10:38 PM:

Case study
Patient
58 year old

CC
The patient presented to her physician because of tiredness and fatigue of several months duration, which was increasing in severity. She also complained of tingling and numbness in her feet and legs for the past 3 -4 weeks.

Medical History
The patient has been previously healthy, except for an appendectomy at age 18.

Drug history
No medications

Physical examination
The patient was pale and her skin had a sallow appearance. Neurologic exam revealed diminished vibratory sense and decreased sensation in the lower extremities.



Blood Film examination
Decreased red cells with marked anisopoikilcytosis and numerous oval macrocytes. Frequent hypersegmented neutrophils.

Questions to ask
What is the most likely diagnosis in this patient ?
How do the presenting clinical features relate to the diagnosis ?
How should this patient be treated ?


Diagnosis
Pernicious anemia

10:19 PM:

Definition of Schilling test
Robert F. Schilling worked on urine radioactivity testing for Vitamin B12 absorption in 1953, eventually leading to the “Schilling test”.

Schilling test or Vitamin B12 absorption test is used to determine if Vitamin B12 is absorbed normally by the body. This test has been recommended by the International Committee for Standardisation in Haematology.

How the test is performed
Stage I consists of two doses of vitamin B12 (cobalamin). The first dose is radioactive and taken by mouth. This oral dose of vitamin B12 is tagged with radioactive cobalt. The second dose is not radioactive and is given as a shot 2 – 6 hours later. The intramuscular injection of vitamin B12 is given to saturate the liver and serum protein-binding sites, which allows radioactive vitamin B12 to be excreted in the urine. 24-hour urine analysis will then be done, to measure the body’s ability to absorb vitamin B12 normally.

Since this is not diagnostic of any diseases, Stage II will be done 3 – 7 days later if stage I is abnormal. Stage II consists of radioactive B12 along with intrinsic factor.

Intrinsic factor is a protein produced by glands in the stomach lining which attaches to vitamin B12. It is necessary for the absorption of vitamin B12 by the intestines. Therefore, Stage II of the test can determine if the vitamin B12 deficiency is caused by damages of the stomach that prevent it producing intrinsic factor. If the Stage II test is abnormal, a Stage III test is performed.

Stage III requires you to take antibiotics for 2 weeks, stage II is then repeated. This stage can determine whether the low vitamin B12 levels are the result of abnormal bacterial growth.

In Stage IV, you will take pancreatic enzymes for three days, followed by a radioactive dose of vitamin B12. This shows if deficiency of vitamin B12 is caused by pancreas problems.

24-hour urine sample
Morning urine on day 1 is not collected. Urine is subsequently collected for the next 24 hours. The final urine sample is collected on day 2 morning. The urine sample is kept in the refrigerator and labelled with patient’s particulars. For infants, a urine collection bag is used.

The patient should fast for 8 hours before starting the test. During the next 24 hours, the patients are expected to eat normally. Drugs that might affect the test are discontinued.

Why the test is performed
Schilling test is performed to check for the efficiency of vitamin B12 absorption.

Intrinsic factor is produced in the stomach and is required for vitamin B12 absorption. Without the production of intrinsic factor, the body cannot absorb vitamin B12 and excreted in the urine. Deficiency of vitamin B12 can be due to the lack of intrinsic factor, abnormal bacterial growth and pancreas diseases.

The lack of intrinsic factor can be due to the damage of the stomach or its linings. Examples are pernicious anemia, partial removal of the stomach (gastrectomy), autoimmunity against gastric parietal cells and atrophic gastric mucosa.

Vitamin B12 is needed for the formation of the red blood cells. Since vitamin B12 is not absorbed, there is no formation of red blood cells and hence causing pernicious anemia where red blood cells are not providing adequate oxygen to body tissues. Pernicious anemia is a type of megaloblastic anemia, where blood cells are larger than normal.

This picture shows large, dense, oversized, red blood cells (RBCs) that are seen in megaloblastic anemia.

Excessive bacteria in the intestine lead to increased consumption of vitamin B21.

Patients undergoing Schilling tests are given doses of vitamin B12. Hence, if the patient’s diet is lacking in vitamin B12, for example, in veganism, Stage I should produce a normal result. This is indicates dietary deficiency in vitamin B12.

If Stage I is abnormal, this shows malabsorption of vitamin B12. Thus, stage II is performed to check for gastric pernicious anaemia. The result should be normal since the patient is given a dose of vitamin B12 along with intrinsic factor which solves the lack in production of intrinsic factor by the stomach linings.

If both Stages I and II of the test are abnormal, it shows that the lack of intrinsic factor is not the cause for the deficiency and the patient does not have classical pernicious anaemia or gastric defects. This points to an intestinal cause.
Stage III of the test is then carried out; Stage II is repeated with antibiotics. The antibiotics target and reduce the amount of bacteria in the intestines. If absorption of vitamin B12 returns to normal after Stage III, it shows that reducing bacteria amounts in the intestines has resolved the deficiency; bacterial overgrowth in the intestines was the cause.

However, if all Stages I, II and III results are abnormal, a Stage IV is done. In stage IV, the patient will be given pancreatic enzymes for 3 days followed by the radioactive vitamin B12 to test for pancreatic disorders. Pancreatic insufficiency is the inability of the exocrine pancreas to produce enough digestive enzymes. It usually presents with symptoms of malabsorption, malnutrition and vitamin deficiencies. The pancreas provides critical enzymes and calcium required for vitamin B12 absorption, therefore pancreatic insufficiency may contribute to B12 deficiency. Receptors on the surface of the small intestine take up the IF-B12 complex only in the presence of pancreas-supplied calcium.

Normal Results
The amounf of the excreted radioactive B12 is determined and expressed as a percentage of the given dose. 8 – 40% of the radioactive vitamin B12 in the 24-hour urine sample is normal. Normal values can indicate near-normal kidney function.

What abnormal results mean
With little absorption of the oral dose and therefore excrete little radioactive material in the urine, it means, that the patient might have pernicious anemia. This test can be falsely positive, often due to poor or inadequate urine collection and renal insufficiency. Other reasons include kidney disease or problems with the lining of the small intestine.

Risks
The risks are local reaction to vitamin injection, nausea and feeling lightheaded. An allergic reaction may occur to the radioactive B12 used in the test, in rare cases. The amount of radiation exposure is too low to be harmful, except for the fetus of a pregnant woman. Therefore, the schilling test is not done on women who are pregnant or who are breast-feeding.


References
http://www.webmd.com/a-to-z-guides/schilling-test?page=3
http://healthguide.howstuffworks.com/schilling-test-dictionary.htm