Haematology Lecture 2: Haematopoiesis & Blood Indices

Haematology Lecture 2: Haematopoiesis & Blood Indices

• Haematopoiesis is the formation of blood cells
• In the foetus, haematopoiesis occurs in the liver, spleen, and blood
• After birth, haematopoiesis mainly occurs in red bone marrow
• Haematopoiesis requires interaction with stromal cells in the bone marrow
• Development and differentiation depend on specific growth factors and cytokines

Learning Objectives

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

Haematopoietic Stem Cells

• Self-renewing, multipotent stem cells residing in bone marrow
• Respond to haematopoietic growth factors (e.g., erythropoietin, colony-stimulating factors, interleukins)
• Capable of self-renewal and differentiation into committed progenitor cells
• Committed progenitors belong to myeloid or lymphoid lineages
• Lymphoid lineage gives rise to lymphocytes
• Myeloid lineage gives rise to other leukocytes, erythrocytes, and platelets

Acute Lymphoblastic Leukaemia (ALL)

• Diagnosis based on very high numbers of abnormal early-stage lymphoid precursor cells (lymphoblasts)
• Patients often have reduced neutrophils and decreased myeloid cells due to bone marrow overcrowding
• Diagnosis requires 20% bone marrow lymphoblasts

Chronic Myeloid Leukaemia

• Extremely high white blood cell (WBC) count and platelet count
• Mature white blood cells and normal red blood cells indicate early stage of differentiation
• Cancer arises during a later stage (chronic)
• Increased cells originate from the myeloid lineage
• Median age of diagnosis is 56, often asymptomatic

Erythropoiesis

• Erythrocytes (red blood cells) have a lifespan of 120 days
• 2.5 million erythrocytes are replaced every second
• Requires iron, vitamin B12, and folic acid
• Stimulated primarily by erythropoietin (EPO) produced by the kidneys in response to need
• EPO circulates in plasma with a 7-8-hour half-life
• EPO acts by binding to receptors on pronormoblasts in bone marrow

Iron

• Essential for haemoglobin synthesis and function
• Absorbed from the diet in the small intestine (only 1mg/day of the 15mg required is absorbed to replace lost iron)
• Remainder recycled from dead red blood cells
• 65% of body’s iron is in haemoglobin
• Stored as ferritin (a complex of protein and Fe²⁺)
• Free iron is transported in the blood as Fe³⁺ bound to transferrin

Iron-Deficiency Anaemia

• The most common type of anaemia
• Findings include low ferritin, possible low red blood cell count, low haemoglobin, low haematocrit, and microcytic/hypochromic erythrocytes
• Erythrocytes may be microcytic (low mean corpuscular volume (MCV))
• Erythrocytes can be hypochromic (low mean corpuscular haemoglobin (MCH) and mean corpuscular haemoglobin concentration (MCHC))
• Target cells and pencil cells may be observed

Folic Acid & Vitamin B12

• Essential for DNA synthesis
• Deficiency impairs DNA synthesis, causing normoblast apoptosis
• Deficiency resulting in larger, more immature reticulocytes (macrocytic erythrocytes, megaloblastic anaemia)
• Asynchronous maturation between cytoplasm and nucleus
• Vitamin B12 binds to intrinsic factor for absorption in the ileum
• Deficiency can be caused by dietary restrictions (strict vegan diet), age-related absorption problems, or autoimmune diseases (pernicious anaemia)

Other Blood Disorders

• Categories of anaemia: haemorrhagic (sudden or persistent blood loss), haemolytic (premature erythrocyte rupture), aplastic (bone marrow destruction or inhibition), etc
• Other blood disorders include leukaemia, leukopenia, various anaemias, haemochromatosis, and polycythemia

Haemochromatosis

• Iron overload, causing abdominal pain, weakness, fatigue, joint pain, liver disease, and endocrine/cardiac abnormalities
• High transferrin saturation is an early indication of the disease
• Commonly due to mutation in the HFE gene
• Autosomal recessive condition
• High prevalence in Ireland (1 in 5 carry the gene, 1 in 83 have both genes)
• Treatment involves regular phlebotomies

Polycythemia Vera

• Myeloproliferative disorder of red blood cells with overproduction of red blood cells
• Prevalence of 22 cases per 100,000
• Male-to-female ratio: 2:1
• Caused by an acquired genetic mutation leading to EPO oversensitivity
• Increased risk of thrombotic events (e.g., stroke, deep vein thrombosis)

Common Haematological Tests

• Complete blood count (CBC)
• Red blood cell (RBC) count
• Total/differential white blood cell (WBC) count
• Platelet count
• Haematocrit (packed cell volume)
• Haemoglobin (Hb%)
• Iron profile

Calculated Blood Indices

• Mean corpuscular volume (MCV) - average volume of red blood cells (normal range 80-100 fL)
• Mean corpuscular haemoglobin (MCH) - average haemoglobin per red blood cell (normal range 27-31 pg/cell)
• Mean corpuscular haemoglobin concentration (MCHC) - average concentration of haemoglobin per red blood cell (normal range 32-36 g/dL or 32-36%)

Summary of Main Points

• All blood cells originate from haematopoietic stem cells in bone marrow (myeloid and lymphoid lineages)
• Erythropoiesis, leukopoiesis, thrombopoiesis
• Rate of cell production equals rate of destruction
• Blood disorders include leukaemia, leukopenia, various anaemias, haemochromatosis, and polycythemia
• Blood tests and indices are used for diagnosis and monitoring. Some are directly measured while others are calculated.

Explore the intricacies of haematopoiesis and blood indices in this insightful quiz. Learn about the formation of blood cells, the role of haematopoietic stem cells, and key growth factors influencing erythropoiesis. Test your knowledge on associated blood disorders and haematology tests.