parent will be as follows.
For autosomal recessive conditions with an affected parent:

• both male and female offspring can be carriers
• all offspring will be carriers.
Sex chromosomal conditions

X-linked recessive inheritance
X-linked disorders involve faulty genes found on the X chromosome. Since females have two X
chromosomes, having one faulty chromosome is of minor consequence with a recessive disorder, because
the other X chromosome is normal. Males, however, have only one X (but also one Y) chromosome. A
faulty X chromosome in a male will therefore result in phenotypical effects.
If a female has one abnormal X chromosome, they are termed ‘a carrier’ and generally do not exhibit any
features of the disorder. Occasionally mild signs of disease may be present.
The inheritance pattern for a carrier mother and a normal father will be as follows (X = normal
chromosome, X = abnormal chromosome):
For X-linked recessive disorders with a carrier mother:

• only males can be affected
• 50% of male offspring will have the disorder
• 50% of female offspring will be carriers
• 50% of all offspring will be normal.
The inheritance pattern for an affected father and a normal mother will be as follows:
For X-linked recessive disorders with an affected father:
• no offspring will be affected
• all daughters will be carriers
• all sons will be normal.
X-linked dominant inheritance

In these disorders, only one faulty X chromosome is necessary for the disease to be manifest. Thus,
diseases can occur in both male and females.
The inheritance pattern for an affected mother and a normal father will be as follows:
For X-linked dominant disorders with an affected mother:

• 50% of male offspring will have the disorder
• 50% of female offspring will have the disorder.
The inheritance pattern for an affected father and a normal mother will be as follows:
For X-linked dominant disorders with an affected father:

• only female offspring can be affected
• all daughters will have the disorder
• all sons will be normal.
Other modes of inheritance

Mitochondrial inheritance
Mitochondria are cellular organelles that have a major role in energy production. They have their own
DNA, which may undergo mutations. Diseases caused by mitochondrial genetic problems have an
interesting inheritance pattern resulting from the fact that female ova all contain mitochondria; however,
male sperm do not. Therefore, mitochondrial disorders can be passed on only by females. To summarise:
• affected females can pass on the disorder to all offspring
• affected males cannot pass on the disorder.
Genetic imprinting
This phenomenon relates to the fact that certain genes are expressed only if inherited from a particular
parent. This can best be explained by looking at two conditions – Prader–Willi and Angelman syndromes.
For Prader–Willi syndrome, only the paternal gene is important. Failure to inherit the paternal copy will
therefore result in the syndrome. Angelman syndrome results from failure to inherit the maternal gene. The
disorders may result from gene deletion mutations, where the gene from a particular parent is deleted.
Alternatively, they may arise when two chromosomes are inherited from one parent rather than one from
each. This is known as uniparental disomy.
MEMORY AID
In Prader–Willi syndrome – the Paternal gene is inactive
In Angelman syndrome – the Maternal gene is inactive
Other points
Variable expression relates to the fact that a person may carry the necessary genetic make-up for a
condition, but not exhibit all the phenotypical features. At the extreme of this is ‘non-penetrance’ where
the person has no features of the condition.
Genetic disorders may appear to arise out of the blue, with no family members being affected. This is
most commonly due to a new genetic mutation, but can also result from gonadal mosaicism where a parent
carries the mutated genes only in the germ cells.
Family tree interpretation

When faced with a family tree, and asked to comment on inheritance patterns, the flow diagram below
should be helpful.
Examples of genetic conditions with different inheritance patterns
Those most commonly tested in undergraduate examinations are highlighted in bold in the following table.
MODE OF INHERITANCE EXAMPLES

Achondroplasia
Adult polycystic kidney disease
Dystrophia myotonica
Ehlers–Danlos syndrome
Familial adenomatous polyposis
Familial hypercholesterolaemia
Hereditary haemorrhagic telangiectasia
Autosomal dominant
Huntington disease
Marfan syndrome
Neurofibromatosis
Noonan syndrome
Osteogenesis imperfecta
Otosclerosis
Tuberous sclerosis
Albinism
Congenital adrenal hyperplasia
Cystic fibrosis
Friedreich ataxia
Galactosaemia
Glycogen storage diseases
Hereditary haemochromatosis
Autosomal recessive
Hurler syndrome
Oculocutaneous albinism
Phenylketonuria
Sickle cell disease
Tay–Sachs disease
Thalassaemia
Wilson’s disease
X-linked dominant Vitamin D-resistant rickets
Alport syndrome
Becker muscular dystrophy
Duchenne muscular dystrophy
Fragile X syndrome
X-linked recessive
Glucose-6-phosphate dehydrogenase deficiency
Haemophilia A
Haemophilia B
Hunter syndrome
Mitochondrial Leber hereditary optic neuropathy
Karyotype analysis
The following table lists the common chromosomal abnormalities that you would be expected to
recognise.
CHROMOSOMAL
CONDITION
ABNORMALITY
Trisomy 21 Down syndrome
Trisomy 18 Edward syndrome
Trisomy 12 Patau syndrome
45, XO Turner syndrome
47, XXY Klinefelter syndrome
47, XXX Triple X syndrome
47, XXY Associated with behavioural problems
5p– Cri-du-chat syndrome
Microdeletion at 22q11 DiGeorge syndrome
Microdeletion at 7q11 Williams syndrome

Common mutations
DISEASE COMMON MUTATION

ΔF508 mutation on long arm of chromosome 7. This codes for the cystic fibrosis transmembrane conductance
Cystic fibrosis
regulator
Haemochromatosis C282Y mutation on the HFE gene on the short arm of chromosome 6. The H63D mutation can also be found
Case 12.1
What is the inheritance pattern in the following family tree?
Answer 12.1
• Both males and females are affected
• Male-to-male inheritance is possible
• One of the parents of all affected cases is also affected.
If one parent is affected, there appears to be approximately a 50% chance that a child will also be
•
affected.
The inheritance pattern is therefore autosomal dominant.

Case 12.2
Some members of the following family suffer from a rare bone disease. What is the inheritance pattern?
unaffected male
Answer 12.2
• There are no instances of male-to-male transmission
Male-to-female transmission is possible, with all daughters of an affected male having the
•
condition.
The likely diagnosis is vitamin D-resistant rickets, with the inheritance pattern being X-linked dominant.
Case 12.3
Some family members have a rare genetic disorder. This is their family tree. What is the likely inheritance
pattern?
Answer 12.3
• Male-to-male and male-to-female transmission do not occur
• Affected females pass the condition on to all offspring.
The inheritance pattern is mitochondrial.

RESPIRATORY MEDICINE
Arterial blood gas analysis
Arterial blood gas (ABG) analysis provides a wealth of information about a patient’s state of health. The
test is most commonly used in acute illness but may also be used in the assessment of patients with
chronic respiratory disease. In acute situations, multiple analyses are often made to assess response to
treatment. Trends are usually more helpful than one-off readings. Never forget to consult old medical
records if possible, since the patient’s baseline may be well outside ‘normal’ limits.
Interpretation of four key indices – pH, partial pressure of oxygen (PaO2), partial pressure of carbon
dioxide (PaCO2) and bicarbonate (HCO3–) – will provide most of the information needed in clinical
practice. A fifth index, base excess (BE), can also be used, but will not be discussed here in detail.
Sophisticated blood gas analysers will provide other useful information such as blood levels of lactate
and methaemoglobin.
NORMAL RANGES (BREATHING ROOM AIR AT SEA LEVEL)

pH 7.35–7.45
PaO2 11–13 kPa
PaCO2 4.7–6.0 kPa
HCO3– 24–30 mmol/l
Base excess –2 to +2 mmol/l
Anion gap 12–16 mmol/l
Of all the normal ranges for values listed in this book, it is recommended that all students learn the normal
values in an ABG sample. This is for two reasons:
1. ABGs are commonly tested, so knowing the normal values will help you as an undergraduate.
More importantly, in real medical practice, ABGs are often encountered in stressful situations
2. involving critically unwell patients. Knowing normal values can speed up analysis and reduce
stress.
Oxygen levels in the air fall with increasing altitude. Bear this in mind if you are interpreting ABGs taken
at any significant height above sea level. For the purposes of simplicity, for the remainder of this chapter,
it will be assumed that samples have been taken at sea level.
Systematic interpretation of an ABG

The two main steps involved are to assess oxygenation, then acid–base status.
Assess oxygenation
You will note that the normal range for PaO2 given in the box above was 11–13 kPa. This value holds true
for a patient breathing room air that contains 21% oxygen. It is crucial to appreciate that a patient with
normal lungs will have a much higher PaO2 if their inspired oxygen concentration (FiO2) is increased.
The physiology behind this is summarised in the alveolar gas equation, which will be dealt with shortly.
Unless you are someone who particularly enjoys equations, a useful rule of thumb is that, for a healthy
person at sea level, the expected PaO2 (kPa) is roughly 10 less than the FiO2 (%). This will not compute
exactly, but will highlight patients with serious problems. Exact expected values are shown in the table
below. Thus, if a patient is receiving 85% oxygen and the PaO2 is 11 kPa, there is a serious problem.
INSPIRED OXYGEN RULE OF THUMB EXPECTED PaO2

CONCENTRATION METHOD FOR WITH HEALTHY
(%) ESTIMATING PaO2 LUNGS (kPa)
28 18 21
35 25 27
40 30 32
60 50 51
85 75 75
100 90 89
MEMORY AID
As a rule of thumb, the expected PaO2 (kPa) is roughly 10 less than the FiO2 (%).
It is therefore impossible to interpret the PaO2 without knowing the FiO2. If the PaO2 is lower than
expected, this implies that a disease process in the lungs is interfering with gas exchange. This can occur
with a variety of conditions, from pulmonary fibrosis to pulmonary embolism, and pneumonia to
pulmonary oedema, to name but a few.
DON’T FORGET
Always interpret the PaO2 with the FiO2 in mind.
The first step in interpreting an ABG sample is to assess oxygenation. So, with the above in mind, decide
whether oxygenation is normal or abnormal.
The label of ‘respiratory failure’ is used when the PaO2 is less than 8 kPa. It is divided into two types
depending on the PaCO2, as follows:
RESPIRATORY PaO2 (kPa) PaCO2 (kPa)

FAILURE TYPE
Type 1 <8 <6.5
Type 2 <8 >6.5
MEMORY AID
In type ONE respiratory failure, ONE gas is abnormal (ie low O2, without high CO2). In type TWO respiratory failure, TWO gases
are abnormal (low O2 and high CO2).
COMMON CAUSES OF RESPIRATORY FAILURE
TYPE 1 TYPE 2
Chronic obstructive pulmonary disease
Pulmonary oedema (COPD)
Pneumonia Respiratory centre depression
Pulmonary embolism Respiratory muscle weakness
Pulmonary fibrosis Abnormal chest wall architecture
THE ALVEOLAR GAS EQUATION AND THE ALVEOLAR–ARTERIAL GRADIENT

The assessment of oxygenation described above will suffice in most situations. It is possible to be more precise, however, so, if you are
particularly interested in this subject, there are two further equations that are of interest.
The alveolar gas equation

This equation allows the calculation of the expected oxygen level in the alveoli of an individual (PAO2).
It is rarely used in clinical practice:
where Patm = atmospheric pressure, PH2O= saturated vapour pressure of water at that particular
temperature and pressure, and RQ = respiratory quotient (a ratio of CO2 eliminated to O2 consumed).
So, for example, for someone breathing 21% oxygen at sea level with PaCO2 of 5 kPa:
The alveolar–arterial gradient

This equation allows the calculation of the difference in oxygen concentration between alveoli and the
arterial system:
So for example, for someone breathing 40% oxygen at sea level with PaO2 12 kPa and PaCO2 5 kPa:
There is no established normal range for A–a gradient. It has been defined in the following ways:
No more than 2.66 kPa. This is a simplistic approach, however, as the A–a gradient normally
•
increases with age.
• No more than
• Or compare the value with ‘normal’ age-based values in the literature.
Stein PD et al. (1995) Alveolar–arterial oxygen gradient in the assessment of acute pulmonary embolism. Chest 107:139–43.
Assess acid–base status

This has five main components.
Look at the pH
Is it:
• normal (7.35–7.45)?
• low (<7.35) indicating acidosis?
• high (>7.45) indicating alkalosis?
Small deviations from normal are extremely relevant. Abnormalities of pH can be due to a problem with
either respiration (respiratory acidosis or alkalosis) or metabolism (metabolic acidosis or alkalosis). The
body’s homeostatic mechanisms will attempt to correct pH problems, so evidence of compensation might
be seen. In general, for respiratory problems, metabolic compensation occurs but this can take some time.
For metabolic problems, respiratory compensation occurs, which can happen quickly.
Once you have identified a problem, next try to decide on the cause by proceeding with the next stages.
Look at the PaCO2

Is it normal, low or high?
Carbon dioxide is an acidic gas (remember that carbon dioxide plus water → carbonic acid), so:
• If the pH is acid and the CO2 is high, the problem is a respiratory acidosis (excess acidic CO2).
If the pH is alkaline and the CO2 is low, the problem is a respiratory alkalosis (lack of acidic
•
CO2).
Look at the HCO3−
Is it normal, low or high?
Bicarbonate is an alkaline substance (remember that some people take sodium bicarbonate to combat
stomach acid), so:
If the pH is acid and the bicarbonate is low, the problem is a metabolic acidosis (lack of alkaline
•
bicarbonate).
If the pH is alkaline and the bicarbonate is high, the problem is a metabolic alkalosis (excess
•
alkaline bicarbonate).
DON’T FORGET
In some circumstances, patients can have more than one abnormality, eg a combined respiratory and metabolic acidosis.
Look for compensation

As mentioned above, the body will attempt to compensate for a pH abnormality. Respiratory
compensation happens faster than metabolic compensation. The body will never overcompensate. The
following patterns are commonly seen:
In an acute metabolic acidosis, the body responds by getting rid of extra CO2, thus losing acid and
•
shifting the pH towards normality.
In a chronic respiratory acidosis, the body responds by holding onto extra bicarbonate, thus
•
retaining alkalinity and shifting the pH towards normality.
Fig 13.1: Interpretation of common arterial blood gas abnormalities
Try to determine the cause

Respiratory acidosis
Respiratory acidosis can be due to any of the causes of respiratory failure.
Respiratory alkalosis
Respiratory alkalosis is always due to hyperventilation. Be wary of attributing hyperventilation
exclusively to anxiety, however, since it may occur secondary to an underlying severe disease process,
such as sepsis or stroke.
Metabolic acidosis
There are a wide range of causes for a metabolic acidosis. To narrow down this list, and help you come
to a diagnosis, it is helpful to calculate the anion gap. If this is high (>16 mmol/l), the acidosis is due to
the presence of excess acids in the body that are not routinely analysed in the laboratory. The anion gap is
calculated as follows:
Anion gap = (Na+ + K+) – (cl– + HcO3–)
A patient with the following biochemical findings – Na+ 136 mmol/l, K+ 3.5 mmol/l, cl– 100 mmol/l,
HcO3– 24 mmol/l – would therefore have an anion gap of 15.5 mmol/l.
DON’T FORGET
Always calculate the anion gap in a patient with a metabolic acidosis.
COMMON CAUSES OF A METABOLIC ACIDOSIS
NORMAL ANION GAP RAISED ANION GAP

Ketoacidosis
Renal failure
HCO3– loss from gut, eg diarrhoea Lactic acidosis
Renal tubular acidosis Salicylate toxicity
Methanol ingestion
Ethylene glycol (antifreeze) ingestion
Metabolic alkalosis
There are several causes of metabolic alkalosis (see box below). Most commonly, it is seen in patients
with excessive vomiting.
COMMON CAUSES OF A METABOLIC ALKALOSIS

Losses from the gut, particularly vomiting (classically pyloric stenosis) Primary or secondary hyperaldosteronism
Hypercalcaemia
Use of diuretics
Bicarbonate ingestion
Pulmonary function tests
Peak expiratory flow rate

Peak expiratory flow rate (PEFR) is a simple bedside test that gives a useful insight into the respiratory
function of a patient. The PEFR is measured in litres per minute using a basic plastic device. An average
recording of three attempts is documented on a peak flow chart. The trend in PEFR and its relationship to
symptoms are a guide to the severity of illness and the effectiveness of treatment.
Some patients with asthma will keep records of their PEFR. For comparative purposes recordings should
be taken at the same time each day. This will eliminate changes due to normal diurnal variation. There is a
normal variation in PEFR in people with asthma, with a typical dip first thing in the morning.
It is important to appreciate when interpreting values that the normal PEFR varies with age, height and
sex.
NORMAL PEFR
PATIENT HEIGHT (cm)
(l/min)
25-year-old man 175 630
25-year-old woman 175 505
60-year-old man 160 545
60-year-old woman 160 445
DON’T FORGET
PEFR varies with age, sex and height.
Spirometry
Spirometry provides a wealth of information about lung volumes and function. Spirometry reports can
appear confusing. However, by looking at four indices, most of the important patterns of lung disease can
be distinguished.
KEY RESULTS IN SPIROMETRY
INDEX ABBREVIATION INTERPRETATION

Forced expiratory volume in 1 FEV1 The volume of air that can be expired in 1 second
second
Forced vital capacity FVC The volume of air expired in a complete expiration
Ratio of FEV1 to FVC FEV1/FVC _
Carbon monoxide transfer A measure of the rate of diffusion of carbon monoxide from the alveoli into
Kco
coefficient the capillary blood
Values obtained by spirometry should always be compared with age- and sex-matched control values.
Often results are converted into percentages of the predicted value in order to simplify interpretation.
Arguably the most useful index is the FEV1/FVC. This test can be used to distinguish between obstructive
airway disease (eg asthma, COPD) and restrictive lung disease (eg pulmonary fibrosis). In an obstructive
defect, the FEV1/FVC will be less than 70%. The percentage is greater than 80% with a restrictive defect.
COMMON PATTERNS OF FEV1/FVC

<70% in obstructive airway disease
>80% in restrictive lung disease
The theory underlying these patterns is easily understood. In a patient with obstructive airway disease,
airway obstruction makes expiration slow (and usually wheezy). The FEV1 is therefore typically low,
since only a small volume of air can be expired in 1 second. These patients also ‘trap air’ so the FVC
will usually be high. A low FEV1 and a high FVC combine to give a low FEV1/FVC. In other words, the
volume of air in the lungs is normal or high, but it is not easily forced out.
In restrictive lung disease, on the other hand, there is no airway obstruction. The FEV1 is therefore
typically higher than with an obstructive defect (although it is still usually reduced compared with
normal). Small lung volumes contribute to a low FVC. A relatively high FEV1 and a low FVC combine to
give a high FEV1/FVC. Put simply, the patient can force air out of their lungs, but as the lung volume is
reduced there is less of it to force out.
The three main patterns of lung function (normal, obstructive and restrictive) are shown pictorially on Fig
13.2.
Fig 13.2
The Kco measures the ease of diffusion of carbon monoxide from alveolar air to capillary blood.
Anything that hinders gas transfer from alveolus into blood will therefore result in a low Kco. Common
causes of low Kco are shown in the box below.
CAUSES OF A LOW Kco

Interstitial lung disease
Emphysema
Pulmonary oedema
Pulmonary embolism
Anaemia
In rare cases, the Kco can be raised. In such circumstances, gas transfers more easily than normal from
alveolus into blood. Examples include polycythaemia (see Chapter 1) or in cases of pulmonary
haemorrhage (eg Goodpasture syndrome).
Note that anaemia is the classic case where a patient will have a low Kco with normal spirometry. The
Kco is low because there is less haemoglobin present to carry gas away from the alveoli.
Case 13.1
The blood gas below was taken following admission of an elderly patient to the acute medical unit. He
was breathing room air.
1. Outline the abnormalities on this ABG.

