L8 - iron metabolism and microcytic anaemia Flashcards
Microcytic anemia is caused either by a reduction in haem synthesis or reduced globin synthesis. The only way we can get a microcytic anaemia (low MCV/small RBC’s) in this case is via a thalassaemia (alpha or beta). There are four ways of getting one from reduce haem synthesis, what are they?
Anaemia of chronic disease (ACD)
Iron deficiency (most common)
Lead poisoning
Sideroblastic anaemia
NOTE - the causes of microcytic anaemia can be remembered by the mnemonic TAILS
NOTE - microcytic anaemias are often hypochromic (paler than normal) as well
We need 10-15mg/day of iron in our diet. Give two examples of good dietary sources of haem and non-haem iron
haem iron (think animal products) - Liver/kidney/chicken/duck/salmon
non-haem iron - raisins/beans/figs/rice/iron-fortified cereals/oats
free iron is toxic because it can cause generation of free radicals. The body however has no mechanism for regulating excretion of iron so it needs to be properly absorbed and utilised. What is it used for in the body, give two examples?
Haemoglobin and myoglobin production/as a co-factor with cytochromes, krebs cycle enzymes, catalase (protects against oxidative damage)
There are two forms of iron, ferrous (Fe2+) and ferric (Fe3+) . Under what conditions is Fe3+ reduced to Fe2+?
Reduction in acidic (low) pH of Fe3+ to Fe2+
Oxidation of Fe2+ to Fe3+ takes place in alkaline (high) pH
What areas of the small intestine does iron absorption occur?
Duodenum and jejunum
Briefly iron absorption into the bloodstream and to the requiring tissues starting from the chyme in the duodenum
1) haem iron is directly absorbed into the enterocyte (hence why it is considered better)
2) The Fe3+ components of the non-haem iron are reduced to Fe2+ by a vitamin C dependent enzyme
3) The Fe2+ is now absorbed into the enterocyte via DMT1
4) From here iron can either be stored in ferritin or released into the bloodstream via ferroportin
5) Once in the bloodstream the iron is then oxidated again to the ferric form and transported via transferrin to the necessary tissues
What are the constituents of haem and non-haem iron separately?
Haem - Ferrous iron only (Fe2+)
Non-haem - Ferrous and ferric iron (Fe2+ and Fe3+)
Give 2 factors that promote the absorption of non-haem from the blood and 2 factors that inhibit it. Hint - This would be important dietary advice for iron deficient patients
Inhibit - Tannins in tea/pulses/fibre/ANTACIDS
Promote - vitamin C/ citrate
Total iron can be divided into ‘funcitonal’ (available) iron which is available to our tissues to use and stored iron. Stored iron can be in a soluble or insoluble form, what are the names of each?
Soluble store - Ferritin
insoluble store - haemosiderin (accumulates in macrophages)
Once transferrin takes ferric iron to the tissues how is it absorbed for use?
At the cells the transferrin is endocytosed, it then encounters an acidic microenvironment which reduces it to the Fe2+ form. Fe2+ is then transported into the cytosol via DMT1 just as it was at the enterocyte level. From here it is then stored in ferritin or used by the mitochondrial cytochrome enzymes
Although we need a dietary source or iron, the majority of our requirements are fulfilled by iron already in the body via iron recycling. Explain this concept
1) Old RBC’s are phagocytosed by macrophages in the spleen and liver (Kupffer cells)
2) The macrophages catabolise the haem released from the RBC’s
It is important to regulate our iron absorption from the diet depending on the need for iron. Dietary iron levels are sensed by the enterocytes, what is then done to regulate absorption?
Regulation of ferroportin
Regulation of transferrin receptor
Hepcidin (in liver, inhibits ferroportin) - hepcidin is upregulated in iron overload
What causes a downregulation of the protein hepcidin which inhibits and degrades ferroportin
high erythropoietic activity - realises that iron is needed for this
Considering hepcidin, explain how anaemia results from chronic inflammatory conditions in Anaemia of chronic disease (ACD)
Inflam condition -> release of pro-inflammatory cytokines (e.g. IL-6) -> this causes increased production of hepcidin in the liver -> This means increased inhibition of ferroportin -> iron can’t be released from it’s stores and iron absorption is decreased -> reduced plasma iron -> inhibition of erythropoiesis in the bone marrow
Although we can’t regulate the excretion of iron, how do we lose it involuntarily?
bleeding/sweat/pregnancy/sudden growth
What organ contains most of our iron stores?
liver
What is the most common nutritional disorder worldwide?
iron deficiency
Name three major causes of iron deficiency
insufficient iron in the diet/Bleeding (menstrual cycle problems/internal bleed)/ACD/pregnancy/malabsorption of iron i.e. vegan or vegetarian diet
You take a patients blood after suspecting anaemia and notice that they are iron deficient, what are some questions to ask them?
- Are you vegan/vegetrarian?
- Have you had any trauma/ how is your menstruation? Are there any bleeds?
- What’s your diet like?
- Do you have any inflammatory diseases you are aware of?
What groups are most at risk of iron deficiency?
Infants/children/women of child bearing age/older people
Name two common symptoms of anaemia and two common signs of anaemia specifically linked to iron deficiency
Anaemic symptoms - tired/pale/reduced exercise tolerance (due to less haemoglobin)/palpitations/headache/dizzy
Iron deficient signs - Cold extremities/ epithelial changes such as ‘spoon nails’ glossy tongue (smooth centre), angular chelitis (inflammation of corners of mouth) / pica (cravings for srange substanves
You suspect a patient is iron deficient and send for a FBC. What are the results you expect back if he is?
most importantly - Low ferritin, low iron and high transferrin (TIBC) in serum obviously
-also low MCV/ low MCHC (mean cell haemoglobin concentration)/often elevated platelet count/low reticulocyte haemoglobin content (CHr)
To confirm an iron deficiency you send off a blood smear, what do you see if they are?
- RBC’s are microcytic and hypochromic
- Change in size and shape
- Sometimes we see pencil cells and target cells (LOOK AT THESE)
CHr (reticulocyte haemoglobin content) is the test recommended by NICE to order to diagnose iron deficiency anaemia. What patients can you not use this in however?
-Patients with thalassaemia’s as their CHr is low
also note - CHr remains low in inflammatory responses
So this is the main test
Reduced plasma ferritin definitively indicates an iron deficiency HOWEVER normal or increased ferritin does not exclude iron deficiency. Why would these be normal or high in such a patient?
infection/cancer/inlfalmmation/liver disease/ alcoholism
What are the treatments for mild and severe iron deficiencies?
Mild - dietary advice/ oral iron supplements
severe - intramuscular iron injections/IV iron/ blood transfusion
excess iron can be bad to as it promotes free radical formation and organ damage via deposition as haemosiderin in end organs. How could excess iron occur?
Hereditary haemochromatosis (mutation in the HFE gene which should negatively regulate the transferrin receptor, treated with regular venesection) or transfusion associated haemosiderosis (repeated blood transfusions can cause a build up of iron )
what are the symptoms of haemochromatosis?
Hyperpigmentation of skin/ cardiomyopathy/arthropathy/liver cirrhosis (all to do with end organ damage/hypogonadism
