Iron Hemostasis Flashcards


Large amounts of free iron are toxic to cells, therefore most of it is bound to plasma proteins or storage molecules. Every cell in the body is capable of storing iron. In the cell cytoplasm, iron combines with ????? to form ??????
Apoferritin
Ferritin
Ferritin is the primary protein responsible for safe storage of iron in cells. Smaller quantities of iron are in an an extremely insoluble form called ???????. This is most commonly found in the ???????? of the reticulo-endothelial system. Iron is primarily stored in which organ
hemosiderin
macrophages
liver
Very small amounts of ferritin are found in serum. This is directly related to the amount of iron in macrophages in the ??????
Reticulo-endothelial system
What happens to serum feritin in iron deficiency?
What happens to serum ferittin in iron overload?
Iron overload can lead to tissue damage, causing increased levels of ????????, an inflammatory marker
- decreases
increases
Acute phase protein
What protein is responsible for iron transport in the plasma? What cells produce this? How many binding sites does it havre for iron, and what typical iron saturation levels would you expect to see in the blood?
- Transferrin -formed when iron combies with apotransferrin
- Produces by hepatocytes in liver
- has two binding ites
- Woud expect to see 30% saturation
Excess iron in the blood is deposiyed in what two main places?
- Liver hepatocytes
- Reticuloendothelial cells
Why are women more like to suffer from iron deficiency?
Blood loss from menstruation
What is the daily iron requirement in mg? How much does a typical Western diet contain?
1-2mg
15-20m/g
Haem iron and non-haem iron are found in what food sources?
Haem: red meat
non-heam: white meat, vegetables, cereals
RBCs circulate for 120 dys, then they are digested, and broken down by the ?????????? Iron released from the RES will enter the plasma and once again bound transferrin. The RES stores around ?????of iron in the form ferritin/haemosiderin.
Macrophaes of the reticuloendothelial system
500mg
State the only way in which humans regulate iron balance
By regulating how much iron is absorbed.
Where does iron absorption occur?
Duodenum
Haem iron is very easily absorbed by duodenal enterocytes. Non-haem iron, in order to be released from foodsuffs, requires ???? digestionand ???????? enzymes in stomach.
- acid
- proteolytic enzymes
Non haeme iron must be reduced from the ?????? form to the ????? form of iron. Which enzyme does this in the duodenum? What vitamin plays a role in this process?
Ferric (Fe3+) must be transformed into Ferrous (Fe2+)
Duodenal Cytochrome B1
Vitamin C
What transporter is ferrous iron passed through to get from intestinal lumen into the enterocyte
- DMT1 (DMT1 expession is upregulated during iron deficiency)

In the basolateral membrane of the enterocyte, iron is exported to circulation by ??????, which is also crucial for the release of iron from ?????????
Ferroportin
macrophages of the reticuloendothelial system

State how hepcidin controls iron absorption. WHere is hepcidin produced?
Hepcidin binds feroportin, causing it to be internalised and remain inside the hepatocyte.
Made in the liver.
Iron released from entercoytes is transported in the circulation bound to transferrin. How much iron is bound to bound to transferrin at once, and how much is transported via this method per day?
4mg
50mg
Iron is delivered to tissues by binding to what receptor? The highest concentration - 80%- of transferin receptors are found on what cells? The next most concentrated area of transferin receptors is?
Transferrin receptor - which then uptakes the iron by receptor mediated endocytosis.
RBCs
Liver

