NUTRITION IN ANEMIA

dr. Marlina Dewiastuti MKes

PATHOLOGY, SYMPTOMS, AND SIGNS OF ANEMIA

MORPHOLOGICAL CLASSIFICATION OF ANEMIA

CAUSES OF IRON DEFICIENCY ANEMIA

ANGULAR CHEILITIS AND SMOOTH TONGUE IN IRON DEFICIENCY

CAUSES OF MEGALOBASTIC ANEMIA

COMPARISON OF FEATURES OF VITAMIN B12 AND FOLIC ACIDDEFICIENCY STATES

Iron

• Iron homeostasis is regulated at the level of intestinal absorption, and it is important that adequate but not excessive quantities of iron be absorbed from the diet. Inadequate absorption can lead to iron-deficiency disorders such as anemia. On the other hand, excessive iron is toxic because mammals do not have a physiologic pathway for its elimination.

Dietary source

• Iron is available from foods of both animal (heme iron) and plant (non-heme iron) origin. It is better absorbed from heme iron sources. Absorption of iron is enhanced when vitamin C foods are eaten with iron rich foods. Iron cookware also adds to the iron content of cooked foods. The best sources of iron include liver and other organ meats, oysters. Good food sources include spinach, beans, and peas. Fair sources include lean meats, other shellfish, egg yolks, nuts, dried fruit, other green leafy vegetables, whole grains, poultry, and fish.

• The Recommended Daily Allowance (RDA) of iron for people who are not iron deficient varies by age group and other risk factors. (Iron supplements are rarely recommended in people without evidence of iron deficiency or anemia.) The RDA recommends these daily amounts of iron:

• Children 1 - 3 years old: 10 mg• Teenage boys: 12 mg• Teenage girls and premenopausal women: 15 mg• Pregnant or nursing women: 30 mg• Adult men (up to age 50): 10 mg• Older men and women (over age 50): 10 mg

Ingestion, Absorption, excretion

• Ferric iron (Fe+++) in the duodenal lumen is reduced to its ferrous form through the action of a brush border ferrireductase. Iron is the cotransported with a proton into the enterocyte via the divalent metal transporter DMT-1. This transporter is not specific for iron, and also transports many divalent metal ions.

• Once inside the enterocyte, iron follows one of two major pathways. Which path is taken depends on a complex programming of the cell based on both dietary and systemic iron loads:

• Iron abundance states: iron within the enterocyte is trapped by incorporation into ferritin and hence, not transported into blood. When the enterocyte dies and is shed, this iron is lost.

• Iron limiting states: iron is exported out of the enterocyte via a transporter (ferroportin) located in the basolateral membrane. It then binds to the iron-carrier transferrin for transport throughout the body.

• Iron in the form of heme, from ingestion of hemoglobin or myoglobin, is also readily absorbed may be transported intact into the circulation.

Iron Utilization

• A model of hemoglobin at low resolution. The alpha chains in this model are yellow, the beta chains are blue, and the heme groups red.

• hemoglobins have molecular weights of about 64,500. Composed of four peptide chains called globins each of which is bound to a heme. Normal human hemoglobin is composed of a pair of two identical chains.

• Iron is coordinated to four pyrrole nitrogens of protoporphyrin IX, and to an imidazole nitrogen of a histidine residue from the globin side of the porphyrin. The sixth coordination position is available for binding with oxygen and other small molecules.

STRUCTURE OF HEME

• Ferrous iron (Fe2+)

• Protoporphyrin IX: contains 4 pyrrole rings linked together by methenyl bridges

Heme

8

8

Succinyl CoA

Glycine**

HEME SYNTHESIS

** Amino acid (building blocks of protein) synthesized in your body

Disorders of Heme Synthesis

• Acquired: Lead poisoning

• Congenital: Porphyrias

• Deficiency of heme has far-reaching effects (hemoglobin, cytochromes, etc.)