2. What are the likely causes for these abnormalities?
Answer 13.1
1. Oxygenation is abnormal, ie the PaO2 is lower than normal for a patient breathing room air.
The pH is high, indicating an alkalosis. The PaCO2 is normal, and the HCO3– is high. Using the
flow diagram on page 427, you can work out that this represents an uncompensated metabolic
alkalosis.
Poor oxygenation could reflect any disease process affecting the lungs. Common causes would be
2. pulmonary oedema or pneumonia. The causes of a metabolic alkalosis are listed in the box on page
428. The patient in this case had a lower respiratory tract infection and vomiting.
Case 13.2
A 68-year-old man with a 40-pack-year smoking history was admitted short of breath and with a cough
productive of green sputum. On examination he was tachypnoeic and using his accessory muscles of
respiration. Auscultation of his chest revealed widespread expiratory wheeze with bibasal coarse
crepitations. He was placed on 28% oxygen and his initial ABG is shown below.

3. What type of assisted ventilation could be considered in the management of this condition?
Answer 13.2
Oxygenation is abnormal. The patient has type 2 respiratory failure, with low PaO2 and high
PaCO2.
1. The pH is low, indicating an acidosis. The PaCO2 is high, as is the HCO3–. Using the flow chart
you can see that this pattern could represent either respiratory acidosis with metabolic
compensation, or a predominant respiratory acidosis with a coexistent metabolic alkalosis.
The most likely diagnosis is an acute exacerbation of chronic obstructive pulmonary disease
(COPD). This would be in keeping with the clinical findings. The acid–base disturbance would
therefore represent respiratory acidosis with metabolic compensation. Note that the compensation
is only partial, since the patient remains acidotic. An acute exacerbation of COPD is the most
common cause of a respiratory acidosis with a raised HCO3–.
2.
Many patients with COPD have high resting CO2 levels, causing a respiratory acidosis. However,
with time, the kidneys compensate for this acidosis by retaining HCO3–. Thus, in the ‘normal’ state,
many patients with COPD have a normal pH, with a raised PaCO2 and a raised HCO3–, such as that
shown in the ABG below:
During an acute exacerbation, however, the PaCO2 levels increase, giving rise to a respiratory acidosis.
Patients may often benefit from non-invasive ventilation (NIV) using bilevel positive airway
3.
pressure (BiPAP). If deterioration occurs, intubation and ventilation may be required.
Case 13.3
An anxious 27-year-old student was admitted with shortness of breath and tingling in her hands. On
examination, she had a respiratory rate of 28 breaths per minute. Chest examination was unremarkable.
Chest X-ray and routine blood tests were normal. An ECG showed sinus tachycardia. An ABG was taken
on 35% oxygen.

2. What is the likely cause?
3. How might one treat this woman?
Answer 13.3
Oxygenation is normal given that the FiO2 is 35%.
1. The pH is high indicating an alkalosis. The PaCO2 and HCO3– are both low. Using the flow chart,
you can see that this pattern could be due to either a respiratory alkalosis with metabolic
compensation or a predominant respiratory alkalosis with coexistent metabolic acidosis.
The likely cause for this ABG given the clinical history is hyperventilation. Thus the acid–base
disturbance is a respiratory alkalosis with metabolic compensation. One of the most common
causes is anxiety, but it may occur as a result of organic pathology such as a stroke or subarachnoid
2. haemorrhage affecting the respiratory centre.
A full history and examination would be essential to help rule out a serious cause of this acid–base
disturbance.
Reassurance would be a key aspect of treatment in the case of anxiety. Re-breathing one’s own
3.
exhaled air, using a paper bag, may also be beneficial.
Case 13.4
A 32-year-old French tourist is brought to A&E feeling generally unwell. No history is available. He
appears dehydrated and has a respiratory rate of 22 breaths per minute. The following ABG and
biochemical profile are taken on admission, breathing room air.
1. Outline the abnormalities seen.

2. What tests should you request?
3. Which drugs or substances taken in overdose could give a similar pattern?
Answer 13.4
Oxygenation is normal.
The pH is low indicating an acidosis. The PaCO2 and HCO3– are both low. Using the flow chart
you can see that this indicates either a metabolic acidosis with respiratory compensation or a
1. predominant metabolic acidosis with coexistent respiratory alkalosis.
Remember to calculate the anion gap with any case of metabolic acidosis. In this case the anion gap
is calculated as follows: (131 + 4.5) – (96.1 + 12.6) = 26.8. Thus this is a raised anion gap
metabolic acidosis.
Bearing in mind the causes of a raised anion gap metabolic acidosis shown in the box on page 428,
2. the following tests would be helpful: urinalysis for ketones, plasma lactate levels and salicylate
levels.
This pattern can be seen when salicylates (eg aspirin), methanol or ethylene glycol is taken in
3.
excess.
Case 13.5
A 57-year-old man is medically retired from his former job in the local shipyard. For the past 6 years his
health has deteriorated with an exercise tolerance now reduced to 10 metres on the flat. He is a life-long
non-smoker. A recent high-resolution CT (HRCT) scan of the chest demonstrated diffuse bibasal
interstitial changes. His ABG was taken on room air without any intercurrent illness.
1. Outline the abnormalities seen.

2. What are the likely causes for an ABG such as this?
3. What long-term therapy might be considered?
Answer 13.5
Oxygenation is abnormal. The patient has type 1 respiratory failure, with a low PaO2 and normal
1.
PaCO2.
The pH is normal, as is the HCO3–.
This man’s clinical history when taken in conjunction with his clinical signs and ABG is highly
suggestive of pulmonary fibrosis. The fact that he worked in a shipyard may suggest exposure to
2.
asbestos, which is a potential cause of pulmonary fibrosis – especially at the lung bases as the CT
scan suggests. Other causes for type 1 respiratory failure are listed in the box on page 423.
Long-term oxygen therapy (LTOT) could be considered. However, there are strict guidelines that
3.
must be met before LTOT is commenced.
Case 13.6
The following chart plots changes in PEFR of a patient with asthma during her hospital stay.
How would you interpret this chart?

Answer 13.6
In this bedside chart, the patient’s known baseline PEFR of 410 l/min has been documented. Using the
patient details at the top of the chart, one can look up the predicted PEFR, which is 505 l/min. Thus, even
when at ‘her best’ she has a reduction in expiratory flow compared with a ‘normal’ adult of the same
build. At the time of admission her PEFR is only 200 l/min – less than half of her baseline. Over the
course of the next 2 days there is little change in her PEFR. Her condition has stabilised. Days 4 and 5 of
her stay show a significant and sustained increase in her readings. A steady rise to 340 l/min is seen.
Either there has been a natural resolution of her asthma attack or the instigation of effective treatment has
caused this change.
Case 13.7
A 70-year-old man with a long history of rheumatoid disease is reviewed at clinic. He complains that he
is unable to make it to the newsagents any longer without having to stop to catch his breath. He has no
history of chest or cardiovascular disease. He has no other symptoms. On examination, fine end-
inspiratory crepitations are heard at both lung bases. Spirometry is requested.
1. Outline the abnormal findings in the results above.

2. What is the most likely cause for these abnormalities in this patient?
3. What imaging test would be most useful here?
Answer 13.7
1. This man has a restrictive defect on spirometry as shown by the raised FEV1/FVC.
The most likely cause would be pulmonary fibrosis, either secondary to his rheumatoid disease or
2.
as a side effect of its treatment with methotrexate.
An HRCT scan of the chest would best aid diagnosis and management. This would identify any
3.
pulmonary changes associated with fibrosis.
Case 13.8
A 68-year-old man who has been a life-long smoker is admitted with a lower respiratory tract infection.
He was noted to be wheezy at the time of admission to hospital, and was treated with antibiotics and
nebulised bronchodilators. His inflammatory markers settled, but he remained wheezy. Pulmonary
function tests were performed 3 weeks later after resolution of his acute illness.

2. What is the most likely cause for these abnormalities in this patient?
Answer 13.8
This patient’s spirometry shows an obstructive pattern. His Kco is low, indicating that something is
1.
interfering with gas transfer in the lungs. In this case, it is a reflection of his airway disease.
Given that this patient is a life-long smoker, it is likely that he has COPD. Consideration should be
2.
given to optimising inhaled bronchodilator therapy before discharge.
Case 13.9
A 64-year-old woman is admitted from A&E complaining of increasing shortness of breath. This has been
increasing over a period of 2 months. There is little of note on examination. The admitting doctor arranges
for pulmonary function tests to assess her symptom.

2. What blood test would you order?
Case 13.10
A 36-year-old woman has been attending the respiratory outpatient department for 5 years because of
sarcoidosis. Her disease has been well controlled recently, and her dose of oral steroids has been
gradually reduced over a period of several months. On her most recent visit, she complains of increasing
shortness of breath over the preceding 3 weeks. Her pulmonary function tests are shown alongside a set
taken when she was feeling well.
What parameter has changed significantly between the two sets of readings, and how would you
account for this?
Answer 13.9
FEV1 and FVC are considered normal unless they are less than 80% of the predicted value.
1.
Spirometry is essentially normal in this example. The only abnormality shown is a low Kco.
A classic cause of reduced Kco with normal spirometry is anaemia. This patient should have a full
2.
blood picture analysed as a first-line measure.
Answer 13.10
The FEV1 and FVC remain fairly similar between both sets of readings, indicating a restrictive lung
defect. The major deterioration lies with the Kco, which has taken a marked turn for the worse. This is
most likely due to a deterioration in the underlying disease process because of the reducing dose of
steroids. Consideration should be given to increasing the steroid dose.
INTERPRETING BEDSIDE CHART DATA
The most easily measured and readily available data on a patient lie at the bedside on a series of
observation charts. Nursing staff dutifully complete a number of observations on a regular basis. The
nature of these and the frequency at which they are taken vary, depending on the clinical status of the
patient. Analysis and interpretation of bedside chart data are an extension of the clinical assessment of a
patient, and may provide the first evidence of a downward trend in clinical condition. The best way to
learn from bedside charts is to pick them up and try to interpret them during your clinical attachments.
DON’T FORGET
Data interpretation begins at the end of the bed.
Vital signs
The so-called ‘vital signs’ represent the basic set of observations that are recorded regularly for all
patients and include the parameters listed in the box below.
BASIC OBSERVATIONS MEASURED (WITH NORMAL RANGES)

Pulse rate 60–100 beats/min
Abnormally high – >140 mmHg systolic or
90 mmHg diastolic
Blood pressure
Abnormally low – <90 mmHg systolic or a drop of 20 mmHg or more systolic from the
patient’s baseline
Respiratory rate 14–18 breaths per minute
Oxygen saturation 96–100% on room air
Temperature 36.5–37.5°C
Looking at how a particular physiological parameter varies with time can be highly informative. For
example, taking a one-off temperature recording may or may not be useful in a patient with a particular
symptom, but much more useful is the way in which the patient’s temperature varies with time. In the
example in Fig 14.1, the temperature can be seen to be ‘swinging’ and this pattern is highly suggestive of a
serious infection or inflammatory process.
Fig 14.1: Swinging fever
Similarly, a steadily rising respiratory rate or pulse rate, or a falling blood pressure can highlight
evolving physiological changes much more readily than can a snapshot recording at one moment in time.
Early warning scores

‘Early warning scores’ are becoming increasingly used. Examples are the Physicians’ Early Warning
Score (PEWS) and the Medical Early Warning Score (MEWS). To calculate such a score, weightings are
given for deviations in set physiological parameters away from normality. The higher the deviation, the
greater the score. An example is shown in the table below. There are several advantages to such a system.
A patient with seemingly minor abnormalities in several parameters will be identified as acutely unwell
because their score will be quite high. Also, nursing staff who might not be confident in knowing when to
call for medical assistance can be assured that a high score equates to a seriously unwell patient who
requires urgent help from a senior doctor. As with any vital sign measurement, a change in early warning
score is more informative than a one-off reading.
Prytherch DR, Smith GB, Schmidt PE, Featherstone PI. ViEWS – Towards a national early warning score for detecting adult inpatient
deterioration. Resuscitation 2010;81:932–7.
Neurological observations
Neurological observations are recorded at intervals in patients who are at risk of deterioration in their
level of consciousness. Two commonly used systems are described.
1. AVPU
This is a quickly recorded summary measure of neurological status. The patient is graded as:
A – if they are Alert
V – if they respond to Voice
P – if they respond only to Pain
U – if they are Unresponsive.
2. Glasgow Coma Scale (GCS)

This is more time-consuming to measure than the AVPU score, but also provides more information. It is
scored out of 15, with a minimum score of 3 and a maximum of 15. The patient’s best response at the time
of assessment should be recorded.
TASK PERFORMANCE SCORE

Spontaneously 4
To speech 3
Eyes open
To pain 2
None 1
Oriented 5
Confused 4
Best verbal response Inappropriate words 3
Incomprehensible sounds 2
None 1
Obey commands 6
Localises pain 5
Flexion withdrawal 4
Best motor response
Abnormal flexion 3
Extension to pain 2
None 1
Figure 14.2 shows a GCS chart from a patient who exhibits a sudden drop in GCS at 11am.
Fig 14.2: Sudden drop in GCS.
Fluid balance chart

A carefully completed fluid balance chart can be extremely helpful in making management decisions for
patients. In essence, these charts record the quantity and type of all fluid entering and leaving the body.
Examples of fluid entering the body:
• Food and drink taken orally
• Intravenous fluid
Nutrition given enterally (eg via a nasogastric or percutaneous gastrostomy tube) or parenterally (ie
•
intravenous feeding)
• Blood products (eg packed red cells, platelets, cryoprecipitate, fresh frozen plasma)
• Intravenous drugs.
Examples of fluid leaving the body:
• Urine
• Bowel motions
• Blood (from any orifice, including blood loss during surgery)
• Fluid from drains (eg chest drain).
One should also bear in mind insensible fluid loss. This refers to fluid that is lost but not normally
recorded and includes moisture lost in expired air and sweat. A general rule of thumb is that, in normal
circumstances, a patient loses approximately 500 ml/day of fluid through insensible losses. These losses
can increase massively, eg if a patient has extensive burns or if they have a fever.
Interpreting a fluid balance chart should incorporate several steps:
Compare total input to total output, remembering to account for insensible losses. Are they equal, or
is there a positive or negative fluid balance? A positive fluid balance means that more fluid has
entered the patient than has left, and would be entirely appropriate, for example, in a patient being
treated for dehydration. A negative fluid balance means that more fluid has left the patient than has
1.
entered, and would be entirely appropriate, for example, in a patient with heart failure who is fluid
overloaded and being treated with diuretics. Is the total volume of fluid entering the patient too
little, adequate or too much for requirements? This will depend on the age, sex and weight of the
patient, and also on the state of health (particularly current illnesses, cardiac and renal function).
Look at the type of fluid that the patient has received and correlate this with the clinical
2.
circumstances.
Think about electrolytes. Is the patient receiving enough electrolyte replacement to account for his
or her body’s daily requirements as well as compensating him or her for any abnormal electrolyte
losses. For example, an elderly person might require 40 mmol potassium per day to maintain
3. potassium equilibrium when healthy. If he develops severe diarrhoea, however, he will lose a lot of
potassium from the gut and may well need much more than 40 mmol potassium per day to prevent
him becoming hypokalaemic. Output from drains can often be important sources of electrolyte
losses and can easily be overlooked.
Drug charts
A great deal of information about a patient can be gleaned by examining their drug chart. Errors are
common and doctors at all levels should be vigilant and watch for potentially dangerous mistakes or
oversights in drug prescriptions.
Other bedside data
Stool chart
Patients with altered bowel activity often have bowel movements recorded using a stool chart based on
the ‘Bristol Stool Chart’ (Fig 14.3). Although not very appealing, a chart such as this allows staff to
record the frequency and nature of bowel activity.
Bristol Stool Chart
Fig 14.3: Bristol Stool Chart. (From Lewis SJ, Heaton KW. Stool form scale as a useful guide to intestinal transit time. Scand J Gastroenterol
1997;32:920–4.)
Weight chart
It is often helpful to monitor a patient’s weight with time. Malnourished patients might be monitored for
weight gain after the establishment of a feeding programme, whereas patients with fluid overload are
often monitored for weight loss as they are treated with diuretics and their oedema improves. Sudden
dramatic changes in weight are, however, uncommon. Unless the patient has had a procedure (eg a large
quantity of fluid drained or limb amputation), be wary that a sudden change in weight might simply be an
error.
Blood glucose (and ketones)

