FIGURE 14-18 Schematicillustration of vitaminB12 absorption.IF, intrinsic factor;R-binders,cobalophilins
Schilling testInvestigation 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 patients 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 + IFIf 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 – Whipples 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 Schillings 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
DD for microcytic hypochromicanemiaDiagnosis of Microcytic AnemiaTests Iron Deficiency Inflammation Thalassemia Sideroblastic AnemiaSmear Micro/hypo Normal Micro/hypo Variable micro/hypo with targetingSI <30 <50 Normal to high Normal to highTIBC >360 <300 Normal NormalPercent <10 10–20 30–80 30–80saturationFerritin ( g/L) <15 30–200 50–300 50–300Hemoglobin Normal Normal Abnormal NormalpatternNote: SI, serum iron; TIBC, total iron-binding capacity.
Anemia of Chronic DiseaseImpaired red cell production associated with chronic diseases• Reduction in the proliferation of erythroid progenitors and• Impaired iron utilizationIt’s due to the production of inflammatory cytokines
Anemia of Chronic DiseaseThis form of anemia can be grouped into three categories:1. Chronic microbial infections2. Chronic immune disorders3. Neoplasms
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 bodys 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 anemiaThe presence of : – increased storage iron in marrow macrophages, – a high serum ferritin level, and – a reduced total iron-binding capacityreadily rule out iron deficiency as the cause of anemia.