Blood, Anemia, Leukemia, and Blood Tests

Pathophysiology of anemia

Ghazal Sokhanran

Learning Objectives

By the end of this section, you will be able to:

  • Define anemia and be able to describe the general classification of anemia
  • describe the basic characteristics of anemia
  • Name some signs and symptoms of anemia and be able to explain why they occur.

Anemia is one of the most common hematological diseases, affecting up to 33% of the global population. It is described as a decrease in hemoglobin (Hb) concentration in the blood, below the standard value (i.e. population-based ‘normal’ range of values) based on the age and gender of an individual. As hemoglobin is transported only in RBCs, a decrease in hemoglobin may also reflect the number of RBCs in circulation. 

The Hb concentration is determined by both changes in total circulating plasma volume and total circulating Hb mass. Reduced plasma volume (as in dehydration) may conceal anemia or even induce an abnormally high number of RBCs in the blood (i.e. relative polycythemia); on the other hand, increased plasma volume (as in pregnancy or fluid excess) may cause anemia despite normal total circulating RBC and Hb mass (i.e. dilutional anemia).

Anemia caused by a decrease in circulating Hb – with or without an associated drop in RBC number – will be the focus of this chapter.

General classification of anemia

There are two ways to classify anemia: by etiology (i.e. what has caused the anemia) and by morphology of the RBC

By determining what has caused it (Etiology).
  • Decreased hematopoiesis. This could be due to:
    • Nutritional deficiencies affecting DNA synthesis or Hb production
    • Bone marrow failure
  • Abnormal hematopoiesis. Due to errors in progenitor cell formation.
  • Increased loss of RBCs. Generally, because of a bleeding problem, which could be acute (e.g., trauma) or chronic (e.g., Gastrointestinal bleeding).
    • Keep in mind that anemia does not appear immediately after acute major blood loss because the total blood volume is reduced. It takes some time (about a day) for plasma volume to be replenished, then the degree of anemia can be assessed. Regeneration of RBCs and Hb mass takes much longer (approximately a week). Therefore, the initial clinical features of major blood loss are a result of the reduction in blood volume rather than of anemia.
  • Increased destruction of RBCs.
    • Destruction of abnormal RBCs can be due to:
      • Inherited disorders
        • RBC cell membrane disorders, for example, cause the formation of spherocytes (round like a sphere instead of normally donut-shaped RBC), which leads to autoimmune hemolysis
        • Enzyme deficiencies, for example, G6PD deficiency
        • Abnormal Hb production, for example, sickle cell disease
      • Acquired disorders, for instance, with PNH (paroxysmal nocturnal hemoglobinuria).
    • Destruction of normal RBCs can be caused by
      • Immune-mediated, as in immune hemolytic anemia
      • Mechanical problems, for example, with repetitive trauma (hand drummers, marathon runners)
      • Infections such as Malaria
      • Chemical or toxic injury, for example, lead poisoning or snake venom
By morphology and structure.

This is done by assessing the size and shape of erythrocytes (by doing peripheral blood smears) and chemically analyzing Hb and other major constituent proteins of RBCs (through antibody-mediated tests or PCR).

  • Upon assessment of the RBC size in the sample, it is then categorized as microcytic (small), normocytic (normal), macrocytic (large)
  • Depending on the amount of Hb content which determines the ‘colour of RBCs’, the sample can be categorized as hypochromic (pale) or normochromic (normal)

Another chapter (Diagnosis of Anemia & Leukemia)  will discuss the quantitative measurements of blood components.

Clinical Characteristics of Anemia

Surprisingly, there may be no symptoms nor signs in some patients with relatively severe anemia; whereas, in contrast, others with milder anemia may experience severe effects. To address the anemia, the body compensates for the decreased hemoglobin, and thus decrease oxygen carrying capabilities, by influencing the cardiovascular system: most commonly by increasing stroke volume and tachycardia. As well, the body can compensate by shifting the Hb-O2 dissociation curve (i.e. factors that influence how well oxygen can bind to and release from Hb).  Thus, the body’s ability to compensate for anemia – whether through cardiovascular or Hb-O2 binding adaptation – determines how symptomatic a patient may feel.

Other clinical characteristics can be considered and classified as follows:

  1. Speed of onset. As evident as it can be, fast and rapidly progressive anemia leads to more symptoms than anemia of slow onset because there is less time for changes in the body to occur.
  2. Severity. Mild anemia often produces no symptoms or signs, but these are usually present when the Hb is less than 90g/L. Even severe anemia may produce remarkably few symptoms when there is a very gradual onset in a young subject who is otherwise healthy.
  3. Age. Young patients can tolerate anemia much better than the elderly because cardiovascular compensation is better in younger patients.

Section Review

Anemia is a common problem worldwide and involves an abnormally low amount of hemoglobin.  The cause of the anemia can be classified with problems with hemoglobin or RBC production (e.g. iron or Vit B12 deficiency, problems with erythropoiesis) or with loss of red blood cells.  Loss can be subclassified as pure loss of blood (e.g. bleed) or abnormal destruction of the RBCs (e.g. autoimmune, RBC fragility).

Anemia can also be described by how the RBCs look, based on size and colour, and how quickly the symptoms of anemia appear.

Review Questions




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