S4 L2 - Iron metabolism and microcytic anaemias Flashcards
- *Microcytic anaemia**
- Causes of microcytic anaemia (5)
- *Iron:**
- Required for
- Can it be toxic? Why? One way it can…
Microcytic anaemia
Iron:
- Required for:
• Oxygen carriers: Haemoglobin in red cells Myoglobin in myocytes
• Co-factor in many enzymes: Cytochromes (oxidative phosphorylation) Krebs cycle enzymes Cytochrome P450 enzymes (detoxification) Catalase
- Can it be toxic? Why? One way it can…
Free iron potentially very toxic to cells. Complex regulatory systems to ensure the safe absorption, transportation & utilisation
• Body has no mechanism for excreting iron
(pic)
- *Ferrous vs ferric ion**
- What are these
- How is one related to the other?
- Which form can iron be absorbed as?
- *Haem vs non-haem iron**
- How much iron do you need a day?
- Absorbed where?
- Sources of haem and non-haem iron?
Ferrous vs ferric ion
Haem vs non-haem iron
- How much iron do you need a day?
Need 10-15 mg/day iron in diet
- Absorbed where?
Absorption occurs in duodenum & upper jejunum
- Sources of haem and non-haem iron?
• Haem iron best source • Some foods fortified with iron e.g. breakfast cereals
Good sources of haem iron: Liver, kidney, beef steak, duck
Good sources of non-haem iron: beans, rice, potatoes, figs
(see pic)
- *Dietary absorption of iron**
- Recall diagram
- *Factors affecting absorption of non-haem iron from food**
- Negative influence
- Positive influence
Dietary absorption of iron
Factors affecting absorption of non-haem iron from food
- Negative influence:
• Tannins (in tea) • Phytates (e.g. Chapattis, pulses) • Fibre • Antacids (e.g. Gaviscon)
- Positive influence:
Vitamin C & Citrate: • Prevent formation of insoluble iron compounds • Vit C also helps reduce ferric to ferrous iron
(pic)
- *Functional vs stored iron**
- What are functional stores
- What are stored iron stores
- How much roughly in each
- *Cellular iron uptake**
- Recall diagram
- *Iron recycling:**
- What is meant by this?
- How is iron recycled?
- *Regulation of iron absorption:**
- This depends on…
- Control mechanism
Iron recycling:
- What is meant by this?
Only small fraction of total daily iron requirement gained from the diet.
• Most (>80%) of iron requirement met from recycling damaged or senescent red blood cells
- How is iron recycled?
• Old RBCs engulfed by macrophages (phagocytosis) -> Mainly by splenic macrophages and Kupffer cells of liver
• Macrophages catabolise haem released from red blood cells
• Amino acids reused and Iron exported to blood (transferrin) or returned to storage pool as ferritin in macrophage.
Regulation of iron absorption:
- This depends on…
• Depends on dietary factors, body iron stores and erythropoiesis
• Dietary iron levels sensed by enterocytes
- Control mechanism
• Regulation of transporters e.g. ferroportin
• Regulation of receptors e.g. transferrin receptor & HFE protein (interacts with transferrin receptor)
• Hepcidin and cytokines
- *Hepcidin:
- **When are hepcidin levels increased and decreased?
- What does hepcidin do?
- *Anaemia of Chronic Disease:**
- Map showing how AofCD leads to anaemia
Hepcidin
- When are hepcidin levels increased and decreased?
• Hepcidin synthesis is increased in iron overload.
• Decreased by high erythropoietic activity
- What does hepcidin do?
Hepcidin induces internalisation and degradation of ferroportin
Anaemia of Chronic Disease:
(pic)
- *Overview of iron homeostasis:
- ** Diagram recall
- *Iron deficiency:**
- Causes of iron deficiency
- At risk groups of iron deficiency
- Signs and symptoms
Overview of iron homeostasis:
Iron deficiency:
- Causes of iron deficiency:
Insufficient iron in diet - e.g. Vegan & vegetarian diets
Malabsorption of iron - e.g. Vegan & vegetarian diets
Bleeding - e.g. Menstruation, gastric bleeding due to chronic NSAID usage
Increased requirement - e.g.Pregnancy, rapid growth
Anaemia of chronic disease - e.g. Inflammatory bowel disease
- At risk groups:
Infants, children, women of child bearing age (period), geriatric age group
- Signs and symptoms:
Physiological effects of anaemia…: • Tiredness • Pallor • Reduced exercise tolerance (due to reduced oxygen carrying capacity) • Cardiac – angina, palpitations, development of heart failure • Increased respiratory rate • Headache, dizziness, light-headedness • Pica (unusual cravings for non-nutritive substances e.g. dirt, ice) • Cold hands and feet • Epithelial changes
Epithelial changes:
Angular somatitis, koilonychia
(pic)
- *Testing:**
- Peripheral blood smear results of iron deficient anaemia
MAIN - How do you test for iron deficiency
Testing:
- Peripheral blood smear results of iron deficient anaemia:
• RBCs are microcytic and hypochromic in chronic cases
• Anisopoikilocytosis: change in size and shape
• Sometime pencil cells and target cells
HOW DO YOU TEST FOR IRON DEFICIENCY:
1. Plasma ferritin commonly used as indirect marker of total iron status -> Reduced plasma ferritin definitively indicates iron deficiency • BUT.. Normal or increased ferritin does not exclude iron deficiency (because ferritin levels can also increase considerably in cancer, infection, inflammation, liver disease, alcoholism)
2. CHr (reticulocyte haemoglobin content) recommended by NICE to test for functional iron deficiency • CHr remains low during inflammatory responses etc.
(CHr is also low in patients with thalassaemia so can’t be used in this setting)
- *Treatment of iron deficiency:**
- list of 5
- when should you see an improvement?
- *Iron excess can be dangerous:**
- what happens then, if too much iron that exceeds the capacity of transferrin (equations etc…)
Treatment of iron deficiency:
- List of 5
• Dietary advice
• Oral iron supplements (may have GI side effects)
• Intramuscular iron injections
• Intravenous iron
• Blood transfusion (only if severe anaemia with imminent cardaic compromise)
- When should you see an improvement?
20g/L rise in Hb in 3 weeks
Iron excess can be dangerous:
- What happens then, if too much iron that exceeds the capacity of transferrin (equations etc…)
pic
- *Transfusion associated haemosiderosis**
- Cause
- Symptoms
- *Hereditary haemochromatosis:**
- Cause and why
- Symptoms