Patients with diabetes mellitus will have their blood glucose level checked frequently during their stay
using finger-prick blood draws and glucometers. Adjustments to their treatment may be required if they
have either hyper- or hypoglycaemia. Patients with diabetic ketoacidosis will also have measurements
taken of ketone levels in the blood or urine. Blood ketone levels are increasingly being measured with
bedside ketometers, which work like glucometers. Urinary ketones are measured using urinalysis. As
treatment for diabetic ketoacidosis is administered, ketone levels should fall into the normal range.
Blood glucose recording is not limited to patients with diabetes, however. Other examples of patients
who should have blood glucose measured include:
• Patients who have been treated with insulin for hyperkalaemia
• Patients who are malnourished and are at risk of hypoglycaemia
• Patients with liver failure who are at risk of hypoglycaemia
• Patients on high doses of corticosteroids who are at risk of hyperglycaemia.
Respiratory function
Patients with respiratory difficulty often have simple respiratory tests performed at regular intervals. The
most common example would be the peak expiratory flow rate (PEFR) in patients with obstructive airway
disease such as asthma. In addition, patients at risk of neuromuscular weakness affecting respiration
should have their vital capacity checked regularly. A falling vital capacity can indicate the need for
assistance with ventilation.
Cardiac telemetry
Patients with cardiac disease and critical illness are at risk of cardiac arrhythmia and cardiac arrest, and
their heart’s electrical activity is often monitored using a bedside ECG machine. Interpretation of such
data is included in Chapter 10. A useful function of many telemetry machines is that the heart rhythm strips
are stored for several days. Patients who exhibit intermittent cardiac arrhythmias can have their heart
rhythms analysed retrospectively, thus allowing the identification of serious problems.
Other information at the bedside

The area around a patient’s bed often has a wealth of additional information for the astute observer to
note. Therapists who have assessed a patient may record information such as the following on signs
around the bed:
Details about mobility, including devices to be used when mobilising or how many staff members
•
will be required to help a patient mobilise.
Communication difficulties: patients with deafness, dysphasia or who do not speak the native
•
language may therefore be identified.
Swallowing difficulties: signs such as ‘nil orally’ or ‘yoghurt consistency foods only’ might be
•
seen.
• Dietary and fluid requirements such as fluid restrictions, salt restrictions, etc.
Case 14.1
Summarise the findings on the stool chart and list the potential causes
Answer 14.1
This patient is having bowel motion activity recorded formally using a faeces chart. At least eight motions
each day have been passed. The consistency has been Bristol type 6 and 7 indicating very soft, watery
motions. Furthermore it is mucoid and bloody. It would be important clinically for the fluid balance sheet
to be assessed in conjunction with the stool chart to assess for adequate hydration. Possible causes for
this pattern of bowel activity are listed in the box below.
Inflammatory bowel disease

Infective diarrhoea (eg Shigella, Salmonella)
Colorectal malignancy
Ischaemic colitis
Case 14.2
1. Explain the findings on this daily weight chart for this patient with liver cirrhosis and ascites.
2. What could be the reason for the sudden loss of nearly 7 kg on 14/06/05?
Answer 14.2
Daily weight charts are an extension of the standard fluid balance (‘input/output’) chart. In the short
term (hours and days) changes usually reflect a change in body fluid content. It is paramount (as
seen from the chart) that the recordings are taken at the same time each day. Dietitians keep weight
records for those who are undernourished, receiving enteral or parenteral nutritional
supplementation, or enrolled in dietary programmes. In such cases, changes in the longer term
become more important. The common reasons for recording daily weight are conditions in which
excess fluid is retained by the body – severe congestive cardiac failure, ascites or renal failure
1. being prime examples.
A response to treatment, in particular diuretics, and dietary sodium restriction may be monitored
using a weight chart in conjunction with a fluid balance chart.
This example documents a patient with significant ascites (excess fluid in the peritoneal cavity)
over a period of several days after treatment. Over the initial 4 days a steady, albeit relatively
small, daily reduction in weight is observed. This is in response to the introduction or increased
dosing of diuretic therapy.
On 14/06/05 a more substantial reduction of 6.8 kg is observed. This is due to paracentesis with the
2.
removal of a substantial volume of fluid.
Case 14.3
1. Describe each abnormality on the observation chart and the overall impression.
2. Where should this patient be cared for?
Answer 14.3
The diagnosis of sepsis requires a full patient assessment. However, the bedside chart may provide
the first evidence of impending sepsis. Taking an assessment of the chart over several hours, rather
1. than a snapshot, aids in the diagnosis as one views the alteration of three key parameters – blood
pressure, pulse rate and temperature. A persistent pyrexia or swinging fever is seen in the context of
haemodynamic instability (hypotension and tachycardia).
This example clearly shows a rising and sustained pyrexia with a maximum temperature of 39.9°C.
A falling blood pressure, to a low of 78/38 mmHg, with an accompanying tachycardia of 130
beats/min, demonstrates a haemodynamically unstable state.
If this patient fails to respond to initial treatment with fluids and antibiotics they should be
transferred to an HDU/ICU environment where inotropic support (eg noradrenaline) may be
2.
administered to support the cardiovascular system until the underlying infection has been identified
and treated.
Case 14.4
Give your impression of the problem in this patient.

Answer 14.4
This chart outlines the blood oxygen saturations taken at 2-h intervals by pulse oximetry throughout a 24-h
period. The vast majority are normal while breathing room air. If one was not to record the saturations
during sleeping hours the patient may be deemed to be entirely normal. However, during the period
02:00–06:00 hours there is evidence of significant deoxygenation with a low of 84% at 04:00 hours.
The likely diagnosis here is obstructive sleep apnoea (OSA). If one was to waken the patient purposefully
and then record the oxygen saturations they would probably return to normal. This diagnosis may be
confirmed through formal sleep studies.
Case 14.5
1. What abnormality is seen?

2. Suggest a list of potential underlying diagnoses.
Answer 14.5
This basic chart demonstrates a series of blood pressure measurements. Unlike a conventional
recording it indicates that some have been taken in different positions of posture. The likely
1. indication for this is a patient with a history of falls, especially an elderly patient. For changes to
be deemed significant, there must be a change in systolic blood pressure of greater than 20 mmHg
when the patient changes from lying to standing. This patient has postural (orthostatic) hypotension.
2. Potential diagnoses are listed below:
CAUSES OF POSTURAL HYPOTENSION

Idiopathic
Dehydration (hypovolaemia)
Drug induced (eg diuretics, vasodilators, anti-parkinsonian medication)
Addison’s disease
Autonomic neuropathy
Multisystem atrophy
Case 14.6
1. Explain the findings on the neuro-observation chart.

2. What are the potential causes?
Answer 14.6
The GCS is a routinely used method of accurately and objectively recording a patient’s level of
consciousness. It is an easy-to-use scoring system which may be recorded in a reproducible fashion
by nursing or medical staff. It comprises three independent categories – EYE OPENING, VERBAL
1.
RESPONSE and MOTOR RESPONSE. It is scored out of 15. The GCS must be measured in
patients with head injury and after any neurosurgical intervention. This bedside chart illustrates its
use in a patient after a fall.
On admission the GCS is 14/15 on the basis of the patient being confused. At midnight the
conscious level takes a drop from 14/15 to 10/15. Two hours later one can observe that the GCS
has returned to its admission level of 14/15. Further frequent monitoring throughout the morning
shows a repeat of this pattern – the GCS IS FLUCTUANT. An intracranial cause should be sought
with urgent imaging.
This pattern is typically seen in subdural haematoma. Following a fall, the patient is lucid at times
2. but the conscious level is variable. Extracranial causes, eg sepsis or hypoglycaemia, may also
account for such patterns.
Case 14.7
Explain what action one would take on becoming aware of these observations.
Answer 14.7
Changes in conscious level may be sudden and permanent as well as fluctuant. A significant drop in the
GCS should be acted upon without delay. This bedside chart records a large drop from 13 to 7. This
sudden change requires both a fast answer to establish the cause, and action to be taken to ensure the
welfare of the patient. A GCS of less than 8/15 is an indication for consideration of intubation as the
patient’s airway is likely to become compromised.
CAUSES OF LARGE SUDDEN DROP IN GCS

Intracerebral bleed Trauma – diffuse
(including subarachnoid haemorrhage) axonal injury
Cerebral oedema Metabolic causes
Drugs and alcohol (such as hypoglycaemia)
Case 14.8
Describe the findings on this chart.

Answer 14.8
There is a simple but striking finding on the general observation chart over a period of several hours. The
trend in temperature recordings is highly abnormal. It can be seen that the patient is apyrexic at times but
has a significantly elevated temperature on other occasions. This is a swinging or spiking fever. Each
temperature peak probably represents the shedding of bacterial toxins into the bloodstream. This finding
may be due to any underlying infective source – although the pattern is characteristically seen in the
setting of an abscess. A similar pattern can be seen in several rheumatological diseases e.g. Still’s
disease.
Case 14.9
Describe the findings on these charts and what investigation(s) are needed to confirm the cause.
Answer 14.9
Most patients will have several observation charts at the end of the bed. These should all be viewed in a
systematic fashion to maximise the information obtained. In this scenario, both the vital signs chart and the
bowel habit chart reveal the likely diagnosis.
An inpatient for several days following admission with dark stools and rectal bleeding, this patient has
remained stable, albeit with persistently abnormal bowel motions. It can be seen that on occasion the
motion is both loose and dark in nature, but is always relatively small in volume and the patient’s general
observations initially remain normal.
Fluid resuscitation, possibly with blood products, has occurred. Note on day 4 (08/06) that the patient
becomes progressively more tachycardic and with this the blood pressure falls. This corresponds to an
increase in the frequency of the motions, which are noted to be black and foul smelling in nature – this
patient has melaena.
The melaena has been present to an extent since admission; however, on this occasion the patient has
become haemodynamically unstable. There has been a significant upper gastrointestinal tract bleed. The
patient should now undergo emergency endoscopy to locate and if possible treat the cause. In the
meantime, intravenous fluids and packed cells should be administered. Any coagulopathy should be
corrected. One can see the blood pressure and tachycardia respond to fluid replacement (08/06 from
18:00 hours onwards).
Case 14.10
What electrolyte is likely to be deranged in this patient?

Answer 14.10
This relatively simple drug chart illustrates the importance of appreciating the actions of common
medications and the problems that can arise. On admission, the patient is on a K+-sparing diuretic
(spironolactone) at a dose that suggests an indication for liver disease rather than heart failure. On day 1
of his admission, an angiotensin-converting enzyme (ACE) inhibitor is introduced. The combination of an
ACE inhibitor (lisinopril) and spironolactone, although acceptable, should be appreciated and initially
the serum potassium should be checked to ensure that it does not rise to a dangerous level. Therefore,
when supplemental potassium is started the following day – perhaps by a busy doctor who does not
usually cover this patient and who has limited understanding of the patient’s overall case – we have a
potential disaster. If left unchecked the K+ may increase to a level causing cardiac dysrhythmias or,
worse, cardiac arrest.
Case 14.11
What has caused the difficulties in the INR level?

Answer 14.11
This scenario is based upon both a patient’s drug chart and warfarin chart. Those patients on warfarin
while in hospital should be placed on a dedicated warfarin chart. This generally outlines the indication
for its prescription, the desired target INR (international normalised ratio) range and the daily warfarin
dose and INR if taken. It is easy, but also dangerous, to view this chart in isolation. Following admission
this patient is started on erythromycin and the warfarin dose remains at the usual level from admission.
The INR was recorded before the first inpatient dose and was 2.35, perfectly placed in the desired range
for the indication, atrial fibrillation. On day 3 it is checked again and found to be 2.98. The dose is
decreased by 1 mg, but again 2 days later the INR has continued to rise to 3.99. This is not in the highly
dangerous range, but is enough to warrant consideration. The drug erythromycin is the cause. A macrolide
antibiotic, it is known to enhance the anticoagulant effect of warfarin through its effect as an enzyme
inhibitor in the liver.
Case 14.12
A patient’s heart rate is monitored frequently after an admission with a suspected myocardial infarction.
What is your interpretation, and what would you do for the patient?
Answer 14.12
The patient has a marked bradycardia. The blood pressure seems acceptable, so gathering more
information seems most appropriate at this stage. You should record a 12-lead ECG and attach the patient
to a cardiac monitor.
After a short time, you are called to interpret the cardiac monitor. You see the following on the screen:
What is your interpretation of the heart rhythm?

The rhythm is complete heart block (or third-degree heart block) (see page 350 for further details). The
patient requires drug treatment to speed the heart up, and will probably require the insertion of a
pacemaker.
MISCELLANEOUS
Ankle brachial pressure index
The ankle brachial pressure index (ABPI) is an easily measured clinical parameter that is often used to
assess the adequacy of blood flow to the lower limbs.
The patient should lie flat on a bed when having an ABPI measured. The systolic blood pressure in the
brachial artery is measured using a stethoscope and sphygmomanometer. The systolic blood pressure at
the ankle is then measured using a sphygmomanometer wrapped around the calf and a Doppler probe
positioned over the posterior tibial or dorsalis pedis artery. Cuff pressure is inflated until blood flow to
the foot is cut off. Flow is slowly re-established by deflating the cuff, and the pressure at which the first
Doppler signal is obtained is noted.
After performing these tests, the observer will have two figures – the systolic blood pressures in the
brachial artery and at the ankle. The ABPI is calculated simply by finding their ratio. In health, the ratio
should be greater than or equal to 1. As the value decreases, symptoms and signs of arterial insufficiency
to the lower limbs would be expected. Values lower than 0.5 may result in critical ischaemia. ABPIs of
lower than 0.2 can be associated with ulceration and gangrene.
ABPI INTERPRETATION
>1 Normal
<0.5 At risk of critical ischaemia
<0.2 At risk of ulceration and gangrene
One potentially complicating factor relates to the fact that some patients (particularly those with long-
standing diabetes mellitus) have calcified arteries which cannot be compressed with a blood pressure
cuff. In such cases, Doppler signals will be obtained even when the cuff is inflated to very high pressures.
ABPIs cannot be reliably measured in these patients.
DON’T FORGET
The ABPI must be interpreted with caution in patients with diabetes mellitus.
Synovial fluid analysis

Patients with acute monoarthritis often have synovial fluid aspirated for diagnostic purposes. It is
important to be able to differentiate between the common causes of the acutely red, hot and swollen joint
on the basis of fluid analysis.
APPEARANCE
LEUKOCYTE ON PLANE
DIAGNOSIS APPEARANCE COUNT POLARISED
(/mm3) LIGHT
MICROSCOPY
Septic arthritis Purulent >750 000
Haemarthrosis Heavily blood stained
Gout Cloudy 3000–40 000 Negatively birefrin-gent needle-shaped crystals
Pseudogout Cloudy 3000–40 000 Weakly positively birefringent rhomboidal crystals
MEMORY AID
Gout – remember the letter ‘N’ –
Negatively birefringent, Needle-shaped crystals of sodium urate
Pseudogout – remember the letter ‘P’ – weakly Positively birefringent rhomboidal
crystals of sodium Pyrophosphate
Schirmer test
Keratoconjunctivitis sicca is the term used to describe dry eyes. This phenomenon can occur in isolation
(primary Sjögren syndrome) or in association with many other rheumatological conditions.
The test is performed by attaching a specially shaped piece of filter paper to the lower eyelid. This is left
for 5 min, and the distance that has become wet is then measured. Normally 10 mm or more of the paper
will become wet.
Fig 15.1
It is important to bear in mind, however, that normal tear production is reduced in old age. Also, drugs
with anticholinergic properties, such as tricyclic antidepressants, reduce tear production and may result in
a false-positive Schirmer test.
PABA test
The PABA test is used to detect pancreatic exocrine insufficiency, ie failure of the pancreas to produce
sufficient enzymes for complete digestion.
The principle behind the test is simple. After fasting overnight, the patient is given a fixed dose of a
peptide comprising N-benzoyl-L-tyrosyl-pa-aminobenzoic acid (NBT-PABA). In a patient with normal
pancreatic exocrine function, pancreatic enzymes break down NBT-PABA into the smaller compound
PABA, which is then absorbed and excreted in the urine. Normally more than 70% of the dose
administered appears in the urine. Less than 70% excretion implies that the exocrine activity of the
pancreas is impaired.
DON’T FORGET
Normally >70% of the oral PABA dose is detected in the urine.
Tests for the presence of Helicobacter pylori

