1. Hemtology Lecture 10

2. Definition the study of blood, the blood-forming organs, and blood diseases. Hematology includes Etiology Diagnosis Treatment Prognosis Prevention of blood diseases that affect the production of blood Mechanism of coagulation.

3. Haematological tests are mainly used: – To investigate anaemia, – To investigate infections and pyrexia (fever) of unknown origin (PUO), – To investigate clinically important haemoglobinopathies, – To monitor patients receiving antiretroviral therapy (ART).

4. TESTS Measurement of haemoglobin and basic investigation of anaemia (Hb) Measurement of packed cell volume and calculation of red cell indices (PCV) White blood cell (WBC) count (TLC) Platelet count Differential WBC count (DLC) Reporting blood films: red cells, white cells, platelets Erythrocyte sedimentation rate Reticulocyte count

5. Investigation of sickle cell disease Blood film appearances in thalassaemia syndromes Haemoglobin electrophoresis Tests to screen for a bleeding disorder

6. Standard operating procedures SOPs are written, up to date instructions and information An SOP needs to include:  Value of test, i.e. reasons for performing it.  Principle of test, i.e. type of technology used.  Specimen details, including volume required, container to use  Equipment required: its use, performance checks, cleaning, maintenance and source of replacement parts.  Reagents or stains used

7. Control material Method of test including details of procedure, calculations, quality control Sources of error Reporting test result Verification of test result and action to take when a result is seriously abnormal or unexpected Interpretation of test result and when indicated, a reference range. Information on the cost of a test, e.g. high, medium, low.

8. Composition of blood Pale yellow fluid part plasma (55%) 95% water Solute part (proteins, mineral ions, organic molecules, hormones, enzymes, products of digestion, and waste products for excretion) Cellular part (45%) Red blood cell White blood cell Platelets

9. Main functions of the blood Transportation and distribution

10. Functions of blood Transportation and distribution (oxygen, carbondioxide, nutrients, hormones) Regulatory (buffer system with pH 7.35- 7.45, plasma osmotic pressure, temperature regulation) Protective (coagulation, leukocytes)

11. Blood cell formation All blood cells originate from a common population of pluripotent stem cells in the bone marrow. The pluripotent stem cells proliferate and differentiate into two distinct cell lines: myeloid and lymphoid. Myeloid stem cells: blood cell committed progenitor cells monocytes basophils neutrophils red cells Eosinophils platelets

12. Lymphoid stem cells lymphoid progenitor cells B & T lymphocytes Early development of B lymphocytes takes place in the bone marrow and lymphoid tissues, and development of T lymphocytes in the thymus.

13. Regulation of hematopoiesis Haematopoiesis is regulated by a range of cytokines (growth factors) which include interleukins, stem cell factors, colony stimulating factors, erythropoietin and thrombopoietin. They interact with specific receptors on the surface of haematopoietic cells, regulating the proliferation and differentiation of progenitor cells, and the maturation and functioning of mature cells.

14. Disorders of red blood cells Anaemia Haemoglobinopathies (thalassaemias, abnormal haemoglobins) Disorders due to red cell enzyme defects, e.g. G6PD deficiency Disorders due to red cell membrane defects, e.g. hereditary spherocytosis Polycythaemia

15. Morphologically anaemia can be classified by: Red cell size with the terms: – Normocytic referring to normal size red cells (approximately 8 μm in diameter), – Microcytic referring to smaller than normal red cells, – Macrocytic referring to larger than normal red cells.

16. Haemoglobinization of red cells with the terms: – Normochromic, describing normal staining of red cells as seen when haemoglobinization is adequate. The cells contain a small area of central pallor (no more than one third of the cell’s diameter) due to the biconcavity of red cells. Hypochromic, describing pale staining of red cells, as seen when haemoglobinization is inadequate. Hypochromic cells show an increased area of central pallor.

17. Structure of hemoglobin Adult type hemoglobin contains 4 polypeptide chains. two alpha (α) chains containing 141 amino acids two beta (β) chains containing 146 amino acids Each polypeptide chain is combined with an iron containing porphyrin pigment called haem which is the oxygen carrying part of the haemoglobin molecule.

19. THALASSAEMIA SYNDROMES Thalassaemia syndromes are inherited disorders caused by a reduction in the rate of synthesis of alpha (α) or beta (β) haemoglobin chains. Alpha thalassaemias are caused by defective synthesis of alpha (α) chains. Beta thalassaemias are caused by defective synthesis of beta (β) chains.

20. Significant imbalance in the synthesis of alpha and beta chains leads to: – Inadequate haemoglobin production and the red cells appear microcytic and hypochromic. – Accumulation of free uncombined globin chains in normoblasts and red cells, causing the destruction of red cell precursors in the bone marrow (ineffective erythropoiesis) and red cell destruction by the spleen.

21. ABNORMAL HAEMOGLOBINS HbS which has a wide distribution in tropical Africa, parts of India, the Caribbean, Mediterranean region and elsewhere in people of African descent. valine replaces glutamic acid in the beta globin chain HbC which is found only in West Africa and elsewhere in people of West African descent. glutamic acid is replaced by lysine in the beta globin chain

22. Hemoglobin D In HbSDPunjab disease there is moderate to severe haemolytic anaemia and the blood film is similar to that seen in sickle cell anaemia. HbE The blood film shows microcytosis and hypochromia with target cells