Hemopoiesis and Nutritional anemias (2)
Integrative Module on Hemopoiesis and Nutritional Anemias
Introduction
Dr. Rusul Najah Alnumani, University Of Kufa, Faculty Of Medicine (2024-2025)
Haemopoiesis
Definition: Blood cell formation.
Sites of Haemopoiesis:
Fetus:
0-2 months: Yolk sac
2-7 months: Liver, spleen
5-9 months: Bone marrow
Infants:
Bone marrow (practically all bones)
Adults:
Vertebrae, ribs, sternum, skull, sacrum, pelvis, proximal ends of femurs
Hematopoietic Stem Cells (HSC)
Initiates from pluripotential stem cell.
Asymmetric cell division allows self-renewal while also giving rise to separate cell lineages.
HSC is rare, approx. 1 in every 20 million nucleated cells.
Immunological markers: CD34+ CD38−, negative for lineage markers, resembles small/medium lymphocyte.
Hematopoietic Progenitor Cells Diagram
Various progenitor cells identified by colony type they form, including:
Erythroid progenitors (BFU-E, CFU-E) for red cells
Megakaryocyte progenitor (CFU-Meg)
Granulocyte-monocyte progenitor (CFU-GM)
Lymphoid progenitors leading to T, B, and NK cells.
Erythropoietin (EPO)
A heavily glycosylated polypeptide primarily produced (90%) in kidneys and (10%) in liver.
No preformed stores; production stimulus is oxygen tension in kidney tissues.
EPO promotes erythropoiesis by increasing number of progenitor cells committed to erythropoiesis.
Bone Marrow Dynamics
Development sequence of red cells from pronormoblast through to mature RBCs:
Pronormoblast > Early (60-80% in cell cycle) > Intermediate (polychromatic) > Late (pyknotic) > Reticulocytes > Mature RBCs.
Comparison of Normoblast, Reticulocyte, and Mature RBC:
Nuclear DNA: Yes (Normoblast), No (Reticulocyte and Mature RBC).
RNA in cytoplasm: Yes (Normoblast, Reticulocyte), No (Mature RBC).
In marrow: Yes (all), In blood: No (Normoblast), Yes (Reticulocyte, Mature RBC).
Anemia
Definition: Reduction in hemoglobin concentration below normal for age and sex.
Hb Thresholds:
Adult males: < 135 g/L (WHO: < 130 g/L)
Adult females: < 115 g/L (WHO: < 110 g/L)
Children (2 years to puberty): < 110 g/L
Newborns: Lower limit at 140 g/L.
Physiological Adaptations to Anemia
Acute Blood Loss:
Rapid increase in heart rate, respiratory rate, cardiac output, redistribution of blood flow to vital organs.
Slowly Developing Anemia:
Days to weeks: Increase in erythrocyte 2,3-bisphosphoglycerate, increased EPO production enhances erythropoiesis.
Clinical Features of Anemia
Symptoms: Shortness of breath, weakness, palpitations, headaches.
Older patients may show signs of cardiac failure or confusion.
Physical signs: Pallor of mucous membranes, tachycardia, bounding pulse, cardiomegaly, flow murmur.
Specific signs associated with types of anemia, e.g., koilonychia (spoon nails) in iron deficiency.
Classification of Anemia
Microcytic, Hypochromic (MCV < 80 fL): Iron deficiency, Thalassaemia, etc.
Normocytic, Normochromic (MCV 80-95 fL): Numerous causes, from haemolytic anemias to renal disease.
Macrocytic (MCV > 95 fL): Megaloblastic (B12 or folate deficiency), Non-megaloblastic (alcohol, liver disease).
Diagnostic Approach
History, physical examination, complete blood count (CBC), blood film analysis, reticulocyte count, specific tests (iron studies, vit B12/folate), bone marrow evaluation if other tests inconclusive.
Iron Deficiency Anemia (IDA)
Iron Absorption and Metabolism:
Dietary iron sources differ, with meat being a better source; approx. 10% is absorbed.
Absorption: Occurs in the duodenum, enhanced by certain factors like acidic pH and low molecular weight soluble chelates (vit C).
Causes of Iron Deficiency
Chronic blood loss (GI, menstrual), increased physiological demands (infancy, adolescence, pregnancy), and dietary deficiencies.
Clinical Features of IDA
Symptoms: Pallor, palpitations, tinnitus, irritability, weakness, dizziness.
Non-hematologic signs: Glossitis, angular stomatitis, gastric atrophy, koilonychia, pica.
Laboratory Investigations for IDA
Full blood count and blood film examination.