The Gram-negative bacillus H. pylori can infect the stomach and predispose to the development of peptic
ulcer disease. Testing for the presence of the organism should be carried out in all patients with a peptic
ulcer, and eradication should be attempted in affected individuals.
There are several methods that can be used to test for the presence of H. pylori.
Breath testing
This test relies on the fact that H. pylori organisms produce urease, an enzyme that breaks down urea to
form ammonia and carbon dioxide. The ammonia produced raises the pH and helps the organism survive
the acidic environment in the stomach.
In a H. pylori breath test, the patient is given a tablet containing radiolabelled urea ([13C]urea). If
infection is present, the organisms act on the urea to liberate radiolabelled carbon dioxide (13CO2). A
sample of breath is collected (eg in a tube or balloon), and analysed for the presence of 13CO2. If this is
detected, the test is positive and the patient can be assumed to be infected.
This test rapidly becomes negative if H. pylori is eradicated.
Detection of H. pylori antibodies

A sample of blood can be tested for the presence of IgG antibodies to H. pylori. The test can remain
positive for up to a year after eradication therapy, and so it is not a particularly useful way of testing for
clearance.
Campylobacter-like organism (CLO) test

This test also requires a biopsy sample obtained at oesophagogastro-duodenoscopy (OGD). The sample
of tissue is placed into a medium that contains urea and phenol red. Phenol red is a dye that turns red in
alkaline conditions. If H. pylori is present in the biopsy sample, its urease enzyme will liberate ammonia
from the urea in the medium, causing the pH to rise. The colour of the medium will therefore turn red (Fig
15.2).
Fig 15.2
Tissue histology
A stomach biopsy sample can be stained and examined under a microscope. This may reveal curved
organisms at the mucosal surface.
Tissue culture
A biopsy sample obtained at OGD can be cultured to look for the presence of offending organisms.
Audiograms
Audiograms illustrate, in graphic form, how well a person can hear noises at different frequencies. A
healthy ear can hear sounds transmitted in the air better than those conducted by bone. This is because the
ossicles in the middle ear amplify sound waves in the air.
Several patterns of abnormalities should be recognised.
Conductive deafness
Anything that impedes the progression of sound waves down the ear canal can result in conductive
1. deafness. The classic example of this is the patient with severe ear wax. In these conditions, sounds
conducted by bone will be heard louder than those conducted by air. The audiogram will show a gap
between the hearing level for air and bone conduction. This is termed a wide air–bone gap.
Fig 15.3
Sensorineural deafness
2. A patient with unilateral auditory nerve damage (eg due to an acoustic neuroma) will have reduced
hearing for both air conduction and bone conduction.
Fig 15.4
Presbyacusis
3. This describes the loss of hearing of sounds at high frequencies that is a common finding in elderly
patients. It represents a form of sensorineural deafness.
Fig 15.5
Noise-induced hearing loss

4. Patients with noise-induced hearing loss typically have difficulty hearing sounds with a frequency
around 4000 Hz. Their audiograms usually have a trough at this frequency level.
Fig 15.6
Cardiovascular risk
Until relatively recently, clinical judgement has been the main method of deciding which patients require
drug therapy for primary prevention against cardiovascular disease. Guidelines are now available that
aim to help doctors decide which patients require treatment. One part of a cardiovascular risk assessment
chart is shown here.
Fig 15.7 Reproduced with kind permission of Manchester University Press.

These charts are easily interpreted as follows.
Choose the correct chart using the patient’s sex, smoking status and age group. Whether or not a
patient is classified as a smoker depends on their lifetime exposure to smoke, not just their current
1.
smoking status. Thus, patients who are ex-smokers, but gave up smoking within the last 5 years,
should be classified as smokers for the purposes of interpreting these charts.
Knowledge of the patient’s systolic blood pressure and details of their lipid profile are plotted to
obtain the patient’s cardiovascular risk over the next 10 years. Note that the x-axis on the charts
2. plots the ratio of total cholesterol to high-density-lipoprotein (HDL) cholesterol, and this value
should be used when available. When only the serum cholesterol concentration is known, assume
that the HDL level is 1 mmol/l.
Ambulatory blood pressure monitoring
Ambulatory blood pressure monitoring (ABPM) is being increasingly used as an investigative tool in the
management of people with high blood pressure. It gives a lot more information than a one-off office
blood pressure measure, and can help identify people with various blood pressure patterns, such as:
White-coat hypertension: blood pressure ‘artificially’ high when measured by a doctor or nurse, ie
•
ABPM lower than clinic pressure.
Masked hypertension: blood pressure ‘artificially’ low when measured by a doctor or nurse, ie
•
ABPM higher than clinic pressure.
Nocturnal dipping: it is normal for the blood pressure to drop overnight when sleeping. The mean
•
arterial pressure should drop by at least 10 mmHg.
• Non-dipping: blood pressure that does not fall in sleep.
• Reverse dipping: blood pressure that increases during sleep.
To interpret an ABPM results summary take the following steps:
Look at how many of the attempted readings were successful. If the vast majority of readings were
• successful, the study is useful. If only a few readings were successful, the results of the study are
of questionable value.
Look at the average daytime pressure. Apply a ‘correction factor’ of 10/5 mmHg to this to
calculate an equivalent clinic blood pressure, eg if the average daytime pressure is 140/80 mmHg
•
on the ABPM, the equivalent clinic pressure would be 150/85 mmHg. This is the value that should
be used for making treatment decisions.
Compare the average daytime pressure with the most recent clinic readings and decide if the
•
patient is ‘normal’, or has ‘white-coat’ or ‘masked’ hypertension.
Look at the overnight blood pressure. Compare the mean arterial pressure overnight with that
obtained during the day. If the blood pressure does not dip normally, the patient should be
• questioned. A poor night’s sleep or obstructive sleep apnoea are common causes for blood
pressure failing to dip at night. If the patient slept well on the night of the study, one can use the
ABPM result to classify them into having normal-, non- or reverse-nocturnal dipping.
An ABPM record can also provide much more information, such as detail about the pulse pressure and
heart rate at various times of the day. These data may also be helpful in stratifying a patient’s cardiac risk.
Case 15.1
A 74-year-old woman attends the diabetes clinic for a routine appointment. Her medical history includes
type 2 diabetes (diagnosed 15 years previously), two previous myocardial infarctions and previous
varicose vein surgery. She has noticed an ulcer on her left leg. Examination reveals the presence of
varicose eczema, and a shallow ulcer of diameter 4 cm affecting the medial aspect of the left leg.
1. How would you manage this woman?

The ABPI was 0.9.
2. What treatment should the patient receive?
Answer 15.1
Leg ulcers can be the result of several underlying disease processes. Most commonly, ulcers can be
due to venous insufficiency, arterial insufficiency or a combination of both. The patient’s medical
history puts her at risk of both venous (previous varicose vein surgery) and arterial (diabetes and
ischaemic heart disease) ulcers. Findings on examination are, however, more in keeping with a
1. venous ulcer.
Management of venous ulceration is complex, but the mainstay relies on graduated pressure
bandages. However, these bandages can exacerbate arterial insufficiency, and should not be
routinely applied to all patients without first performing an ABPI measurement. The first step in the
management of this patient’s ulcer should therefore involve measurement of the ABPI.
The patient should be treated with graduated pressure bandages. Patients with an ABPI of less than
2.
0.8 should not, in general, have compression bandages applied.
COMPLETE CLINICAL CASES
Case 16.1
DATA COVERED IN THIS CLINICAL CASE SCENARIO
• Haematology: full blood picture

• Biochemistry: urea and electrolytes, amylase, glucose, ketones
• Respiratory: arterial blood gas
• Urinalysis
• Bedside chart: vital signs
An 18-year-old shop assistant is admitted with generalised abdominal pain that has been worsening for
36 hours. On examination, you find the abdomen to be generally tender, although there is no clinical
evidence of peritonism. The nurse hands you her observations recording sheet.
1. What parameters are notably abnormal? Does this narrow your differential diagnosis?
Shortly, you receive her initial blood results.
What is the major abnormality? Are any possible diagnoses less likely bearing these results in
2.
mind?
On account of the abnormalities seen, you perform a blood gas analysis. The results are shown. The
patient is breathing room air.
What are the causes of the acid–base abnormality demonstrated and what tests might you
3.
arrange to differentiate between them?
You request urinalysis. The results are shown.
4. Based on all the results so far, what is the apparent cause of the abdominal pain?
Treatment is commenced, and the patient appears to improve. You are asked to review her in 4 hours. Her
bedside charts on the opposite page show the trend of vital signs.
5. Are you satisfied that the patient is improving?

Repeat blood tests show the following:
6. What action would you take now?

Answer 16.1
The patient’s respiratory rate is increased. Your first thought might be that the patient has a problem
with breathing, and indeed this could be the case. A basal pneumonia, for example, can present with
abdominal discomfort. However, there are many reasons for tachypnoea outside the chest, eg
1. patients breathe faster when they are in pain or if they have a metabolic acidosis (to facilitate
respiratory compensation). As a result of the wide range of problems that can manifest with
increased respiratory rate, this sign is often regarded as the most sensitive parameter that something
serious is wrong with a patient.
The patient’s blood pressure is low. Again this could be due to a wide variety of reasons.
Commonly, blood pressure falls with blood loss, sepsis and dehydration. Bearing in mind the
abdominal pain, sensible suggestions would include a bleeding peptic ulcer, appendicitis or colitis.
Taking abdominal pain in context with tachypnoea and hypotension, the range of possible diagnoses

remains wide and further tests are required.
The major abnormality is the very low bicarbonate level. This is highly suggestive of a metabolic
2.
acidosis, although a measure of pH and PaCO2 would be required to be sure of this.
The normal haemoglobin is reassuring in terms of the fact that major blood loss would seem less
likely. It should be borne in mind, however, that, after an acute bleed, it takes some time before the
haemoglobin concentration falls – bleeding cannot therefore be ruled out using this test alone. The

normal white cell count makes an infective cause less likely. The normal amylase level makes acute
pancreatitis less likely, although sometimes the level can rise after a few hours, so if there is
suspicion of pancreatitis, the level should be repeated.
The blood gas analysis shows first that oxygenation is adequate. There is a metabolic acidosis
present with respiratory compensation. You should then proceed to calculate the anion gap based on
information presented earlier in the case. This is calculated as (142 + 3.9) – (94 + 7.6) = 44.3
mmol/l, and is therefore markedly raised. Note that it would also be reasonable to use the
3. bicarbonate level from the initial set of blood tests for your calculation, although it is good practice
always to use the most up-to-date results when making impressions about a patient’s current state.
Please refer to page 428 for a list of causes of this pH abnormality. Tests that would be useful at this
stage could include; blood glucose, urinary glucose, blood ketones, urinary ketones, blood lactate
and blood salicylate level if there is any suggestion of poisoning.
The presence of significant quantities of glucose and ketones on urinalysis, taken in context with an
increased anion gap metabolic acidosis, is highly suggestive of diabetic ketoacidosis (DKA). This is
4. recognised as an uncommon cause of abdominal pain and should always be borne in mind because it
can be easily missed. The diagnosis should be confirmed by measuring blood glucose and ketone
levels.

The chart shows an improving respiratory rate and blood pressure. This is good evidence that the
patient is improving. The administration of fluid and insulin to a patient with DKA is life saving and
can result in a dramatic improvement in condition. The falling blood ketone level is more important
than the normalisation of glucose levels. It would be important to see that the patient’s acid–base
5. status is normalising as a result of the treatment that you are giving. An important point to note is that
there is often a precipitating factor for DKA. Sometimes, as in this case, DKA can represent the first
presentation of type 1 diabetes. More commonly, in patients with known diabetes, DKA results from
missing insulin doses or an infection. In a case such as this one, you should be very vigilant not to
miss an underlying intra-abdominal precipitant for the DKA (eg appendicitis).
Repeat blood tests show the following:

The patient’s potassium level has fallen to an extremely low level due to the insulin given to treat the
DKA. This could result in a cardiac arrhythmia. The patient should have a 12-lead ECG recorded to
6.
look for evidence of hypokalaemia, and should be connected to a bedside cardiac monitor. The
patient should then receive an intravenous infusion of potassium.
The patient still has a high anion gap metabolic acidosis, but this is improving as the DKA is treated.
This would be expected to normalise entirely when the ketone level is back to normal and the patient

has received sufficient fluid replacement. If it does not, another concomitant cause for the acidosis
should be sought.
CASE SUMMARY
Wide anion gap metabolic acidosis due to diabetic ketoacidosis Hypokalaemia due to insulin treatment
Case 16.2
• Imaging: CT scan of brain

• Bedside chart: neurological observations
• Cardiology: ECG
• Biochemistry: troponin
A 72-year-old man with a history of hypertension and ischaemic heart disease was admitted 90 minutes
after the witnessed onset of acute right-sided arm and leg weakness, and right-sided facial droop.
1. What is the diagnosis, and what treatment should be considered?

Treatment is administered and the patient makes a reasonable recovery in the first few hours. You are then
called to assess him due to a deterioration in his condition. This is his neurological observations chart:
2. What do you think has happened, and what are your priorities?
You arrange another CT scan which shows haemorrhagic transformation in the same region as the
abnormality seen on the first scan.
3. What are your priorities now?

A blood test result comes back showing the following:
4. How will this affect your management?

The patient stabilises, and over the course of 2 weeks makes a reasonable improvement in conscious
level. The limb weakness remains profound. You review him because he has developed anterior chest
pain that reminds him of a previous myocardial infarction.
5. How would you interpret his ECG?
His chest pain settles after 1 hour; 12 hours later you request a blood test that shows the following:
6. What has happened and what are the challenges in management?

Answer 16.2
The patient has had a stroke caused by infarction in the territory of the left middle cerebral artery.
All patients presenting with infarction strokes should be considered for thrombolytic therapy. It is
important to ensure that there are no contraindications for thrombolysis. These include, but are not
1.
limited to, recent trauma or surgery, bleeding disposition and uncontrolled hypertension.
Thrombolysis must be administered relatively soon after symptom onset (current evidence suggests
within 4.5 h).
The patient’s level of consciousness has dramatically worsened. The integrity of the patient’s
airway should be assessed and the airway protected if necessary. Breathing and circulation should
be assessed next. A sudden drop in blood pressure might be indicative of a large amount of
bleeding somewhere in the body, precipitated by the thrombolytic agent. A bedside blood glucose
2.
reading should be taken because hypoglycaemia could present like this. Assuming that all these
parameters are satisfactory, you should then rapidly consider the intracranial status. Options
include extension of the infarction or intracerebral haemorrhage. A repeat CT scan of the brain
should be performed without delay.
The CT scan confirms that the patient’s infarct has undergone haemorrhagic transformation. The
priorities always start with ensuring that the ‘ABCs’ are stable. The patient may require airway
protection if the level of consciousness means that it is not secure. The next priority would be to
3. correct any problem that might increase bleeding propensity and increase blood loss into the brain.
Blood tests of coagulation and a platelet count should be arranged urgently. A haematologist should
be contacted about blood product replacement. A neurosurgeon should also be contacted for an
opinion as to whether surgical intervention with evacuation of haemorrhage might be helpful.
A patient with intracranial bleeding in the setting of thrombocytopenia should receive an infusion of
4. platelets with the intention of increasing the platelet count to a safe level. In the longer term, the
patient should be investigated to find out why the platelet count was so low.
This ECG shows horizontal ST depression in the anterior and lateral leads. This might simply
represent myocardial ischaemia (angina) but the possibility of a non-ST elevation myocardial
5.
infarction (NSTEMI) should be borne in mind. Biochemical testing for cardiac troponin will be
necessary to distinguish between these two possibilities.
The elevated blood troponin level would suggest that the patient has had a myocardial infarction.
Given the ECG noted earlier, the most likely diagnosis is NSTEMI. In ‘normal circumstances’ the
patient would receive anti-platelet therapy and heparin. The complicating factor in this case is that
6.
the patient is recovering from a recent intracerebral haemorrhage and any treatment given for the
heart might result in further bleeding in the brain. Difficult decisions will have to be made by senior
clinicians.
CASE SUMMARY
Stroke (infarction)
Haemorrhagic transformation of ischaemic stroke post-thrombolysis
Thrombocytopenia
Case 16.3
• Bedside chart: fluid balance chart

• Haematology: full blood picture, ESR
• Biochemistry: urea and electrolytes, glucose, protein, immunoglobulins
• Imaging: skull X-ray
A 64-year-old man is admitted for investigation of generalised aches and pains, and lethargy. He is
previously healthy and is on no prescribed medication. His fluid balance is monitored and, for the first
day of hospitalisation, is as follows:
1. How would you interpret the fluid balance chart? What is your differential diagnosis?
You request a panel of blood tests that come back showing the following. His kidney function had been
found to be normal 4 months before.
2. What are the abnormalities, and what is the likely diagnosis?
A skeletal survey is performed. Here is the skull x-ray.
3. How does the X-ray appearance relate to the likely diagnosis?

After several days, the laboratory phones through the following results:
You request a blood calcium level. It is returned as 2.59 mmol/l.

4. What is the cause of the abnormality seen on the fluid balance chart at the start of the case?
Answer 16.3
The patient’s urinary output seems excessive when compared with the amount of fluid consumed.
The most common cause for this pattern is treatment with diuretics (eg for oedema in heart failure).
1. We are told, however, that the patient is on no treatment, so this is not the cause. Other causes of
polyuria include diabetes mellitus, diabetes insipidus, hypercalaemia and following the relief of
urinary tract obstruction.
Several abnormalities are demonstrated, and the key to making the diagnosis is thinking of a
condition that could explain all the results. It is possible that several disease processes coexist in the
patient, but a single unifying diagnosis would be much more likely. The abnormalities are:
2.
normocytic anaemia, elevated ESR, acute kidney injury, high total protein and low albumin. The
glucose level is normal making diabetes mellitus less likely. The normal sodium concentration
makes diabetes insipidus less likely, but does not exclude it.
The key to suspecting the correct diagnosis here lies with correct interpretation of the protein and
albumin results. Total protein is a measure of albumin plus globulins. As this patient’s albumin level
is low and the total protein level is high, one can extrapolate that the globulin (IgG, IgA and IgM)
level must be high. The disease most likely to give an elevated globulin level along with all the
other abnormalities documented is multiple myeloma.
Lytic bone lesions are a recognised feature of multiple myeloma. Patients would routinely undergo a
3.
‘skeletal survey’ to identify bony pathology in this condition.

