MD137 Haematology Lecture 2

Haematology Lecture Notes

• MD137 Haematology, Lecture 2
• Lecturer: Dr. Louise Horrigan
• Topic: Haematopoiesis and Blood Indices

Learning Objectives

• Understand the pathways of haematopoiesis
• Learn about disorders of haematopoiesis
• Study erythropoiesis
• Examine factors impacting erythropoiesis
• Review haematology tests
• Understand calculated blood indices

Haematopoiesis

• The formation of new blood cells (erythropoiesis, leukopoiesis, thrombopoiesis)
• In the fetus, haematopoiesis occurs in the liver, spleen, and blood.
• After birth, primarily in red bone marrow.
• Requires interaction with stromal cells in the bone marrow.
• Development and differentiation of blood cells depend on specific growth factors and cytokines.
• Haematopoiesis predominantly occurs in the bone marrow. This is found in both the cortical (hard bone) and trabecular (spongy bone) regions of bones.

Haematopoietic Stem Cells

• Self-renewing multipotent stem cells
• Located in bone marrow
• Respond to haematopoietic growth factors (e.g., erythropoietin, colony-stimulating factors, interleukins).
• Capable of both self-renewal and differentiation into committed progenitor cells.
• Committed progenitor cells belong to either the myeloid or lymphoid lineages.

Myeloid Lineage

• Gives rise to all other leukocytes (e.g., neutrophils, eosinophils, basophils), erythrocytes, and platelets.
• Specific stages: Myeloblast, Erythroblast, Megakaryoblast, Monoblast

Lymphoid Lineage

• Gives rise to lymphocytes (e.g., B cells, T cells).
• Specific stages: common lymphoid progenitor, pro-B cells, Pro T cells

Acute Lymphocytic Leukemia (ALL)

• Diagnosis based on a high number of abnormal, early-stage lymphoid precursor cells (lymphoblasts) in the bone marrow.
• Patients often have reduced neutrophil counts and decreased counts of other cells from the myeloid lineage due to overcrowding in the bone marrow.
• Diagnosis includes at least 20% bone marrow lymphoblasts.

Chronic Myeloid Leukemia (CML)

• Characterized by an extremely high white blood cell (WBC) count and high platelet count.
• Mature white blood cells and red blood cells appear normal, which suggests early stage of differentiation.
• A later stage of differentiation results in uncontrolled cell proliferation.
• Mean Diagnosis age is 56.

Erythropoiesis

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

Process of Erythropoiesis

• Myeloid stem cell differentiates into a pronormoblast
• Early normoblasts produces huge ribosomes
• Haemoglobin synthesis and iron accumulation occur during early normoblast differentiation.
• When haemoglobin accumulates, organelles are ejected and the nucleus degenerates.
• Cell collapses into a biconcave shape.
• Process takes 15 days.
• Reticulocyte enters bloodstream.
• Within 2 days, ribosomes degraded by enzymes and mature erythrocyte is formed

Hypoxia as Erythropoiesis Stimulus

• Hypoxia is the main stimulus for erythropoiesis.
• Hypoxia induces an increase in the transcription of erythropoietin (epo) messenger RNA (mRNA).

Iron

• Essential for haemoglobin synthesis and function.
• Absorbed from the diet in the small intestine.
• Only about 1 mg of the required 15 mg per day is absorbed to replace lost iron.
• Remainder is recycled from dead red blood cells.
• 65% of the body's iron is in haemoglobin.
• Remainder is stored in the liver, spleen, and bone marrow as ferritin (complex of protein and Fe³⁺).
• Free iron is transported in the blood as Fe³⁺ bound to transferrin.

Iron-Deficiency Anemia

• Common type of anemia.
• Findings include low ferritin (sensitive index of early iron deficiency), possible low red blood cell count, low hemoglobin, and low hematocrit.
• Erythrocytes may be microcytic (low MCV), and hypochromic (low MCH and MCHC).
• Possible presence of target cells and pencil cells (on microscopic analysis).

Folic Acid and Vitamin B12

• Both required for DNA synthesis.
• Deficiency impairs DNA synthesis, causing normoblast apoptosis.
• Deficiency can lead to macrocytic erythrocytes (megaloblastic anaemia), asynchrony in maturation between cytoplasm and nucleus.
• Vitamin B12 from food binds to intrinsic factor in stomach & absorbed in ileum; deficiency can be age-related or due to dietary factors (strict vegan diet) or autoimmune disease (pernicious anemia).

Other Blood Disorders and Blood Indices

• Includes conditions like anemia, leukemias, leukopenia, haemochromatosis, polycythemia.
• Common blood tests are complete blood cell count (CBC), RBC count, total/differential WBC count, platelet count, hematocrit, hemoglobin level, and iron profile.
• Rouleaux effect: Stacking of red blood cells in blood

Calculated Blood Indices

• Mean Corpuscular Volume (MCV): Average volume of a red blood cell (normal range: 80-100 fL).
• Mean Corpuscular Haemoglobin (MCH): Average amount of haemoglobin per red blood cell ((normal range: 27-31 pg/cell).
• Mean Corpuscular Haemoglobin Concentration (MCHC): Average concentration of haemoglobin within a red blood cell ((normal range: 32-36 g/dL).

Other Types of Anemia

• Haemorrhagic anemia: Due to blood loss (either sudden or persistent)
• Haemolytic anemia: Erythrocytes rupture prematurely due to various factors (e.g. abnormalities, transfusion mismatch, infections)
• Aplastic anemia: Destruction or inhibition of bone marrow (due to chemicals, radiation, viruses)
• Sickle Cell Anemia (next lecture): Discussed later (not in detail in this lecture)

Haemochromatosis

• Iron overload
• Symptoms include abdominal pain, weakness, fatigue, joint pain, liver disease, endocrine and cardiac abnormalities.
• High transferrin saturation is an early indicator.
• Mostly due to HFE gene mutation.
• Autosomal recessive condition.
• High prevalence in people of Irish descent (1 in 5 carry the gene; 1 in 83 have both genes).
• Treatment involves regular phlebotomies.

Polycythemia Vera

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

This quiz explores key concepts in haematology, focusing on haematopoiesis and blood indices as discussed in the second lecture of the MD137 course. Students will delve into the pathways, disorders, and factors affecting the production of blood cells. Understanding these fundamentals is essential for future clinical practice.