NUTRITIONAL ANAEMIAS Anaemia Def.

ef. a reduced haemoglobin level Chronic anaemia is associated with ill health, loss of productivity, poorer mental activity, an increased susceptibility to disease & an increased risk of maternal and neonatal death Threshold for defining anaemia: gender Non-pregnant women pregnant women Children (yrs) 0.5-4.9 5-11.9 12-14.9 Men (>15yrs) amount (g/L) <120 <110 <110 <115 <120 <130

main causes 1. Nutritional - lack of iron, folic acid, vitamin B12, protein and vitamin A 2. Infection - helminths (worms). Malaria, schistosomiasis, AIDS, TB 3. Genetic disorders of haemoglobin - sickle cell diseases, thalassaemia, G6PD. The pathophysiological reasons for anaemia a) Decreased production b) Increased destruction (shorter RBC life span - haemolysis) or loss (bleeding) c) A combination of decreased production and shortened RBC life span d) Redistribution of RBCs in splenomegaly - "pooling" of RBCs in the spleen. A haematinic deficiency is due to one of three causes: 1. Decreased dietary intake 2. Impaired absorption 3. Increased loss or utilization

Anaemias are considered in three groups: Microcytic, hypochromic (MCV 78 fL) Normocytic, normochromic Macrocytic (MCV 100 fL) Microcytic, hypochromic anaemia (low MCV & MCH), A number of chemical tests may be used to differentiate between these disorders, which are listed in the table below summarized in the figure:

Iron deficiency anaemia is due to: An inadequate dietary iron intake Increased loss of iron from: o gastrointestinal bleeding o increased menstrual blood loss o impaired iron absorption as in coelic disease (gluten sensitivity) o competition from gut parasites (plus increased blood loss) Anaemia of chronic disease is common in: Chronic infection Inflammation Connective tissue diseases (e.g. rheumatoid arthritis) neoplasia Severity of the anaemia depends on the time it has been present Thalassaemia trait - a genetic disorder of globin chain synthesis, most commonly affecting the or globin chain. iron deficiency may need to be excluded and frequently complicates the condition in pregnancy. Sideroblastic anaemia seen in the elderly usually a mild macrocytic anaemia with a variable population of small, hypochromic red cells (Dimorphic - two populations of red cells) Due to ineffective erythropoiesis; it may be severe and is generally refractory to treatment. The causes of microcytic hypochromic anaemia

Nutrition and the blood - "Haematinics" IRON - a very common element, but iron deficiency is the most common cause of anaemia Body iron distribution Free iron is toxic and must always be transported and stored bound to a protein: transferrin (Tf), transferrin receptor 1 (TfR1) and ferritin a) Transferrin, the main carrier of iron in serum; each molecule can carry up to 2 atoms of iron; Delivers iron to tissues that have transferrin receptors. b) Iron is stored in tissue macrophages in the liver, bone marrow and spleen. as: i. Ferritin, a water-soluble complex Ferritin is present in the plasma and can be measured; the amount bears an approximate relationship to the total body iron stores. ii. Haemosiderin The iron in both ferritin and haemosiderin is in the ferric (Fe3+) form and must be reduced to the ferrous (Fe2+) form before it can be mobilized.

The daily kinetics of iron Plasma iron in a dynamic state continuosly circulates bound to transferrin with iron balance being finely maintained Each day, about 20 mL of red cells are destroyed by bone marrow and splenic macrophages, liberating about 20 mg of iron, with daily external losses of 1 mg or 2 mg, in men and women respectively. The rest is recycled, largely back to the bone marrow for new RBC production. In effect, iron loss is balanced by iron absorption

Iron absorption and balance takes place through the epithelial cells of the duodenum From a normal diet is just sufficient to compensate for the loss of 1-2 mg/day from desquamation of gut cells and menstruation. The amount of Iron absorbed is controlled by the iron level The rate of red cell production and the control of iron balance is at the level of absorption as there is no physiological mechanism for iron excretion. The overall controller of iron metabolism is HEPCIDIN, which is synthesised in the liver. o The level is low in persons with a normal haemoglobin level and in irondeficiency anaemia; o it is raised, in response to cytokines, in infection, inflammation and neoplasia to limit the supply of iron to developing red cells, to reduce iron absorption and it reduces the level of iron in the plasma.