You request a blood calcium level. It is returned as 2.59 mmol/l.
The IgG level is highly elevated, and the levels of other immunoglobulins are suppressed. The
4. particular type of myeloma in this patient is one in which abnormal plasma cells are producing
massive quantities of IgG. This test confirms myeloma as the diagnosis.
Although the blood calcium level is apparently normal, the cause of the polyuria documented is
hypercalcaemia. Don’t forget to correct calcium levels for abnormalities with serum albumin. As

this patient’s albumin level is 30 g/l, the ‘corrected calcium’ level is 2.84 mmol/l which is high (see
page 67 for details).
CASE SUMMARY
Multiple myeloma
Hypercalcaemia
Case 16.4

• Cardiology: ECG, echocardiogram
• Imaging: chest X-ray, renal ultrasound
• Biochemistry: U&Es, lipids, glucose, oral glucose tolerance test, urine catecholamines, albumin:creatinine ratio
• Endocrinology: aldosterone, renin
• Miscellaneous: ambulatory blood pressure recording
A 51-year-old male teacher is referred for investigation of high blood pressure. He has been started on an
ACE inhibitor by his GP after two readings showing moderate hypertension. He does not smoke. You
arrange ambulatory blood pressure monitoring.
1. What is your interpretation of this recording?

As a result of this investigation, you arrange a series of tests, the results of which are shown below.
2. What are your conclusions based on these results? What further tests would be helpful?
3. Calculate the 10-year cardiovascular risk using the prediction chart on page 504.
You arrange an oral glucose tolerance test, which shows the following:
4. How would you interpret the test, and how does this affect cardiovascular risk?
You decide to stop treatment to allow a hormone test to be carried out.
5. What are the implications of this test, and how might you investigate further?
Answer 16.4
Ninety-six per cent of blood pressure readings were successful, meaning that the study is valid and its
results meaningful. The average daytime pressure was 162/88 mmHg. Applying a correction factor of
10/5 mmHg, we might assume that the equivalent clinic blood pressure is 172/93 mmHg and is in
keeping with significant hypertension. The other major finding on the report is that the patient’s blood
1.
pressure rises at night. This is abnormal. Assuming that the patient had a good night’s sleep on the night
of the study and that he does not have obstructive sleep apnoea, this is a worrying finding. ‘Reverse
dipping’ of blood pressure at night increases the chances of finding a secondary cause for the
hypertension.

A chest X-ray in a patient with hypertension can potentially show evidence of coarctation of the aorta,
in the form of rib notching. More commonly, cardiomegaly or signs of cardiac failure might be seen.
The absence of cardiomegaly on a chest X-ray does not rule out the possibility of left ventricular
hypertrophy (LVH). The ECG has findings in keeping with LVH. The ECG is, however, only really a
screening test for LVH, and echocardiography is necessary to establish its presence with certainty.
2.
LVH is confirmed on the echocardiogram. This signifies evidence of target organ damage from
hypertension and suggests that measures should be taken to lower the pressure as soon as possible. The
ultrasound study was normal, but might have shown findings such as a renal tumour, echobright kidneys
(common in ‘medical’ kidney disease) or abnormal Doppler tracings (associated with renal artery
stenosis).
The biochemistry results show mild hypokalaemia and a sodium concentration towards the upper end
of the normal range. The hypokalaemia is particularly surprising as the patient is taking an ACE
inhibitor, which would be expected to cause hyperkalaemia if anything. The finding of hypokalaemia in
a patient with hypertension should raise suspicions of an underlying diagnosis of primary
hyperaldosteronism.
The glucose level is raised, but we are not given any information explaining whether this is a fasting
level or whether in fact the patient had just eaten a sugary substance. It is not in the ‘normal’ range,
however, and further steps should be taken to clarify the patient’s glycaemic status. The lipid profile is
suboptimal for a patient at risk of cardiovascular disease.
The urinary albumin:creatinine ratio is a measure of protein excretion from the kidneys. The level seen
in this patient is in the ‘microalbuminuric’ range. The level requires repeating to ensure that it is truly

abnormal. Assuming that it is a true value, however, this would be further evidence of target organ
damage – this time to the kidney.
Using the chart for a non-diabetic, non-smoking, 51-year-old man, and plotting the ‘corrected’
3. ambulatory daytime systolic blood pressure and cholesterol:HDL ratio, it should be apparent that this
patient’s 10-year cardiovascular risk is in the ‘greater than 20%’ zone (>30% if the line is used).
The patient has impaired glucose tolerance because, although the fasting glucose level is normal, the
4.
level after glucose loading is between 7.8 and 11.0 mmol/l.
We have already estimated the cardiovascular risk as more than 20% in the next 10 years. The
particular risk tool that was used did not, however, have any way for impaired glucose tolerance to be
taken into consideration. As this is a further cardiovascular risk factor, we can assume simply that the

patient’s risk is even higher than that calculated. If the fact that the patient has LVH and
microalbuminuria is also taken into consideration, the actual risk will be considerably higher than
20%.
The test was performed in a patient suspected of having primary hyperaldosteronism. In this condition,
aldosterone levels will be high and, because of negative feedback, renin levels will be low. The
5.
suggested cutoff value for an abnormal ratio, as detailed on page 146, is 30. In this case, the hormone
patterns are in keeping with primary hyperaldosteronism and the ratio is greatly increased.
The patient should be investigated further by arranging a further test such as a saline suppression test.
Imaging of his adrenal glands to search for a tumour (could be a carcinoma or more likely an adenoma)
should then be undertaken. Adrenal hyperplasia can also cause this hormone abnormality. A CT scan
would be the first imaging modality used in most instances. Nuclear imaging can also be used, and
adrenal vein hormone sampling may also be required.
CASE SUMMARY
Hypertension
Left ventricular hypertrophy
Impaired glucose tolerance
Primary hyperaldosteronism
Case 16.5
• Respiratory: blood gas analysis

• Biochemistry: U&Es, liver function tests, glucose
• Cardiology: ECG, cardiac arrest rhythm recognition
• Toxicology blood levels
A 45-year-old woman with a history of depression is admitted at 1.30am after the ingestion of an
unknown quantity of antidepressants (specific type unknown) 5 hours before. She is fully conscious on
arrival at the hospital and insists that she does not want to live, but is refusing to answer your questions.
You perform a blood gas analysis:
1. How would you interpret this test? What else would you like to measure?
The biochemistry laboratory phones through her initial results to a member of the team:
2. How would you interpret these tests, and how would your management change?
An ECG is performed and a rhythm strip printed.
3. What substance has she taken in overdose, and what is the priority in management?
While you are preparing to give her a drug, her monitor starts to alarm. There is no response from the
patient and there is no pulse. Her bedside cardiac monitor shows the following rhythm:
4. What is the rhythm and how will you manage the patient?
Answer 16.5
Oxygenation is adequate given that the patient is breathing 40% oxygen. The pH is low in keeping
with an acidosis. The bicarbonate and carbon dioxide levels are also low, so the patient has a
metabolic acidosis with respiratory compensation. It would be helpful to perform a U&E profile, so
that the anion gap can be calculated. Given the clinical scenario, however, a raised anion gap
1.
acidosis would be expected. You should also measure paracetamol concentrations, because,
although the patient denies taking paracetamol, its level should generally be measured in all patients
presenting after an overdose (as the treatment of paracetamol toxicity is simple, and not treating
could have catastrophic consequences).
The bicarbonate is low in keeping with the known metabolic acidosis. The anion gap is 35.8 mmol/l
which is raised. Please note that the list of causes for acid–base abnormalities listed in page 170.
2. Given that the blood sample was drawn at 5 hours post-ingestion, we can be confident that treatment
for paracetamol poisoning is not required in this case. Her blood alcohol level is reasonably high,
indicating that she has recently consumed alcohol.
The major abnormality with the ECG is the broadening of the QRS complexes. Taken in the context
of a patient who has ingested an antidepressant and has a metabolic acidosis, we can be fairly
3. certain that she has taken a tricyclic antidepressant. Given the ECG abnormalities, she is at high risk
of cardiac arrhythmia and/or seizures. She should be placed on a cardiac monitor and intravenous
sodium bicarbonate administered to correct the cardiac arrhythmia and the acidosis.
You should instantly recognise this rhythm tracing as ventricular tachycardia. On occasion, this
rhythm can generate sufficient cardiac output such that a pulse is felt. In this case, no pulse can be
felt and the patient is in cardiac arrest. The cardiac arrest treatment algorithm should be started
4.
without delay (treatment details outside the scope of this text). As this rhythm often responds to
defibrillation, this should be a treatment priority. Sodium bicarbonate should also be administered to
the patient.
CASE SUMMARY
Tricyclic antidepressant overdose
Ventricular tachycardia
Case 16.6

• Toxicology: blood levels
• Biochemistry: liver function tests, U&Es
• Haematology: coagulation
• Imaging: chest X-ray
• Microbiology: sputum
• Bedside chart: vital signs
An 18-year-old student is found by her housemates. She is in a confused state on the floor and is
surrounded by several packets of paracetamol. It is 22:00 hours and they are able to ascertain that she
took the tablets around 15:30 hours that day. She smells of alcohol. She had been on medications for low
mood but is otherwise healthy. On arrival at hospital half an hour later blood tests were taken which are
shown.
1. With the above results in mind outline the treatment approach for this patient.
Following the commencement of her treatment blood tests are taken on a regular basis and are shown
below.
Outline the trend and significance of these results. What treatment should be considered
2.
now?
She is transferred to a regional centre where she undergoes surgery. In the initial days postoperatively she
progresses well, but on day 5 becomes short of breath and a chest X-ray is taken which is shown below.
3. Report the findings on this chest X-ray.
At the same time a sample is sent for arterial blood gas analysis. The patient was breathing room air.
4. What abnormality is observed on the arterial sample?
She is commenced on antimicrobial therapy and sputum is sent for analysis. The following day the results
of her sputum analysis are conveyed from microbiology.
During the middle of the night you are called by the nurse to see her as some of her vital signs are
concerning. Her bedside chart is shown.
5. Describe the findings on the chart and the underlying cause.

Answer 16.6
1. The following should have been interpreted from the data provided in this scenario.
This woman has probably taken a substantial overdose of paracetamol in combination with alcohol.
The level of 160 mg/l is 6½ hours after ingestion. The significance of this is seen below on the
paracetamol nomogram. At 6½ hours, the line intersects the normal treatment line of the graph at 125
mg/l making treatment necessary at levels higher than this: 160 mg/l is well above this line.

The patient should be treated with an intravenous infusion of N-acetylcysteine. The exact dose
2.
depends on the weight of the patient.
This chart shows the changes in liver function over the 2–3 days following overdose. A huge surge
in transaminases is seen from 20 hours indicating substantial hepatocellular damage from the toxic
effects of paracetamol. Hepatic necrosis is taking place and the liver is failing. This can be seen
because the prothrombin time is rising and the albumin is falling, as the ability of the liver to
synthesise protein is diminishing. A liver transplantation should be considered.
Her transfer to a regional centre was to facilitate liver transplantation. Five days after her operation
3. her chest X-ray, sputum analysis and ABG indicate that she had developed a postoperative
pneumonia.

The arterial blood gas shows a marked hypoxia with a normal pH. She has type 1 respiratory failure,
4.
caused by pneumonia.
From the sputum analysis a specific causative organism has been identified – Streptococcus
pneumoniae. It must be emphasised that culturing takes time. Treatment should be instigated with
empirical therapy, and altered later, if necessary, on the basis of the growth and sensitivities.
5. The bedside chart shows three key findings:
1. Pyrexia
2. Hypotension
3. Tachycardia.
In the context of an established pneumonia this may be in keeping with septic shock.
CASE SUMMARY
Paracetamol overdose requiring treatment
Development of hepatic failure requiring liver transplantation
Postoperative type 1 respiratory failure due to pneumonia
Development of septic shock
Case 16.7
• Bedside chart: neurological observations

• Imaging: CT of the brain
• Neurology: CSF analysis
• Neurology: EEG
A 38-year-old teacher is brought to hospital by her concerned husband due to her unusual behaviour and
sleepiness over the past 48 h. She has recently returned from supervising a school trip.
Her observation chart from the initial 6 h of her admission is shown.
CT of the brain is arranged and the following report is telephoned to her doctor.
Clinical examination revealed no signs of raised intracranial pressure. After discussion with the patient’s
consultant, lumbar puncture is performed. The details are below.
Summarise the findings from the CSF analysis and suggest one further specific test that might
1.
be performed on the CSF given the clinical history.
In the meantime an electroencephalogram is also performed. The report is sent back with the patient.
2. Given the result of the EEG, CSF analysis and CT brain imaging what is the likely diagnosis?
Answer 16.7
Given the finding of an altered conscious level, the patient is placed on a neuro-observation chart.
1. The observation chart shows a stable Glasgow Coma Scale of 13/15. The patient is deemed to be
confused and opens her eyes to speech.
The CT brain imaging is abnormal. Lumbar puncture and an EEG are therefore performed to help

come to a diagnosis.
This collection of findings is termed a CSF pleocytosis.
CAUSES OF A CSF PLEOCYTOSIS

Viral meningitis
Encephalitis
Partially treated bacterial meningitis
TB or fungal meningitis
Intracranial abscess
Post-subarachnoid haemorrhage
One should have inferred from the clinical scenario so far that the cause of her symptoms and CSF
findings is a viral meningitis/encephalitis. An additional test would be for PCR serology of the CSF to
enable detection of viruses, especially herpes simplex virus (HSV).
2. The EEG findings demonstrate the characteristic neurophysiological findings of HSV encephalitis.
Further tests in HSV encephalitis would include:
• MRI of brain:
• Oedema within the temporal lobes bilaterally (better seen than on CT)
• PCR serology of CSF:
• HSV-1: present.
CASES SUMMARY
A CSF pleocytosis
Herpes simplex encephalitis
Case 16.8
• Haematology: iron studies

• Biochemistry: liver function tests
• Genetics
• Peritoneal fluid analysis
• Haematology: coagulation
A 34 year-old oil-rig engineer is required to attend a medical before a secondment to his company’s
overseas operation in Brunei. He has been fortunate with his health with no previous attendance within
the health service. He admits to smoking 20 cigarettes a day and drinking approximately 38 units of
alcohol a week. His conscientious doctor sends several tests. The following results were of some
concern.
1. What can one infer from this iron profile?

2. Ferritin is an acute phase reactant. Name some other acute phase reactants.
His liver function tests are recalled on the computer and are shown below.
3. What do the liver function tests show?
The doctor is concerned about an underlying genetic disorder and a blood sample is sent to the genetics
laboratory. The result below was obtained.
The doctor tries to arrange treatment, but unfortunately the patient leaves his job and no further medical
action is taken. Nothing is heard of him for several years, until he is admitted to a local hospital with a
distended abdomen and fever.
Physical examination demonstrates the presence of ascites. Peritoneal aspiration is performed and shown
below.
He is treated for the acute condition and further blood tests are performed to assess his liver function.
5. What do these liver function tests suggest?

Answer 16.8
These results suggest a state of iron overload. The most likely reason for this in an otherwise healthy
1.
person found at screening is hereditary haemochromatosis. Haemochromatosis may present with:
• Cardiomyopathy
• Liver disease
• Pituitary disease
• Diabetes mellitus
• Joint problems (pseudogout).
All manifestations are related to the deposition of iron within organs.
2. Other acute phase reactants include:
• CRP
• ESR
• Ceruloplasmin.
Note that albumin acts as a ‘negative acute phase reactant’ – its levels decreasing with inflammation.
As is commonly the case, both at diagnosis and in established disease, the LFTs are essentially
3. normal. The only abnormal LFT is the GGT which is mildly elevated. Given his clinical history this
is likely to reflect heavy alcohol consumption rather than haemochromatosis.
Idiopathic haemochromatosis is an inherited autosomal recessive condition. Only homozygotes
develop clinically overt disease. There is now a gene test for haemochromatosis and screening of
first-degree relatives of patients is offered. The most common genetic defect is homozygosity of the
C282Y missense mutation of the HFE gene on chromosome 6p. In addition, a different mutation –
H63D – can play a role in some cases.
With appropriate management, patients with haemochromatosis should, in large part, not develop
liver failure.
The presentation with ascites implies the development of liver cirrhosis with portal hypertension.
4.
The peritoneal aspiration performed tells us three things:
The serum–ascites albumin gradient (SAAG) is 32 – 19 = 13 g/l. This tells us that the patient
•
probably has portal hypertension.
• The ascitic fluid is infected with the Gram-negative micro-organism E. coli.
• There is a high neutrophil count.
This all implies spontaneous bacterial peritonitis. In the acute setting, the most important result to
note would be the WCC. An elevated WCC should be taken as evidence for peritonitis and
appropriate therapy instituted before culture results are obtained. If the WCC had been normal, one
should consider ascites secondary to the development of hepatocellular carcinoma.
Haemochromatosis patients with cirrhosis are susceptible to this primary liver malignancy.
5. The accompanying LFTs show:
• Poor synthetic function (prothrombin time UP and albumin DOWN)
• Mildly deranged liver function
The patient has developed liver failure as a result of the combined hepatotoxic insults of iron and
•
alcohol.
CASE SUMMARY
Haemochromatosis
Spontaneous bacterial peritonitis
Liver failure
Case 16.9
• Haematology: full blood count

• Biochemistry: bone profile, urate and CRP
• Immunology: autoimmune screen
• Miscellaneous: knee aspirate analysis
• Respiratory: spirometry
• Imaging: chest X-ray and DEXA scan
A 39-year-old secretary attends hospital with a painful and swollen right knee, pains in the fingers and
fatigue. The finger pains have been with her for several weeks and are especially bad first thing in the
morning, making her work difficult. The knee is a more recent complaint.
On examination there is active synovitis in the small joints of the hands and a large effusion of the right
knee.
Among the initial blood tests from the A&E officer are those shown.
1. Describe the findings.