When iron enters a cell, it can be either stored as ??? or?????, or it can be moved to the mitochondria where it generates ???????
- Ferritin
- Hemosiderin
A key aspect of iron metabolism is the recycling of iron. ???????????? recycle iron from ingested ???????? erythrocytes and release it to plasma Tf for delivery to the bone marrow and other tissues. COnversley, it can also be stored as ferritin or haemosiderin. Iron release from those cells is mediated by ?????? and ?????, as was the case with absorption from GI tract and is in the form of?????
Reticuloendothelial macrophages
sensecent
Ferroportin
Hepcidin.
Transferrin
What happens to transferrin levels when iron is low and high?
- transferrin levels increase when iron is low
- Transferrin levels decrease when iron is high
Summarise iron recycling
- senescent red blood cells are removed by the macrophages of RES - after 120 days
- RES system holds about 500mg of iron
- RES iron is stored in ferritin/hemosiderin
- RES releases iron to transferrin plasma
- Tf iron uptake is via TF receptors on eryhtroblasts, hepatocutes
Hepcidin acts to prevent the rise of seurm iron. Hepcidin binds what protein inhibit it’s function? What are the two key effects that this produces?
- Ferroporin
- Reduces ferroporin expression on basal side of duodenal enterocytes
- Reduces ferroproin expression on Macrophages of the reticuloendothelial system
State factors that appear to reglulate levels of hepcidin
- circulating transferrin levels
- RES iron levels
- Hypoxia
- Inflammation
Describe the difference between anemic blood and normal blood

- anemic cells are very pale, smaller (hypochromic and microcytic)
Haemoglobin is able to bind oygen without undergoing?
Oxidation or reduction
What are the “Golden rules”
- Iron deficiency in young males and post-menopausal woman is the result of a GI bleed until proven otherwise
-
In yonung woman, iron deficiency is a result of menstrual blood loss and/or pregnancy
- For them, only perform GI investigations for GI symptoms or blood in the stool
WHat GI condition affects iron absorption? Caused by villous atrophy.
Coeliac disease
Heamatinic defeiciency in coleliac disease is common (this means deficiency in Iron, folate, B12. Order them in terms which one is most likely to be affected from coeliac. A haemanitic deficiency refers to a substance required for the formation of red blood cells.
Most likely: Folate
Next: Iron
Least: B12

Blood film in coeliac disease. Can show various haematinic deficienices in folate, ferritin. Patients can also be hyposplenic (an absent spleen like, because the spleen is known to atropy in coeliac disease. - what would you expect to see for this?
Hyposplenism, which may be a complication of chronic folate deficiency, the result of excessive loss of lymphocytes through the damaged GI tract or related to the mucosal lesion,[135] is a well-documented complication of celiac disease in historical case series
- “target” like appearance
- Contain Howell Jolly bodies
- Also can have an “irregularly contracted appearance”, basically dont have normal circular biconcave shape

At the level of the genome, what gene is cruical for hepcidin synthesis.
HFE - diagram just for illustration

Loss of HFE function results in reduced heparin production/ What disease does this lead to? This disease causes iron overload.
Hereditary Haemochromatosis -
What is the most common and next most common mutations of the HFE gene
- Homozygous C282Y
- H63D
hereditary haemochromatomois in what sex? What factors make it less likely for females to be affected? WHat race in particular is at higher risk?
Men
Periods, babys
Celts - 1 in 8 re carriers, heterozygous C282Y

none of this should be hugely surprising. The disease HHC will lead to accumualtion of iron.

in HHC, transferrin saturation is greatly elevated. If serum transferrin becomes saturated, this can lead to ??????? in the blood, which is very toxic.
unbound iron
Under low-hepcidin conditions, macrophages continually release iron derived from erythrophagocytosis. These phenomena probably account for the elevation in what measurable factors
Iron levels
Transferrin saturation
HHC leads to mass iron accumulation. In the advanced stages, it accumulates in various organs. State some of the main organs where this occurs
- Liver
- Skin
- Joints,
- Hearts
- Pancreas
What conditions can iron overload lead to?
Name some for liver, pancreas, bronzing and arthritis
- Liver cirrhosis
- Cirrhosis
- Arthritis
- Skin Bronzing - happens becasue iron overload increases melanin prodiction
- Restrictive cardiomyopathy - heart walls become stiffened due to iron
- Diatebtes - due to endocrine insufffiencies
treatments for HHC
- Repeated phlebotomy - removal of blood by venesection - approx 500ml weekly initially which removes 250mg of blood
- montor ferritin and tranfserrin sat
- prevnet organ damage
study
