Lecture 7 (Part 2) - Iron deficiency Flashcards
Causes of microcytic anaemia and results in
- Results in microcytic and hypochromic RBC & pencil cells (long, thin RBC)
- Anisopoikilocytosis: change in size n shape of RBC
- Causes:
Thalassemia
Anaemia of chronic disease
Iron deficiency
Lead poisoning
Sideroblastic anaemia
What is importance of iron?
- O2 carriers: Hb in RBC & myoglobin
- Co-factor of enzyme: cytochromes (oxidative phos.), Krebs cycle enzyme, catalase
- free iron toxic to cell
- No mechanism for secretion for iron
- Ferric iron (Fe3+) must be reduced to ferrous iron (Fe2+) before it can be absorbed
What is recommended daily intake of iron? Where does absorption occur? Good sources of haem and non-haem iron?
- 10-15mg/day
- Absorption in duodenum & upper jejunum (same as folate)
- Haem: liver, kidney, beef, chicken, pork
- Non-haem: fortified cereals, raisins, beans, oats, rice
Desc. the dietary absorption of iron
- Divalent metal transporter 1 (DMT1) facilitates uptake of Fe2+ (non-haem)
[Fe3+ in intestinal lumen is reduced before uptake] - In enterocyte, haem is degraded to release ferrous iron
- Iron within enterocyte stored as ferritin or transferred to blood via ferroportin
- In blood, iron bounded to protein transferrin –> bone marrow for erythropoiesis or taken up by macrophages for splenic pooling
What regulates absorption of iron? How?
- Hepcidin (peptide) expressed in liver
- Binds to ferroportin resulting in its degeneration –> prevent iron from leaving cell
- Inhibit transcription of DMT1 gene –> reduced iron uptake
What has (-) and (+) influence on non-haem iron absorption from food?
(–)
- Tannin (tea)
- Fibre
- Phytates (chapati)
[all 3 bind to non-haem iron = reduce absorption]
- Antacids (gaviscon)
[disrupt acidic pH needed to reduce Fe3+]
(+)
- Vit C and citrate
[prevent formation of insol. iron compounds]
[reduce ferric to ferrous]
What are functional (available) iron in?
- Hb
- Myoglobin
- Enzymes (cytochromes)
- Transferrin
What are some examples of stored iron (~1000mg)?
- Ferritin (sol.)
- Globular protein w hollow core
- Pores allow iron to enter and go - Haemosiderin (insol.)
- Aggregates of clumped ferritin & denatured protein/lipid
- Accumulates in macrophages (liver, spleen, BM)
[looks brown-ish irregular shaped macrophages]
How is iron taken up by cells?
- Fe3+ bound transferrin binds to transferrin receptor and enters via receptor mediated endocytosis (like LDL)
- Fe3+ within endosome released in acidic enviro. and reduced
- Fe2+ transported to cytoplasm of cell via DMT1
- Once inside, Fe2+ stored in ferritin; exported by ferroportin; taken up by mitochondria for cytochrome enzymes
Where is main source of iron recycling?
- Small fraction from diet
- Most from dmg RBC (engulfed by phagocytes)
- Mainly splenic and Kupffer cells
What are factors that influence iron absorption? Control mechanisms?
- Dietary factors/iron storage/erythropoiesis
- Dietary factors sensed by enterocytes
- Control mechanisms:
1. Regulation of ferroportin
2. Regulation of transferrin and HFE protein (interacts w transferrin)
3. Hepcidin and cytokines
4. Crosstalk
What is anaemia of chronic disease?
- Anaemia associated w inflammatory condition (RA, malignancy)
Why does anaemia of chronic disease occur?
- Cytokines (IL6) released by autoantibodies
- Results in ⬆️hepcidin production by liver
- Leads to decreased iron absorption from gut & iron release from reticuloendothelial system
- Inhibition of erythropoietin in BM –> anaemia
- Leads to func. iron deficiency: enough iron, but X utilised
What are the causes of iron deficiency?
*Sign, not diagnosis!
- Most common nutritional disorder
- Causes:
1. ⬇️supply: nutritional deficiency (vegan/vegetarian) OR malabsorption (also vegan)
2. ⬆️demand: ⬆️requirement due to pregnancy or rapid growth
3. Loss: Bleeding (menstruation or chronic NSAID usage –> GI tract bleed)
4. Anaemia of chronic disease
Who are the at risk groups for iron deficiency?
- Infants
- Children
- Pregnant women
- Old ppl
Signs and symptoms of iron deficiency
- (same as anaemia) pallor, headache, angina, breathlessness
- Pica (craving for ice)
- Changes in epithelial:
1. Angular cheilitis (side lips inflammed)
2. Glossitis (tongue)
3. Koilonychia (spoon nails)
(particularly affects epithelial cells due to their high turnover rate –> new enzymes need iron as cofactor)
How is iron deficiency diagnosed?
- Plasma ferritin marker for total iron status
[cytosolic proteins, function as carrier] - Reduced ferritin = iron D.
[BUT normal/increased X cancels out iron D]
[increase can be due to cancer/inflammation] - CHr (reticulocyte Hb content) test for func. iron D, more reliable
[BUT x used in thalassemia, CHr also low (low during inflammatory response]
What is the treatment for iron D? Expected response?
- Diet (⬆️meat/fortified cereals)
- Oral iron supplements (safest/first line of therapy)
[many ppl experience GI side effects –> poor compliance] - Intramuscular iron injections or intravenous iron
- Blood transfusion (severe)
- Response: improvement in symptoms, 20g/L rise in 3 weeks
Why is iron excess dangerous?
- Excess iron > binding capacity of transferrin –> deposited in organs as haemosiderin
- Promotes free radical formation & organ dmg
- Fenton reaction: hydroxyl/hydroperoxyl radical –> lipid peroxidation; dmg to protein/DNA
What causes transfusion associated haemosiderosis? How to curb?
- Repeated blood transfusions –> accumulation of iron
- 400mg blood = 200mg iron
- Prob w transfusion dependant anaemias (thalassemia & sickle cell)
- Iron chelating agents (desferrioxamine) delay but X stop effects
What does Transfusion associated haemosiderosis or HH cause?
- Liver cirrhosis
- DM
- Hypogonadism
- Cardiomyopathy
- Increased skin pigmentation (grey)
What is hereditary haemochromastosis? Mechanism?
- Autosomal recessive disease caused by mutation in HFE gene (Chr 6)
- Normally, HFE interacts w transferrin receptor –> reduce affinity for iron-bound transferrin & promotes hepcidin expression (liver)
- Mutated HFE: loss of (-) influence on iron uptake –> too much iron –> dmg
How is HH treated?
- Through venesection/therapeutic phlebotomy: periodically draw blood from patient
