WHO: a condition in which the amount of haemoglobin and consequently the oxygen-carrying capacity of RBCs is insufficient to meet the body's physiologic needs.
Name the nutritional causes of microcytic and macrocytic anaemia.
- Microcytic - iron deficiency
- Macrocytic - B12/folate deficiency
Outline the absorption and distribution of iron.
- Iron is absorbed from duodenum via enterocytes into plasma, where it binds to transferrin.
- Transported via transferrin to bone marrow to make RBCs.
- Excess iron absorbed is stored as ferritin.
- The hormone hepcidin decreases absorption from the duodenum and release from macrophages and iron-storing hepatocytes - this process is driven by ferroportin (iron channel) internalisation and regulated by negative feedback mechanisms.
What happens to ferritin and transferrin during a state of iron deficiency?
- Ferritin stores are depleted.
- Increased transferrin levels, but low saturation.
- Transferrin saturation calculated by ratio of serum iron to total iron binding capacity (TIBC).
- In iron deficiency, TIBC is very high compared to serum iron > low saturation.
Name the main causes of iron deficiency anaemia (IDA).
Not enough in:
- Poor diet
- Increased physiological needs
Losing too much:
- Blood loss - menstruation, GI tract loss, parasites
What tests are likely to diagnose iron deficiency anaemia at an earlier stage and why?
- IDA initially normocytic and normochromic.
- FBC will show microcytic RBCs and low Hb but not until later on.
- Ferritin levels fall before other markers, so ferritin test is good for early diagnosis.
A patient presents with moderate anaemia, microcytic and hypochromic erythrocytes, reticulocytopenia and a ferritin level of 8. What is the diagnosis and why?
- Microcytic and hypochromic RBCs consistent with iron deficiency anaemia.
- Reticulocytopenia - reduced reticulocyte count indicates poor erythrocyte production from the bone marrow.
- Ferritin < 20, 8 is very low - severe depletion of iron stores - confirms iron deficiency.
- High TIBC and low transferrin saturation would corroborate the findings.
What is the most common cause of iron deficiency anaemia in adult men and postmenopausal women?
- Blood loss from the GI tract
- Menstrual blood loss is the most common cause in premenopausal women
Describe the common signs and symptoms of iron deficiency anaemia.
- Symptoms - fatigue, lethargy, dizziness
- Signs - pallor of mucous membranes, bounding pulse, systolic flow murmurs, smooth tongue, koilonychias
Outline the different causes of megaloblastic and nonmegaloblastic macrocytic anaemia.
- Megaloblastic - caused by B12/folate deficiency or drug-related interference with B12/folate metabolism.
- Nonmegaloblastic - alcoholism, liver disease, hypothyroidism, myelodysplastic syndromes, reticulocytosis.
In B12/folate deficiency, which of these nutrients is likely to be depleted from the body's stores more quickly and why?
- B12: 2-3mg stored over 2-4 years, easy to obtain sufficient amounts from animal and dairy products.
- Folate: 10-12mg stored over 3-4 months, found in vegetables and animal liver and harder to obtain in diet.
- Folate stores depleted quicker because required daily intake is higher, stores are short-term, harder to obtain in typical Western diet and cooking produces 60-90% loss.
Outline the role of vitamin B12 (cobalamin) and folic acid (folate) in erythrocyte production.
- Both important for final RBC maturation and DNA synthesis.
- Both needed for thymidine triphosphate synthesis.
Describe the characteristic changes seen on a peripheral blood smear in B12/folate deficiency anaemia.
- Changes are megaloblastic.
- Macroovalocytes - large oval RBCs.
- Hypersegmented neutrophils.
Describe the main causes of folate deficiency.
- Increased demand - pregnancy/breast feeding, growth spurts, haemolysis/rapid cell turnover, disseminated cancer, urinary loss.
- Decreased intake - poor diet, elderly, chronic alcohol intake.
- Decreased absorption - medication (folate antagonists), coeliac, jejunal resection, tropical sprue.
How is folate absorbed and stored?
- Absorbed in the jejunum.
- Body stores enough folate for 3-5 months.
Outline the cellular role of vitamin B12 (cobalamin).
- Essential co-factor for methylation in DNA and cell metabolism.
- Co-factor in metabolism of methylmalonic acid (MMA) - thus high MMA may indicate B12 deficiency.
- Co-factor in homocysteine metabolism - producing methionine.
Describe the absorption and transport of vitamin B12.
- Absorbed in the terminal ileum - requires intrinsic factor (IF) which is made in gastric parietal cells.
- Transcobalamin I and II transport vitB12 to tissues.
What is pernicious anaemia?
- Anaemia caused by impaired vitB12 absorption.
- Intrinsic factor/IF receptor deficiency.
- May be congenital or autoimmune - e.g. anti-parietal cell antibodies.
- Most common cause of vitB12 deficiency anaemia.
Outline the clinical consequences of vitamin B12 deficiency.