An enthusiastic junior doctor carries out knee aspiration, to exclude septic arthritis. The results are
shown.
A few days later the result of her autoimmune screen is sent to the ward.
She is treated for her arthritis and attends regular review for many years with a variable course to her
illness. On one occasion she complains of increasing shortness of breath and on auscultation of the chest
there are inspiratory crepitations at the bases.
Spirometry is arranged. The results are shown.
The accompanying chest X-ray is shown.
2. What problem does this patient now have and how may it be related to her treatment?
3. What further radiological investigation would be of benefit?
Six months later the patient sustains a forearm fracture. She is referred for a DEXA scan. The results can
be seen below.
4. Outline the significance of these results.
Answer 16.9
1. The important findings from the FBC, bone profile and other biochemistry tests are:
• A normocytic anaemia (low haemoglobin and normal MCV)
• A substantially raised CRP
• A normal urate
• A normal bone profile.
Sometimes normal blood results are as important as positive ones. In this case, gout is on the list of
differential diagnoses for an acute-onset, painful, swollen joint so the urate level is important to
measure. However, remember that the urate level can be normal in acute gout.
The knee aspirate sample is normal. No white cells or organisms were identified, and culture was

negative, excluding septic arthritis. Similarly, no crystals were seen to suggest a crystalline arthritis.
The result of the autoimmune screen is important. The rheumatoid factor is highly elevated, which in
the context of the clinical symptoms and earlier finding of a raised CRP and normochromic anaemia

implies a diagnosis of rheumatoid disease. There are three important points to remember about
rheumatoid factor:
• Its level does not necessarily reflect disease activity.
• It can be raised in a number of states other than rheumatoid disease (ie poor specificity).
It does not need to be positive for the diagnosis of rheumatoid disease to be made (20% of
•
patients are rheumatoid factor negative).
Interestingly, the screen also has antibodies to gastric parietal cells and intrinsic factor in keeping
with a diagnosis of pernicious anaemia. It is common for patients to suffer from several coexisting
autoimmune diseases.
2. The positive findings from spirometry with transfer factor are:

• A reduced FEV1
• A reduced FVC
• A high FEV1/FVC ratio
• A reduced transfer factor.
This demonstrates a restrictive pattern wholly in keeping with interstitial lung fibrosis.
The presence of fibrosis may be due to:
The disease itself – pulmonary fibrosis is one of the pulmonary manifestations of rheumatoid
•
disease
A side effect of treatment with methotrexate (first-line disease-modifying anti-rheumatic drug
•
treatment for this condition).
As seen in the report above HRCT is advisable as this will help clarify in greater detail the nature
3.
and extent of the disease.
Patients with rheumatoid disease often have exacerbations (‘flares’) of their disease requiring
treatment with either intravenous or oral steroids. The disease itself and steroid treatment put such
4. patients at risk of developing osteoporosis which is diagnosed by dual energy X-ray absorptiometry
(DEXA) scanning. A T score of less than –2.5 indicates osteoporosis. A score of –1.5 to –2.5 implies
the presence of osteopenia.
CASE SUMMARY
Knee effusion (due to rheumatoid disease)
Interstitial lung fibrosis (rheumatoid lung)
Steroid-induced osteoporosis
Case 16.10

• Biochemistry: urea and electrolytes
• Bedside chart: fluid input/output
• Cardiology: ECG
• Imaging: abdominal X-ray
A 74-year-old man is admitted with a painful abdomen. He has a history of hypertension and atrial
fibrillation. He had a laparotomy as a younger man for a gastric ulcer. He has not passed a motion in
several days. On examination his abdomen is tender with rebound.
An abdominal X-ray is taken and shown below.
1. Interpret this X-ray.

The patient’s condition rapidly deteriorates. An arterial blood gas is analysed.
2. Interpret this ABG.
The patient has emergency surgery. After a short stay in the high dependency unit (HDU) he returns to the
ward. Several days later he complains of further abdominal discomfort after his patient-controlled
analgesia (PCA) device is stopped. On examination he is tender in the suprapubic space and this area is
dull to percussion. A urinary catheter has been in situ since surgery.
His fluid (input/output) chart is observed.
3. Describe the findings.
Blood and urine are sent for analysis
4. What problem has occurred?
Immediate treatment is given for hyperkalaemia.

5. An ECG was done just before treatment. Describe the findings on the ECG seen below.
Answer 16.10
2. Interpretation of the ABG.
The findings on arterial blood analysis are:

• Oxygenation is adequate.
• A low pH. This patient is profoundly acidotic.
• A low PaCO2. Respiratory compensation is occurring.
• A low HCO3–. The origin of excess acid is metabolic in nature.
A high lactate. This is a ‘rogue’ acid being produced in large quantities. In this case ischaemia of
•
the large bowel is the cause.
The anion gap can be calculated:
Anion gap = (Na+ + K+) – (Cl– + HCO3–) = 23.6 mmol/l
This patient has a high anion-gap metabolic acidosis, most likely due to lactic acidosis, secondary to
3.
an ischaemic bowel.
One should infer from the bedside chart that:

• there is a significant positive balance
• the urine output has tailed off in the last 4 hours
• before becoming anuric the urine output was poor.
This patient has anuria which was preceded by a period of oliguria. In the first instance the urinary
4.
catheter should be checked and flushed to ensure that there is no blockage.
The blood results show that this patient has developed acute renal failure. From the clinical history it

appears that this is due to obstruction of the renal tract.
The patient has life-threatening hyperkalaemia. A potassium of greater than 6.5 mmol/l (in the context

of acute renal failure) requires immediate treatment.
5. The ECG shows classic changes related to hyperkalaemia. The T waves are tall and peaked.
CASE SUMMARY
Large bowel obstruction
Bowel ischaemia with metabolic acidosis
Acute renal impairment (due to bladder outlet obstruction)
ECG abnormality (due to hyperkalaemia)
Case 16.11

• Biochemistry: urea, electrolytes and CRP
• Haematology: full blood picture (FBP)
• Imaging: chest X-ray
• Pleural fluid analysis
• Microbiology: stool analysis
A 54-year-old pilot is admitted to the local hospital with a complaint of increasing shortness of breath.
He has noted this especially while flying recently and he has been seen by his occupational health doctor
and prohibited from flying until investigation has been undertaken. He also complains of a cough and
intermittent fever.
On examination the trachea is sited centrally. The left lung base is dull to percussion, vocal resonance is
decreased and breath sounds are decreased.
Included in your initial investigations are a chest X-ray, FBP, U&Es, CRP and ABG. All are shown below
for interpretation.
1. What abnormalities are

2. Describe the findings on this ABG.
3. Comment on this chest X-ray.
A decision is made to perform a pleural tap for diagnostic purposes based on the findings from the initial
investigations. The results are shown.
He is treated with a cephalosporin antibiotic based on known sensitivities. Three days into this treatment
he develops diarrhoea. Stool samples are sent by his nurse. The result is shown below.
5. What is the best course of action based on these findings?
Answer 16.11
1. From the initial investigations one should have identified the following:
There is a raised WCC (predominantly comprising neutrophils), along with a raised CRP. The
•
possibility of infection should be entertained.
• In addition, you will note a mildly raised urea, reflective of a mild degree of dehydration.
2. The ABG features two findings:

• A low PaO2. The patient is hypoxic. He has type 1 respiratory failure.
A low PaCO2. The patient is short of breath and hyperventilating, causing a low CO2. This has
•
led to a respiratory alkalosis.
3. The chest X-ray indicates the likely cause for the findings so far.
4. From the pleural fluid analysis one can see:

• This is an exudate with an elevated total protein and LDH level.
Putting all this information together and correlating it with the patient’s clinical features, the likely
5. cause for this pleural effusion is an underlying pneumonia. This is termed a ‘parapneumonic pleural
effusion’.
The patient goes on to develop diarrhoea. The most likely cause is simple diarrhoea secondary to the
commencement of antibiotics. However, one must be suspicious of Clostridium difficile as a

causative organism for the diarrhoea, particularly since this patient has received a cephalosporin
antibiotic.
The stool sample indicates the presence of C. difficile toxin. Ideally the causative antibiotic should
be stopped and a suitable alternative used instead. Oral metronidazole should also be commenced to
treat the C. difficile.
CASE SUMMARY
Pneumonia
Exudate pleural effusion (parapneumonic)
Type 1 respiratory failure with hyperventilation
Clostridium difficile infection (secondary to antibiotic treatment)
Case 16.12
• Biochemistry: U&Es
• Endocrine: thyroid function tests
• Endocrine: short Synacthen® test
• Biochemistry: urinary electrolytes and osmolality
A 62-year-old male patient with inoperable lung cancer is admitted on the general medical take-in with
acute confusion. Physical examination is unremarkable. Routine blood tests are sent, and the following
results are obtained.
1. His weight is 61 kg. Estimate his glomerular filtration rate.
On the basis of these tests, a host of other investigations are organised. The results of these are shown
below.
2. What is his thyroid status?
3. Interpret this test result.

4. His blood glucose is 4.6 mmol/l. Calculate his plasma osmolality.
5. What is the overall diagnosis?
Answer 16.12
From the information given, the eGFR could be calculated (see page 62 for details). Alternatively, the
1.
following formula could be used to give an approximation of the GFR:
2. His thyroid status is normal.
3. This is a normal short Synacthen® test indicating normal adrenal gland function.
4. Plasma osmolality is calculated as:

Plasma osmolality = 2 × (115 + 4.4) + 3.5 + 4.6 = 246.9 mosmol/kg.

This patient fits the diagnostic criteria for SIADH, which is most likely secondary to his lung cancer,
5.
most commonly with the small cell subtype. His confusion is probably due to hyponatraemia.
CASE SUMMARY
Hyponatraemia
SIADH
Case 16.13
• Biochemistry: sweat analysis

• Genetics: mutation analysis
• Miscellaneous: PABA test
• Haematology: D-dimer
• Microbiology: sputum culture
• Miscellaneous: audiogram
A 28-year-old patient is admitted to hospital on account of weight loss. She has an inherited condition.
Browsing through old medical notes, the admitting doctor noted the following results.
1. What genetic condition does this patient have, and what is the inheritance pattern?
The medical team are concerned about pancreatic exocrine insufficiency and organise a PABA test. The
following result is returned.
2. Does the patient have pancreatic exocrine insufficiency?
During the course of her inpatient stay, the patient develops a cough with a degree of haemoptysis. The
doctor is concerned about the possibility of a pulmonary embolism, and requests the following test
urgently.
3. How does the D-dimer result help in managing the patient?
The patient then becomes pyrexic, and clinical signs suggest pneumonia. The medical team commence
co-amoxiclav. Sputum is sent for culture. Two days later the following result is obtained.
On the basis of these sensitivities, and a worsening clinical state, the patient’s antibiotics are changed to
gentamicin.
A short time later the patient complains of hearing loss. The following audiogram is obtained.
4. What type of hearing loss has she developed, and how would you explain it?
Answer 16.13
1. This patient has cystic fibrosis, which is inherited in an autosomal recessive manner.
Yes. Pancreatic insufficiency is common in cystic fibrosis. More than 70% of the oral PABA should
2.
normally be excreted in the urine.
The D-dimer is normal. This indicates a very low probability of a thromboembolic event such as a
pulmonary embolism. Other causes of haemoptysis should be sought. In very rare situations, the D-
3.
dimer can be normal in the presence of thrombosis, so clinical judgement is always essential when
interpreting this result.
The audiogram shows sensorineural deafness. This is a rare but characteristic side effect of
4.
aminoglycoside antimicrobials such as gentamicin.
CASE SUMMARY
Cystic fibrosis
Pancreatic exocrine insufficiency
Pneumonia
Gentamicin-induced hearing loss
Case 16.14

• Haematology: haematinics
• Haematology: blood film
• Miscellaneous: CLO test
• Pathology: biopsy result
A 72-year-old man presents with increasing epigastric discomfort. He has been troubled with heartburn
for several years. He admits to drinking ‘more than he should’. The admitting doctor noted pallor, and
requested the following.
A blood film is examined. The following report is obtained.
2. Is this result in keeping with your answer to question one?
He proceeds to have an oesophagogastroduodenoscopy (OGD). Two abnormalities are noted. First, he is

noted to have an abnormal appearance of the lower oesophagus. Second, gastritis is observed. A biopsy
is taken from the lower oesophagus and the stomach. A CLO test is performed. You note the following
after 24 h.
3. What treatment should be commenced on the basis of this CLO result?
One week later, the following result is phoned through from the pathology laboratory:
4. What is the condition affecting the oesophagus?

Answer 16.14
This patient has a microcytic anaemia. The mild thrombocytosis may be due to active bleeding. The
1.
haematinics show iron deficiency.
2. Yes. The abnormal blood cells described can all be found with iron deficiency.
The result is CLO positive, indicating gastric infection with Helicobacter pylori. The patient should
3. be commenced on a course of antibiotics with a proton pump inhibitor, in an attempt to eradicate the
infection.
The patient has a Barrett oesophagus, and will require surveillance OGDs for monitoring the
4.
disease.
CASE SUMMARY
Iron deficiency anaemia
Helicobacter pylori-positive gastritis
Barrett’s oesophagus
Case 16.15

• Haematology: red cell mass
• Biochemistry: urinary sodium
• Microbiology: urinalysis
An 85-year-old man who is a smoker is admitted complaining of abdominal discomfort. No abnormalities

are detected on clinical examination, but some routine blood tests are requested. Your colleague is
concerned about the following test result, and asks for your help.
1. What is this abnormality called, and how would you proceed?
The result is repeated and confirmed. He proceeds to have an estimation of red cell mass.
2. What does this result indicate?
On the basis of this result, arterial blood gas analysis was performed when the patient was breathing
room air.
3. How would you interpret the blood gas?
An ultrasound scan of the abdomen revealed a mass in keeping with a renal cell carcinoma.
The patient proceeded to surgery, and underwent a nephrectomy. He spent 2 days in the intensive care
unit after the operation, but returned to the ward on day 3 after the operation. His urine output
deteriorated on day 4, and a urine specimen was sent for analysis.
What does this result tell you about the cause of the oliguria, and how would you treat the
4.
patient?
The patient’s urine output recovers. Several days later he complains of a burning pain on passing urine,
and of having to pass urine more often than normal. The following result is obtained on urinalysis.
5. How would you interpret the urinalysis, and what further urine test would you request?
Answer 16.15
The PCV is elevated, indicating polycythaemia. A measurement of the red cell mass is required to
1.
distinguish true polycythaemia from apparent polycythaemia.
2. The red cell mass result indicates true polycythaemia, and a cause should be sought.
3. The arterial blood gas analysis is entirely normal.
The urinary sodium concentration is low, suggesting that the oliguria is due to prerenal causes, ie
4.
hypovolaemia. The patient requires intravenous fluid resuscitation.
The urine contains nitrites and leukocyte esterase. In keeping with the clinical history, these changes
5. are most commonly caused by a urinary tract infection. The most useful next investigation would be a
urine culture.
CASE SUMMARY
Renal cell carcinoma
Postoperative prerenal uraemia
INDEX
Page numbers in bold refer to the clinical cases.
abdominal X-rays (AXR) ref1, ref2

