L6-iron Metabolism Flashcards
What is iron
Essential trace elements needed for various metabolic process in every cell of the body
What are the functions of iron
O2 transport: iron is essential component of both hemoglobin and myoglobin
Cellular respiration: Iron is present in the iron sulfur clusters of the election transport chain proteins and therefore plays an important part in the generation of energy from cellular respiration
Antioxidant mineral:catalase Is a heme enzyme that is present in nearly all aerobic cells
catalase converts the reaction reactive oxygen species hydrogen peroxide to water and oxygen and iron is a cofactor for this antioxidant enzyme
How does iron participate in the formation of hydroxide and hydroxyl radical
As it exists in its 2 stable states Ferrous and ferric iron by reaction between iron two and hydrogen peroxide known as Fenton reaction
Reaction is most dangerous in free radical-mediated toxicity in cells
What is the total body content of normal iron in normal adult and how much is required per day for hb synthesis
4 g
Approximately 30 mg per day is required for hemoglobin synthesis in new red cells and the majority of this is supplied from the reticuloendothelial macrophages that recycle iron from senescent red cells
What is the recommended daily allowance in males and females for iron
10 mg in males and 18 mg in females
What are the two forms of dietary iron
Heme and non-heme
Heme is the derived from the hemoglobin and myoglobin of food sources like meat poultry and seafood
non heme is found in plant foods seeds, legumes etc.
Where does absorption of ferrous iron occur
In proximal Duodenum
What aids in the absorption of Ferris iron
Low pH of the hydrochloric acid secreted in the gastric lumen and the presence of reducing agent such as ascorbic acid which helps maintain the iron in the more soluble Ferrous form
What inhibits absorption of ferrous iron
Tannis,phytates and phosphates also lowered gastric acidity
What happens when ferric iron is reduced to ferrous iron
A protein on the apical membrane of enterocytes called divalent metal cation transporter 1(DMT1) transports iron across the apical membrane and into the cell
What are the options for iron ones it’s inside the enterocyte
Can be oxidized and stored as ferritin or transported to the basolateral membrane into the circulation bound to ferroportin
How is control of absorption of iron regulated and how does it work
Action of hepcidin an iron regulating hormone made in the liver
it controls the delivery of iron to blood from intestinal cells
Acts by binding to and in activating ferroportin
What simulates production of hepcidin
By increase plasma iron which leads to decreased iron absorption matching iron supply to demand
What are the important proteins for iron transport and storage
Ferritin: oxidizes Fe2+ to Fe 3+ for storage of normal amounts of Fe3+ in tissues
Hemosiderin: produced under conditions of iron overload and generated from ferritin denaturation
Binds excess Fe3+ to prevent its escape in to blood where its toxic
Ferroxidase/ceruoplasmin: oxidizes Fe2+ to Fe3+ for transport
Transferrin:carries Fe3+ in blood and delivers it to tissues for synthesis of heme
What are the two cases of abnormal iron metabolism
Iron deficiency anemia and iron overload
What is the definition of abnormal iron metabolism
Failure to maintain iron levels within the healthy damage can lead to clinical consequences i
What is iron deficiency anemia
One of the most common causes of anemia worldwide
it is a hypochromic Microcytic anemia with clinical features including pallor, fatigue koilonychia and brittle hair causing alopecia
What are the causes of iron deficiency anemia
▪️Decreased iron loss: iron deficiency is most commonly secondary to excessive bleeding usually from gastrointestinal or menstrual sources
▪️hookworm infestation resulting in gastrointestinal blood loss is the commonest cause of iron deficiency anemia
▪️Decreased iron uptake: ex:diet low in iron rich foods or malabsorption due to diseases associated with flattening of the duodenal mucosal villi
Describe iron overload
Systemic iron overloaded leads to pathological increase in body iron stores leading to the deposition diseases
What are the causes of iron overload
▪️Hemochromatosis: Due to genetic disorder caused by hepicidin deficiency and is characterized by excessive intestinal absorption of dietary iron resulting in systemic deposition of iron in the liver,pancreas,heart and other organs causing serious tissue damage
▪️primary hemochromatosis is sometimes referred to as bronze diabetes because it can lead to darkening of the skin
▪️Hemosiderosis: is the deposition of hemosiderin in the reticuloendothelial system which includes the reticuloendothelial cells of the spleen and bone marrow and the kupffer cells of the liver usually due to multiple blood transfusion or hemorrhage itself
▪️when reticuloendothelial system is saturated deposition occurs in other body tissues leading to secondary hemochromatosis
How can both conditions be treated(overload)
Iron chelation therapy using defroxamine
Test that Measures the amount of iron in the blood
Serum iron level
What does the serum ferritin test determine
Ferritin is a cytoplasmic iron storage protein
small amount of secreted in the serum where its functions as iron carrier providing an accurate reflection of iron stores
What does the level of transferrin total iron binding capacity determine
In plasma Each molecule of transferrin binds up to two atoms of ferric iron and serum transferrin are normally only 1/3 saturated with iron
The total iron binding capacity of plasma reflects the amount of transferrin in blood that’s available to attach to iron therefore in case of iron deficiency where Iron level is expected to be low the total iron binding capacity will be high and an iron overload where the eye level is high the total iron binding capacity will be low
