iMLS-HEMATOLOGY

Heme biosynthesis occurs in the mitochondria and cytoplasm of bone marrow erythroid precursors

Neutrophil development occurs in the BM and share common progenitor with monocytes (GM-). Neutrophil production is stimulated by G-CSF. Three pools of developing neutrophils in the BM exist: the stem cell pool, the proliferation pool, and the maturation pool. The stem cell pool consists of HSCs capable of self-renewal and differentiation; The proliferation (mitotic) pool consists of cells that are dividing in order of maturation include: Common myeloid progenitors (CFU-GEMMs), GM progenitors, myeloblasts; promyelocytes; and myelocytes. Maturation (storage) pool consist of cells undergoing nuclear maturation and are available for release: metamyelocytes, band neutrophils, and segmented neutrophils.

Iron deficiency anemia develops when the intake of iron is inadequate to meet a standard level of demand, when the need for iron expands without compensated intake, when there is impaired absorption, or when there is chronic loss of hemoglobin from the body.

Anemia of chronic inflammation only ranks behind Iron deficiency anemia found mostly in hospitalized patients, Associated with systemic diseases/chronic inflammation such as rheumatoid arthritis, chronic infections such as tuberculosis or HIV infection, and malignancies. Sideroblastic anemias result from diseases that interfere with the production of protoporphyrin. As in iron deficiency, the anemia may be microcytic and hypochromic. In contrast to iron deficiency, however, iron is abundant in the bone marrow. Iron overload may be primary, as in hereditary hemochromatosis, or secondary to chronic anemias and their treatments. In both cases the toxic effects of excess iron lead to serious problems as lipids, proteins, nucleic acids, and heme iron become oxidized.

The root cause of megaloblastic anemia is impaired DNA synthesis. When either folate or vitamin B₁₂ is deficient, thymidine nucleotide production for DNA synthesis is impaired. Megaloblastic anemia is one example of a macrocytic anemia.

The root cause of megaloblastic anemia is impaired DNA synthesis. When either folate or vitamin B₁₂ is deficient, thymidine nucleotide production for DNA synthesis is impaired. Megaloblastic anemia is one example of a macrocytic anemia..

Hemoglobinopathies are the most common genetic diseases, affecting approximately 7% of the world’s population. All hemoglobinopathies result from a genetic mutation in one or more genes that affect hemoglobin synthesis. Mutated gene may code for either globin chains or proteins involved in their synthesis. All hemoglobinopathies affect hemoglobin synthesis in one of two ways: Qualitatively or Quantitatively

Thalassemias are divided into β-thalassemias, which include all the disorders of reduced globin chain production arising from the β-globin gene cluster on chromosome 11, and α-thalassemias, which involve the genes for the α1 and α2 chains on chromosome 16. Deletional and non-deletional mutations can cause each of these disorders. 

Intrinsic hemolytic anemias comprise a large group of disorders in which defects in the red blood cells (RBCs) result in premature hemolysis and anemia. Intrinsic disorders can be divided into abnormalities of the RBC membrane, metabolic enzymes, or hemoglobin. Most of these defects are hereditary.

Intrinsic hemolytic anemias comprise a large group of disorders in which defects in the red blood cells (RBCs) result in premature hemolysis and anemia. Intrinsic disorders can be divided into abnormalities of the RBC membrane, metabolic enzymes, or hemoglobin. Most of these defects are hereditary.

Hereditary ovalocytosis or Southeast Asian ovalocytosis (SAO) is a condition caused by a mutation in the gene for band 3 that results in increased rigidity of the membrane and resistance to invasion by malaria. It is common in the malaria belt of Southeast Asia, where its prevalence can reach 30%. The inheritance pattern is autosomal dominant, and all patients identified are heterozygous.

Extrinsic hemolytic anemias comprise a diverse group of disorders in which RBCs are structurally and functionally normal, but a condition outside of the RBCs causes premature hemolysis. The extrinsic hemolytic anemias can be divided into conditions with nonimmune and immune causes.

A common feature in the nonimmune extrinsic hemolytic anemias is the presence of a condition that causes physical or mechanical injury to the RBCs. This injury can be caused by abnormalities in the microvasculature (microangiopathic) or the heart and large blood vessels (macroangiopathic), infectious agents, chemicals, drugs, venoms, or extensive burns.

In immune hemolytic anemia, hemolysis is mediated by antibodies, complement, or both.

Examination of a peripheral blood film (PBF) is important in suspected extrinsic hemolytic anemias, because observation of abnormal RBC morphology, such as schistocytes, spherocytes, or the presence of intracellular organisms, provides an important clue to the diagnosis.

This chapter concentrates on leukocyte disorders that are not caused by clonal or neoplastic changes in hematopoietic precursor cells.