ANEMIA+IRON DEFICENCY ANEMIA

ANAEMIA
Anaemia refers to a state in which the level of haemoglobin in the blood is below the normal range appropriate for age and sex. Other factors, including pregnancy and altitude. also affect haemoglobin levels and must be taken into account when considering whether an individual is anaemic. The clinical features of anaemia reflect diminished oxvsen supply to the tissue and depend upon the degree of anaemia. the rapidity of its development and the presence of cardiorespiratory disease. A rapid onset of anaemia (e.g. due to blood loss) will cause more profound symptoms than a gradually developing anaemia. Individuals with cardio¬respiratory disease will have symptoms of anaemia at higher haemoglobin levels than those with normal cardiorespira¬tory function.  .
The diagnosis of anaemia not only includes the assess¬ment of its clinical severity but must also define the under¬lying cause. This rests on the clinical history and examination, assessment of the full blood count and blood film, and further appropriate investigations. .
History 
of anaemia in females still menstruating. so women should always be asked about their periods.
• A dietary history should assess the intake of iron and folate which may become deficient in comparison to needs (e.g. in pregnancy or during periods of rapid growth-p. 1027).
• Past medical history may reveal a disease which is known to be associated with anaemia, such as rheumatoid arthritis (the anaemia of chronic disease). or previous surgery (e.g. resection of the stomach or small bowel which may lead to malabsorption of iron and/or vitamin B12.
• Family history and ethnic background of the patient are important. Haemolytic anaemias such as the haemoalobinopathies and hereditary spherocytosis may be suspected from the family history. Pernicious anaemia may also be familial.
• A drug history may reveal the ingestion of drugs which can be associated with blood loss (e.g. aspirin and anti-inflammatory drugs) or drugs that may cause haemolysis or aplasia.
Physical examination
As well as the general physical findings of anaemia shown on page 1001, there may be specific findings related to the aetiology of the anaemia; for example, a patient may be found to have a right iliac fossa mass due to an underlying caecal carcinoma. Haemolytic anaemias can cause jaundice. Vitamin B12 deficiency may be associated with neurological signs including peripheral neuropathy, dementia and signs of subacute combined degeneration of the cord (p. 1245). Sickle-cell anaemia (p. 1035) may result in leg ulcers. Anaemia may be -multifactorial and the lack of specific symptoms and signs does not rule out silent pathology.
Schemes for the investigation of anaemias are often based on the size of the red cells, which is most accurately indicated by the mean cell volume (MCV) in the FBC. Commonly, in the presence of anaemia:
A normal MCV (normocytic anaemia) suggests either acute blood loss or the anaemia of chronic disease (ACD) (Fig. 24.12).
v A low MCV (microcytic anaemia) suggests iron deficiency or thalassaemia ).
• A high MCV (macrocytic anaemia) suggests vitamin B,2 or folate deficiency ().
 
Around 30% of the total world population is anaemic and half of these, some 600 million people, have iron deficiency. The classification of anaemia by the size of the red cells (MCV) indicates the likely cause. Red cells in the bone marrow must acquire a minimum level of haemoglobin before being released into the blood stream (Fig. 24.18). Whilst in the marrow compartment red cell precursors undergo cell division driven by erythropoietin. If red cells cannot acquire haemoglobin at a normal rate they will undergo more divisions than normal and will have a low MCV when finally released into the blood. The MCV is low because component parts of the haemoglobin molecule are not fully available: that is, iron in iron deficiency, globin chains in thalassaemia, haem ring in congenital sideroblastic anaemia and, occasionally, poor iron utilisation in the
 )
Normal DNA synthesis I Haemoglobinisation e.g. Iron deficiency Thalassaemia Sideroblastic anaemia
 
 
Normal
I DNA synthesis e.g. .l,B1z IFolate Cytotoxic drugs Myelodysplasia
Elevated plasma lipids Liver disease Hypothyroidism Alcohol
Hyperlipidaemia Pregnancy
ANAEMIAS
Factors which influence the size of red cells in anaemia. (I MCV is < 76 fl; T MCV is > 100 fl)
 
 
 
 
Defective DNA synthesis
 
 
 
anaemia of chronic disease. In megaloblastic anaemia the biochemical consequence of vitamin B,2 or folate deficiency is an inability to synthesise new bases to make DNA. A similar defect of cell division is seen in the presence of cytotoxic drugs or haematological disease in the marrow such as myelodysplasia. In these states, cells haemoglobin¬ise normally but undergo fewer cell divisions, resulting in circulating red cells with a raised MCV The red cell membrane is composed of a lipid bilayer which will freely exchange with the plasma pool of lipid. Conditions such as liver disease, hypothyroidism, hyperlipidaemia and pregnancy are associated with raised lipids and may cause a raised MCV.
IRON DEN
This occurs when iron losses or physiological requirements exceed absorption.
Wood loss
The most common explanation in men and post-menopausal women is gastrointestinal blood loss (p. 866). This may result from occult gastric or colorectal malignancy, gastritis, peptic ulceration, inflammatory bowel disease, diverticu¬litis, polyps and angiodysplastic lesions. On a world-wide
basis, hookworm and schistosomiasis are the most prevalent causes of gut blood loss (pp. 360 and 367). Gastrointestinal blood loss may be exacerbated by the chronic use of aspirin or NSAIDs, which cause intestinal erosions and impair platelet function. In women of child-bearing age, menstrual blood loss, pregnancy and breastfeeding contribute to iron deficiency by depleting iron stores; in developed countries one-third of women in this age bracket have low iron stores but only 3% display iron-deficient haematopoiesis. Rarely, chronic haemoprysis or haematuria may cause iron deficiency.
 
