Transcription
Okay, good morning! Today, we are starting with our hematology review.
Let us begin with hematopoiesis. Hematopoiesis includes erythropoiesis, leukopoiesis (the production of white blood cells), and thrombopoiesis (the production of platelets). However, we will focus on erythropoiesis and granulopoiesis.
Starting with erythropoiesis, or the production of red blood cells, let us first note the key regulatory factors that drive this process. These include erythropoietin, which is produced by the kidneys, and GM-CSF (Granulocyte Macrophage Colony Stimulating Factor). These are the key regulatory factors for erythropoiesis.
The process of erythropoiesis starts from the burst-forming unit (BFU-E) until a mature red blood cell (RBC) is formed. This takes approximately 18 to 21 days.
Here are the stages of erythropoiesis:
1. **Pronormoblast** (also known as rubriblast) - As the cell matures, the nucleus-to-cytoplasm (N:C) ratio decreases, and the cell size also decreases. The nuclear chromatin becomes clumped or condensed. You will notice a more compact nucleus as the cell matures due to the condensation and clumping of chromatin. Eventually, the nucleoli disappear. The cytoplasm changes from dark blue to grayish-blue and finally to pink, which is characteristic of mature red blood cells.
2. In the **pronormoblast stage**, globin production starts, which is necessary for hemoglobin production.
3. Next is the **proerythroblast stage** (or basophilic normoblast). In this stage, hemoglobin synthesis begins, but it is not yet evident.
4. The **polychromatic normoblast** (or rubricyte stage) is where hemoglobin becomes evident. This is the last stage capable of mitosis. The cytoplasm becomes more basophilic due to the presence of significant amounts of hemoglobin.
5. The **orthochromatic normoblast** (or metarubricyte) is the last nucleated phase of erythropoiesis. This stage is confined to the bone marrow. Once it becomes a reticulocyte, it will only stay in circulation for approximately one day before maturing into a red blood cell.
6. The reticulocyte is the first stage released into peripheral circulation and will remain as a reticulocyte for about one to two days before maturing into a mature erythrocyte. An immature erythrocyte has a size of 6 to 8 micrometers in diameter, lacks a nucleus, and has pink to reddish-pink cytoplasm.
In general, during erythropoiesis, the cell size decreases, the N:C ratio decreases, and the nuclear chromatin becomes clumped or condensed. In the case of red blood cells, the nucleus is expelled during the orthochromatic normoblast stage, which is why reticulocytes do not have a nucleus.
Now, let us proceed to granulopoiesis. Granulopoiesis is part of leukopoiesis, which is the general term for the production of white blood cells. Granulocytes include neutrophils, basophils, and eosinophils, which have similar stages of maturation. We also have monocytes and lymphocytes.
For granulopoiesis, we need to note the key regulators of this process. These include GM-CSF, G-CSF (Granulocyte Colony Stimulating Factor), and interleukin-5 for eosinophil maturation, and interleukin-3 and interleukin-4 for basophil maturation.
The early stage is the **myeloblast**. As the cell matures, the cell size decreases, and the nuclear-cytoplasmic ratio also decreases. The nucleus can assume several lobes, but it is not lobulated compared to erythrocytes.
In the **myeloblast stage**, CD34 is present. As the myeloblast matures into a promyelocyte, it loses CD34 but gains CD55. The promyelocyte is the first stage where CD66b appears.
The **myelocyte stage** is morphologically recognizable, allowing differentiation into neutrophils, basophils, or eosinophils. This is the last stage capable of mitosis. As the promyelocyte becomes a myelocyte, it loses CD45R and CD117, while CD11, CD24, and CD66a appear.
Next is the **metamyelocyte stage**, also known as the juvenile cell stage, where CD16 first appears.
The **band or stab cell** is the first stage normally found in peripheral blood. In my exam, I was asked about the absolute neutrophil count, and I learned that the band is included in this count.
Finally, we have the **polymorphonuclear neutrophil** (segmented neutrophil), where CD10 and CD14 appear.
In my exam, I was asked about CD markers and their association with different stages of granulopoiesis. CD markers aid in the identification of cells, especially in classifying or identifying malignancies.