Sources of iron There are 2 sources of iron:

haem iron: Meat (best source), liver and fish non-haem iron: oatmeal, vegetables, fortified bread and cereals, nuts, dried fruit, red wine, chocolate Foods rich in vitamin C enhance iron absorption

Factors affecting Iron Absorption Increased by Inorganic iron Ferrous form Gastric acidity Vitamin C Iron deficiency anaemia Increased erythropoiesis Pregnancy Hypoxia Iron deficiency ( IDA ) The commonest cause of anaemia throughout the world. The development of IDA goes through well-recognized stages: depletion of tissue iron stores iron-deficient erythropoiesis frank iron deficiency with a low haemoglobin level Reduced by Organic iron Ferric form Alkalis Phosphates & pyrates Tea, bran Decreased erythropoiesis Iron overload Inflammation (Hepcidin)

Causes: Inadequate dietary iron increased physiological requirement - pregnancy/lactation, growth Excessive loss (chronic blood loss) - GI bleeding, menorrhagia, hookworm Malabsorption - coeliac disease, gastrectomy Intravascular haemolysis - renal excretion of iron

Assessment of iron status Microcytic, hypochromic anaemia (low MCV and MCH) Reduced serum iron, raised total-iron binding capacity, and a reduced transferrin saturation Low serum ferritin (caution- ferritin may be raised if infection, inflammation or o malignancy is present. Ferritin is an acute phase protein) Raised transferrin receptor concentration (can differentiate IDA from anaemia of o chronic disease. TfR is not an acute phase protein, unlike ferritin)

MACROCYTIC ANAEMIA FOLIC ACID In nature, folates are present as polyglutamates, which humans cannot absorb. It is biochemically active when reduced to dihydrofolic acid (by hydrolysis) and then to tetrahydrofolic acid. Folate deficiency causes a megaloblastic anaemia due to defective DNA synthesis Humans cannot synthesise folates Diet: present in most foods - liver, yeast, spinach, greens & nuts(cooking destroys) Requirements - 100-200 pg/day Stores - 10-25 mg (3-4 months supply) Absorption - jejunum, Monoglutamate is very quickly absorbed

Causes of deficiency: Diet: the poor, the elderly, alcoholics, food fads, ill, mad Malabsorption: coeliac disease, jejunum resection, tropical sprue Increased requirement: pregnancy, prematurity, haemolytic anaemia, myelofibrosis, malignancy, chronic inflammation Increased urinary loss: long term dialysis, heart failure, acute liver disease Drugs -anticonvulsants, folate antagonists, alcohol

Folic acid is an important factor in the causation of neural tube defects (spina bifida and anencephaly) and folate therapy is recommended in pregnancy. An elevated level of homocysteine in folic acid deficiency (& B12) is a risk factor for coronary artery disease and other vascular disorders. Bread/flour is now a fortified product. Vitamin B12 Family of cobalamins (cobalt-containing) The B12 molecule is composed of: i) A planar corrin nucleus of 4 pyrrole rings, ii) A ribo- nucleotide at right angles to the planar group iii) A cobalt atom linked to the corrin nucleus. MW 1355

Synthesised by bacteria An external source is required for humans. Diet: animal products liver, fish, eggs and dairy produce, contaminated vegetables Requirements - 1 pg/day Stores - 5 mg (3-5 years)

Absorption: a) b) c) d) e) Food B12 released from protein by pepsin in stomach and binds to R-binder B12 released from R-binding protein in jejunum by pancreatic trypsin Intrinsic factor produced by gastric parietal cells B12/IF complex allows B12 absorption in terminal ileum (site of IF receptor) Transport: transcobalamin

Function: A Coenzyme for 2 biochemical reactions methyl B12 is a cofactor for methionine synthase for the methylation of homocysteine to methionine. Essential for DNA synthesis conversion of methylmalonyl CoA to succinyl CoA

Clinical effects of vitamin B12 and folate deficiency: Macrocytic, megaloblastic anaemia macrocytic anaemia neutropenia and hypersegmented neutrophils thrombocytopenia bone marrow - hypercellular, nuclear abnormalities in all cell lines megaloblasts, giant metamyelocytes) Vitamin B12 neuropathy - peripheral neuropathy, sub-acute combined degeneration of the spinal cord (not folate deficiency)

Mechanisms and causes of vitamin B12 deficiency Nutritional (Inadequate intake) - vegans Inadequate secretion of Intrinsic factor - Pernicious anaemia, gastrectomy, congenital deficiency of IF (rare) Intestinal causes: Blind loop syndrome, jejunal diverticula, Crohn's disease, ileal resection, tropical sprue, fish tapeworm, congenital selective B12 malabsorption