16. Pemeriksaan laboratorium MCV Hapusan Darah Tepi Vitamin B₁₂ serum Folat serum dan eritrosit Methylmalonic acid (MMA) dan homocysteine Antibodi antiparietal cell dan anti IF Tes Schilling 12
17. Mean Corpuscular Volume (MCV) MCV > 100 fL Penyebab makrositosis : Megaloblastik atau non megaloblastik MCV meningkat sebelum terjadi penurunan kadar Hb. Bila defisiensi vitamin B₁₂ bersamaan dengan defisiensi besi MCV normal MCV kurang spesifik 13
18. Oval makrosit kesan penyakit megaloblastik Stomatosit dengan makrosit alkoholism Hipersegmentasi sensitif dan spesifik untuk anemia megaloblastik Hapusan darah tepi 14
19. Vitamin B₁₂ serum Digunakan untuk diagnosis dan monitoring terapi defisiensi vitamin B₁₂ Batas bawah normal biasanya sekitar 148 pmol/L (200 pg/mL) Belum ada baku emas sensitivitas dan spesifisitasnya bervariasi lebar. Metode pemeriksaan : automated non-isotopic procedure menggunakan chemiluminescence 15
20. Lanjutan vitamin B₁₂ serum.... Pada gagal ginjal vitamin B₁₂ serum tinggi Defisiensi vitamin B₁₂ pada penderita penyakit mieloproliferatif, gangguan ginjal/liver kadar vitamin B₁₂ bisa normal/tinggi Kolonisasi bakteri usus tinggi palsu 16
21. Folat serum dan folat eritrosit Batas bawah normal folat serum : 6,8 nmol/L Kadar folat serum dipengaruhi diet. Kadar folat eritrosit lebih mencerminkan simpanan folat jaringan. Belum ada metode baku emas 17
22. Methylmalonic acid (MMA) dan homocysteine Defisiensi vitamin B₁₂ MMA dan homocysteine Defisiensi folat homocysteine MMA dan homocysteine sensitif untuk diagnosis defisiensi vitamin B₁₂ Hati-hati interpretasi peningkatan metabolit bila tanda-tanda defisiensi (-) Setelah 7-14 hari pemberian terapi kadar metabolit menjadi normal 18
24. Antibodi anti sel parietal dan anti Intrinsic Factor (IF) Antibodi anti sel parietal : Non spesifik Terdapat pada penderita autoimun, orang sehat Antibodi anti IF : Tidak sensitif, namun cukup spesifik, walaupun masih mungkin ada pada penderita Graves disease. 20
25. Tes Schilling Untuk konfirmasi gangguan absorbsi vitamin Terdiri dari 2 tahap : 21
36. Tabel 6. Evaluasi penderita dengan kelainan hematologi dan vitamin B₁₂ <74 pmol/L 25
37. Gbr. 8. Evaluasi penderita yang diduga defisiensi vitamin B₁₂ dengan CBC normal 26
38. Diagnosis defisiensi vitamin B₁₂ dan folat hal yang kompleks. Belum ada tes yang mudah sebagai baku emasnya Perlu integrasi hasil laboratorium, klinis, respon terapi 27
40. 29 Gambar 6. Prinsip Beckman ACCESS Immunoassay System untuk pengukuran Vitamin B12. Serum.5
41. 30 Treatment B12 can be supplemented in healthy subjects by oral pill; sublingual pill, liquid, or strip; intranasal spray; or by injection. B12 is available singly or in combination with other supplements. B12 supplements are available in forms including cyanocobalamin, hydroxocobalamin, methylcobalamin, and adenosylcobalamin (sometimes called "cobamamide" or "dibencozide"). Oral treatments involve giving 250 ug to 1 mg of B12 daily.[28] Vitamin B12 can be given as intramuscular injections of hydroxycobalamin, methylcobalamin, or cyanocobalamin. Body stores (in the liver) are refilled with half a dozen injections in the first couple of weeks and then maintenance with monthly to quarterly injections throughout the life of the patient. B12 has traditionally been given parenterally to ensure absorption. However, oral replacement is now an accepted route, as it has become increasingly appreciated that sufficient quantities of B12 are absorbed when large doses are given. This absorption does not rely on the presence of intrinsic factor or an intact ileum. Generally 1 to 2 mg daily is required as a large dose [3]. By contrast, the typical Western diet contains 5–7 µg of B12 (Food and Drug Administration (FDA) Daily Value [29]).
