W1L2 - Iron Deficiency Anaemia Flashcards
Iron Metabolism Overview
- Ferrous iron (Fe2+) in heme within RBC is the ultimate objective
- Delivered from ferritin stores in macrophages
- Delivered to macrophages via transferrin
- Absorbed from dietary sources of iron via the duodenum
Iron Absorption from the Gut
To move from the lumen of the intestine into the bloodstream, iron must cross both the apical brush-border membrane and the basolateral membrane of enterocytes
- Nonheme iron traverses the brush-border membrane via divalent metal transporter 1 (DMT1)
- DMT1 requires ferrous iron (Fe2+) as a substrate, but most dietary iron is in the ferric (Fe3+) form => iron needs to be reduced before it can be absorbed
- Duodenal cytochrome B is one brush-border reductase
- When not immediately required, iron becomes sequestered in the cell within ferritin
- If the iron is required, it can be exported rapidly across the enterocyte basolateral membrane via ferroportin-1 (FPN1)
How is the efficiency of iron absorption from the gut enhanced?
It’s enhanced by copper dependent iron oxidase hephaestin
- converts newly transported Fe2+ to the Fe3+ form
Iron Transport
- Diferric transferrin delivers iron to cells by binding to transferrin receptor 1 (TfR1)
- The transferrin-TfR1 complex is internalised via clathrin-mediated endocytosis
- Reduction of transferrin bound Fe3+ releases iron from transferrin
- The iron moves into the cytoplasm across the endosomal membrane via DMT1
- The iron may be used metabolic functions, sequestered within the iron-storage protein ferritin for later use, or exported through FPN1
Transferrin
Major transport protein for iron
Each transferrin molecule can bind 2 atoms of iron (Fe3+).
Under normal circumstances, ∼30% of the iron-binding sites on the plasma transferrin pool are occupied (i.e. 30% total saturation)
Total saturation of transferrin less than ∼16% is correlated with a reduced erythropoiesis
Iron Storage
- It is critical that iron is stored in a nontoxic state so that it can be used for future metabolic needs
- Ferritin is the major intracellular iron-storage protein
- When high concentrations of iron-laden ferritin accumulate within the cell, the ferritin molecules aggregate, and ultimately fuse with lysosomes
- This process leads to the degradation of ferritin, and the resulting mixture of Fe3+ cores and peptides is known as hemosiderin
- Small amounts of ferritin are secreted from the cell, and the amount that is secreted strongly correlates with the concentration of intracellular iron
Iron Metabolism in Erythropoiesis
Erythroblastic island
Nurse cell transfers iron to erythroid cells
Nurse cell = iron containing macrophage
Iron Deficiency Anaemia (IDA) - Clinical Features
Slow onset - months to years Early - no apparent clinical signs As IDA develops: - weakness/lethargy - koilonychia (concavity of nails) - glossitis - pica (abnormal appetite) eating ice, dirt/clay - muscle dysfunction - inability to regulate body temp - irreversible mental & motor development, learning difficulties
Underlying Causes of Iron Deficiency
Most common nutritional deficiency in the world Insufficient dietary intake - made worse by rapid growth - predominantly affects children Poor uptake of dietary iron - achlorhydria - gastrectomy Blood loss - parasitic infections - elderly: GIT bleeds, malignancy, peptic ulcers - females: menstrual loss, pregnancy - frequent blood donation
Stages of Iron Deficiency
- Iron Depletion (ID)
- Iron Deficient Erythropoiesis (IDE)
- Iron Deficiency Anaemia (IDA)
Laboratory Assessment of IDA - Blood Film
Microcytes Hypochromasia Poikilocytosis - elliptocytes - target cells Decreased reticulocyte count
Laboratory Assessment of IDA - Bone Marrow
Cellularity is normal or increased
Mild to moderate erythroid hyperplasia
Decreased M:E ratio
Fe stain Perl’s Prussian Blue shows absence of hemosiderin in macrophages
Laboratory Assessment of IDA - FBC
Decreased haemoglobin
Decreased MCV (< 75 fL) (microcytosis)
Decreased MCH (14 - 26 pg)
Decreased MCHC (220 310 g/L) (hypochromic)
Increased RDW (due to microcytosis)
Increased sub-populations of microcytic, hypochromic RBC
Cellular Haemoglobin in Reticulocytes (CHr)
RBC parameter
Used to detect hypochromic reticulocytes
Reticulocytes persist 1-2 days after release into PB => Hb content in reticulocytes is more reflective of Fe status in erythropoiesis
CHr can be accurately and inexpensively measured by automated hematology analysers
CHr has been shown to be more effective than other indices of iron metabolism for the diagnosis of iron deficiency
Further Assessment - Iron Studies
Serum iron (SI) Transferrin (Tf)/TIBC % saturation Ferritin (SF) Soluble transferrin receptor (sTfR) (iron content of bone marrow iron)
