Iron is a vital element for all the organisms because it is essential for multiple metabolic processes, including oxygen transport via binding to hemoglobin, DNA synthesis, and electron transport. Iron deficiency is defined as a decreased total body iron content. And, iron deficiency anemia develops when the iron deficiency is severe enough to diminish the process of red blood cell production, erythropoiesis. It is important to note that iron deficiency is the most prevalent single deficiency state on a worldwide basis. So, before we move on to the disease itself, we may recall our physiology knowledge on the iron metabolism within a normal individual.
Total body iron content in an average 70 kg person is about 4 grams. The vast majority of this iron, about 2500 mg, is in the erythrocytes, in the form of hemoglobin. About 4 mg of iron is circulating in plasma.
About 1000 mg of iron is stored as ferritin in various parts of the body. And about 300 mg of iron is in the form of myoglobin and other respiratory enzymes. Plasma receives about 1 to 2 mg of iron daily via intestinal absorption of dietary iron. And about the same amount of iron is lost from the body daily.
About 20 mg of iron is required daily for the production of red blood cells. But the daily intake of iron into the plasma is not sufficient for this. However, about 20 milligrams of iron is released daily into the circulation through destruction of older red blood cells, and they are reused to produce new red blood cells. Iron is absorbed into the body by the proximal small intestine.
There are two forms of dietary iron. Heme iron, which is mainly derived from animal food, and non-heme iron, which is mainly derived from plant food. and the majority of non-heme iron is in the form of ferric ion.
This diagram illustrates the intestinal absorption of both heme iron and non-heme iron. I will discuss about these steps one by one. Heme iron enters the cell as an intact metalloporphyrin, presumably by a vesicular mechanism, as indicated by number 1 in the diagram. After entering the cell, iron within heme is converted to ferric by the enzyme heme exogenous, as indicated by number 2. Non-heme iron should be converted to ferrous form in order to be absorbed by the intestinal cells, as indicated by number 3 in this diagram. This conversion is catalyzed by an enzyme called duodenal cytochrome B.
Then ferrous is absorbed into the cells through a transporter called divalent metal transporter 1, or DMT1, as indicated by number 4. Then ferrous leaves the cell through a transporter in the basolateral membrane called ferroportin, in order to be absorbed into the circulation. This is indicated by number 5 in the diagram. However, to enter the circulation, ferrous should be converted back into the ferric form.
This is enabled by a protein called hephastin, which is also located in the basolateral membrane. This process is indicated by number 6. Then ferric enters into the circulation and binds to transferrin, which is the major iron transporter in the plasma. Excess iron is stored within the enterocyte in the form of ferritin, as indicated by number 7. Hepcidin, a peptide. Synthesized by the liver is the principal regulator of iron metabolism.
Its main function is to inhibit the action of ferroportin and thereby reduce the plasma iron concentration when elevated. Now we know the basic things about normal iron metabolism. Next we see what are the causes of iron deficiency anemia.
One of the major causes is dietary factors. As mentioned earlier, there are two forms of dietary iron, heme iron and non-heme iron. Heme iron is well absorbed into the body because its absorption is not impaired by other dietary constituents. Non-heme iron, however, is poorly absorbed into the body because its absorption is impaired by other dietary constituents, such as phosphates, oxalates, and phytates.
Meat is an important source of heme iron because heme iron is mainly derived from animal foods. In contrast, non-heme iron is mainly derived from plant foods. Therefore, The prevalence of iron deficiency anemia is less common in geographies where meat is an important constituent of the diet.
On the other hand, less intake of animal foods may lead to iron deficiency anemia. Another major cause of iron deficiency anemia is hemorrhage. Bleeding for any reason can cause iron deficiency.
When there is bleeding, blood cells are lost from the body. So the bone marrow starts producing new red blood cells using body stores of iron. With time, Body stores of iron get depleted, which leads to iron deficiency anemia.
Lack of iron results in less hemoglobin per red blood cell. So, they are pale in color. Chronic bleeding is often associated with iron deficiency anemia. Major causes of chronic bleeding include pregnancy, benign or malignant tumors. Long-term treatment with non-steroidal anti-inflammatory drugs, such as aspirin, gastritis, and inflammatory conditions like Crohn's disease.
There are many more causes for chronic bleeding other than these. I would like to suggest you to find the causes for chronic bleeding associated with certain body systems and make a list. So that you will not miss anything.
Malabsorption of iron is another cause for iron deficiency anemia. Common situation where malabsorption of iron occurs is prolonged echlorhydria. Because, acidic conditions are required for the absorption of iron.
In addition, extensive surgical removal of the proximal small intestine and inflammatory conditions like celiac disease also cause malabsorption of iron. And also, gastric bypass surgeries, such as bariatric surgery, may also cause malabsorption of iron because postoperative gastric hypochlorhydria impairs the absorption of iron. In addition, Patients tend to eat less food, often less meat after bariatric surgery, which may ultimately lead to iron deficiency anemia. Another rare cause of iron deficiency anemia is iron refractory iron deficiency. It is a hereditary disorder marked by iron deficiency anemia that is typically unresponsive to oral iron supplementation and may be partially responsive to parenteral iron therapy.
