Definition Aetiology
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1 Definition Anaemia is a fall in haemoglobin below the reference ranges for age and sex (adult female <115g/L, adult male <130g/L). It can be further characterised by the mean cell volume (MCV). Aetiology Anaemia itself is not a disease it is simply a laboratory finding that can be caused by many other pathological processes. Our aim as clinicians is to identify the underlying cause of an anaemia (importantly to exclude any malignancy or sinister cause) and manage it appropriately.
2 Basic iron physiology Iron is present in the diet red meat, cereals and vegetables The main site of absorption is the duodenum ph is necessary for absorption Transferrin = iron- transfer protein in plasma Total iron binding capacity (TIBC) = indirectly measures transferrin Levels rise when iron is deficient, in an attempt to maximise use of available iron Ferritin = iron- storage protein Also an acute phase protein, so can be elevated in infammation Iron is used for haem synthesis in maturing red blood cell in the bone marrow Signs/symptoms specific to IDA Koilonychia Brittle nails and hair Atrophy of the papillae of the tongue Angular stomatitis IDA - causes 1. Reduced iron intake Poor diet Malabsorbtion (coeliac disease, gastrectomy, PPIs) 2. Increased iron utilisation Infancy/adolescence/pregnancy 3. Blood loss Menorrhagia GI bleed Hookworm (largest cause of IDC worldwide due to low grade GI blood loss to the hookworm parasite. Seen in tropics, rare in developed world). IDA investigations Blood smear Hypochromic (pale), microcytic RBCs Pencil cells Target cells Variation in RBC shape (poikilocytosis) Variation in RBC size (anisocytosis) Iron study result Serum iron Bone marrow iron TIBC Transferrin saturation Ferritin High Treatment Oral iron tablets (ferrous sulphate) 200mg TDS for 4/6 months S/E = nausea, abdo pain, constipation, diarrhoea
3
4 Commonly seen in hospital patients. It is associated with: TB Crohns Rheumatoid arthritis SLE Malignancy Investigations Blood results MCV Serum iron Bone marrow iron TIBC Ferritin Normal (but can be low!) High Normal/high Because iron storage is high, production of transferrin tends to decrease, giving a low TIBC. This helps differentiate from iron deficiency, where TIBC is raised. Treatment Identify cause! Patients do not respond to iron replacement EPO can be given particularly useful in pts with chronic kidney disease
5 MEGALOBLASTIC ANAEMIA is characterised by the finding of megaloblasts in the bone marrow. Megaloblasts are RBCs that have delayed nuclear maturation. They are large cells with immature nuclei. Megaloblastic anaemia is caused by B12 or folate deficiency. Folate physiology - Folate is found in green vegetables and offal such as liver and kidney, though the cooking process often causes a loss of 60-90% of the folate present - Folate is absorbed in the proximal ileum - Once absorbed folate is transported to target tissue where it is involved in the synthesis of DNA Signs and symptoms Glossitis may be present No neurological symptoms Pathophysiology of folate deficiency Deficiency of folate leads to a failure in DNA production in developing red blood cells and the production of less, larger erythrocytes. There is also the presence of megaloblasts in the bone marrow. Body stores of folate are adequate for 3 months. Causes of folate deficiency: - Inadequate intake: this is the most common cause though is often present with decreased absorption (alcoholics) - Decreased absorption: Coeliac, Crohns - Increased consumption: pregnancy - Anti- folate drugs: methotrexate, trimethoprim - Alcohol: In alcoholics a combination of decreased intake due to poor diet and malabsorption due to the effect of alcohol on the gut leads to folate deficiency Investigations Full blood count will show low Hb and raised MCV Serum and red cell folate will be low Management Find and treat underlying cause. Assess diet with dietician input. Give folate supplements - these should be given prophylactically during pregnancy as folate deficiency has been linked to neural tube defects.
6 B 12 physiology Investigations - B 12 intake is solely dietary it is found in meat, fish, eggs and dairy products - Gastric enzymes liberate B 12 from protein complexes! it becomes bound to R protein - Pancreatic enzymes release B 12 from R protein! it becomes bound to intrinsic factor secreted by gastric parietal cells - B 12 is carried by intrinsic factor to specific transporters in the distal ileum where it is absorbed and intrinsic factor is excreted - In the blood B 12 is transported to different tissues in association with glycoprotein transcobalamins - In target cells (including developing erythrocytes) B 12 acts as a co- enzyme in the production of DNA - Body stores of B 12 may be adequate for up to 2 years after absorptive failure so onset is slow - Full blood count will show low Hb and raised MVC >96 - Serum bilirubin may be raised due to increased haemolysis - Serum B 12 will be well below normal range - Serum folate will be normal or raised - Bone marrow: will show characteristic megaloblasts - If pernicious anaemia is suspected antibodies against parietal cells and intrinsic factor should be tested. - If coeliac disease is suspected tissue transglutaminase should be tested - If Crohns is suspected a colonoscopy may give more information Causes of B 12 deficiency - Decreased dietary intake (vegans) - Decreased absorption (coeliac disease, chrons disease, pancreatitis) - Pernicious anaemia: this is the most common cause of B 12 deficient anaemia in the adult population and is common in the elderly. It is an autoimmune gastritis that targets parietal and chief cells and results in a deficiency of intrinsic factor production thereby preventing adequate absorption of B Increased utilisation blind loop syndrome (bacterial overgrowth of gut) Signs and symptoms - A lemon- yellow skin colour due to the combination of palor and mild jaundice from increased haemolysis - Glossitis - Angular stomatitis - Progressive polyneuropathy: symmetrical paraesthesia of the fingers and toes, early loss of vibration sense and proprioception, progressive weakness and ataxia (may be irreversible if left untreated) - Psychiatric problems: confusion, hallucinations, delusions and dementia (may be irreversible if left untreated) Management Give B 12 supplementation (advice as prophylaxis in vegans). Find and treat underlying cause.
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