bowel obstruction ref1, ref2, ref3, ref4
masses ref1
pancreatitis ref1
renal calculi ref1
volvulus ref1
ABG see arterial blood gases
ABPI (ankle brachial pressure index) ref1, ref2
abscesses ref1, ref2, ref3
cerebral ref1
N-acetylcysteine (NAC) ref1
acidosis ref1
compensation ref1, ref2, ref3
diabetic ketoacidosis ref1
metabolic ref1, ref2, ref3, ref4, ref5, ref6, ref7, ref8, ref9
respiratory ref1, ref2
see also alkalosis
acromegaly ref1, ref2, ref3
ACTH see adrenocorticotrophic hormone
activated partial thromboplastin time (APTT) ref1, ref2, ref3
acute phase reactants ref1, ref2
CRP ref1, ref2, ref3, ref4
ESR ref1, ref2, ref3
acute tubular necrosis ref1
Addison disease ref1, ref2, ref3
ADH see antidiuretic hormone
adrenal hormones ref1
Cushing syndrome ref1, ref2
hypoadrenalism ref1, ref2
phaeochromocytoma ref1
primary hyperaldosteronism ref1, ref2
adrenocorticotrophic hormone (ACTH) ref1, ref2, ref3
short Synacthen test ref1, ref2, ref3, ref4
adult respiratory distress syndrome ref1
AFP (α-fetoprotein) ref1, ref2, ref3
alanine aminotransferase (ALT) ref1, ref2
see also liver function tests
albumin
calcium and ref1, ref2
in multiple myeloma ref1, ref2
SAAG ref1, ref2
alcohol abuse
biochemistry ref1, ref2, ref3, ref4
histopathology ref1
peritoneal fluid analysis ref1
aldosterone ref1, ref2
alkaline phosphatase (ALP)
bone disease ref1, ref2
liver disease see liver function tests
alkalosis ref1
compensation ref1, ref2, ref3
metabolic ref1, ref2
respiratory ref1, ref2, ref3
see also acidosis
ALP (alkaline phosphatase)
liver disease see liver function tests
α-fetoprotein (AFP) ref1, ref2, ref3
ALT (alanine aminotransferase) ref1, ref2
alveolar gas equation ref1
alveolar–arterial gradient ref1
Alzheimer disease ref1
amaurosis fugax ref1
ambulatory blood pressure monitoring (ABPM) ref1, ref2, ref3
amylase ref1, ref2, ref3, ref4
anaemia ref1
blood film abnormalities ref1, ref2, ref3
haematinic deficiencies ref1, ref2, ref3, ref4, ref5, ref6
haemolytic ref1, ref2, ref3
spirometry ref1, ref2
thalassaemia ref1
Angelman syndrome ref1
angina pectoris ref1, ref2
anion gap ref1, ref2, ref3, ref4
ankle brachial pressure index (ABPI) ref1, ref2
antibiotics
causing deafness ref1, ref2
causing diarrhoea ref1, ref2
monitoring ref1
sensitivity testing ref1
warfarin and ref1
antibodies see immunoglobulins
anticoagulants
heparin ref1, ref2
warfarin ref1, ref2
antidepressant overdose ref1, ref2
antidiuretic hormone (ADH) ref1, ref2
SIADH ref1, ref2, ref3
anti-phospholipid syndrome ref1
aortic aneurysm ref1
APTT (activated partial thromboplastin time) ref1, ref2, ref3
arrhythmia ref1
atrial ref1, ref2, ref3, ref4
heart block ref1, ref2, ref3
ventricular ref1, ref2, ref3, ref4
arterial blood gases (ABG) ref1
acid–base status ref1, ref2, ref3, ref4, ref5, ref6, ref7, ref8, ref9
CO poisoning ref1
COPD ref1
hyperventilation ref1, ref2
normal ref1, ref2, ref3
overdose ref1, ref2, ref3, ref4, ref5
pneumonia ref1, ref2, ref3, ref4
pulmonary fibrosis ref1
respiratory failure ref1
type 1 ref1, ref2, ref3
type 2 ref1
arthritis ref1
gout ref1, ref2, ref3, ref4
synovial fluid analysis ref1, ref2, ref3, ref4
asbestos ref1
ascites ref1
malignancy ref1
pancreatitis ref1
SBP ref1, ref2, ref3, ref4
weight chart ref1
aspartate transaminase (AST) ref1, ref2, ref3
aspirin overdose ref1
asthma ref1, ref2
asystole ref1
atelectasis (collapsed lung) ref1, ref2, ref3
atrial fibrillation ref1, ref2, ref3, ref4
atrial flutter ref1
atrioventricular block ref1
audiography ref1, ref2, ref3
autoantibodies ref1, ref2, ref3, ref4
in haemolytic anaemia ref1, ref2, ref3
in PBC ref1, ref2
in pernicious anaemia ref1, ref2, ref3
autosomal inheritance
dominant ref1, ref2, ref3
recessive ref1, ref2
AVPU scale ref1
AXR see abdominal X-rays
B-type natriuretic peptide (BNP) ref1, ref2

bacteria ref1
Barrett oesophagus ref1, ref2, ref3
Bazett’s correction (Q–T interval) ref1, ref2
bedside charts ref1
drugs ref1, ref2
ECG ref1, ref2
fluid balance ref1, ref2, ref3, ref4, ref5
neuro-observations ref1, ref2, ref3, ref4
stools ref1, ref2, ref3
vital signs see vital signs charts
weight ref1, ref2
-HCG (-human chorionic gonadotrophin) ref1, ref2
bicarbonate ref1, ref2
biliary disorders ref1, ref2, ref3, ref4
see also primary biliary cirrhosis
bilirubin
in CSF ref1
haemolysis ref1, ref2
bleeding time ref1
see also coagulation
blood film abnormalities ref1, ref2, ref3
blood pressure monitoring ref1, ref2, ref3
see also hypertension; hypotension
BNP (B-type natriuretic peptide) ref1, ref2
bone disorders ref1, ref2, ref3, ref4, ref5, ref6
bowels
absorption of haematinics ref1, ref2, ref3, ref4
cancer ref1, ref2
coeliac disease ref1, ref2
gas on AXR ref1
inflammatory bowel disease ref1, ref2
obstruction ref1, ref2, ref3
stool charts ref1, ref2, ref3
volvulus ref1
bradycardia ref1, ref2
brain
abscess ref1
anoxia ref1
CT scans ref1, ref2, ref3, ref4
encephalitis ref1
extradural haematoma ref1
glioma ref1
histopathology ref1
hydrocephalus ref1
meningitis ref1, ref2
metastatic disease ref1
stroke ref1, ref2, ref3, ref4
subarachnoid haemorrhage ref1, ref2
subdural haematoma ref1, ref2
breast, mastectomy ref1
breath test ref1
breathing rate ref1, ref2, ref3
bronchial carcinoma ref1, ref2
bundle branch-block ref1, ref2
burns victims ref1
C-peptide ref1
C-reactive protein (CRP) ref1, ref2, ref3, ref4
CA-19-9 ref1
CA-125 ref1, ref2
caecal volvulus ref1
calcification ref1, ref2
calcium ref1, ref2, ref3, ref4, ref5
Campylobacter-like organism (CLO) test ref1, ref2, ref3
cancer
brain ref1
gastrointestinal ref1, ref2
intraperitoneal ref1
liver ref1
lung ref1, ref2, ref3
lymphoma ref1, ref2
metastatic
to bone ref1, ref2
to brain ref1
to lung ref1
multiple myeloma ref1, ref2, ref3
ovary ref1
pituitary gland ref1, ref2, ref3, ref4, ref5
renal cell carcinoma ref1
testis ref1
tumour markers ref1, ref2
carbon dioxide (CO2) ref1, ref2, ref3
carbon monoxide (CO) poisoning ref1
carbon monoxide transfer coefficient (KCO) ref1, ref2, ref3
carcinoembryonic antigen (CEA) ref1, ref2
cardiovascular system
biomarkers ref1, ref2, ref3, ref4
cardiac failure ref1, ref2, ref3, ref4, ref5
CT and MRI ref1
CXR ref1, ref2, ref3, ref4
digoxin toxicity ref1, ref2, ref3
dynamic testing ref1
ECG ref1, ref2, ref3
echocardiography ref1, ref2, ref3, ref4
heart rate ref1, ref2
heart rhythm ref1
atrial fibrillation ref1, ref2, ref3, ref4
cardiac arrest ref1, ref2
sinus rhythm ref1, ref2
ventricular tachycardia ref1, ref2, ref3, ref4
myocardial infarction ref1, ref2, ref3, ref4, ref5, ref6, ref7
potassium levels and ref1, ref2, ref3
risk profile ref1, ref2, ref3
valvular disease ref1, ref2
carpal tunnel syndrome ref1
catecholamines ref1
catheters, problems with coagulation profile ref1, ref2
CEA (carcinoembryonic antigen) ref1, ref2
central nervous system see brain
cerebrospinal fluid (CSF) ref1, ref2, ref3
cerebrovascular accident see stroke; subarachnoid haemorrhage
chest X-rays (CXR) ref1
cancer ref1, ref2, ref3
cavitation ref1
collapsed lung ref1, ref2, ref3
cystic fibrosis ref1
foreign bodies ref1, ref2
heart conditions ref1, ref2, ref3, ref4
mastectomy ref1
mediastinal abnormalities ref1, ref2, ref3
pleural effusions ref1, ref2, ref3, ref4
pneumonia ref1, ref2, ref3
pneumoperitoneum ref1, ref2
pneumothorax ref1, ref2
pulmonary fibrosis ref1
pulmonary oedema ref1
cholangitis ref1
cholecystitis ref1
cholestatic disease ref1, ref2, ref3
chromosomal abnormalities ref1
chronic obstructive pulmonary disease (COPD) ref1, ref2, ref3
Churg–Strauss syndrome ref1, ref2
cirrhosis
ascites ref1, ref2
histopathology ref1
PBC ref1, ref2, ref3, ref4
CLO test ref1, ref2, ref3
clonidine suppression test ref1
Clostridium difficile ref1, ref2, ref3
coagulation
bleeding disorders ref1, ref2, ref3
warfarin/INR charts ref1, ref2
colon
cancer ref1, ref2
gas on AXR ref1
inflammatory bowel disease ref1
obstruction ref1, ref2
volvulus ref1
computed tomography (CT) ref1, ref2, ref3, ref4
head ref1, ref2, ref3, ref4
conductive deafness ref1
confusion
cerebral causes ref1
metabolic causes ref1, ref2, ref3
consciousness, monitoring ref1
fluctuating ref1
reduced ref1, ref2, ref3
sudden drop ref1, ref2, ref3, ref4
Coombs test ref1, ref2
COPD (chronic obstructive pulmonary disease) ref1, ref2, ref3
copper overload ref1
cortisol ref1
high levels ref1, ref2
creatine kinase ref1
creatinine ref1, ref2
creatinine clearance ref1, ref2, ref3, ref4
Creutzfeldt–Jakob disease ref1
Crohn disease ref1, ref2
CRP (C-reactive protein) ref1, ref2, ref3, ref4
CSF (cerebrospinal fluid) ref1, ref2, ref3
CT see computed tomography
culturing of microorganisms ref1, ref2
cystic fibrosis ref1, ref2, ref3, ref4
D-dimer ref1, ref2, ref3, ref4, ref5

deafness ref1, ref2, ref3
deep venous thrombosis ref1, ref2, ref3, ref4
defibrillation ref1
dehydration (hypovolaemia) ref1, ref2, ref3
dementia ref1
dermatomyositis ref1
dexamethasone suppression test ref1, ref2
diabetes insipidus ref1, ref2
diabetes mellitus ref1, ref2, ref3, ref4
diabetic ketoacidosis (DKA) ref1, ref2
diarrhoea ref1, ref2, ref3, ref4
diffuse alveolar damage ref1
digoxin ref1, ref2, ref3
direct antiglobulin test ref1, ref2
disseminated intravascular coagulation (DKA) ref1, ref2
drips, sampling from ‘drip’ arm ref1
drug charts ref1, ref2
drug monitoring ref1, ref2
drug overdose see overdose
drugs of abuse ref1, ref2
dual energy X-ray absorptiometry (DXA) scan ref1, ref2
early warning scores ref1

ECG see electrocardiography
echocardiography ref1, ref2, ref3, ref4
EEG (electroencephalography) ref1, ref2, ref3, ref4
eGFR see glomerular filtration rate
electrocardiography (ECG) ref1
antidepressant overdose ref1, ref2, ref3
bedside ref1, ref2
cardiac axis ref1
digoxin toxicity ref1, ref2, ref3
exercise stress testing and ref1
heart rate ref1
heart rhythm ref1
atrial fibrillation ref1, ref2, ref3
cardiac arrest ref1, ref2
sinus rhythm ref1, ref2
ventricular tachycardia ref1, ref2, ref3, ref4
myocardial infarction ref1, ref2, ref3, ref4
P waves ref1, ref2, ref3, ref4
pacemakers and ref1
potassium levels and ref1, ref2, ref3
QRS complexes ref1, ref2, ref3, ref4, ref5
Q–T interval ref1, ref2
ST segment ref1, ref2, ref3
T waves ref1, ref2, ref3, ref4
electroencephalography (EEG) ref1, ref2, ref3, ref4
electrolytes
alcohol abuse ref1, ref2
anion gap ref1, ref2, ref3, ref4
input/output ref1, ref2
osmolarity/osmolality ref1, ref2, ref3
re-feeding syndrome ref1, ref2
see also potassium; sodium
electromyography (EMG) ref1, ref2
encephalitis ref1
endometriosis, ovarian ref1
eosinophilia ref1, ref2, ref3
epilepsy ref1
erythrocyte sedimentation rate (ESR) ref1, ref2, ref3, ref4
erythrocytes see red blood cells
exercise stress test ref1
extradural haematoma ref1
exudates
ascites ref1, ref2, ref3
pleural ref1, ref2, ref3, ref4
see also transudates
eye
dry ref1, ref2
loss of vision ref1
faeces charts ref1, ref2, ref3

familial disease see genetic disease
FBP see full blood picture
ferritin ref1, ref2, ref3, ref4
FEV1 ref1
FEV1/FVC ref1, ref2
fever (pyrexia) ref1, ref2, ref3, ref4
fibrin/fibrinogen ref1, ref2
fibrosis see pulmonary fibrosis
FiO2 ref1
fluid balance
ADH and ref1, ref2, ref3
dehydration ref1, ref2, ref3
input/output charts ref1, ref2, ref3, ref4, ref5
problems with IV fluids ref1
weight charts ref1
folate ref1, ref2, ref3
forced expiratory volume in 1 second (FEV1) ref1
forced vital capacity (FVC) ref1
foreign bodies in X-rays ref1, ref2
fractures ref1
fructosamine ref1
full blood picture (FBP) ref1
anaemia ref1, ref2, ref3, ref4, ref5
arthritis ref1, ref2
platelet abnormalities ref1, ref2
polycythaemia ref1, ref2, ref3, ref4, ref5
SLE ref1
white cell abnormalities ref1, ref2, ref3
FVC (forced vital capacity) ref1
gallbladder disease ref1

gamma-glutamyl transpeptidase (GGT) ref1, ref2
gas, on X-rays ref1, ref2
gastrointestinal (GI) tract
anaemia and ref1, ref2, ref3, ref4
Barrett oesophagus ref1, ref2, ref3
bleeds ref1, ref2
bowel obstruction ref1, ref2, ref3
cancer ref1, ref2
diarrhoea ref1, ref2, ref3, ref4
gas on AXR ref1
H. pylori ref1, ref2, ref3
histopathology ref1
volvulus ref1
GCS see Glasgow Coma Scale
genetic disease
chromosomal abnormalities ref1
inheritance patterns ref1, ref2
see also cystic fibrosis;
haemochromatosis
gentamicin ref1, ref2
gestational diabetes mellitus ref1
GGT (gamma-glutamyl transpeptidase) ref1, ref2
GH see growth hormone
Glasgow Coma Scale (GCS) ref1
fluctuating score ref1
reduced score ref1, ref2, ref3
sudden drop ref1, ref2, ref3, ref4
glioma ref1
glomerular filtration rate (GFR) ref1, ref2, ref3, ref4
glucocorticoids ref1
glucose
in blood ref1, ref2, ref3, ref4, ref5, ref6
in CSF ref1
Goodpasture syndrome ref1
Gram-staining of bacteria ref1
Graves disease ref1
growth hormone (GH)
acromegaly ref1, ref2
deficiency ref1
Guillain–Barré syndrome ref1
haematinics ref1, ref2, ref3, ref4

haemochromatosis ref1, ref2, ref3, ref4
haemoglobin ref1, ref2, ref3, ref4
carboxyhaemoglobin ref1
glycated ref1
haemoglobinopathies ref1, ref2, ref3
haemolytic anaemia ref1, ref2, ref3
haemostasis see coagulation
Hashimoto thyroiditis ref1, ref2
HCG (human chorionic gonadotrophin) ref1, ref2
head CT scans ref1, ref2, ref3, ref4
head injuries ref1, ref2
head X-rays ref1, ref2
hearing loss ref1, ref2, ref3
heart see cardiovascular system
Helicobacter pylori ref1, ref2, ref3
helminths ref1
heparin ref1
heparin-induced thrombocytopenia (HIT) ref1
hepatic disease see liver
hepatitis ref1, ref2, ref3
hepatocellular carcinoma ref1
hereditary disease see genetic disease
hereditary spherocytosis ref1
herpes simplex encephalitis ref1
histopathology ref1
Hodgkin disease ref1
human chorionic gonadotrophin (-HCG) ref1, ref2
hydrocephalus ref1
hydrogen breath test ref1, ref2
hyperaldosteronism, primary ref1, ref2
hypercalcaemia ref1, ref2, ref3, ref4
hyperglycaemia ref1, ref2, ref3, ref4
hyperkalaemia ref1, ref2, ref3, ref4, ref5
hypernatraemia ref1, ref2
hyperparathyroidism ref1, ref2
hyperprolactinaemia ref1, ref2
hypertension ref1
ABPM ref1, ref2, ref3
endocrine causes ref1
malignant ref1
portal ref1, ref2, ref3
pulmonary ref1, ref2, ref3
hyperthyroidism ref1, ref2, ref3
hypoadrenalism ref1, ref2
hypoglycaemia ref1
hypokalaemia ref1, ref2, ref3, ref4, ref5
hyponatraemia ref1, ref2, ref3, ref4, ref5
hypotension
postural ref1
in sepsis ref1
hypothyroidism ref1, ref2
hypovolaemia (dehydration) ref1, ref2, ref3
hypoxia see respiratory failure
immunoglobulins
autoantibodies ref1, ref2, ref3, ref4, ref5
oligoclonal bands ref1, ref2
plasma cell dyscrasias/multiple myeloma ref1, ref2, ref3
serological tests ref1, ref2, ref3
impaired fasting glucose/impaired glucose tolerance ref1, ref2, ref3
imprinting ref1
infections ref1
ascites (SBP) ref1, ref2, ref3, ref4
CSF ref1, ref2, ref3
helmintic ref1
urinary tract ref1, ref2, ref3
see also pneumonia
inflammatory markers ref1, ref2
CRP ref1, ref2, ref3, ref4
ESR ref1, ref2, ref3, ref4
ferritin ref1
infusions, electrolyte measurements and ref1
inheritance patterns ref1
autosomal dominant ref1, ref2, ref3
autosomal recessive ref1, ref2
genetic imprinting ref1
mitochondrial genes ref1, ref2, ref3
X-linked dominant ref1, ref2, ref3
X-linked recessive ref1, ref2
insulin ref1
insulin tolerance test ref1
international normalised ratio (INR) ref1, ref2
interstitial lung disease see pulmonary fibrosis
intrinsic factor ref1, ref2
iron
deficiency ref1, ref2, ref3, ref4, ref5, ref6
haemochromatosis ref1, ref2, ref3, ref4
ischaemia
bowel ref1
cardiac see myocardial infarction
cerebral (stroke) ref1, ref2, ref3
lower limb ref1, ref2
jaundice, obstructive ref1, ref2, ref3
karyotypes ref1
keratoconjunctivitis sicca ref1, ref2
ketones ref1, ref2, ref3
kidney
calculi ref1
GFR and creatinine ref1, ref2, ref3, ref4
histopathology ref1
renal cell carcinoma ref1
renal failure ref1, ref2, ref3, ref4
urea ref1, ref2, ref3, ref4
urinary sodium ref1, ref2, ref3
lactate dehydrogenase (LDH) ref1

