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Pathology

Haematology

Question 157 of 180

Regarding iron regulation, which of the following statements is CORRECT:

Answer:

Iron absorption is tightly regulated as excess iron is potentially toxic, and the body has no physiological mechanism for upregulating excretion. Iron absorption can be increased when body stores are low or when there is a need to increase erythropoiesis e.g. an increase in absorption may be seen about 3 - 4 days following haemorrhage. Hepcidin is the main hormonal regulator of iron homeostasis; it lowers cell levels of ferroportin, the protein that allows iron entry into the portal circulation from duodenal enterocytes and into the blood circulation from macrophages. Hepcidin therefore reduces both iron absorption and iron release from macrophages. Synthesis of hepcidin is suppressed by iron deficiency and increased erythropoiesis but upregulated in inflammation and iron overload.

Iron Requirements

Iron is contained in haemoglobin, the reticuloendothelial system (as ferritin and haemosiderin), muscle (myoglobin), plasma (bound to transferrin) and cellular enzymes (e.g. cytochromes, catalase). The total amount of iron in the body is about 3 - 4 g, of which about two-thirds is in haemoglobin.

Iron Intake and Absorption

The average Western diet contains 10 - 15 mg/day of iron and typically about 5 - 10% of this is absorbed through the upper small intestine to make up for daily loss.

Dietary iron may be in the form of haem or non-haem iron. Haem iron is degraded after absorption through the cell surface to release Fe2+. Most non-haem iron is in the form Fe3+, which is reduced at the luminal surface to the more soluble Fe2+, facilitated by hydrochloric acid in gastric secretions (and enhanced by ascorbic acid). Fe2+ is taken from the intestinal lumen into the cell across the enterocyte apical membrane  by the divalent metal transporter (DMT1).

In the enterocyte, Fe2+  is then either stored in enterocyte epithelial cells as ferritin, or released into portal plasma via the transmembrane protein ferroportin at the basolateral membrane.

Iron Transport and Storage

On entry to portal plasma, Fe2+ is reoxidised to Fe3+ and then bound to the transport protein transferrin. Iron is transferred to the bone marrow for erythropoiesis or to the liver or other parenchymal cells for storage as ferritin or haemosiderin.

Reticuloendothelial cells (macrophages) also gain iron from the breakdown of haemoglobin of senescent red blood cells, and can release this to plasma transferrin for transfer to other tissues.

Iron Regulation

Iron absorption is tightly regulated as excess iron is potentially toxic, and the body has no physiological mechanism for upregulating excretion.

Iron absorption can be increased when body stores are low or when there is a need to increase erythropoiesis e.g. an increase in absorption may be seen about 3 - 4 days following haemorrhage.

Hepcidin is the main hormonal regulator of iron homeostasis; it lowers cell levels of ferroportin, the protein that allows iron entry into the portal circulation from duodenal enterocytes and into the blood circulation from macrophages. Hepcidin therefore reduces both iron absorption and iron release from macrophages. Synthesis of hepcidin is suppressed by iron deficiency and increased erythropoiesis but upregulated in inflammation and iron overload.

CC BY-SA 3.0 https://it.wikipedia.org/wiki/File:Metabolismo_del_ferro.jpg

Iron Handling. (Image by unknown, [CC BY-SA 3.0 https://commons.wikimedia.org/wiki/File:Metabolismo_del_ferro.jpg])

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  • Biochemistry
  • Blood Gases
  • Haematology
Biochemistry Normal Value
Sodium 135 – 145 mmol/l
Potassium 3.0 – 4.5 mmol/l
Urea 2.5 – 7.5 mmol/l
Glucose 3.5 – 5.0 mmol/l
Creatinine 35 – 135 μmol/l
Alanine Aminotransferase (ALT) 5 – 35 U/l
Gamma-glutamyl Transferase (GGT) < 65 U/l
Alkaline Phosphatase (ALP) 30 – 135 U/l
Aspartate Aminotransferase (AST) < 40 U/l
Total Protein 60 – 80 g/l
Albumin 35 – 50 g/l
Globulin 2.4 – 3.5 g/dl
Amylase < 70 U/l
Total Bilirubin 3 – 17 μmol/l
Calcium 2.1 – 2.5 mmol/l
Chloride 95 – 105 mmol/l
Phosphate 0.8 – 1.4 mmol/l
Haematology Normal Value
Haemoglobin 11.5 – 16.6 g/dl
White Blood Cells 4.0 – 11.0 x 109/l
Platelets 150 – 450 x 109/l
MCV 80 – 96 fl
MCHC 32 – 36 g/dl
Neutrophils 2.0 – 7.5 x 109/l
Lymphocytes 1.5 – 4.0 x 109/l
Monocytes 0.3 – 1.0 x 109/l
Eosinophils 0.1 – 0.5 x 109/l
Basophils < 0.2 x 109/l
Reticulocytes < 2%
Haematocrit 0.35 – 0.49
Red Cell Distribution Width 11 – 15%
Blood Gases Normal Value
pH 7.35 – 7.45
pO2 11 – 14 kPa
pCO2 4.5 – 6.0 kPa
Base Excess -2 – +2 mmol/l
Bicarbonate 24 – 30 mmol/l
Lactate < 2 mmol/l

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