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