Malabsorpt6oet
A dietary assessment should be made in all patients to ascertain their iron intake. Gastric acid is required to release iron from food and helps to keep iron in the soluble ferrous state (Fig. 24.19). Hypochlorhydria in the elderly or that due to drugs such as proton pump inhibitors may contribute to the lack of iron availability from the diet, as may previous gastric surgery. Iron is absorbed actively in the upper small intestine and hence can be affected by coeliac disease (p. 894). Anyone with features of malabsorption or recurrent deficiency in the absence of other explanations, young men with normal diet or young women with normal menstruation and diet in association with iron deficiency, should be screened for coeliac disease.

BLOOD DISORDERS
 
Dietary iron `¬
u, 7 mg/1000 kCal
Haem iron CNon-haem iron~
(< io°i total) (> 9o°i° total)
acids
~,~?= @Amino acids
Available for Vitamin C absorption OPhytates Tannins
< F/.) Phosphates
 
Transferrin
SO
 
Ferritin  Tissue iron Enzymes (2%) Myoglobin (4%)
Ferritin (29%)¬
e
 
Physiological demands
At times of rapid growth such as infancy and puberty, iron demands increase and may outstrip absorption. This may be exacerbated by prematurity and breastfeeding in infants or menstruation in girls. In pregnancy, iron is diverted to the fetus, the placenta and the increased maternal red cell mass, and is lost with bleeding at parturition. There is no consensus about the routine use of iron supplementation in pregnancy but if women with a poor dietary history or previous heavy menstrual losses become pregnant and the side-effects are acceptable, it is a justifiable practice.
Investigations
Confirmation of iron deficiency
Plasma ferritin is a measure of iron stores and the best single test to confirm iron deficiency (Box 24.29, p. 1030). It is a very specific test; a subnormal level is due to iron deficiency, hypothyroidism or vitamin C deficiency. Levels can be raised by liver disease and in an acute phase response; in these conditions a ferritin level of up to 100 pg/1 may still be associated with absent bone marrow iron stores. Plasma iron and total iron binding capacity (TIBC) are measures of iron availability, hence are affected by many factors besides iron stores. Plasma iron has a marked diurnal and day-to-day variation and becomes very low during an acute phase response but is raised in liver disease and haemolysis.
Transferrin levels are lowered by malnutrition, liver disease, an acute phase response and nephrotic syndrome but raised by pregnancy or the oral contraceptive pill. A transferrin saturation of less than 16% is consistent with iron deficiency but is less specific than a ferritin measurement.
All proliferating cells express membrane transferrin receptors to acquire iron; a small amount of this receptor is shed into blood and found in a free soluble form there. At times of poor iron stores, cells up-regulate transferrin receptor expression; hence the levels of soluble plasma transferrin receptor increase. This can now be measured by immunoassay and used to distinguish storage iron depletion in the presence of an acute phase response or liver disease where a raised level indicates iron deficiency. In difficult cases it may still be necessary to examine a bone marrow aspirate for iron stores.
Investigation of the cause
This will depend upon the age and sex of the patient as well as the history and clinical findings. In men over the age of 40 years and in post-menopausal women with a normal diet, the upper and lower gastrointestinal tract should be investigated by endoscopy or barium studies. If coeliac disease is suspected, serum antigliadin and anti¬endomysium antibodies and duodenal biopsy are indicated (p. 894). In the tropics stool and urine should be examined for parasites (.
Anaemia
Hypoxia 6 I Fe stores
Fe absorption maximum ;,3.5 mg/day
 
ANAEMIAS
Management
Unless the patient has angina, heart failure or evidence of cerebral hypoxia, transfusion is not necessary and oral iron supplementation is appropriate. Ferrous sulphate 200 mg 8-hourly (120 mg of elemental iron per day) is more than adequate and should be continued for 3-6 months to replete iron stores. The occasional patient is intolerant of ferrous sulphate, with dyspepsia and altered bowel habit. In this case a reduction in dose to 200 mg 12-hourly or a switch to ferrous gluconate 300 mg 12-hourly (70 mg of elemental iron per day) should be made. Delayed-release preparations are not useful since they release iron beyond the upper small intestine where it cannot be absorbed.
The haemoglobin should rise by 10 g/1 every 7-10 days and a reticulocyte response will be evident by 1 week. A failure to respond adequately may be due to non¬compliance, continued blood loss, malabsorption or an incorrect diagnosis. The occasional patient with malabsorp¬tion or chronic gut disease may need parenteral iron with deep intramuscular injection of iron sorbitol (1.5 mg of iron per kg body weight). This will produce a haematological response and rapidly replete iron stores. Patients should be warned that a brown skin discoloration like a tattoo is likely to develop at the sites of administration.