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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
Micro/hypo
with targeting
Variable
SI <30 <50 Normal to high Normal to high
TIBC >360 <300 Normal Normal
Percent
saturation
<10 10–20 30–80 30–80
Ferritin ( g/L) <15 30–200 50–300 50–300
Hemoglobin
pattern
Normal Normal Abnormal Normal
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.
E N D
Dr.CSBR.Prasad, M.D.,
Associate Professor of Pathology,
Sri Devaraj Urs Medical College,
Kolar-563101,
Karnataka,
INDIA.
csbrprasad@reiffmail.com
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