LEAD TOXICITY

Symptoms Irritibility Poor appetite Lethargy Abdominal pain (with or Sleeplessness without vomiting) Headaches Constipation

Pathophysoiology Binds to any compound with a sulfhydryl group Inhibits multiple enzyme reactions including those

involved in heme biosynthesis (ALA synthase & ferrochelatase)

One symptom of lead toxicity is increases in 5-ALA without concomitant increases in PBG

B12 Vitamin

• Vitamin B12 is the largest and most complex of all the vitamins. The name vitamin B12 is generic for a specific group of cobalt-containing corrinoids with biological activity in humans. Interestingly it is the only known metabolite to contain cobalt, which gives this water-soluble vitamin its red colour. This group of corrinoids is also known as cobalamins. The main cobalamins in humans and animals are hydroxocobalamin, adenosylcobalamin and methylcobalamin, the last two being the active coenzyme forms. Cyanocobalamin is a form of vitamin B12 that is widely used clinically due to its availability and stability. It is transformed into active factors in the body.

Functions

• Essential growth factor • Formation of blood cells and nerve sheaths • Regeneration of folic acid • Coenzyme-function in the intermediary

metabolism, especially in cells of the nervous tissue, bone marrow and gastrointestinal tract

• Vitamin B12 is necessary for the formation of blood cells, nerve sheaths and various proteins. It is therefore, essential for the prevention of certain forms of anaemia and neurological disturbances. It is also involved in fat and carbohydrate metabolism and is essential for growth. In humans, vitamin B12 functions primarily as a coenzyme in intermediary metabolism. Two metabolic reactions are dependent on vitamin B12:

• The methionine synthase reaction with methylcobalamin • The methylmalonyl CoA mutase reaction with adenosylcobalamin• In its methylcobalamin form vitamin B12 is the direct cofactor for

methionine synthase, the enzyme that recycles homocysteine back to methionine. There is evidence that vitamin B12 is required in the synthesis of folate polyglutamates (active coenzymes required in the formation of nerve tissue) and in the regeneration of folic acid during red blood cell formation.

• Methylmalonyl CoA mutase converts 1-methylmalonyl CoA to succinyl CoA (an important reaction in lipid and carbohydrate metabolism). Adenosylcobalamin is also the coenzyme in ribonucleotide reduction (which provides building blocks for DNA synthesis).

Dietary sources• Vitamin B12 is produced exclusively by microbial synthesis

in the digestive tract of animals. Therefore, animal protein products are the source of vitamin B12 in the human diet, in particular organ meats (liver, kidney). Other good sources are fish, eggs and dairy products. In foods, hydroxo-, methyl- and 5'-deoxyadenosyl-cobalamins are the main cobalamins present. Foods of plant origin contain no vitamin B12 beyond that derived from microbial contamination. Bacteria in the intestine synthesise vitamin B12, but under normal circumstances not in areas where absorption occurs.

Ingestion & Absorption• Vitamin B12 from food sources is bound to proteins and is only released

by an adequate concentration of hydrochloric acid in the stomach. Free vitamin B12 is then immediately bound to glycoproteins originating from the stomach and salivary glands. This glycoprotein complex protects vitamin B12 from chemical denaturation. Gastrointestinal absorption of vitamin B12 occurs in the small intestine by an active process requiring the presence of intrinsic factor, another glycoprotein, which the gastric parietal cells secrete after being stimulated by food. The absorption of physiological doses of vitamin B12 is limited to approximately 10µg/dose. The vitamin B12 intrinsic factor complex is then absorbed through phagocytosis by specific ileal receptors. Once absorbed, the vitamin is transferred to a plasma-transport protein which delivers the vitamin to target cells. A lack of intrinsic factor results in malabsorption of cobalamin. If this is untreated, potentially irreversible neurological damage and life-threatening anaemia develops (see deficiency).

