FOLIC ACID DEFICIENCY.pptx

folic acid deficiency manifestations,diagnosis and management

1. FOLIC ACID DEFICIENCY Dr G VENKATA RAMANA MBBS DNB FAMILY MEDICINE

2.   Folic ( pteroylglutamic ) acid is a yellow, crystalline, water-soluble substance . RDI of F olic acid Adults : 400mcg Pregnancy: 600mcg Lactation: 500mcg

3. Folic acid Absorption

4. 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.

5. 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.

6. 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 Neural tube defects S pina bifida

7. 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

8. 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 .

9. 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 .

10. Serum folic acid levels 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.

11. 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  — RBC folate is a 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 ).

12. Treatment of folate deficiency O ral  folic acid 1 to 5 mg daily Duration R eversible 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 ) S evere 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 Prevention of folate deficiency   Enrich cereals and grain products with  folic acid  to reduce the risk of neural tube defects.

13. Folic acid prophylaxis 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