5. Erythrocytes and iron Flashcards
Describe the normal measurements in a full blood count (FBC).
- RBC: 4.4-5.9 x 10^12 cells/L
- Hb: 120-170 g/L
- mean cell volume: 80-100 fL
- WBC: 4-11 x 10^9/L
- platelets: 150-400 x 10^9/L
How much do RBCs normally make up of the total blood volume?
40-50%
What are the functions of RBCs?
Deliver O2 from lungs to all tissues and carry CO2 away
- carry Hb
- maintain Hb in reduced (ferrous) state
- generate ATP (maintain membrane and osmotic equilibirum to maintain structure)
How does the structure of RBCs improve their function?
- Anucleate biconcave discs ~8um in diameter with a flattened depressed centre
i) high surface area:volume ratio - more gas exchange
ii) optimises laminar flow properties of blood in large vessels
iii) allows cells to deform and facilitate passage through microcirculation (min. diamter of 3.5um) - Cell membrane contains proteins such as spectrin, Ankyrin, Band 3 and protein 4.2
iv) facilitate vertical interactions with the cytoskeleton of cell which are essential for maintaining the RBC’s biconcave shape and deformability.
Which disease can cause RBCs to lose their shape?
Hereditary spherocytosis: gene mutation in erythrocyte cell membrane proteins - lose biconcave shape
What % of the RBC volume does Hb take up?
95%
REVIEW HAEMOGLOBIN LECTURE
MCBG
Why is iron an essential element in all living cells?
- transports and stores oxygen
- integral part of many enzymes inc. cytochromes (ETC and energy production), neurotransmitter production, collagen formation and immune system function
Why is free iron very toxic to cells?
acts as catalyst in formation of free radicals from reactive oxygen species
What are the different sources of available and stored iron in the body?
Available/functional iron:
- mainly haemoglobin (2000mg)
- myoglobin: O2 reserve in muscles
- tissue iron: enzyme systems (e.g. cytochromes)
- transported (‘serum’) iron (3mg)
Stored iron (1000mg):
- ferritin: soluble
- haemosiderin: insoluble macrophage iron
What are the pathways for iron intake and loss from the body?
~1-2mg/day iron lost from body from skin and GI mucosa.
Well-balanced diet contains sufficient iron to balance this loss (~10% of the 10-20 mg dietary iron in a balanced diet is absorbed each day) from haem (animal sources) and non-haem sources.
Are iron requirements different in different individuals?
Yes, greater requirement during childhood/adolescence, pregnancy, menstruation, blood loss (e.g. from cancer)…
Which type of iron (haem/non-haem) is more readily absorbed?
Haem iron more readily absorbed than inorganic iron which consists of both ferric (Fe3+) and ferrous (Fe2+) iron. Ferric iron most be reduced to ferrous form before it is absorbed.
Where does most of our active iron come from?
80% of active iron from breakdown and recycling of RBCs, not from gut absorption.
Via reticuloendothelial system: old RBCs phagocytosed mainly splenic macrophages and Kupfer cells of liver.
How is iron stored in liver tissue?
- 95% in hepatocytes as ferritin
- 5% as haemosiderin, predominantly in Kupffer cells
Where does dietary iron absorption occur?
in duodenum and upper jejenum
Describe the process of dietary iron absorption.
- Reduction of Fe3+ from non-haem iron to Fe2+ in intestinal lumen by stomach acid (duodenal cytochrome B reductase - DcytB).
- Uptake of non-haem Fe2+ by DMT1 transporter protein on apical surface of enterocytes (uptake of haem iron remains unclear).
- In enterocyte, degradation of haem to release ferric iron (Fe3+).
- Fe3+ either stored as ferritin or reduced to Fe2+ and transferred to bloodstream via ferroportin protein.
- In blood, Fe2+ bound by transferrin and mostly transported to BM for erythropoiesis or taken up by macrophages of RES as storage pool.
How is iron in the bloodstream taken up by body cells?
Binding of iron-transferrin complex to transferrin receptor (TfR).
RBCs contain highest no. of TfR - for iron incorporation into Hb.
How is the process of iron absorption regulated?
Depends on dietary factors, body iron stores and erythropoiesis. Dietary iron levels sensed by enterocyte villi.
- Citrate in citrus fruit can form complexes with iron that increase absorption. Tannins (e.g. tea, coffee) can decrease absorption by causing precipitation/chelation.
- Hepicidin (small peptide expressed by liver):
- directly binds to ferroportin resulting in its degradation - prevents iron from leaving enterocyte or enrering macrophages
- inhibits transcription of DMT1 gene - downregulates iron uptake - expression of receptors, e.g. HFE, and transferrin receptor - no cellular uptake
When is the production of hepicidin increased or decreased? What regulates this peptide?
Synthesised by liver (and excreted by kidney):
- increased in iron overload
- decreased by high erythropoietic activity
Regulated by: HFE, transferrin receptor and inflammatory cytokines
What is the most common nutritional deficiency worldwide?
Iron deficiency (causes at least 1/2 of anaemia)
Why might iron deficiency occur?
- insufficient intake/poor absorption (e.g. vegan diet, gut problems and diarrhoea)
- increased use
- physiological, e.g. pregnancy, menstruation
- pathological, e.g. bleeding
What are the symptoms and signs of anaemia?
Symptoms:
- tiredness
- reduced oxygen carrying capacity (pallor, reduced exercise tolerance)
- cardiac symptoms - angina, palpitations, dev of heart failure
Signs:
a) pallor
b) tachycardia
c) increased resp rate
d) epithelial changes
Which blood parameters and blood film features indicate iron deficiency?
- hypochromic: low Hb content
- microcytic: small RBCs, low mean cell volume (MCV)
- anisopoikilocytosis: change in cell size and shape (pencil cells, target cells)
- low serum ferritin, serum iron and % transferrin saturation, raised total iron binding capacity (TIBC)
- low reticulocyte haemoglobin content (CHR)
