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Chapter 12: Haemoglobin disorders and anaemia 471

Investigations Table 12.4 Schilling test
Full blood count demonstrates anaemia with macrocy-
Part I
tosis (raised MCV). Blood film also reveals neutrophils A loading dose of parenteral vitamin B 12 is given to
with a hypersegmented nucleus. Serum vitamin B 12 and the fasting patient to saturate plasma and liver
redcell folate levels should be measured. For further in- binding sites. Oral radioactive vitamin B 12 is then
vestigations and management see below. given.
Urinary excretion of labelled vitamin B 12 is then

measured.
Vitamin B 12 deficiency A high urinary excretion indicates a primary deficiency
of B 12 intake, whereas a low urinary excretion
Definition indicates malabsorption of B 12 , which should be
Deficiency of vitamin B 12 (cobalamins) causes macro- further investigated.
cytic megaloblastic anaemia. Part II
Oral radioactive B 12 complexed to intrinsic factor is

given.
Aetiology
If excretion is increased, this indicates that lack of IF is
Low intake occurs in vegans and chronic alcoholics. responsible for the malabsorption. If not, there is

Vitamin B 12 is found in animal products such as liver, malabsorption due to some other cause.
kidney, fish, red meats, eggs and cheese. Increased re-
quirements occur in pregnancy and haemolysis.
Malabsorption may occur in pernicious anaemia (see
intramuscularly if due to malabsorption. Complications
below), terminal ileal disease (e.g. Crohn’s disease), of treatment include hypokalaemia, gout and the un-
pancreatic failure and following gastrectomy or small masking of iron deficiency.
bowel resection.
Pernicious anaemia
Pathophysiology
Vitamin B 12 is absorbed mainly in the terminal ileum, by Definition
bindingtointrinsicfactor(IF)secretedbygastricparietal In pernicious anaemia, atrophy of the gastric mucosa
cells.Thereis3–4yearssupplystoredintheliver.Vitamin causes failure of intrinsic factor production, vitamin B 12
B 12 is involved in nucleic acid synthesis (see Fig. 12.4). deficiency and megaloblastic anaemia.
It also controls fatty acid synthesis in myelin sheaths of
nerves. Incidence
1in 8000 over 60 years.
Clinical features
In addition to symptoms of anaemia, patients with vita- Age
min B 12 deficiency may have neurological complications More common in the elderly.
such as peripheral neuropathy, optic atrophy, subacute
combined cord degeneration and dementia. Sex
F>M
Investigations
The diagnosis is made by serum B 12 levels. The Schilling Aetiology/pathophysiology
test is used to identify the cause of the deficiency (see The gastric parietal cells normally produce intrinsic fac-
Table 12.4). Gastrointestinal endoscopy can be used to tor (IF) that binds to vitamin B 12 allowing it to be ab-
demonstrates gastric atrophy and achlorydia. Intrinsic sorbed in the terminal ileum.
factor antibodies can be detected in the serum of 50% of 90%ofpatientswithperniciousanaemiahaveautoan-
patients with pernicious anaemia as the cause. tibodies to the gastric parietal cells; however, autoan-
tibodies may occur in association with gastric atrophy
Management without pernicious anaemia.
Treatment is by vitamin B 12 replacement, which may 50% of patients have antibodies to intrinsic factor,
be given orally if due to dietary insufficiency or which are specific for this diagnosis and may be