Anemia (Part 1)

The primary function of blood, its identification, is oxygen transport. Anemia comes from Greek (Αναιμία), meaning "without blood," referring to a deficit of erythrocytes resulting in a decrease in Hb (found only within erythrocytes), leading to pallor and fatigue.

Although from a pathophysiological perspective, anemia is defined as a reduction in the total mass of circulating erythrocytes, functionally it is defined as a decrease in the blood transport capacity (Hb found only within erythrocytes) for O2, resulting in tissue hypoxia.

The blood's transport capacity for oxygen is reduced by a decrease in Hb levels (the direct transporter of oxygen), with or without a decrease in the number of circulating erythrocytes. All human cells depend on oxygen for survival, and varying degrees of anemia (lack of Hb) will have different clinical consequences, determined by the speed of anemia onset, its severity, patient age, and the Hb dissociation curve from oxygen – as discussed below.

Anemia must be distinguished from hypoxemia (reduction in the partial pressure of oxygen in the blood), although both conditions cause tissue hypoxia.

It is important to note that iron (Fe) pigment provides the red color of Hb. Erythrocytes, and consequently blood, have the majority of colored elements (the remaining part of blood without erythrocytes has no red color).

When the Hb value decreases, with or without a decrease in the number of erythrocytes, there will be a decrease in blood color, resulting in pallor of the skin and mucous membranes. Therefore, the use of the term "anemia" is not entirely illogical. However, there is no lack of blood (the total volume of blood remains the same, only the volume of erythrocytes will decrease, and the plasma volume will increase, while the volume of the other blood components is constant). A more accurate term would be achromia (an – not, hemi – the pigment that gives color to erythrocytes and all blood). Still, achromia does not imply a complete lack of color, of Hb, so the term hypochromia is used to describe the reduction in erythrocyte color.

Therefore, if there is a decrease in Hb (and/or RBC), there will be a decrease in blood color, resulting in pallor of the skin and mucous membranes. The color of the skin and mucous membranes is determined by the amount of Hb, the number of vessels in the submucosa and the mucous membranes' zone, as the epidermis and epithelium do not have blood vessels, so they are transparent. This does not happen if the other two series' volumes decrease or increase.

The more accurate term to describe the decrease in the number of erythrocytes (resulting in a decrease in Hb) is erythropenia.

The term 'anemia' used in clinical medicine refers to the reduction below the accepted normal values of Hb (according to the age and gender of the individual) with or without a decrease in the absolute number of circulating erythrocytes. Anemia is defined as a reduction in the total amount of Hb, compared to normal physiological values. A decrease in Hb, with or without a decrease in the absolute number of erythrocytes, leads to the onset of clinical symptoms and signs of anemia.

In terms of quantity, anemia is a 20% reduction in the respective reference values (for Hb), i.e., less than 12 g% in women and 13 g% in men.

Preferably, Hb is used more than the RBC count because there are hypochromic microcytic anemias (Iron Deficiency Anemia, Thalassemic Syndromes, etc.) where the number of erythrocytes is normal or even above normal (thalassemia).

In daily practice, instead of the less common, more expensive, and time-consuming method of directly measuring erythrocyte mass, which would be more accurate, the following parameters are used:

• Hb concentration.
• Hematocrit values (Hct).
• Number of erythrocytes.

These parameters are expressed as numbers in g/dl, %, and mm3, representing erythrocytes in comparison to plasma (the fluid environment in which they are found).

So when evaluating anemia, the plasma volume must also be assessed (whether it is increased, resulting in hemodilution of blood elements, or decreased, resulting in a not real increase in the number of blood elements). In these cases, the assessment should be made after correcting the plasma volume or after some time.

In normal values, all three parameters are influenced by several important factors such as sex, age, race, and the altitude of the place where they live.

Regulation of Hematopoiesis

A perfect dynamic balance is required between controlled cell death (apoptosis of aging or structurally altered cells) and controlled cell production.

The basic function of erythrocytes is to create and maintain a healthy environment for the physical and functional integrity of hemoglobin.

Erythrocytes are the simplest cells in the body but highly specialized (destined to die after completing their function). They are a sacrificial cell to ensure the structure and function of the primary oxygen transporter in the body, Hb. After the nucleus is ejected (no DNA and RNA), it cannot be considered a complete cell, even though it performs a major duty to provide as much space as possible for Hb. It lacks the essential organelles for regenerating damaged structures during its existence (ribosomes for protein synthesis, enzymes). It lacks mitochondria necessary for energy synthesis through the Krebs cycle and Oxidative Phosphorylation but obtains energy through an inefficient pathway like anaerobic glycolysis (cytoplasm) while transporting oxygen. It takes a shape to provide the largest surface area for a specific volume, requiring continuous energy, and obtains the necessary energy through an inefficient pathway like anaerobic glycolysis when it transports oxygen. It follows a unique route, such as the production of 2,3 DPG, which consumes more energy. It circulates many times a day in microcirculation (mechanical stress and hypoxia), makes a circulation every 20 seconds throughout the body (170,000 cycles), and does all this for 120 days (4 months).

The total blood volume is the sum of plasma volume + erythrocyte mass (RCM-Red cell mass). TCRV-total red cell volume or RCM is measured with Cr or Tc radioactively, and normal values in men are 25-35 ml/kg and in women 22-32 ml/kg. Plasma volume is 40-50 ml/kg (2.25 liters of erythrocyte volume in the total circulating blood volume or 2250 ml: 70 kg ≈ 32 ml/kg).

Blood is a special fluid connective tissue. The fluid is plasma water. Therefore, all hydrodynamic laws are used for blood (in the case of blood as a fluid, hemodynamics is spoken). Erythrocytes, leukocytes, thrombocytes, lipids, circulating proteins, etc., are spoken of because they are in continuous circulation within a closed system of tubes and a pump that autonomously pushes them continuously. Of an average of 5 liters of blood, only 2.25 liters (45%) are cells. The rest is plasma, which itself is 93% water and 7% solid substances (mostly proteins like albumin, fibrinogen, but also lipids, electrolytes, sugar, etc.). Of 2.25 liters of cells, only 0.037 liters (1.6%) are leukocytes, and less than 0.0065 liters (a teaspoon) is the volume of all circulating platelets.

The diameter of erythrocytes is 6-8 µm (average 7.5 µm).

1. With normal size, they are called normocytes.
2. When sizes are < 6 micrometers, they are called microcytes (small cells).
3. When sizes are > 9 micrometers, they are called macrocytes (large cells).
4. When sizes are > 12 micrometers, they are called megalocytes.

Regarding color, erythrocytes are normochromic, hypochromic, but not hyperchromic. A normochromic erythrocyte means it is filled to its maximum capacity for its size.