Interpreting the erythron (Proceedings)


Interpreting the erythron (Proceedings)

Apr 01, 2008

Although one of the most frequently utilized diagnostic tools, the full power of the complete blood count and ancillary testing is often untapped. As a routine part the initial steps of patient work up to serial monitoring of a wide variety of diseases to determining efficacy of treatment, evaluation of the erythron can be extremely useful. The erythron is the sum total of the balance between stem cells, progenitor cells, precursor cells, mature erythrocytes and senescent erythrocytes

To fully understand the erythron and the tests that are available, basic physiology and kinetics should be reviewed. The main factor that controls total body iron is need, with control regulated by absorption. Diets contain ferric (Fe3+, better absorbed) and ferrous (Fe2+) iron. Iron is transported inside of transferrin. In health, only about 33% of transferrin's binding sites are occupied. Ferrotransferrin is made up of Fe3+ (one or two molecules) and apotransferrin. Less than 0.05% of total body iron is lost every day. Apoferritin in mucosal cells binds iron and forms mucosal ferritin, which can then be lost in the feces when that cell is sloughed. About 50-70% of total body iron can be found within hemoglobin (Hb). Each molecule contains four iron atoms and is 0.34% iron by weight. About 25 - 40% is in the storage pool (ferritin and hemosiderin). Ferritin is iron plus the apoferritin protein. This form is considered to be more available to the body. Ferritin is considered a positive acute phase protein; thus, the inflammatory status of an animal should be considered when evaluating serum ferritin. Hemosiderin is structurally similar to ferritin, but has a higher iron:protein ratio. This form of iron is is insoluble in water and can be seen on cytology and histology as an amorphous blue-grey or a golden pigment, respectively. If uncertainty exists when identifying this protein, Prussian Blue or Perl's staining can be used to readily identify it. Hemosiderin is primarily found in macrophages of the spleen, liver and bone marrow. In addition, approximately 3-7% is of body total is within myoglobin, with higher amounts seen in horses and dogs.

There are several avenues that can be taken to assess body iron. The first and most accessible route is to evaluate the peripheral blood. Blood is the largest pool of iron; however, iron is preferentially shunted to this pool for hemoglobin synthesis; therefore, this is the last place that may show abnormalities. You may be able to visually identify hypochromasia and/or microcytosis in cases of iron deficiency; however, this is a relatively insensitive method and somewhat unreliable in large animals. Other morphologic changes that may be seen include: leptocytes, codocytes, ovalocytes, polychromasia. Measuring or calculating data such as RBC, Hct, PCV and Hb allows for the determination of several indices, which can be used to evaluate iron status. The mean corpuscular volume (MCV)fl= (PCV x 10) / RBC (millions) indicates the average volume of the erythrocytes. With severe iron deficiency, hemoglobin synthesis is slowed in immature erythrocytes, while nucleated precursors continue to divide until a critical concentration of hemoglobin in present to stop DNA synthesis and cell division. The result is mature erythrocytes that are small and may have a central pallor. It is wise to consider that the MCV (as the name implies) is the mean; therefore, a significant population of Hypochromic cells can be present before the mean begins to shift. The mean corpuscular hemoglobin concentration (MCHC) g/dl = (Hb g/dl x 100) / Hct % indicates the amount of hemoglobin within each erythrocyte. It is the most accurate of the indices because it is not reliant on the RBC. This is not necessarily true; however, if the value for Hct is calculated. The MCHC may be decreased in cases of iron deficiency.

Serum Iron (SI) is generally a poor estimate of total body stores. It assesses the transport component, essentially all transferrin; however, serum ferritin can contribute slightly if there is a marked hyperferritinemia. Hypoferremia (Decreased Fe in blood) is most likely due to iron deficiency, usually due to chronic blood loss in adults; however dietary factors may play a part in young animals on iron poor diet. Serum iron will also decrease with a shift of Fe to storage sites or sequestration of iron in macrophages; therefore, blood is iron deficient but the body isn't. The classic example of this is an anemia of chronic inflammation. A decreased SI is also rarely seen with severe intestinal disease preventing Fe absorption. Hyperferremia rarely occurs and may signal excessive intake, iatrogenic administration of iron or repeated, overzealous transfusions.