Screening tests for iron status: serum iron, total iron-binding capacity, transferrin saturation, serum ferritin.
Bone marrow iron stores evaluation if needed.
Treatment of IDA
Address the underlying cause, administer oral iron (e.g., Ferrous sulfate), and ensure treatment lasts for at least 6 months to replenish stores.
Monitor hemoglobin rise rate of ~20 g/L every 3 weeks.
Other Hypochromic Anemias
Include conditions like Thalassemia, Anemia of Chronic Disease, Lead Poisoning, and Sideroblastic Anemia.
Megaloblastic Anemia (MBA)
Characterized by delayed maturation of the nucleus relative to cytoplasm; commonly due to vitamin B12 or folate deficiency.
Laboratory Findings: Macrocytic anemia, with hypersegmented neutrophils and large erythroblasts.
Clinical Features of MBA
Symptoms: Gradual onset of anemia, jaundice, glossitis, and neuropathy (for B12 deficiency).
Consequences for fetal development if maternal deficiency is present.
Treatment of MBA
Vitamin B12 supplementation (Hydroxocobalamin) and folic acid administration as required.
Integrative Module on Hemopoiesis and Nutritional Anemias
Introduction
Instructor: Dr. Rusul Najah Alnumani, University Of Kufa, Faculty Of Medicine (2024-2025)
Haemopoiesis
Definition: Blood cell formation.
Sites of Haemopoiesis:
Fetus:
0-2 months: Yolk sac
2-7 months: Liver, spleen
5-9 months: Bone marrow
Infants: All bones (Bone marrow)
Adults: Vertebrae, ribs, sternum, skull, sacrum, pelvis, proximal ends of femurs
Hematopoietic Stem Cells (HSC)
Characteristics: Rare (1 in 20 million nucleated cells), initiates from pluripotential stem cell, features asymmetric cell division for self-renewal.
Immunological Markers: CD34+, CD38−.
Hematopoietic Progenitor Cells
Colony types include:
Erythroid progenitors (BFU-E, CFU-E) for red cells
Megakaryocyte progenitor (CFU-Meg)
Granulocyte-monocyte progenitor (CFU-GM)
Lymphoid progenitors (T, B, NK cells).
Erythropoietin (EPO)
Production: 90% in kidneys and 10% in liver; responds to oxygen tension in kidneys.
Function: Promotes erythropoiesis by increasing progenitor cells for red cells.
Bone Marrow Dynamics
Development Sequence: Pronormoblast > Early > Intermediate > Late > Reticulocytes > Mature RBCs.
Comparison of Cell Types:
Normoblast: Yes DNA, Yes RNA, present in bone marrow; Absent in blood.
Reticulocyte: No DNA, Yes RNA, present in both bone marrow and blood.
Mature RBC: No DNA, No RNA, present only in blood.
Anemia
Definition: Reduction in hemoglobin concentration below normal.
Hb Thresholds:
Adult males: < 135 g/L
Adult females: < 115 g/L
Children: < 110 g/L
Newborns: Lower limit at 140 g/L.
Physiological Adaptations & Clinical Features
Adaptations:
Acute blood loss: Increased heart rate, respiratory rate, cardiac output.
Slowly developing anemia leads to increased erythrocyte 2,3-bisphosphoglycerate and EPO production.
Symptoms: Shortness of breath, weakness, palpitations, headaches; older patients may exhibit cardiac failure or confusion.
Physical Signs: Pallor, tachycardia, bounding pulse, flow murmur.
Classification of Anemia
Microcytic, Hypochromic (MCV < 80 fL): Iron deficiency, Thalassemia.
Normocytic, Normochromic (MCV 80-95 fL): Hemolytic anemias, renal disease.
Macrocytic (MCV > 95 fL): Megaloblastic (B12 or folate deficiency), Non-megaloblastic (alcohol, liver disease).
Diagnostic Approach
Evaluation includes history, physical examination, CBC, blood film analysis, reticulocyte count, iron studies, bone marrow evaluation.
Iron Deficiency Anemia (IDA)
Causes: Chronic blood loss, increased physiological demands, dietary deficiencies.
Symptoms: Pallor, palpitations, tinnitus, weakness.
Laboratory Investigations: Serum iron, total iron-binding capacity, transferrin saturation, serum ferritin.
Treatment: Address underlying cause, oral iron supplementation, treatment duration of at least 6 months.
Other Anemias
Hypochromic Anemias: Thalassemia, Anemia of Chronic Disease, Lead Poisoning.
Megaloblastic Anemia: Characterized by nuclear-cytoplasmic maturation delay; treated with B12 and folic acid supplementation.