55. Deficiency anaemias

From greek.doctor

Deficiency anaemias are anaemias characterised by deficiencies of one of the essential components of RBC production. They all lead to reduced RBC production.

Iron deficiency anaemia

Iron deficiency is the most frequent deficiency state in developed countries. It can occur due to:

  • Deficiency iron intake
    • Bad diet
    • Protein-calorie malnutrition (PCM)
    • Strict vegans
    • Anorexia
  • Malabsorption
    • Low stomach acid (hypochlorhydria)
    • Vitamin C deficiency
    • Chronic diarrhoea
    • Inflammatory bowel disease
  • Increased iron requirement
    • Pregnancy
    • Periods of rapid growth
    • Breast feeding
  • Chronic blood loss
    • Occult (hidden) bleeding due to colon cancer
    • Menorrhagia

The characteristics or iron deficiency anaemia are:

  • Microcytic hypochromic anaemia (due to impaired heme synthesis)
  • Mean corpuscular volume is 70 – 90 femtoliter (fL)
  • RBC count around 3 T/L
  • Hypoproliferative bone marrow

Iron absorption is strictly regulated in the intestine. The transporter DCT-1 transports Fe2+ into intestinal epithelial cells. It will be oxidized into Fe3+ and bound to transferrin. Transferrin will then transport Fe3+ to tissues, where it will be stored with apoferritin as ferritin.

A protein called iron regulatory protein 1 (IRP-1) regulates iron balance. When serum levels of iron are low will IRP bind to the mRNA for apoferritin. This causes the apoferritin mRNA to not be translated into protein, which decreases the level of apoferritin in the cells. The cells will therefore “store” less iron, and instead use more iron.

IRP also binds to mRNA for transferrin receptor. In contrast with the mRNA for apoferritin will this enhancing the translation of transferrin receptor mRNA into protein. This increases the number of transferrin receptor on the cell surface. This causes the cell to take in more transferrin molecules from the blood.

In addition to the anaemic consequences of iron deficiency will iron deficiency cause:

  • Angular stomatitis
  • Not painful glossitis
  • Flatting of the nails

Folic acid and B12 deficiency

The function of folic acid is to carry molecular groups containing 1 carbon atom, like methyl groups, formyl groups and methylene groups. It’s important in purine synthesis (a component of ATP, DNA, RNA and so on), which obviously makes it important for proliferating cells, like the cells of the bone marrow, causing fewer RBCs to develop. To compensate for the fewer cells produced will the cells that are produced contain more haemoglobin, which is what’s causing the macrocytic-“ness”.

Deficiency of folic acid in pregnant women causes the foetus to develop spina bifida.

Some causes of folic acid deficiency include:

  • Deficient intake
    • Common in alcoholics
  • Deficient absorption
    • Chronic diarrhoea
    • Coealic disease
  • Increased demand
    • Pregnant women
    • Chronic haemolysis
  • Anti-folic acid drugs
    • Methotrexate

Vitamin B12 is essential for the regeneration of the cofactor THF (which is derived from folic acid). THF is important in amino acid synthesis and therefore protein synthesis. If B12 is deficient will THF levels be low, too.

B12 is also essential for methylmalonyl-CoA mutase. B12 deficiency causes accumulation of non-physiologic, weird fatty acids, which causes demyelinisation of axons. This causes peripheral and central neuropathy.

Causes of B12 deficiency include:

  • Deficient intake
    • Vegetarians
    • Alcoholism
  • Deficient absorption
    • Pernicious anaemia
    • Gastritis
    • Surgical removal of stomach
    • Diseases of terminal ileum, like Crohn’s disease
  • Impaired storage
    • Liver cirrhosis

Pernicious anaemia is an autoimmune disease where autoantibodies are produced against intrinsic factor or the parietal cells, which produce IF. These antibodies will either destroy the parietal cells or block B12 from binding to IF, both of which result in B12 malabsorption

The deficiency of folic acid or B12 causes a type of anaemia called megaloblastic anaemia. The characteristics are:

  • Hyperchromic and macrocytic
  • Hypersegmented neutrophils
  • RBC level may be extremely low, around 1 T/L
  • In the bone marrow is not only the RBC development impaired but platelet and WBC as well, causing pancytopaenia.

Other symptoms of B12 and folic acid deficiency are:

  • Painful glossitis