Nutritional Anaemias

Question 1

Define anaemia.

Answer 1

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.

Question 2

Name the nutritional causes of microcytic and macrocytic anaemia.

Answer 2

• Microcytic - iron deficiency
• Macrocytic - B12/folate deficiency

Question 3

Outline the absorption and distribution of iron.

Answer 3

• 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.

Question 4

What happens to ferritin and transferrin during a state of iron deficiency?

Answer 4

• 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.

Question 5

Name the main causes of iron deficiency anaemia (IDA).

Answer 5

Not enough in:

• Poor diet
• Malabsorption
• Increased physiological needs

Losing too much:

• Blood loss - menstruation, GI tract loss, parasites

Question 6

What tests are likely to diagnose iron deficiency anaemia at an earlier stage and why?

Answer 6

• 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.

Question 7

A patient presents with moderate anaemia, microcytic and hypochromic erythrocytes, reticulocytopenia and a ferritin level of 8. What is the diagnosis and why?

Answer 7

• 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.

Question 8

What is the most common cause of iron deficiency anaemia in adult men and postmenopausal women?

Answer 8

• Blood loss from the GI tract
• Menstrual blood loss is the most common cause in premenopausal women

Question 9

Describe the common signs and symptoms of iron deficiency anaemia.

Answer 9

• Symptoms - fatigue, lethargy, dizziness
• Signs - pallor of mucous membranes, bounding pulse, systolic flow murmurs, smooth tongue, koilonychias

Question 10

Outline the different causes of megaloblastic and nonmegaloblastic macrocytic anaemia.

Answer 10

• Megaloblastic - caused by B12/folate deficiency or drug-related interference with B12/folate metabolism.
• Nonmegaloblastic - alcoholism, liver disease, hypothyroidism, myelodysplastic syndromes, reticulocytosis.

Question 11

In B12/folate deficiency, which of these nutrients is likely to be depleted from the body’s stores more quickly and why?

Answer 11

• 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.

Question 12

Outline the role of vitamin B12 (cobalamin) and folic acid (folate) in erythrocyte production.

Answer 12

• Both important for final RBC maturation and DNA synthesis.
• Both needed for thymidine triphosphate synthesis.

Question 13

Describe the characteristic changes seen on a peripheral blood smear in B12/folate deficiency anaemia.

Answer 13

• Changes are megaloblastic.
• Macroovalocytes - large oval RBCs.
• Hypersegmented neutrophils.

Question 14

Describe the main causes of folate deficiency.

Answer 14

• 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.

Question 15

How is folate absorbed and stored?

Answer 15

• Absorbed in the jejunum.
• Body stores enough folate for 3-5 months.

Question 16

Outline the cellular role of vitamin B12 (cobalamin).

Answer 16

• 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.

Question 17

Describe the absorption and transport of vitamin B12.

Answer 17

• Absorbed in the terminal ileum - requires intrinsic factor (IF) which is made in gastric parietal cells.
• Transcobalamin I and II transport vitB12 to tissues.

Question 18

What is pernicious anaemia?

Answer 18

• 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.

Question 19

Outline the clinical consequences of vitamin B12 deficiency.

Answer 19

• Brain - cognition, depression, psychosis.
• Neurology - myelopathy, ataxia, sensory changes.
• Infertility.
• Cardiomyopathy.
• Tongue - glossitis.
• Blood - pancytopenia.