Constituents of the blood: Red and white blood cells Dr D J Hampshire University of Sheffield

Two phases of the blood Cellular component (45%) Haematocrit 0.45 Red cells White cells Platelets Plasma Fluid component (55%) Haematocrit 0.45

Haematopoiesis Formation of the blood cells Mature cells with a finite life span Red cells 120 days Anucleate White cells ~6 hours Platelets 7-10 days Anucleate

Haematopoiesis Precursors of mature cells derive from bone marrow Precursor cells are not found in the blood Adults Axial skeleton Children All bones In utero Yolk sac Liver and Spleen

Haematopoiesis Precursor cell = Stem cells Pluripotent: replicate and differentiate Red cells White cells Platelets Stem cells vital for marrow transplantation

Haematopoiesis Replication and differentiation stimulated by hormonal growth factors Red cells Erythropoietin (EPO) White cells Granulocyte-colony stimulating factor (G-CSF) Platelets Thrombopoietin (THPO)

Membrane encloses glycolysis enzymes and haemoglobin Red blood cells (RBC) Simple cells No nucleus No mitochondria Membrane encloses glycolysis enzymes and haemoglobin 4 x 1012 / L Have 5L blood

Haemoglobin (Hb) Carries oxygen from lungs to tissues Allows oxygen to reversibly combines with iron (Fe2+) in an aqueous environment Tetrameric protein 2 α-chains 2 β-chains Image obtained from the Protein Data Bank (http://wwpdb.org/)

Anaemia Symptoms Signs Tiredness / Lethargy / Malaise Shortness of breath on exertion Reduced exercise tolerance Angina and claudication Symptoms of underlying cause Pallor Pale mucus membranes and palmar creases Glossitis / Angular stomatitis Signs of underlying cause

Acute anaemia Bleeding resulting in loss of RBC and plasma Low Hb (normal range 12.5-15.5 g/dL) Haematocrit 0.45

Low Hb (normal range 12.5-15.5 g/dL) Chronic anaemia Loss of RBC Low Hb (normal range 12.5-15.5 g/dL) Haematocrit 0.20

Iron deficiency anaemia Iron necessary for Hb production Lack of iron leads to reduced RBC production Caused by: Poor diet, malabsorption, bleeding Low Hb (normal range 12.5-15.5 g/dL) Mean cell volume (red cell size) <80 fL (normal range 82-96 fL)

Macrocytic anaemia RBC MCV >100 fL results in macrocytosis Macrocytosis caused by liver disease, alcohol and hypothyroidism Macrocytic anaemia caused by vitamin B12 or folate deficiency

B12 and folate Required for DNA synthesis Affects all dividing cells Manifests first in bone marrow as this is the most active source of dividing cells Pancytopenia (decreased RBC, WBC and platelets)

Deficiency can result from: B12 deficiency B12 absorbed from terminal ileum B12 requires an intrinsic factor from gastric parietal cells Deficiency can result from: Lack of gastric parietal cells Lack of terminal ileal function

Pernicious anaemia Autoimmune disease Antibodies against gastric parietal cells and intrinsic factor Results in achlorhydria and B12 malabsorption

Folate deficiency Folate found in fruit / veg and food supplements Deficiency can result from: Malabsorption Poor diet Increased requirement (haemolysis, psoriasis)

Haemolysis Normal or increased RBC production Cells have a life span <30 days (normal 120 days) Increases haem turnover leading to jaundice and anaemia

Causes of haemolysis Acquired Congenital Autoantibodies against RBC Fragmentation by mechanical heart valve Intravascular thrombosis in DIC Hereditary spherocytosis (affects RBC membrane) Pyruvate kinase deficiency (affects RBC survival) Sickle cell / thalassaemia (affect Hb)

White blood cells (WBC) Neutrophils Eosinophils Monocytes Basophils Lymphocytes

Neutrophils Most numerous type of white cell Phagocytose bacteria and foreign material Release chemotaxins and cytokines important in the inflammatory response Lack of number or function results in recurrent bacterial infections

Monocytes Macrophages Dendritic cells Phagocytose bacteria and foreign material Present antigens to the immune system

Lymphocytes B lymphocytes T lymphocytes Named after the bone marrow Generate antibodies when stimulated by foreign antigens Named after the thymus Aid B cells and also generate cellular or cell-mediated immunity

T lymphocytes Helper cells (CD4+) Cytotoxic cells (CD8+) Suppress / regulate the immune response Target damaged / infected cells for death

Basophils Relatively rare in peripheral blood Migrate to tissues becoming mast cells Mast cells filled with histamine containing granules and express surface IgE Important role in immunity and allergic response

Eosinophils Also rare in peripheral blood Important role in inflammation and allergic response Special role in protection against parasites

Acute leukaemia Precursor cells (usually found in the bone marrow) proliferate without differentiation Normal bone marrow cells replaced Leads to: Anaemia, neutropenia and thrombocytopenia

Acute myeloblastic leukaemia (AML) Acute lymphocytic leukaemia (ALL) Acute leukaemia Acute myeloblastic leukaemia (AML) Acute lymphocytic leukaemia (ALL) Proliferation of myeloblasts (neutrophil precursor) Primarily of adults: 50% survive 5 years Treatment: Cyclical high dose chemo Bone marrow transplant Proliferation of lymphoblasts (lymphocyte precursor) Primarily of childhood: >80% cured Treatment: Cyclical chemo over 2-3 yr Transplantation (if relapse)

High-grade lymphoma Malignant tumour developing from lymphocytes Classified as Hodgkin lymphoma or Non- Hodgkin lymphoma Usually affects lymph nodes but spreads Treat with aggressive chemo or with radiotherapy (if localised)