This condition results from mutations in the TMPRSS6 gene. which leads to uninhibited production of hepcidin. As we already know, hepcidin reduces serum iron concentration by inhibiting the action of ferroportin. So, increased production of hepcidin results in reduced plasma iron concentration and iron deficiency anemia. Hemoglobinuria, or passing hemoglobin in urine is another cause.
Causes for hemoglobinuria include glomerulonephritis, burns, kidney infection, kidney tumors, and hemolytic uremic syndrome. Pulmonary hemocytosis is another cause. In this condition, repeated episodes of intraalveolar bleeding occurs. This will result in abnormal accumulation of iron as hemocytin in alveolar macrophages, with subsequent development of pulmonary fibrosis and severe anemia. In this picture you can see the hemocytin-laden macrophages stained in brown.
Now let's discuss about the clinical presentation of iron deficiency anemia. It often develops gradually, with small amounts of blood loss. Such people may remain asymptomatic until their iron stores become sufficiently depleted to compromise the red cell production.
At this point, patients develop fatigue, which is a common symptom for any type of anemia. Diminished oxygen-carrying capacity of blood due to the lack of hemoglobin is the reason for fatigue. Many patients with moderate iron deficiency anemia develop pagophagia, a form of pica.
Usually these people crave ice to suck or chew. and some patients prefer cold celery or other cold vegetables instead of ice. Leg cramps, which occur especially when climbing stairs, are also common in patients with iron deficiency anemia.
Due to the lack of circulating hemoglobin, patients develop fatigue and diminished capability to perform hard labor as mentioned earlier. Reduced synthesis of non-hemoglobin proteins that require iron as a structural component will result in muscle dysfunction, dysphagia with esophageal webbing, altered resistance to infection, and altered behavior. Anemia produces nonspecific pallor of mucous membranes.
A number of epithelial tissue abnormalities are seen with iron deficiency anemia, including koilonychia or spoon-shaped nails, angular stomatitis, glycitis, esophageal webbing, and gastric atrophy. Although iron deficiency anemia is an easily treated condition, sometimes it may lead to serious complications. Severe iron deficiency anemia may cause hypoxemia, which enhances the occurrence of coronary insufficiency and myocardial ischemia.
In some patients, webbing of the esophageal mucosa is associated with squamous cell carcinoma of the cricoid area. Gastric atrophy may lead to progressive loss of gastric acid, pepsin, and intrinsic factor secretion, which may result in malabsorption of other nutrients. And rarely, severe iron deficiency anemia is associated with papilledema. and raised intracranial pressure.
However, these are typically resolved with iron therapy. Impaired immune function is also reported with iron deficiency anemia, and this will increase the risk of infection. In infants, iron deficiency anemia causes impaired neurologic development and growth retardation.
In children, it causes reduced scholastic performance. Now let's discuss about the diagnosis of iron deficiency anemia. Although history and physical examination can lead to the recognition of the condition and help establish the etiology, iron deficiency anemia is primarily a laboratory diagnosis. Useful tests include the following. Complete blood count.
Peripheral smear. Serum iron, total iron binding capacity, and serum ferritin levels. Evaluation of hemoglobinuria, hemocidarinuria, and pulmonary hemocidiosis. And, reticulocyte hemoglobin count. In addition, stool testing, incubated osmotic fragility testing, and bone marrow aspiration are useful for establishing the etiology.
I will discuss about the first three tests in more detail in the following sections because they are the most useful tests when diagnosing iron deficiency anemia. Complete blood count documents the severity of anemia. In chronic iron deficiency anemia, complete blood count shows microcytic hypochromic erythropoiesis. Both MCV and MCHC are low, and often the platelet count is elevated.
If complete blood count is obtained after a recent blood loss, cellular indices are usually normal because most of the erythrocytes are produced before the blood loss, as they have a lifespan of 120 days. Examination of a peripheral blood smear is also an important part in the workup of iron deficiency anemia. Peripheral smear shows microcytic hypochromic red blood cells, along with abnormal, pencil-shaped red blood cells in between.
Low serum iron and ferritin, along with elevated total iron binding capacity, is diagnostic of iron deficiency anemia. However, normal serum ferritin levels can be seen in patients who are deficient in iron and have coexistent diseases, such as hepatitis. and anemia of chronic disease.
So, it is important to rule out these conditions to arrive at a precise diagnosis. Finally, let's come to the treatment of iron deficiency anemia. It is an easily treated disorder with an excellent outcome.
However, sometimes it may be caused by an underlying condition with a poor prognosis, like a cancer. In most patients, iron deficiency should be treated with oral iron therapy. And the underlying etiology should be corrected.
so that iron deficiency will not recur. Avoid giving iron to patients who have microcytic iron overloading disorders, such as thalassemia and sideroblastic anemia. Do not administer parenteral iron to patients who should be treated with oral iron because it may cause anaphylaxis. And sometimes, postmenopausal women are unresponsive to iron supplementation, including parenteral iron. Because they have a primary defect in iron reutilization due to androgen deficiency.
These patients respond only to androgen replacement therapy. Okay. That's all I wish to discuss in this video.
Hope you have understood it well. If you have any question or doubt regarding this topic, feel free to post them in the comment section. Thanks for watching.
See you soon in the next video.