Lecture 8 Flashcards
What are the 2 types of microcytic anaemia?
TAILS
Reduced haem synthesis
- Iron deficiency-no iron for Hb
- Lead poisoning-inhibits enzymes involved to make haem
- Sideroblastic anaemia- genetic disease
- Anaemia of chronic disease-hepcidin results in iron deficiency
Reduced globin chain synthesis
-Thalassaemia (alpha/beta globin chain mutations)
What is microcytic anaemia?
- reduced rate of Hb synthesis
- erythrocytes smaller than normal
- cells often paler (hypochromic)
What is iron required for?
Essential element in all living cells
- oxygen carriers (Hb/myoglobin)
- co-factor for many enzymes (cytochromes, Krebs cycle enzymes, CP450, catalase)
What is a problem with iron?
Free iron is very toxic to cells
Complex regulatory systems to ensure homeostasis
How can you excrete iron?
There is no mechanisms in body to regulate excretion.
-Only regulate how much iron enters our body.
What different states are there of iron?
Exist in a range of oxidation states
Ferrous (Fe2+)
- reduced form
- utilise this one
Ferric (Fe3+)
- no mechanisms to absorb this so needs to be converted to reduced form
- most common
- oxidised form
Where do you get haem, or non-haem iron?
Dietary iron consists of haem iron (Fe2+) & non haem iron (mixture of Fe2+/Fe3+)
Haem (readily absorbed)
-liver, kidney, beef, chicken, duck, pork, salmon, tuna
Non-haem (ferrous/ferric:converted to ferrous)
-cereals fortified with iron, raisins, beans, figs, barley, oats, rice, potatoes
Where/how do you absorb iron?
Duodenum/upper jejunum (just after duodenum)
- chyme enters duodenum from stomach
- haem iron is readily absorbed into enterocyte
- any ferric iron is reduced to ferrous iron by reductase enzyme which requires vitamin C as the electron donor
- ferrous can move through DMT1 to enterocyte
- haem is degraded to form Fe2+ by haem oxygenase
- Fe2+ can be stored as ferritin as Fe3+
- or Fe2+ can enter bloodstream via ferroportin in basolateral surface
- ferrous is oxidised to ferric by hephaestin and is transported attached to transferrin (carries 2 Fe3+)
What is hepcidin?
Produced by liver and inhibits ferroportin.
What inhibits absorption of non haem iron?
-tannins (in tea)
-fibre (can bind to iron to prevent it being absorbed)
-phyphates (pulses)
These bind non-haem iron in intestine, reducing absorption
-antacids (require acid environment for conversion of the irons)
What has a positive influence on iron absorption?
-vit C (helps reduce ferric to ferrous iron)
-citrate
(Both prevent formation of insoluble iron compounds)
What is functional iron?
Available iron
- Hb
- Myoglobin
- transported in serum via transferrin
- cytochromes (contain iron)
What are some ways of storing iron?
Ferritin (soluable)
- pores on surface to allow exit/entry of iron
- globular protein with hollow centre
Haemosiderin (insoluble)
- aggregates of clumped ferritin particles, denatured protein, lipids
- accumulates in macrophages, especially in liver/spleen/marrow
- seen as dark precipitates when stained
How do cells take up iron?
- diferric transferrin enters cell via receptor mediated endocytosis into vesicle
- ferric to ferrous (due to acidic environment from H+ pump into endosome) where it can leave vesicle via DMT1
- forming label pool of iron (here iron can be stored as ferritin, used in mitochondria for cytochrome enzymes, or exported via FPN1- ferroportin 1)
Where does our daily total iron usually come from?
Recycled: 80% of iron requirement met via this (only a small amount from our diet)
-macrophages engulf and recycle the iron from the dead/damaged RBC’s
(Mainly splenic macrophages/Kupffer cells)
What can control regulation of iron absorption?
Dietary iron levels sensed by enterocytes
- reguation of transporters (ferroportin)
- regulation of receptors (transferrin receptor & HFE protein)
- hepcidin/cytokines
- cross talk between epithelial cells and other cells
