Haematopoiesis

BONE MARROW STRUCTURE

• Principal organ of adult haematopoiesis
• Formed element of the blood
• RBC, WBC, PLT
• Produced in the bone marrow from a common pluripotent stem cell
• Stem cell: Self-renewal. Differentiates.
• Regulators: Complex microenvironment of stromal cells, growth factors
• Bone marrow
• Haematopoietic cells. Fat cells. Stromal cells
• Different places, different times
• 6w feral life: yolk sac
• 6-14w fetal life: liver & spleen
• 24w feral life onwards: bone marrow
• Children
• Active haematopoiesis in axial skeleton and lon bones
• Marrow more cellular
• Adults
• Fat replaces cellular bone marrow
• Haematopoiesis: Axial skeleton
• 1/2 marrow for blood cell production
• 1/2 marrow taken up by fat
• Disease states
• Marrow cellularity increased
• Long bone active again in haematopoiesis
• Extramedullary haematopoiesis
• Liver and spleen recruited into blood cell production as in feral life
• Organomegaly
• e.g. Myeloproliferative disorders. Thalassaemias (intermedia, major)

THE HAEMOPOIETIC PROCESS

• Bone marrow
• Stem cell
• Common pluripotent. Self-renewal
• Progenitor cells
• In presence of growth factors
• Maturation
• Peripheral blood
• Red cell lose nucleus prior to release into blood
• Platelets from megakaryocyte
• Role of growth factors
• Regulators: Cell-cell and cell-matrix interactions. Growth factors.
• Growth factors
• From endothelial cells, fibroblasts, monocytes, lymphocytes
• Early stage haematopoiesis
• Stem cell factors (SCF)
• Promotes stem cell proliferation
• Affect all cell lines
• Mature cells
• Lineage specifics
• Granulocyte colony-stimulating factor (G-CSF)
• Colony stimulating factors
• G-CSF. GM-CSF
• Shorten duration of neutropenia
• Erythropoietin (EPO)
• Control erythropoiesis
• Produced in kidneys
• Reduced O2 delivery ￫ Cortex of kidney ￫ Erythropoietin
• Controlled by negative feedback loop
• Reduced O2 delivery
• Anaemia: Increased red cell until Hb concentration increases and O2 delivery to kidney back to normal
• Hypoxia ￫ Reduced oxygen to peritubular cells ￫ EPO release ￫ Increased RBC without anaemia ￫ Polycythaemia
• Renal tumour ￫ EPO ￫ Polycythaemia