MD137 Haematology Lecture 2

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Questions and Answers

What is the primary location of haematopoiesis after birth?

Red bone marrow (correct)

Liver

Spleen

Peripheral blood

Which type of cells can haematopoietic stem cells differentiate into?

Committed progenitor cells (correct)

Plasma cells

Mature erythrocytes

Only lymphocytes

What primarily stimulates the differentiation of haematopoietic stem cells?

Mechanical stress

Hormones

Nutrients

Haematopoietic growth factors (correct)

Acute lymphoblastic leukaemia (ALL) is characterized by which of the following?

Presence of lymphoblasts Signup and view all the answers

What lineages can committed progenitor cells belong to?

Myeloid and lymphoid Signup and view all the answers

Which growth factor is known to primarily stimulate erythropoiesis?

Erythropoietin Signup and view all the answers

What role do stromal cells play in hematopoiesis?

They provide structural support in the marrow. Signup and view all the answers

Where does haematopoiesis mainly occur during fetal development?

Liver Signup and view all the answers

What is a significant characteristic of patients diagnosed with Acute Lymphoblastic Leukemia (ALL)?

Presence of 20% bone marrow lymphoblasts Signup and view all the answers

What happens to the nucleus of a pronormoblast during its differentiation into a mature erythrocyte?

It degenerates and is pinched off Signup and view all the answers

What is the primary stimulus for erythropoiesis?

Hypoxia Signup and view all the answers

Which of the following is a hallmark characteristic of Chronic Myeloid Leukemia (CML)?

High white blood cell and platelet counts Signup and view all the answers

What role does erythropoietin (EPO) play in erythropoiesis?

It binds to receptors on pronormoblasts in the bone marrow Signup and view all the answers

How long does the process of erythrocyte maturation typically take?

15 days Signup and view all the answers

What is the average lifespan of erythrocytes in the bloodstream?

120 days Signup and view all the answers

What does the increased presence of myeloid lineage cells indicate in a patient with CML?

Bone marrow is overcrowded with immature cells Signup and view all the answers

What does the Mean Corpuscular Volume (MCV) measure?

The average volume of red blood cells Signup and view all the answers

Which condition is indicated by an MCV value of less than 80 fL?

Microcytic anaemia Signup and view all the answers

What is the normal range for Mean Corpuscular Hemoglobin (MCH)?

27 – 31 pg/cell Signup and view all the answers

Which blood condition is usually associated with macrocytic cells?

Vitamin B12 deficiency Signup and view all the answers

What would a high Mean Corpuscular Hemoglobin Concentration (MCHC) indicate?

Increased hemoglobin content in red blood cells Signup and view all the answers

Which of the following tests is not a common haematology test?

Electrocardiogram (ECG) Signup and view all the answers

Haemoglobin concentration in the blood is typically measured in which unit?

g/dL Signup and view all the answers

What is the significance of the haematocrit value?

It measures the percentage of red blood cells in the blood. Signup and view all the answers

What is the role of haematopoietic stem cells?

They generate new blood cells in the bone marrow. Signup and view all the answers

Which of the following is a common blood disorder?

Leukaemia Signup and view all the answers

What is the most sensitive index of early iron deficiency?

Low ferritin level Signup and view all the answers

Which condition is characterized by the premature rupture of erythrocytes?

Haemolytic anaemia Signup and view all the answers

What does a deficiency in folic acid and Vitamin B12 impair?

DNA synthesis Signup and view all the answers

What is a characteristic finding in microcytic erythrocytes?

Low Mean Corpuscular Volume (MCV) Signup and view all the answers

What genetic mutation is commonly associated with haemochromatosis?

Mutation of the HFE gene Signup and view all the answers

What condition involves the overproduction of red blood cells and is classified as a myeloproliferative disorder?

Polycythemia Vera Signup and view all the answers

What is one of the earliest indications of iron overload in the body?

High transferrin saturation Signup and view all the answers

What dietary factor could lead to Vitamin B12 deficiency?

Strict vegan diet Signup and view all the answers

In megaloblastic anaemia, reticulocytes that survive to late stages are typically:

Fewer and larger Signup and view all the answers

What type of anaemia is primarily caused by significant blood loss?

Haemorrhagic anaemia Signup and view all the answers

Study Notes

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).

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Description

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.