Schilling test

Dr.CSBR.Prasad, M.D.,
FIGURE 14-18 Schematic
illustration of vitamin
B12 absorption.
IF, intrinsic factor;
R-binders,
cobalophilins
 Schilling test
Investigation used for patients with vitamin B12
deficiency
• The purpose of the test is to determine
whether the patient has pernicious anemia
• The Schilling test has multiple stages
 Stage 1: oral vitamin B12 plus
intramuscular vitamin B12
• Oral dose: patient is given radiolabeled Vit B12
– The most commonly used radiolabels are 57Co and 58Co
• An intramuscular injection of unlabeled vitamin B12 is
given an hour later
• The patient's urine is then collected over the next 24
hours to assess the absorption
• A normal result shows at least 10% of the radiolabeled
vitamin B12 in the urine over the first 24 hours
• In patients with impaired absorption, less than 10% of
the radiolabeled vitamin B12 is detected
 Stage 2: Vitamin B12 + IF
If an Stage-I is abnormal:
The test is repeated with additional oral intrinsic factor
• If this second urine collection is normal, this shows a lack of
intrinsic factor production, or pernicious anemia.
• A low result on the second test implies “Malabsorption”
– Coeliac disease
– Biliary disease
– Whipple's disease
– Fish tapeworm infestation (Diphyllobothrium latum), or
– Liver disease
– Immerslund syndrome
– Malabsorption of B12 can be caused by intestinal dysfunction
from a low vitamin level in-and-of-itself
 Stage 3: vitamin B12 and antibiotics
• This stage is useful for identifying patients
with bacterial overgrowth syndrome.
 Stage 4: vitamin B12 and pancreatic
enzymes
• This stage, in which pancreatic enzymes are
administered, can be useful in identifying
patients with pancreatitis.
 Combined stage 1 and stage 2
• In some versions of the Schilling's test, B12 can
be given both with and without intrinsic factor
at the same time, using different cobalt
radioisotopes 57Co and 58Co, which have
different radiation signatures, in order to
differentiate the two forms of B12.
• This allows for only a single radioactive urine
collection
 DDs for
Microcytic Hypochromic Anemia
 DD for microcytic hypochromicanemia
Diagnosis of Microcytic Anemia
Tests Iron Deficiency Inflammation Thalassemia Sideroblastic
Anemia
Smear Micro/hypo Normal Micro/hypo Variable
micro/hypo with targeting
SI <30 <50 Normal to high Normal to high
TIBC >360 <300 Normal Normal
Percent <10 10–20 30–80 30–80
saturation
Ferritin ( g/L) <15 30–200 50–300 50–300
Hemoglobin Normal Normal Abnormal Normal
pattern
Note: SI, serum iron; TIBC, total iron-binding capacity.
Anemia of Chronic Disease
 Anemia of Chronic Disease
Impaired red cell production associated with
chronic diseases
• Reduction in the proliferation of erythroid
progenitors and
• Impaired iron utilization

It’s due to the production of inflammatory

cytokines
 Anemia of Chronic Disease
This form of anemia can be grouped into three
categories:
1. Chronic microbial infections
2. Chronic immune disorders
3. Neoplasms
 Inflammatory cytokines
• TNF
• IL-1
• IL-6
• IF-gamma
• IF-beta
 Effects of chronic inflammation
• Incresed production of IL-6
• IL-6 stimulate the hepatic production of
hepcidin
• Hepcidin inhibits :
– Ferriportin function in macrophages
– EPO production
Regulation of iron absorption
Regulation of iron absorption
Suppression of erythropoiesis by
inflammatory cytokines
 Main lab findings
• Low serum iron,
• Reduced total iron-binding capacity, and
• Abundant stored iron in tissue macrophages
What might be the reason for iron sequestration
in the setting of inflammation?
• The best guess is that it serves to enhance the
body's ability to fend off certain types of
infection, particularly those caused by
bacteria (such as H. influenzae) that require
iron for pathogenicity
• In this regard it is interesting to consider that
hepcidin is structurally related to defensins, a
family of peptides that have intrinsic
antibacterial activity
 DD from Iron deficiency anemia
The presence of :
– increased storage iron in marrow macrophages,
– a high serum ferritin level, and
– a reduced total iron-binding capacity

readily rule out iron deficiency as the cause of

anemia.
END
 Dr.CSBR.Prasad, M.D.,
Associate Professor of Pathology,
Sri Devaraj Urs Medical College,
Kolar-563101,
Karnataka,
INDIA.
csbrprasad@reiffmail.com