44. 33 Hematological findings The blood film can point towards vitamin deficiency: Decreased red blood cell (RBC) count and hemoglobin levels[citation needed] Increased mean corpuscular volume (MCV, >95 fl) and mean corpuscular hemoglobin (MCH) Normal mean corpuscular hemoglobin concentration (MCHC, 32-36 g/dL) The reticulocyte count is decreased due to destruction of fragile and abnormal megaloblastic erythroid precursor. The platelet count may be reduced.[citation needed] Neutrophil granulocytes may show multisegmented nuclei ("senile neutrophil"). This is thought to be due to decreased production and a compensatory prolonged lifespan for circulating neutrophils, which increase numbers of nuclear segments with age.[citation needed] Anisocytosis (increased variation in RBC size) and poikilocytosis (abnormally shaped RBCs). Macrocytes (larger than normal RBCs) are present. Ovalocytes (oval-shaped RBCs) are present. Howell-Jolly bodies (chromosomal remnant) also present. Blood chemistries will also show: In increased lactic acid dehydrogenase (LDH) level. The isozyme is LDH-2 which is typical of the serum and hematopoetic cells. Increased homocysteine and methylmalonic acid in B12 deficiency Increased homocysteine in folat
53. 41 Vitamin B12 Analogues Vitamin B12 is a coenzyme: it is needed for enzymes to do their job of changing one molecule into another. As vitamins go, B12 is large. One part of its structure is known as the corrin nucleus, which holds an atom of cobalt. The corrin resembles the heme of hemoglobin which holds an atom of iron. Any molecule that contains a corrin nucleus is considered a corrinoid. The corrin plus other atoms make up the cobalamin part of B12. There are many different cobalamins and they are named after their attachments. For example, methylcobalamin is cobalamin with a methyl group (one carbon and three hydrogens) attached. All corrinoids (including all cobalamins) are considered B12 analogues. Many corrinoids, and possibly even some cobalamins, are not useable by human B12 enzymes. These are considered inactive B12 analogues.
54. Vitamin B12 Deficiency homocysteine and methylmalonyl CoA Increase in methylmalonyl CoA Increased enzyme activity in fatty acid synthesis Build up of odd fatty acids around peripheral nerves Increase in homocysteine Vascular/nervous problems
82. 57 Methylmalonic acid (MMA) is a dicarboxylic acid that is a C-methylated derivative of malonate. Pathology Increased methylmalonic acid levels may indicate a vitamin B12 deficiency. However, it is sensitive without being specific. MMA is elevated in 90-98% of patients with B12 deficiency. This test may be overly sensitive, as 25-20% of patients over the age of 70 have elevated levels of MMA, but 25-33% of them do not have B12 deficiency. For this reason, MMA is not routinely recommended in the elderly. [1] An excess is associated with methylmalonicacidemia. MMA concentrations in blood are measured by Gas chromatographicMass spectrometry
83. 58 Folic acid and vitamin B12Large amounts of folic acid can mask the damaging effects of vitamin B12 deficiency by correcting the megaloblastic anemia caused by vitamin B12 deficiency [3,5] without correcting the neurological damage that also occurs [1,31]. Moreover, preliminary evidence suggests that high serum folate levels might not only mask vitamin B12 deficiency, but could also exacerbate the anemia and worsen the cognitive symptoms associated with vitamin B12 deficiency [6,11]. Permanent nerve damage can occur if vitamin B12 deficiency is not treated. For these reasons, folic acid intake from fortified food and supplements should not exceed 1,000 mcg daily in healthy individuals [5].
84. Diet Methyltetrahydrofolate Vitamin B12 Methionine Methyl B12 Homocysteine CH3 tetrahydrofolate Serine Dihydrofolate Purine and pyrimidine synthesis + B6 DNA Glycine Thymidylate Deoxyuridylate 5,10 methylenetetrahydrofolate Gambar 4. Jalur metabolik asam folat dan vitamin B12.2. 59
119. 63 The present invention relates to a new method named the COBASORB test, which can be used for testing the cause of cobalamin malabsorption in humans. The COBASORB test contains three separate tests (first, second and third test) than can be performed separately, sequentially or in random order and number. The first test use non-radioactive cobalamin for ingestion, the second test uses non-radioactive cobalamin and recombinant intrinsic factor for ingestion and the third test uses recombinant haptocorrin saturated with cobalamin for ingestion. All three tests involve analysis of changes in the concentration of cobalamin saturated transcobalamin (holo-TC) and cobalamin saturated haptocorrin (holo-HC) in the blood. Also disclosed are fits suitable for use in these methods.
120. 64 Salivary haptocorrin, also known as the R-protein, binds strongly to Vitamin B12 (after it is released from food by gastric pepsin), stabilizing it and preventing its breakdown in the low-pH environment of the stomach. The complex is absorbed by ilealvilli into the blood. HC accounts for 10-40% of B12 serum level.
