The Haematopoietic System

The Haematopoietic System Year 4 · Paediatrics Collection: 4TH YEAR ALL NOTES / PAEDS / PAEDS 4.3 / Munge / HAEMATOLOGY -- Slide 1 The Haematopoietic System Dr Rose Munge Slide 2 Hematopoiesis is the process by which the cellular elements of blood are formed.\n In the developing human embryo and fetus, hematopoiesis has 3 developmental waves and divided into 3 anatomic stages: mesoblastic, hepatic, and myeloid.\n Mesoblastic hematopoiesis occurs in extraembryonic structures, principally in the yolk sac, and begins between the 10th and 14th days of gestation. Slide 3 By 6-8 wk of gestation, the liver replaces the yolk sac as the primary site of blood cell production, and during this time the placenta also contributes as a hematopoietic site.\n By 10-12 wk, extraembryonic hematopoiesis has ceased. Slide 4 Hepatic hematopoiesis occurs through the remainder of gestation and then diminishes during the second trimester while bone marrow (myeloid ) hematopoiesis increases.\n The liver is the predominant erythropoietic organ through 20-24 wk of gestation production of all hematopoietic tissues.\n Hematopoiesis begins with multipotent cells capable of both self-renewal and clonal maturation into all blood cell lineages.\n Progenitor cells differentiate under the influence of transcription factors and hematopoietic growth factors. Slide 5 Hemoglobins in the Fetus and Neonate Hemoglobin is a tetramer of 4 globin chains with an iron-containing porphyrin ring called heme bound to each chain.\n A dynamic interaction between heme and globin gives hemoglobin its unique properties in the reversible transport of oxygen.\n The hemoglobin molecule consists of 2 alpha (α)-like and 2 beta (β)-like polypeptide chains, with each chain having a heme group attached. Slide 6 There are 2 β-globin genes and 4 α-globin genes.\n Within erythrocytes of an early embryo, fetus, child, and adult, 6 different hemoglobins may normally be detected: the embryonic hemoglobins (Gower-1, Gower-2, and Portland), fetal hemoglobin (HbF), and the adult hemoglobins (HbA and HbA2.)\n In embryos up to 6 wk gestation, the Gower hemoglobins predominate but are no longer detectable by 3 mo of gestation. Slide 7 Fetal Hemoglobin By 6-8 wk gestation, HbF (α2 γ2 ) is the predominant hemoglobin; at 24 wk gestation it constitutes 90% of the total hemoglobin.\n HbF declines modestly in the third trimester, such that the HbF comprises 70–80% of the total hemoglobin. HbF production decreases rapidly postnatally, and by 6-12 mo of age reaches adult levels of <2%. Slide 8 Understanding the molecular basis of the fetal- to- adult hemoglobin switch is of interest because of the therapeutic benefits to patients with β-thalassemia and sickle cell disease, whose clinical severity is improved with modest elevation of HbF. Slide 9 Adult Hemoglobins HbA constitutes 5–10% of total hemoglobin at 24 wk gestation and steadily increases, so that at term, HbA averages 30% of total hemoglobin.\n By 6-12 mo of age, individuals reach adult levels of HbA. The minor adult haemoglobin component, HbA2, contains delta (δ) chains and has the structure α2 δ2.\n At birth, <1.0% of HbA2 is detected, but by 12 mo of age the normal level is 2.0– 3.4%.\nThroughout life, the normal ratio of HbA to HbA2 is about 30: 1. Slide 10 The Anaemias Dr Rose Munge Slide 11 Anemia is defined as a reduction of the hemoglobin concentration or red blood cell (RBC) volume below the range of values occurring in healthy persons. “Normal” hemoglobin and hematocrit (packed red cell volume) vary substantially with age and sex.\nThere are also racial differences, with significantly lower hemoglobin levels in African American children than in white non-Hispanic children of comparable age.\nAnemia is a significant global health problem affecting children and reproductive-age women Slide 12 Physiologic adjustments to anemia include increased cardiac output, augmented oxygen extraction (increased arteriovenous oxygen difference), and a shunting of blood flow toward vital organs and tissues.\n In addition, the concentration of 2,3-diphosphoglycerate increases within the RBC.\n The resultant “shift to the right” of the oxygen dissociation curve reduces the affinity of hemoglobin for oxygen and results in more complete transfer of oxygen to the tissues.\n The same shift in the oxygen dissociation curve can also occur at high altitude.\nHigher levels of erythropoietin (EPO) and consequent increased RBC production by the bone marrow further assist the body to adapt. Slide 13 History and Physical Examination A detailed history and thorough physical exam are essential when evaluating an anemic child.\n Important- age, sex, race and ethnicity, diet, medications, chronic diseases, infections, travel, and exposures.\n A family history of anemia and associated difficulties (e.g., splenomegaly, jaundice, early-age onset of gallstones) is also important. Slide 14 Few physical symptoms or signs result solely from a low hemoglobin, parti