Part 1: Vitamins Associated with Anemia
Anemia = reduction in the quantity of hemoglobin or in the number of RBCs in blood relative to standards.
Classification of Nutritional Anemias:
Reduced heme synthesis and hemoglobin synthesis.
Reduced iron use and release for heme synthesis.
Vitamin B12, Folic Acid
Decreased DNA synthesis retards or inhibits cell division.
Storage: Hemoglobin 70%, storage (hemosiderin, ferritin) 25%, plasma iron and iron-containing enzymes 5%.
Requirements: Iron stores are not regulated by excretion. Major control is rate of intestinal absorption. Percent of iron absorbed is therefore variable (3-35%).
Sequence of Iron Deficiency:
- Higher requirements in: infancy, adolescence, fertile females, pregnancy, premature infants.
Non-Hematologic Abnormalities of Iron Deficiency:
- (1) Loss of storage iron (hemosiderin, ferritin)
- (2) Increased serum iron-binding capacity
- (3) Decreased serum iron concentration
- (4) Decreased percent transferrin (transport protein) saturation
- (5) Increased free RBC protoporphyrin (precursor of heme) increased when iron supply is insufficient
- (6) Decreased hemoglobin (10-12 g/dL) Þ mild anemia
- (7) Decreased mean cell volume RBC hypochromia and microcytosis with anemia
- note: Transferrin receptor (disulfide-linked transmembrane glycoprotein) plays a role in iron uptake. Though most is on cell membrane, soluble transferrin receptor (sTfR) circulates in blood and can be used as an indicator of iron deficiency when increased. Further, a lack of transferrin receptor can also lead to iron deficiency.
Causes of Iron-deficiency Anemia:
- Striated muscle dysfunction - ß work capacity.
- Behavioral changes, Impaired psychomotor development, Impaired intellectual performance in infants and children between 6 months and 2 years of age.
- Immunity abnormal cellular immune response, abnormal PMN function.
- Gastrointestinal - ß acid secretion, gut mucosal damage (bleeding).
Dietary Iron Sources and Factors Affecting Availability and Utilization:
- Inadequate intake from diet
- Increased demand infancy, adolescence, pregnancy
- Blood loss
- Decreased absorption severe diarrhea, severe gut disease
Iron Toxicity: Ferrous salts from supplements can be toxic to young children who ingest too much at once. This is the most common reported emergency to poison control centers.
- Increase in absorption of non-heme iron during pregnancy 5 fold at week 24, 9 fold at week 36.
- Individuals iron stores low stores, higher percent absorption.
- Type of iron in diet Heme iron (Hgb and Mgb in meat, fish, poultry) has higher rate of absorption than Non-Heme iron (inorganic iron salts.) Ferrous (Fe2+) salts absorbed best.
- Enhancing factors factors which Ý rate of absorption of non-heme iron: ascorbic acid, and "meat factor" (identity unknown, present in beef, poultry, and fish).
- Inhibiting factors antacids, dietary fiber.
Function: Cu is found in a number of proteins, including cytochrome a-a3 and ceruloplasmin (albumin-bound Cu).
Clinical: Manifestations of Cu deficiency: hypochromic, microcytic anemia, neutropenia, bone abnormalities.
Tests: Nutritional status can be determined by measuring serum copper and serum ceruloplasmin.
Deficiency: More common in preterm infants (reduced liver copper stores and high growth rate), infants fed cow-milk (low in copper), malnourished kids, total parenteral nutrition (often lacking/low in trace minerals), malabsorption syndromes (celiac disease, short bowel syndrome), infants with prolonged or recurrent diarrheal episodes, abnormal bile loss, intestinal resection, high oral intake of zinc decreases copper absorption (competitive inhibition), penicillamine or other cation-chelating agents, Menkes Syndrome (rare inherited defect in copper transport).
- Ceruloplasmin functions as a ferroxidase enzyme converting ferrous iron to ferric iron (Fe2+Þ Fe3+).
- Fe3+ is the form necessary for transferrin transport. Therefore, Cu deficiency can mimic iron deficiency! Results hypochromic, microcytic anemia, which is unresponsive to iron therapy.
Folic Acid pteroylglutamic acid deficiency leads to megaloblastic anemia
Þ monoglutamate in small intestine).
Therefore, only need half as much synthetic folic acid if ingested in an empty stomach!
Liver main storage site, sufficient for only a few months.
Hematologic Features of Deficiency:
- Folic acid (folate) is reduced to THF and used in the one-carbon pool.
- Six Metabolic Roles:
- (1) Conversion of homocystein to methionine N5-Methyl-THF is a methyl donor and utilizes vitamin B12 as a cofactor.
- (2) Conversion of serine to glycine THF is an acceptor of a methyl group from serine and utilizes vitamin B6 (pyridoxine) as a cofactor.
- (3) Histidine metabolism
- (4) Synthesis of thymidylate rate-limiting step in DNA synthesis.
- (5) Synthesis of purines
- (6) Utilization of generation of formate
- Food Sources/Absorption/Storage:
- Best sources green leafy vegetables, some fruits
- Absorbed in duodenum, jejunum.
- Synthetic folic acid (monoglutamate form in vitamin pills) 100% absorbed on empty stomach, 85% after meal.
- Food folates (polyglutamates
Causes of Deficiency:
- Megaloblastic anemia large, abnormal immature RBCs.
- Increased mean corpuscular volume (MCV)
- Hypersegmentation of nucleus of leukocytes.
Folate in Foods: Folate is highly susceptible to oxidative destruction: 50-90% destroyed by prolonged cooking.
- Inadequate intake
- Increased requirements rapid growth, pregnancy.
- Decreased absorption GI disease sprue, drugs: phenytoin, barbiturates
- Impaired metabolism congenital, antimetabolites used in cancer treatment (methotrexate)
- High folate: lentils, blackeyed peas, legumes, orange juice, asparagus, beets, broccoli, corn, spinach.
Vitamin B12 cobalamin deficiency leads to pernicious anemia (megaloblastic)
ß intrnsic factor with congenital pernicious anemia, gastric resection, ileal resection, achlorhydria, hypochlorhydria.
Treatment of Megaloblastic Anemia:
- Folate-cobalamin interaction is critical for normal synthesis of purines and pyrimidines.
- Only source is animal products (meat and milk)
- Actively absorbed in terminal ileum dependent on intrinsic factor secreted by parietal cells in stomach.
- Liver is main storage site, sufficient for about 2-5 years, if eating animal based diet.
- Hematologic features: B12 deficiency is same as folic acid deficiency.
- Non-Hematologic features: sore, smooth tongue, neurologic syndrome (sensory changes, paresthesia in extremities), failure of myelination of long tracts of spinal cord (depending on duration neurologic complications may/not be reversible).
- Causes of Deficiency:
- Deficient intake strict vegetarian, vegan, infant breast fed by B12 deficient mother.
- Decreased absorption -
ß acid secretion) take oral supplement of 25ug-1mg B12, 1% absorbed by mass action.
Folic acid in large doses correct megaloblastic anemia of B12 deficiency, but not neurologic probs. Therefore, Vit B12 deficiency can be masked.
- Food fortified with B12 (fortified soy milk), or B12 pill.
- Pernicious anemia (lack of intrinsic factor) treated with intramuscular injections of B12.
- Gastric atrophy (