red blood cells must

• Anaemias


  A below normal level of haemoglobin
• Haemoglobin


  • A haemoprotein composed of globin and haem that gives red blood cells their characteristic colour
  • Its function is primarily to transport oxygen from the lungs to the body tissues
• Normal adult human haemoglobin


  • A tetramer
  • 4 polypeptide chains
  • Two α chains
  • Two β chains
  • Each of the globin chains has one iron containing molecule, haem, located within a hydrophobic cavity
• Red blood cell gaseous exchange


  • Red cells must be able to pass repeatedly through the microcirculation
  • 300 miles in its 120 day lifespan
  • Have to come into close contact with the tissues
  • Maintain haemoglobin in its reduced ferrous state (Fe++)
  • Maintain osmotic equilibrium
• Iron


  • Plays a vital role in normal function/metabolism of almost every cell in the body
  • Adequate dietary intake of iron is essential for health
  • Iron is essential for haemoglobin production
• Body iron distribution and transport


  • Transferrin- transports iron to developing red cells which have transferrin receptors
  • Transferrin receptor-present on blood cell binds to transferrin/iron complex
  • Iron stores 66% body iron is stored as ferritin, mainly in liver, some in bone marrow, spleen and muscles
  • 33% stored as haemosiderin, found in cells not circulating blood
• Iron intake, absorption and loss


  • Average western diet contains 10-15mg iron daily
  • 5-10% absorbed through the small intestine
  • Absorption is normally adjusted to body needs
  • Iron from animal products is more readily absorbed than vegetable iron
  • Dietary iron makes up from daily loss of about 1mg in hair, skin, urine, faeces and menstrual blood loss
• Sources of dietary iron


  • Red meat
  • Liver
  • Fish
  • Salmon
  • Sardines
  • Pilchards
  • Tuna
  • Egg yolk
  • Wholemeal bread
  • Breakfast cereals
  • Vegetables and pulses
  • Nuts and prunes
  • Marmite Fortified foods
• Normal red cells


  • Anucleate
  • 6.7-7.7 µm
  • Biconcave disc
  • Central area of pallor- about 1/3rd of red cell diameter
• Anaemia


  • A below normal level of haemoglobin
  • Haemoglobin normal range: 130-170g/l adult males, 120-155g/l adult females
• Classification of anaemia


  • Microcytic -small red cells (MCV<78fl)
  • Macrocytic -large red cells (MCV>100fl)
  • Normocytic -normal size red cells (MCV 78-100fl)
• Microcytic anaemais


  • Thalassaemia
  • Anaemia of chronic disease
  • Iron deficiency
  • Lead Poisoning
  • Sideroblastic anaemia
  • Other haemoglobin defects
• Macrocytic anaemias


  • Megaloblastic anaemia
  • Folic acid deficiency
  • B12 deficiency
  • Auto immune disease-pernicious anaemia
  • Myelodysplastic syndromes (MDS)
  • Liver disease
• Normocytic anaemia


  • Haemolytic anaemia
  • Shortened red cell survival
  • Acute blood loss
  • Anaemia of chronic disease
• Iron Deficiency Anaemia


  • Most common cause of anaemia worldwide (25% world population)
  • Most common cause of microcytic anaemia
  • MCV (Mean cell volume)-reduced
  • MCH (mean cell haemoglobin)-reduced
  • Small red cell
  • Pale/empty red cells
• Causes of iron deficiency anaemia


  • Chronic blood loss
  • Menorrhagia
  • Gastrointestinal
  • Increased demands
  • Growth
  • Pregnancy
  • Malabsorption
  • Post gastrectomy
  • Poor diet
• Iron deficiency anaemia


  • Develops slowly
  • Pallor
  • Sore mouth
  • Brittle nails
  • Dysphagia
  • Glossitis
  • Abnormal appetite
  • Hair thinning
  • Lassitude
  • Fatigue
  • Tachycardia
• Brittle nails


  • Pallor
• Laboratory findings of iron deficiency anaemia


  • Microcytic hypochromic anaemia
  • Raised platelet count
  • Bone marrow shows absence of stored iron, erythroblasts with ragged irregular cytoplasm
  • Reduced serum ferritin level
  • Low serum iron level
  • Raised serum transferrin receptor
• Vitamin B12


  • Also known as cobalamin
  • Consists of cobalt atom situated in centre of a corrin nucleus
• Function of vitamin B12


  • A coenzyme for 2 biochemical reactions: Methylation of homocysteine to methionine, Converts methylmalomyl coenzyme A to succinyl coenzyme A
  • Without these reactions the body has a reduced supply of the precursors required for DNA synthesis and Myelin production
• Effect of DNA synthesis on red cell production

  • Erythroblasts in bone marrow show abnormal maturation
  • Maturation arrest
  • Maturation of nucleus being delayed relative to cytoplasm
  • No reticulocytes produced
• Bone marrow showing megaloblastic erythropoiesis