Lambert-Eaton myasthenic syndrome ref1
large bowel see colon
left bundle branch-block (LBBB) ref1, ref2
leg ulcers ref1
leukocytes see white blood cells
leukoerythroblastic blood films ref1
LFT see liver function tests
lithium ref1
liver
alcohol abuse ref1, ref2, ref3, ref4
cancer ref1
cirrhosis see cirrhosis
haemochromatosis ref1, ref2
hepatitis ref1, ref2, ref3
histopathology ref1
paracetamol overdose ref1, ref2, ref3
liver function tests (LFTs) ref1
alcohol abuse ref1
alcohol abuse plus haemochromatosis ref1, ref2, ref3, ref4
infection ref1
obstructive jaundice ref1
paracetamol overdose ref1, ref2
PBC ref1, ref2
Wilson disease ref1
lower limb ulcers ref1
lumbar puncture ref1
see also cerebrospinal fluid
lung
asthma ref1, ref2
cancer ref1, ref2
metastatic ref1
cavitation ref1
collapsed ref1, ref2, ref3
COPD ref1, ref2, ref3
CXR ref1, ref2, ref3, ref4, ref5
cystic fibrosis ref1
fibrosis ref1, ref2, ref3, ref4, ref5, ref6
functional testing ref1, ref2, ref3, ref4, ref5
histopathology ref1
oedema ref1
pneumonia see pneumonia
sarcoidosis ref1, ref2, ref3, ref4
lymphocytosis ref1, ref2, ref3, ref4
lymphoma ref1, ref2
magnetic resonance imaging (MRI) ref1, ref2, ref3

mastectomy ref1
mean cell volume (MCV) ref1, ref2, ref3, ref4
mediastinum, on CXR ref1, ref2, ref3
melaena ref1
meningitis ref1, ref2
metabolic acidosis ref1, ref2, ref3, ref4, ref5, ref6, ref7, ref8, ref9
diabetic ketoacidosis ref1
metabolic alkalosis ref1, ref2
metanephrines ref1, ref2
microbiology ref1, ref2, ref3
microscopy
blood films ref1, ref2, ref3
CSF ref1, ref2
histopathology ref1
microbiology ref1, ref2
minimal inhibitory concentration (MIC) ref1
mitochondrial genes ref1, ref2, ref3
mixed connective tissue disease ref1
Mobitz type I/II heart block ref1
motor neuron disease ref1
MRSA (meticillin-resistant S. aureus) ref1
multiple myeloma ref1, ref2, ref3
multiple sclerosis ref1, ref2, ref3, ref4
myasthenia gravis ref1, ref2
myelofibrosis ref1
myeloma ref1, ref2, ref3
myocardial infarction ref1, ref2, ref3, ref4, ref5, ref6, ref7
myotonic dystrophy ref1
NAC (N-acetylcysteine) ref1

nerve conduction studies ref1, ref2
neurological investigations ref1
bedside observation charts ref1, ref2
CSF analysis ref1, ref2
neurophysiology ref1
neutrophils
in ascites ref1, ref2
in blood ref1, ref2, ref3
in CSF ref1, ref2
noise-induced hearing loss ref1
nutritional profile ref1, ref2
obstructive sleep apnoea ref1

oesophagus ref1, ref2
oligoclonal bands ref1, ref2
opiate overdose ref1
optic nerve ref1
oral glucose tolerance test (OGTT) ref1, ref2, ref3, ref4, ref5, ref6
osmolarity/osmolality ref1, ref2, ref3
osmotic fragility test ref1
osteomalacia ref1, ref2
osteoporosis ref1, ref2, ref3, ref4
ovarian cancer ref1
ovarian endometriosis ref1
overdose ref1
ABGs ref1, ref2, ref3, ref4, ref5
antidepressants ref1, ref2
digoxin ref1, ref2, ref3
lithium ref1
opiates ref1
paracetamol ref1, ref2, ref3, ref4
salicylates ref1
oxygen
ABG analysis (PaO2) ref1, ref2
saturation (SpO2) ref1
P waves ref1, ref2, ref3, ref4

P–R interval ref1, ref2, ref3
PaBa test ref1, ref2, ref3
pacemakers ref1, ref2
packed cell volume (PCV) ref1, ref2
PacO2 ref1, ref2, ref3
Paget disease of bone ref1, ref2
pancreas
acute pancreatitis ref1, ref2, ref3
chronic pancreatitis ref1
primary biliary cirrhosiPABA test ref1, ref2, ref3
pancytopenia ref1
PaO2 ref1, ref2
paracentesis see ascites
paracetamol overdose ref1, ref2, ref3, ref4
paraneoplastic conditions ref1, ref2
parapneumonic pleural effusion ref1
parathyroid hormone (PTH) ref1, ref2
Parkinson disease ref1
PBC (primary biliary cirrhosis) ref1, ref2, ref3, ref4
PCV (packed cell volume) ref1, ref2
peak expiratory flow rate (PEFR) ref1, ref2, ref3
pelvic masses ref1
peptic ulcers ref1
pericarditis ref1
peritoneal cavity, gas in ref1, ref2
peritoneal fluid see ascites
peritonitis ref1, ref2, ref3, ref4
pernicious anaemia ref1, ref2, ref3
pH ref1, ref2
see also acidosis; alkalosis
phosphate
pituitary tumours (hormone-secreting) ref1, ref2, ref3, ref4, ref5
plasma cell dyscrasias ref1, ref2, ref3
platelets ref1, ref2, ref3, ref4
pleural effusions ref1, ref2
CXR ref1, ref2, ref3, ref4
parapneumonic ref1
pneumonia ref1, ref2, ref3
ABGs ref1, ref2, ref3, ref4
CRP ref1
CXR ref1, ref2, ref3
FBP ref1, ref2, ref3
microbiology ref1, ref2, ref3
pneumoperitoneum ref1, ref2
pneumothorax ref1, ref2
polyarteritis nodosa ref1
polydipsia ref1, ref2
polymyositis ref1, ref2, ref3
portal hypertension ref1, ref2, ref3
postural hypotension ref1
potassium
drug interactions ref1
hyperkalaemia ref1, ref2, ref3, ref4, ref5
hypokalaemia ref1, ref2, ref3, ref4, ref5
Prader–Willi syndrome ref1
pregnancy
diabetes ref1
thyroid function ref1
prerenal uraemia ref1, ref2, ref3
presbyacusis ref1
primary biliary cirrhosis (PBC) ref1, ref2, ref3, ref4
prolactin ref1, ref2
prostate-specific antigen (PSA) ref1, ref2
protein
in CSF ref1, ref2
transudates and exudates ref1, ref2
prothrombin time (PT) ref1, ref2, ref3, ref4
pseudogout ref1
PTH (parathyroid hormone) ref1, ref2
pulmonary fibrosis ref1, ref2
ABGs ref1
spirometry ref1, ref2, ref3
pulmonary function tests
PEFR ref1, ref2, ref3
spirometry ref1, ref2, ref3, ref4, ref5
pulmonary hypertension ref1, ref2, ref3
pulmonary oedema ref1
pulse oximetry ref1
pulse rate ref1, ref2
pulseless electrical activity ref1
pyrexia (fever) ref1, ref2, ref3, ref4
Q waves ref1, ref2

Q–T interval ref1, ref2
QRS complexes ref1, ref2, ref3, ref4, ref5
R waves ref1, ref2, ref3

radiology see abdominal X-rays; chest X-rays; computed tomography; head X-rays
recreational drugs ref1, ref2
red blood cells
abnormal cells ref1, ref2, ref3
cell volume (MCV) ref1, ref2, ref3, ref4
in CSF ref1
ESR ref1, ref2, ref3, ref4
red cell distribution width ref1, ref2
red cell mass ref1, ref2, ref3
renal conditions see kidney
renin ref1
respiratory acidosis ref1, ref2
respiratory alkalosis ref1, ref2, ref3
respiratory failure ref1
type 1 ref1, ref2, ref3, ref4
type 2 ref1, ref2
reticulocytes ref1, ref2, ref3
rheumatoid disease ref1
autoantibodies ref1, ref2, ref3
histopathology ref1
Schirmer test ref1
spirometry ref1, ref2, ref3
rheumatoid factor (RF) ref1, ref2, ref3, ref4
right bundle branch-block (RBBB) ref1, ref2
S waves ref1, ref2

SAAG (serum–ascites albumin gradient) ref1, ref2
salicylate poisoning ref1
sarcoidosis ref1, ref2, ref3, ref4
SBP (spontaneous bacterial peritonitis) ref1, ref2, ref3, ref4
Schilling test ref1, ref2
Schirmer test ref1
scleroderma ref1
seizures ref1
self-harm see overdose
sensorineural deafness ref1, ref2, ref3
sepsis/septic shock ref1, ref2, ref3
serological tests ref1, ref2, ref3
serum–ascites albumin gradient (SAAG) ref1, ref2
sex chromosomes see X chromosome
SIADH (syndrome of inappropriate ADH excretion) ref1, ref2, ref3
sick euthyroid syndrome ref1
sickle cell disease ref1, ref2
sigmoid volvulus ref1
sinus rhythm ref1
sinus tachycardia ref1
Sjögren syndrome ref1, ref2
SLE (systemic lupus erythematosus) ref1, ref2
small bowel
absorption of haematinics ref1, ref2, ref3, ref4
gas on AXR ref1
obstruction ref1, ref2
sodium
fractional sodium excretion (FENa) ref1
hypernatraemia ref1, ref2
hyponatraemia ref1, ref2, ref3, ref4, ref5
urinary ref1, ref2, ref3
spirometry ref1, ref2
anaemia ref1, ref2
COPD ref1
pulmonary fibrosis ref1, ref2, ref3
sarcoidosis ref1, ref2
splenomegaly ref1
spontaneous bacterial peritonitis (SBP) ref1, ref2, ref3, ref4
ST segment ref1, ref2, ref3
Staphylococcus aureus ref1
stomach ref1
stroke
haemorrhagic ref1
ischaemic ref1, ref2, ref3
subarachnoid haemorrhage ref1, ref2
subdural haematoma ref1, ref2
sweat test ref1, ref2
syndrome of inappropriate ADH excretion (SIADH) ref1, ref2, ref3
systemic lupus erythematosus (SLE) ref1, ref2
T waves ref1, ref2, ref3, ref4
T3 (triiodothyronine) ref1, ref2, ref3
T4 (thyroxine) ref1, ref2, ref3, ref4
tachycardia ref1
sinus ref1
ventricular ref1, ref2, ref3, ref4
TCA overdose ref1, ref2
tears production ref1
temperature charts ref1, ref2, ref3, ref4
temporal arteritis ref1, ref2
testicular cancer ref1
thalassaemia ref1, ref2
therapeutic drug monitoring ref1, ref2
thirst (polydipsia) ref1, ref2
thrombocytopenia ref1, ref2, ref3, ref4
thrombocytosis ref1
thromboembolism ref1, ref2, ref3, ref4
thrombolysis ref1, ref2
thyroid hormones ref1
euthyroid ref1, ref2
hyperthyroidism ref1, ref2, ref3
hypothyroidism ref1, ref2
in pregnancy ref1
sick euthyroid ref1
thyroid-stimulating hormone (TSH) ref1, ref2, ref3, ref4
thyroxine (T4) ref1, ref2, ref3, ref4
thyroxine-binding globulin (TBG) ref1
total iron binding capacity (TIBC) ref1, ref2
transferrin receptor (sTfR) ref1
transudates
ascites ref1, ref2
pleural ref1, ref2
see also exudates
tricyclic antidepressant (TCA) overdose ref1, ref2
triiodothyronine (T3) ref1, ref2, ref3
trisomy ref1
troponins (I and T) ref1, ref2, ref3, ref4, ref5
TSH (thyroid-stimulating hormone) ref1, ref2, ref3, ref4
tumour markers ref1, ref2
tumours see cancer
U&E profiles see urea & electrolyte profiles

ulcerative colitis ref1
ulcers
leg ref1
peptic ref1
urate (uric acid) ref1, ref2, ref3
urea & electrolyte (U&E) profiles ref1
fluid balance ref1
renal failure ref1, ref2, ref3, ref4
urinalysis
DKA ref1, ref2
haemolysis (urobilinogen) ref1, ref2
urinary tract infections ref1, ref2, ref3
urine
drugs screens ref1
polyuria ref1, ref2
renal function and ref1, ref2, ref3
vasopressin see antidiuretic hormone

ventricular arrhythmias ref1, ref2, ref3, ref4
ventricular hypertrophy ref1, ref2, ref3
viruses ref1, ref2
vision, loss of ref1
visually evoked responses ref1, ref2
vital signs charts ref1, ref2, ref3
bradycardia ref1
GI bleeds ref1
infections ref1, ref2, ref3, ref4
obstructive sleep apnoea ref1
postural hypotension ref1
vitamin B12 deficiency ref1, ref2, ref3, ref4
volvulus ref1
von Willebrand disease ref1
warfarin ref1, ref2

water balance see fluid balance
water deprivation test ref1, ref2
Wegener syndrome ref1
weight charts ref1, ref2
white blood cells
abnormal cells ref1, ref2
in ascites ref1, ref2
in blood ref1, ref2, ref3
in CSF ref1, ref2, ref3
Wilson disease ref1
X chromosome
abnormal karyotype ref1
dominant X-linked inheritance ref1, ref2, ref3
recessive X-linked inheritance ref1, ref2
X-rays see abdominal X-rays; chest X-rays; head X-rays
xanthochromia ref1

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©

2012 PASTEST LTD

PasTest Revision Books and Intensive Courses

Illustrations by Ben Stockham

Preface to second edition

Liver function tests

Urate 0.15–0.50 mmol/l

Therapeutic drug levels

Abnormalities with red blood cells

TYPE OF ANAEMIA SIZE OF ERYTHROCYTES

Vitamin B12 Macrocytic

HAEMATINIC ABSORBED FROM

Vitamin B12 Terminal ileum

Folate Small bowel

COMPONENTS OF AN IRON PROFILE

Serum total iron-binding capacity (serum TIBC)

Serum soluble transferrin receptors

In iron deficiency states, iron studies are as follows:

IRON PARAMETER RESULT

Serum ferritin Reduced – since iron stores are low

IRON PARAMETER RESULT

Serum total iron-binding capacity Reduced

Serum ferritin May be raised as acute phase reactant

Transferrin saturation Reduced

INTRAVASCULAR HAEMOLYSIS IS SUGGESTED BY

Osmotic fragility test

Direct antiglobulin test

Fig 1.2: The causes of haemolytic anaemia.

Red cell mass

Abnormal white cell counts

COMMON CAUSES OF NEUTROPHILIA (NEUTROPHILS >7.5 × 109/l)

Bacterial infections Malignancy

COMMON CAUSES OF NEUTROPENIA (NEUTROPHILS <2.0 × 109/l)

COMMON CAUSES OF LYMPHOCYTOSIS (LYMPHOCYTES >3.5 × 109/l)

COMMON CAUSES OF EOSINOPHILIA (EOSINOPHILS >0.5 × 109/l)

Allergic disorders Skin diseases, eg eczema

Abnormalities with platelets

COMMON CAUSES OF THROMBOCYTOSIS

COMMON CAUSES OF PANCYTOPENIA

COMMON CAUSES OF A RAISED ESR

Abnormal erythrocyte colour or shape

Microcytosis Small cells Iron deficiency or defective haemoglobin synthesis

Megaloblastic anaemia, high alcohol intake, liver

Pencil cells Pencil-shaped cells Iron deficiency

Spherocytes Spherical cells Hereditary spherocytosis, haemolytic anaemia, burns

Hereditary elliptocytosis, thalassaemia major, iron

Abetalipoproteinaemia, post-splenectomy, liver

Thalassaemia, iron deficiency, post-splenectomy, liver

Hereditary stomatocytosis, high alcohol intake, liver

Also known as burr cells – less spiky

Microangiopathic haemolytic anaemia, haemolytic

Myelofibrosis and other causes of extramedullary

Poikilocytosis Abnormal shapes of red cells Iron deficiency

Anisochromia Varying shades of colour Iron deficiency

Abnormalities inside erythrocytes