PATHOPHYSIOLOGY AND CLINICAL PRESENTATION – CORRECT DIAGNOSIS

Iron Deficiency Anemia (IDA) occurs when there are insufficient stores of iron leading to ineffective or insufficient production of erythrocytes. The most common etiologies of IDA are hemorrhagic states such as gastrointestinal (GI) bleeding and pregnancy. In men and postmenopausal women, iron deficiency anemia typically indicates GI bleeding. Lesser common etiologies of IDA are caused by dietary iron insufficiency and decreased stomach acidity (McCance, 2019).

Physiology of Iron Absorption

There are two types of dietary iron that are absorbable by the body: Heme iron is found in animal products and non heme iron that is found in plants and iron fortified foods. Although it is much easier for the body to absorb heme iron, both require an acidic environment (Ems & Huecker, 2019).

After a person consumes a source of dietary iron, absorption primarily occurs in the duodenum and proximal jejunum (Ems, 2019). Heme iron is oxidized and becomes haemin due to the acidic environment of the stomach. Haemin is directly absorbed by cells in the duodenum and proximal jejunum called enterocytes (Deo, 2014).

Non-heme iron is not directly absorbable by the body in its ferric form (Fe3+). Therefore, it must be reduced to ferrous iron (Fe2+). The reduction reaction takes place on the brush border of enterocytes. This process is facilitated by an enzyme called duodenal cytochrome B. This reaction must take place in an acidic environment. Then, a protein on enterocytes called DMT1 brings the ferrous iron into the enterocytes. Heme iron is either stored in the liver or used in other physiologic processes such as erythropoiesis (Ems & Huecker, 2019).

Physiology of Iron use in Erythropoiesis

Iron is essential to the formation of new red blood cells. This process is called erythropoiesis. Normally, iron is constantly fluctuating between stored iron and iron synthesized into hemoglobin (Hgb) during erythropoiesis. Hemoglobin is the functional part of red blood cells that mediates reversible binding of oxygen. Hemoglobin is made up of a heme group (a combination of iron and porphyrin) and a polypeptide chain called globin. When the body’s oxygen requirements increase, or there is need for new red blood cells, iron is taken from iron stores in the liver to the bone marrow where erythropoiesis takes place and is used to synthesize hemoglobin (McCance, 2019).

Pathophysiology of Iron Deficiency Anemia

During IDA development, iron stores begin to deplete without replenishment. There are four main causes of Iron Deficiency:

1) Exsanguination
2) Increased hemoglobin/oxygen requirements
3) Insufficient dietary intake
4) Insufficient iron absorption

At first, there are sufficient amounts of iron to make functioning red blood cells. When there is little to no iron left to transport to the bone marrow, iron deficient erythropoiesis begins. During iron deficient erythropoiesis, insufficient levels of heme groups are synthesized and packaged into newly produced erythrocytes. These cells are much smaller than their predecessors. Mean corpuscular volume (MCV) is a blood test to help determine the size of red blood cells. Normal ranges are 80-100 Fl. Anemias characterized by small erythrocytes fall under the category of microcytic anemias. Since there is a lower saturation of hemoglobin on new erythrocytes, less oxygen can bind, making it more difficult to transport oxygen to tissues in need. As normal, healthy erythrocytes are destroyed, these hemoglobin deficient erythrocytes take their place and over all hemoglobin concentrations drop. When hemoglobin levels drop between 7 and 8 g/dL the patient is considered anemic (McCance, 2019).

In anemic states, heart rate and respiratory rate increase to supplement oxygen exchange since there is less hemoglobin for oxygen to bind to. Without adequate delivery of oxygen, symptoms such as fatigue, weakness, and shortness of breath manifest. Eventually, with ineffective oxygen transport, epithelial tissues begin to change; fingernails become brittle and “spoon shaped” and tongue papillae atrophy, become inflamed, and painful (McCance, 2019). Individuals with IDA can also exhibit pica; an eating disorder where items that are not food and do not contain nutritional value are consumed. Pica is a unique condition that can either be a symptom or a cause of IDA (McCance, 2019).

To differentiate IDA from other anemias, iron stores are measured directly by bone marrow biopsy, or, indirectly by measuring serum ferritin, transferrin saturation, or total iron-binding capacity (McCance, 2019).

 

References:

Deo, A. (2014). All about blood: Intestinal iron absorption. https://allaboutblood.com/2014/01/18/intestinal-iron-absorption/.

Ems, T. & Huecker, M. R. ( 2019). Biochemistry, Iron Absorption. StatsPearls. StatPearls Publishing. https://www.ncbi.nlm.nih.gov/books/NBK448204/.

Enterocyte | biology | Britannica. (2019). In Encyclopædia Britannica. Retrieved from https://www.britannica.com/science/enterocyte

Enzyme Explorer: Hemoglobin, Heme Products and Erythrocytes. (2019). Retrieved November 21, 2019, from Sigma-Aldrich website: https://www.sigmaaldrich.com/life-science/metabolomics/enzyme-explorer/learning-center/plasma-blood-protein/hemoglobin-heme-products.html

McCance, K. L., & Huether, S. E. (2019). The hematologic system. In V. L. Brashers & N. S. Rote (Eds.), Pathophysiology: The biological basis for disease in adults and children (8th ed., pp.890-1016). Elsevier.