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FOLIC ACID DEFICIENCY I N CLINICAL PRACTICEpptx
- 1. FOLIC ACID DEFICIENCY Dr G VENKATA RAMANA MBBS DNB FAMILY MEDICINE
- 2. FOLIC ACID Folic (pteroylglutamic) acid is a yellow, crystalline, water- soluble substance. Most dietary folate is present as polyglutamates These are converted to monoglutamate in the upper small bowel and actively transported into plasma. Reduction to DHFA and methylation also occurs at this site. Alcohol interferes with release of methyl-THFA from hepatocytes. RDI of Folic acid Adults : 400mcg Pregnancy: 600mcg Lactation: 500mcg Total body stores of folate are small and deficiency can occur in a matter of weeks
- 5. Physiologic roles of folic acid DNA synthesis, RNA synthesis, DNA methylation Folic acid play a critical role in DNA and RNA synthesis Folic acid deficiency can therefore impair DNA synthesis, which in turn can cause a cell to arrest in the DNA synthesis (S) phase of the cell cycle, make DNA replication errors, and/or undergo apoptotic death Hematopoiesis Hematopoietic precursor cells are among the most rapidly dividing cells in the body and hence are one of the cell types most sensitive to abnormal DNA synthesis
- 6. Two major effects of the deficiency on hematopoiesis Megaloblastic changes caused by slowing of the nuclear division cycle relative to the cytoplasmic maturation cycle (ie, nuclear- cytoplasmic dyssynchrony). Ineffective erythropoiesis occurs when there is premature death (eg, phagocytosis or apoptosis) of the developing erythropoietic precursor cells in the bone marrow . There may be hypercellularity of the bone marrow laboratory findings of hemolysis, including elevated serum iron, indirect bilirubin, and lactate dehydrogenase (LDH), and low haptoglobin. The reticulocyte count is typically low
- 11. Clinical presentation Macrocytic anemia Symptoms of anemia-fatigue, irritability, cognitive decline,chest pain, shortness of breath,palpitations,light- headedness Yellowed skin Gastrointestinal symptoms Oral ulcers Glossitis Neuropsychiatric changes Depression, irritability, or forgetfulness Neural tube defects Spina bifida
- 12. lnvestigations CBC and blood smear Anemia Macrocytic red blood cells (MCV >100 fL) or macro- ovalocytosis An MCV value >115 fL is more specific to vitamin B12 or folate deficiency Mild leukopenia and/or thrombocytopenia Low reticulocyte count Hypersegmented neutrophils on the peripheral blood smear (ie, >5 percent of neutrophils with 5 lobes or 1 percent of neutrophils with 6 lobes) Increased lactate dehydrogenase Increased bilirubin
- 13. Peripheral smear and Bone marrow Peripheral blood smear showing a hypersegmented neutrophil (seven lobes) and macroovalocytes, a pattern that can be seen with vitamin B12 (cobalamin) or folate deficiency Erythroid precursors in the bone marrow (Left panel) Normal erythropoiesis. (Right panel) Megaloblastic erythropoiesis
- 14. Serum folic acid levels Serum folate measurement is very sensitive to dietary intake; a single folate-rich meal can normalise it in a patient with true folate deficiency, whereas anorexia, alcohol and anticonvulsant therapy can reduce it in the absence of megaloblastosis. For this reason, red cell folate levels are a more accurate indicator of folate stores and tissue folate deficiency Above 4 ng/mL (above 9.1 nmol/L) Normal. Suggests folate is not deficient, unless the individual has recently consumed a folate-containing meal or supplement. In such cases, RBC folate can be obtained or prefer metabolite testing . RBC folate more costly to obtain. From 2 to 4 ng/mL (from 4.5 to 9.1 nmol/L) Borderline Additional testing may be indicated depending on the clinical circumstances and the degree of suspicion for folate deficiency. Below 2 ng/mL (below 4.5 nmol/L) Low Consistent with folate deficiency. Values may be slightly higher in the first six months of life
- 15. MMA and homocysteine normal No deficiency of folate,vitamin B12. MMA and homocysteine elevated Deficiency of vitamin B12 (does not eliminate the possibility of folate deficiency). MMA normal, homocysteine elevated No deficiency of vitamin B12. Consistent with deficiency of folate. RBC folate Surrogate for tissue folate levels. RBC folate provides information about folate status over the lifetime of RBCs, similar to hemoglobin A1C for blood glucose levels. An RBC folate level below 150 ng/mL (<150 mcg/L; <340 nmol/L) is consistent with folate deficiency as long as there is not concomitant vitamin B12 deficiency (RBC folate is lower in individuals with vitamin B12 deficiency). False-normal results -Recent blood transfusion or if a patient has a raised reticulocyte count
- 16. Treatment of folate deficiency Oral folic acid 1 to 5 mg daily Folinic Acid (5-Formyl-THF) stable form of fully reduced folate. It is given orally or parenterally to overcome the toxic effects of methotrexate or other DHF reductase inhibitors, for example, trimethoprim or cotrimoxazole. Duration Reversible cause of deficiency- one to four months or until there is laboratory evidence of hematologic recovery. For those with a chronic cause of folate deficiency, such as chronic hemolytic anemia - indefinitely. Intravenous folic acid indications Unable to take an oral medication (eg, due to vomiting or obtundation) Severe or symptomatic anemia Can partially reverse some of the hematologic abnormalities associated with vitamin B12 deficiency .however, the neurologic manifestations of vitamin B12 deficiency are not treated by folic acid. Thus, administration of folic acid to an individual with vitamin B12 deficiency can potentially mask untreated vitamin B12 deficiency or even worsen the neurologic complications. Because of this, testing for (and treatment of) vitamin B12 deficiency may be appropriate in certain patients being treated with folic acid
- 17. Adverse effects Oral folic acid is entirely nontoxic Injections rarely cause sensitivity reactions Prevention of folate deficiency Enrich cereals and grain products with folic acid to reduce the risk of neural tube defects Folic acid prophylaxis Typical dose, 1 mg orally per day All women,from the moment they begin trying to conceive until 12 weeks of gestation to prevent neural tube defects Hemolytic anemias/hyperproliferative hematologic states Patients with rheumatoid arthritis or psoriasis on methotrexate Patients on antiepileptic drugs Patients with ulcerative colitis