  • Normoblastic erythropoiesis
  • Megaloblastic erythropoiesis
• B12 intake, absorption and loss


  • Adult daily requirement 1 µg
  • Normal mixed diet contains 10-15 µg
  • Stored largely in the liver-enough for 2-4 years
  • Absorbed in ileum attached to intrinsic factor which is secreted in the stomach
  • Lost through urine, faeces and excretion of bile
  • Transported in the plasma bound to transcobalamin
• Dietary sources of B12


  • Liver/Kidney/Heart
  • Clams/Oysters
  • Red meat
  • Seafood
  • Eggs/Milk/Cheese
  • Yoghurt
  • Fortified foods
• Causes of B12 deficiency


  • Inadequate diet-vegans
  • Malabsorption
  • Gastrectomy
  • Intrinsic factor deficiency/antibody
  • Intestinal causes
  • Tapeworm
  • Crohn's disease
  • Ileal resection
  • Excess utilisation
  • Pregnancy
  • Haematological disease
  • Liver disease
  • Drug treatments
• Clinical features of B12 deficiency-Megaloblastic anaemia


  • Gradual onset of anaemia
  • Mild jaundice
  • Glossitis
  • Tingling in feet or hands
  • Difficulty in gait
  • Visual disorders
  • Psychiatric disorders
  • May be asymptomatic
• Glossitis


  • Jaundice
• Laboratory findings of B12 deficiency


  • Macrocytic anaemia with oval red cells
  • Absence of reticulocytes
  • Hypersegmented neutrophils
  • Moderately reduced white blood cell count
  • Moderately reduced platelet count
  • Raised bilirubin
  • Low serum B12
  • Hypercellular bone marrow
  • Maturation arrest
  • Raised serum methylmalonic acid & serum homocysteine levels
• Treatment of B12 deficiency


  • 1 mg hydroxycobalamin intramuscularly every 3 days until six injection have been given, then every 3 months for life unless cause of deficiency has been treated
  • In severe cases potassium supplements are given at the same time as the B12
  • Some patients die suddenly after starting treatment due to the drop in potassium levels
• Vitamin B12 neuropathy (subacute degeneration of the cord)


  • Progressive damage to peripheral sensory nerves
  • Affects spinal cord, brain and peripheral nerves
  • Affects lower limbs in the main
  • Tingling feet
  • Difficulty walking
  • Falls
  • Optic atrophy
  • Psychiatric symptoms
• Cause of B12 neuropathy


  • Accumulation of homocysteine and reduction of methionine in the nervous tissues
  • Defective methylation of myelin
  • Causes abnormal fatty acids to form around cells and nerves
• Pernicious anaemia


  • Auto immune disease
  • Affects more females than males (1.6:1)
  • Most common over 60 years of age
  • Found in all races
  • Most common in northern Europeans
  • Auto antibodies attack the gastric parietal cells
  • Parietal cells secrete intrinsic factor
  • Cannot absorb B12
  • Increased incidence in carcinoma of stomach
• Folic acid (Vitamin B9)


  • Pteroglutamic acid
  • Parent compound of a large group of compounds, the folates
  • Humans cannot synthesize folic acid
  • Heat labile-destroyed by cooking
  • Absorbed in the jejunum
  • Deficiency often seen in diseases of small intestine
  • Body stores only 3 months
• Role of folic acid


  • Needed for a variety of biochemical reactions in the body
  • Homocysteine-methionine
  • Serine-glycine
  • Synthesis of DNA precursors
  • Necessary for production of new cells
  • Deficiency hinders DNA synthesis/cell division
  • Substrate in the important reactions that involves B12
• Sources of Folic acid (Folate)


  • Leafy vegetables - spinach
  • Turnip
  • Lettuce
  • Beans
  • Peas
  • Breakfast cereals
  • Fruit – Banana, Melon, Lemon
  • Liver
• Folate deficiency


  • Clinical feature of folate deficiency same as B12 deficiency
  • Often less severe
  • Develops rapidly
  • Low body stores
  • Does not cause same neuropathy
  • Cause usually dietary
  • Alcoholism
  • Disorders of the intestine
  • Particularly when demand is increased
  • Pregnancy
  • Periods of rapid cell division
• Neural tube defect-opening in spinal cord or brain (spina bifida)


  • Cause: B12 or folic acid deficiency in early pregnancy
  • Lower maternal serum B12 or folate, greater the incidence
  • Build up of homocysteine in foetus
  • Impairs methylation of various proteins and lipids
  • Treatment of cause: Dietary supplements in early pregnancy reduce incidence by 75%
• Other tissue abnormalities associated with B12/folic acid deficiency


  • Sterility (either sex)
  • Morphological abnormalities of cervix, bladder and other epithelia
  • Cleft lip and palate in the foetus/newborn
  • Widespread reversible melanin pigmentation
  • Associated with cardiovascular and malignant disease
• Normocytic anaemias


  • Normal size red cells (MCV in normal range)
  • Not enough of them