• Regardless of dose, approximately 1% of vitamin B12 is absorbed by passive diffusion, so this process becomes quantitatively important at pharmacological levels of exposure. Once absorbed, vitamin B12 is stored principally (60%) in the liver. The average B12 content is approximately 1.0 mg in healthy adults, with 20-30 µg found in the kidneys, heart, spleen and brain. Estimates of total vitamin B12 body content for adults range from 0.6 to 3.9 mg with mean values of 2-3 mg. The normal range of vitamin B12 plasma concentrations is 150-750 pg/ml, with peak levels achieved 8-12 hours after ingestion.

Excretion

• Excretion of vitamin B12 is proportional to stores and occurs mainly by urinary and faecal routes. Vitamin B12 is very efficiently conserved by the body, with 65-75% re-absorption in the ileum of the 0.5-5 µg excreted into the alimentary tract per day (mainly into the bile). This helps to explain the slow development (over several years) of deficiency states in subjects with negligible vitamin B12 intake, such as vegans. Subjects with a reduced ability to absorb cobalamin via the intestine (lack of intrinsic factor) develop a deficiency state more rapidly.

Deficiency

• Clinical cobalamin deficiency due to dietary insufficiency is rare in younger people, but occurs more frequently in older people. Vitamin B12 deficiency affects 10-15% of individuals over the age of 60.

• Deficiency of vitamin B12 leads to defective DNA synthesis in cells, which affects the growth and repair of all cells. Tissues most affected are those with the greatest rate of cell turnover, e.g. those of the haematopoietic system. This can lead to megaloblastic anaemia (characterised by large and immature red blood cells) and neuropathy, with numerous symptoms including: glossitis, weakness, loss of appetite, loss of taste and smell, impotence, irritability, memory impairment, mild depression, hallucination, breathlessness (dyspnea) on exertion, tingling and numbness (paraesthesia).

• Pernicious anaemia: • Pernicious anaemia is the classical symptom of B12 deficiency, but it

is actually the end-stage of an autoimmune inflammation of the stomach, resulting in destruction of stomach cells by the body’s own antibodies. Anaemia is a condition in which red blood cells do not provide adequate oxygen to body tissues. Pernicious anaemia is a type of megaloblastic anaemia.

• Gastric atrophy: • Gastric atrophy is a chronic inflammation of the stomach resulting in

decreased stomach acid production. Because this is necessary for the release of vitamin B12 from the proteins in food, vitamin B12 absorption is reduced.

Recommended Dietary Allowance (RDA

• RDA intakes for vitamin B12 range from 0.3 to 5.0 µg/day in 25 countries. An increase to 2.2 µg/day is recommended during pregnancy and to 2.6 µg/day for lactation to cover the additional requirements of the foetus/infant. The Committee on Nutrition of the American Academy of Paediatrics recommends a daily vitamin B12 intake of 0.15 µg/100 kcal energy intake for infants and preadolescent children. Other authorities have suggested intakes of 0.3-0.5 µg (0-1 year of age), 0.7-1.5 µg (1-10 years of age) and 2 µg (> 10 years). The “average” western diet probably supplies 3-15 µg/day, but can range from 1-100 µg/day.

Folic acid

• Vitamine B9• Function :• Biochemistry of DNA base and amino acid

production• DNA and cell division

– Folate is needed to carry one-carbon groups for methylation reactions and nucleic acid synthesis (the most notable one being thymine, but also purine bases)

• Absorpsed in jejenum, actively transport, excretion 90% urine

Sources

• Certain foods are very high in folate:• Leafy vegetables such as spinach, asparagus, turnip greens• Legumes such as dried or fresh beans, peas and lentils• Egg yolks.[70]

• Baker's yeast• Fortified grain products (pasta, cereal, bread); some

breakfast cereals (ready-to-eat and others) are fortified with 25% to 100% of the recommended dietary allowance (RDA) for folic acid

• Sunflower seeds• Liver and liver products contain high amounts of folate

• RDA: 400 mcg Optimal Level: 400 mcg Maximum: 2 mg

Function

• Biochemistry of DNA base and amino acid production

• DNA and cell division– Folate is needed to carry one-carbon groups for

methylation reactions and nucleic acid synthesis (the most notable one being thymine, but also purine bases)