Module 19

Question 1

What is relatively unique about the elimination of iron?

Answer 1

• There is no way for the body to actively eliminate iron. The major mechanism by which iron is lost is though the sloughing of cells, which contain iron, mostly from the intestine.
  
  • Of course in women of childbearing age the major route of iron loss is through menstruation. Therefore, the control of iron levels is mostly through a very complex mechanism that controls the absorption of iron from the intestine.

Question 2

What is the mechanism and manifestations of acute and chronic iron toxicity?

Answer 2

• Iron is corrosive, and acute iron toxicity (for example a child taking his parent’s iron supplements) is associated with vomiting and diarrhea, often bloody.
  ○ There may be fever and leukocytosis resulting from the damage to the GI tract.
  ○ Later there can be hepatic failure and damage to the pancreas leading to hyperglycemia.
  
  • Sustained elevation of iron levels leads to oxidative stress. The first organ to be affected by chronic iron overload is the liver, and hepatic failure can result. Often death is due to cardiac toxicity, either cardiac failure or arrhythmias. Other possible manifestations of chronic iron overload are diabetes and skin hyperpigmentation.

Question 3

What are the major conditions associated with iron overload, and how are they treated?

Answer 3

• The two major causes of chronic iron overload are hemochromatosis, which is an inherited abnormality leading to an increase in iron absorption, and some condition, especially thalassemia, in which the patient cannot make sufficient red blood cells and requires multiple blood transfusions.
  
  • When the red cells from the transfusion die they release iron.
  • The simplest way to treat iron overload associated with hemochromatosis is to regularly withdraw blood from the patient. Obviously that is not the appropriate treatment in thalassemia. The treatment of iron overload in thalassemia requires the use of an iron chelator. There are several chelators, each with its own advantages and disadvantages.

Question 4

What is the bioavailability of most iron preparations? What factors affect the absorption of iron?

Answer 4

• The oral bioavailability of iron is low and dependent on dose and form of the iron.
  
  • Heme iron, i.e. blood, from a steak, etc is absorbed better than the form of iron present in plants.
  • Ferrous iron is absorbed better than ferric iron, therefore when combined with vitamin C, which can reduce ferric iron to ferrous iron, there is an increase in iron absorption.
  • Tannins, as found in tea, bind iron and decrease absorption. Ferrous sulfate is probably the best form of iron to treat iron deficiency. The % absorbed at a dose of 35 mg is ~40% but drops to about 10% at a dose of 400 mg.
  • Other salts of iron may cause less GI upset but their bioavailability is less; the degree of GI upset probably correlates with the bioavailability.

Question 5

What was the reason that there was some opposition to enrichment of foods with folate?

Answer 5

• Both folate and vitamin B12 deficiencies can cause megaloblastic anemia.
  
  • If an individual receives extra folate it can prevent the megaloblastic anemia caused by vitamin B12 deficiency, but it does not prevent the neuropathies and other problems caused by B12 deficiency. This led to the concern that extra folate would mask vitamin B12 deficiency leading to more serious neuropathies. However, the decrease in neural tube defects resulting from folate enrichment is the more important issue.