Haematology Lecture 2: Haematopoiesis Overview

Haematology Lecture 2: Haematopoiesis & Blood Indices

• Haematopoiesis, the formation of new blood cells, occurs in the liver, spleen and blood in the foetus.
• After birth, haematopoiesis primarily occurs in red bone marrow.
• Haematopoiesis requires interaction with stromal cells in the bone marrow, stimulation from growth factors and cytokines.
• Haematopoiesis is a complex process that involves multiple steps and different lineages: erythropoiesis, leukopoiesis, and thrombopoiesis.

Learning Objectives

• The pathways of haematopoiesis.
• Some disorders of haematopoiesis.
• Erythropoiesis.
• Factors affecting erythropoiesis.
• Haematology tests.
• Calculated blood indices.

Haematopoiesis in Bone Marrow

• Haematopoiesis mainly occurs in the bone marrow.
• Bone marrow consists of cortical bone (hard), trabecular bone (spongy), and marrow.
• Blood vessels are present throughout the bone marrow.

Haematopoietic Stem Cells

• Haematopoietic stem cells are self-renewing multipotent stem cells located in bone marrow.
• These cells respond to haematopoietic growth factors such as erythropoietin, colony stimulating factors and interleukins.
• Haematopoietic stem cells can self-renew and differentiate into various committed progenitor cells.
• Committed progenitor cells belong to either the lymphoid or myeloid lineages.
• Lymphoid lineage gives rise to lymphocytes.
• Myeloid lineage gives rise to other leukocytes, erythrocytes and platelets.

Erythropoiesis

• Erythrocytes have a lifespan of 120 days.
• 2.5 million new erythrocytes are produced every second.
• Erythropoiesis requires iron, vitamin B12, and folic acid.
• Erythropoiesis is stimulated by erythropoietin (EPO) primarily secreted by the kidneys in response to a need.
• EPO circulates in the plasma with a half-life of 7-8 hours.
• EPO acts by binding to receptors on pronormoblasts in the bone marrow.
• Myeloid stem cells differentiate into pronormoblasts.
• Early normoblasts produce a high amount of ribosomes.
• Haemoglobin synthesis and iron accumulation are key steps in the development.
• When haemoglobin has accumulated, the cells ejects its organelles, the nucleus degenerates and is pinched off.
• The cell collapses inward to adopt a biconcave shape.
• The process takes approximately 15 days.
• Reticulocytes enter the bloodstream.
• Within 2 days, ribosomes are degraded by enzymes to form mature erythrocytes.
• The main stimulus for erythropoiesis is hypoxia.

Blood Disorders - Acute lymphoblastic leukaemia (ALL)

• Diagnosis is based on high numbers of abnormal, early-stage lymphoid precursor cells.
• Patients with ALL might have decreased neutrophils and other myeloid cells.
• Diagnosis requires 20% bone marrow lymphoblasts.

Blood Disorders -Chronic Myeloid Leukaemia

• Characterized by extremely high WBC count and platelets.
• Cell morphology of mature white blood cells and red blood cells is mostly normal, indicating that the cancer arose later.
• The increased cells originate from the myeloid lineage.
• Median age of diagnosis is 56, often asymptomatic.

Iron

• Essential for haemoglobin synthesis and function.
• Absorbed from the small intestine of the diet.
• Only 1mg/day of the required minimum 15mg/day is absorbed to replace lost iron.
• Remaining iron is recycled from dead red blood cells.
• 65% of body's iron is in haemoglobin.

Iron-deficiency anaemia

• Most common type of anaemia.
• Findings include low ferritin level, low serum iron, low haemoglobin, low haematocrit and microcytic erythrocytes.

Folic Acid & Vitamin B12

• Both are required for DNA synthesis.
• Deficiency impairs DNA synthesis, leading to normoblast apoptosis.
• Deficient normoblasts produce fewer but larger reticulocytes (macrocytic erythrocytes).
• Asynchronous maturation between cytoplasm and nucleus occurs.
• Vitamin B12 from food binds to intrinsic factor in the stomach for absorption in the ileum.

Other Blood Disorders & Blood Indices

• Other blood disorders include leukaemia, leukopenia, different types of anaemia, haemochromatosis, polycythemia.
• Blood tests (complete blood count) are used to assess RBC, WBC and platelets counts/counts, haematocrit(Packed Cell Volume), haemoglobin, and iron profile.

Other Types of Anaemia

• Anaemia is defined by either a reduced number of erythrocytes or a lower than normal haemoglobin level.
• Causes include haemorrhagic anaemia (sudden or persistent blood loss), haemolytic anaemia (premature erythrocyte rupture), aplastic anaemia (bone marrow suppression), and sickle cell anaemia.

Haemochromatosis

• Iron overload is a characteristic feature.
• Symptoms include abdominal pain, weakness, fatigue, joint pain, liver disease, and endocrine/cardiac abnormalities.
• High transferrin saturation is an early sign of the condition (although not always elevated).
• Most cases are due to the mutation of the HFE gene.
• Human haemochromatosis protein regulates iron absorption.
• Ireland has the highest reported prevalence globally.

Polycythemia Vera

• Myeloproliferative disorder of red blood cells characterized by overproduction.
• Prevalence is roughly 22 cases/100,000 people.
• Male to female ratio is 2:1
• Caused by an acquired genetic mutation that results in an oversensitivity to EPO.
• Increased risk of thrombotic events (e.g., stroke, deep vein thrombosis).

Calculated Blood Indices - Mean Corpuscular Volume (MCV)

• The average volume of a red blood cell.
• Normal range is 80-100 fL.
• MCV = Haematocrit / RBC (cells/L).
• Microcytic anaemia (MCV below 80fL) frequently due to iron deficiency.
• Macrocytic anaemia (MCV above 100fL) commonly due to vitamin B12 and/or folic acid deficiency.

Calculated Blood Indices - Mean Corpuscular Haemoglobin (MCH)

• The average quantity of haemoglobin per red blood cell.
• Normal range is 27-31 pg/cell.
• MCH = Haemoglobin (g/L) / RBC (cells/L).

Calculated Blood Indices - Mean Corpuscular Haemoglobin Concentration (MCHC)

• The average concentration of haemoglobin in a volume of red blood cells.
• Normal range is 32-36 g/dL or 32-36%.
• MCHC = MCH / MCV.

Summary of Main Points

• All blood cells originate from haematopoietic stem cells in bone marrow.
• Erythropoiesis, leukopoiesis, and thrombopoiesis are crucial processes.
• Rates of cell production and destruction are balanced.
• Common blood disorders include leukaemia, leukopenia, anaemias, haemochromatosis, and polycythemia.
• Blood tests, including CBC and calculated indices, are used for diagnosis.

Explore the crucial process of haematopoiesis in this quiz, focusing on the formation of blood cells in the foetus and after birth. Understand the pathways, factors affecting erythropoiesis, and the role of haematopoietic stem cells. Test your knowledge on key concepts and disorders related to blood indices and haematology tests.