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

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

3. 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

4. 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

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

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

7. 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

8. 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 (

9. 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

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

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

12. 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 g/dL)
Mean cell volume (red cell size) <80 fL
(normal range fL)

13. 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

14. 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)

15. 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

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

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

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

19. 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)

20. White blood cells (WBC)
Neutrophils
Eosinophils
Monocytes
Basophils
Lymphocytes

21. 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

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

23. 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

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

25. 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

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

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

28. 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)

29. 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)