As cells mature, they tend to have fine and delicate nuclear chromatin, which becomes coarse and clumped. The cytoplasm is more basophilic in immature cells and becomes more eosinophilic as they mature.
Now, let us proceed to hemoglobin. Heme synthesis and globin synthesis occur in different parts of the cell. Heme synthesis involves the mitochondria and cytoplasm, while globin synthesis occurs in the ribosomes.
Iron is an essential component of hemoglobin. Each hemoglobin molecule is composed of four globin chains, with each chain containing a heme group. In one hemoglobin molecule, there are four iron atoms and 16 pyrrole rings.
The final product in hemoglobin synthesis is protoporphyrin, to which iron is attached, aided by ferrochelatase. Iron absorption and transport involve transferrin receptors in the pronormoblasts binding iron for incorporation during erythropoiesis.
For globin synthesis, the genes coding for globin production are found on chromosomes 11 and 16. Chromosome 11 has genes for epsilon, beta, gamma, and delta chains, while chromosome 16 has genes for alpha chains and one for zeta chains.
Hemoglobin A is the most abundant adult hemoglobin, comprising 95-98% of hemoglobin in adults. Hemoglobin A2 and F are also present in smaller amounts. In newborns, hemoglobin F is the most abundant.
Abnormal hemoglobin derivatives can affect oxygen delivery to tissues. Carboxyhemoglobin has 200 times more affinity for oxygen than normal hemoglobin, while methemoglobin has iron in the ferric state. Sulfhemoglobin is irreversible and can be fatal.
The oxyhemoglobin dissociation curve is normally sigmoid in shape. A right shift indicates decreased affinity for oxygen, leading to increased oxygen delivery to tissues. Factors causing a right shift include increased hydrogen ions, temperature, 2,3-DPG, and carbon dioxide.
A left shift indicates increased affinity for oxygen, resulting in decreased oxygen delivery to tissues. Factors causing a left shift include decreased hydrogen ions, temperature, 2,3-DPG, and carbon dioxide.
Now, let us proceed to hemoglobin electrophoresis. In cellulose acetate electrophoresis, hemoglobins migrate towards the anode, while in acid citrate electrophoresis, hemoglobins migrate differently.
Next, we will discuss erythrocyte destruction. There are two pathways for red blood cell destruction: extravascular and intravascular hemolysis. Extravascular hemolysis occurs in the spleen and liver, while intravascular hemolysis occurs within circulation.
Key features of extravascular hemolysis include spherocytes, increased lactate dehydrogenase, and increased bilirubin. In intravascular hemolysis, schistocytes are present, and haptoglobin is decreased.
Now, let us proceed to the different diseases of erythrocytes. Anemia is characterized by decreased RBC count, hemoglobin, and hematocrit. It can be due to blood loss, impaired RBC production, or increased RBC destruction.
To differentiate anemia, the absolute reticulocyte count is useful. A decreased or normal reticulocyte count indicates ineffective RBC production, while an increased count indicates excessive RBC loss.
Microcytic anemia includes iron deficiency anemia, thalassemia, sideroblastic anemia, and lead poisoning. Macrocytic anemia can be megaloblastic or non-megaloblastic.
For iron deficiency anemia, the causes include excessive iron loss, increased iron requirement, deficient intake, and defective absorption. Peripheral blood findings include microcytosis and hypochromia.
Thalassemia is a genetic condition characterized by a quantitative decrease in globin production. It can be classified into alpha and beta thalassemia, with various clinical conditions based on gene deletions.
Sideroblastic anemia can be acquired or inherited, with peripheral blood findings showing hypochromic RBCs and dimorphic populations.
Anemia of chronic inflammation is common in hospitalized patients and is characterized by defective iron utilization.
Now, let us proceed to macrocytic anemia, which can be due to alcoholism, liver disease, or hemolytic anemia. Megaloblastic anemia is characterized by large red blood cell precursors with nuclear-cytoplasmic asynchrony.
Finally, we will discuss RBC inclusions associated with diseases, such as basophilic stippling, Howell-Jolly bodies, Heinz bodies, and Pappenheimer bodies.
That would be all for red blood cell disorders, and that concludes our session for today. Thank you!