hematological diseases 1

• Functional anatomy and physiology of blood

  Blood flows throughout the body in the vascular system, and consists of: red cells, which transport oxygen from the lungs to the tissues; white cells, which defend against infection; platelets, which interact with blood vessels and clotting factors to maintain vascular integrity and prevent bleeding; plasma, which contains proteins with many functions, including antibodies and coagulation factors.
• Investigation of diseases of the blood

  Blood diseases are investigated by: 1. Full blood count (FBC), 2. Blood film examination, 3. Bone marrow examination, 4. Investigation of coagulation and bleeding disorders: Platelet count, Prothrombin time (PT), Activated partial thromboplastin time (APTT), Fibrinogen concentration, Monitoring anticoagulant therapy
• Full blood count (FBC)

  1. The Cell counts (numbers of circulating cells - RBCs, WBCs and Platelets), 2. The hematocrit (HCT)/Packed cell volume (PCV): the proportion of whole blood volume occupied by red cells, 3. The red cell indices give information about the size of red cells -mean cell volume (MCV) and the amount of hemoglobin present in the red cells -mean cell hemoglobin (MCH), 4. Concentration of hemoglobin (Hb) in blood, 5. Differential white blood cell count (in absolute numbers and percentages) of neutrophils, lymphocytes, monocytes, eosinophils and basophils. Method: automated blood analyzers using anticoagulated (EDTA) blood are widely used to obtain FBC. Spurious false results: a number of conditions can lead to false FBC results from autoanalyzers (e.g. reduced platelet count due to clot in the sample or platelet clumping; reduced hemoglobin as a result of Improper sample mixing, or blood taken from vein into which an infusion is flowing).
• Bone marrow examination


  In adults, bone marrow for examination is usually obtained from the posterior iliac crest. Methods to obtain bone marrow: 1. bone marrow aspiration (routinely used): to assess the composition and morphology of haematopoietic cells or abnormal infiltrates such as: A. To assess malignant disease- immunophenotyping, chromosome and molecular studies, B. for suspected tuberculosis-marrow culture. 2. trephine biopsy: is the removal of a small piece of bone with the marrow inside. It is preferred to assess marrow cellularity (aplastic anemia), marrow fibrosis, and infiltration by abnormal cells such as metastatic carcinoma.
• Haematopoiesis


  Haematopoiesis describes the formation of blood cells, an active process that must maintain normal numbers of circulating cells and be able to respond rapidly to increased demands such as bleeding or infection. During development, haematopoiesis occurs in the yolk sac, liver and spleen. In adults, normal haematopoiesis is restricted to the vertebrae, pelvis, sternum, ribs, clavicles, skull, upper humeri and proximal femora.
• Appearance of white blood cells

  • A Neutrophil, B Eosinophil, C Basophil, D Monocyte, E Lymphocyte
• Structural organisation of normal bone marrow

  Bone marrow contains a range of immature haematopoietic precursor cells and a storage pool of mature cells for release at times of increased demand. Haematopoietic cells interact closely with surrounding connective tissue stroma, made up of reticular cells, macrophages, fat cells, blood vessels and nerve fibres. In normal marrow, nests of red cell precursors cluster around a central macrophage, which provides iron and also phagocytoses nuclei from red cells prior to their release into the circulation. Megakaryocytes are large cells that produce and release platelets into vascular sinuses. White cell precursors are clustered next to the bone trabeculae; maturing cells migrate into the marrow spaces towards the vascular sinuses. Plasma cells are antibody-secreting mature B cells that normally represent less than 5% of the marrow population and are scattered throughout the intertrabecular spaces.
• Anaemia


  Anemia is a blood disorder in which the blood has a reduced ability to carry oxygen. This can be due to reduced number of RBC, a reduction in amount of hemoglobin, or abnormalities in hemoglobin that impair its function. It is a reduction in the level of haemoglobin in the blood below the reference range appropriate for age and sex. Other factors affecting the level of hemoglobin include pregnancy and altitude.
• Causes of anaemia


  • Decreased or ineffective marrow production: Lack of iron, vitamin B₁₂ or folate, Hypoplasia/myelodysplasia, Invasion by malignant cells, Renal failure, Anaemia of chronic disease. Normal marrow production but increased removal of cells: Blood loss, Hypersplenism, Haemolysis.
• Anemia: Classification


  Based on the size of red cells: Microcytic Hypochromic - Iron deficiency, Thalassemia, Sideroblastic, Chronic disease. Normochromic - Hereditary spherocytosis, Hereditary elliptocytosis, Paroxysmal nocturnal hemoglobinuria (PNH), G6PD deficiency. Macrocytic - Defective DNA synthesis: Vitamin B12 deficiency, Folate deficiency. Increased plasma lipids: Liver disease, Alcoholism, Hypothyroidism, Pregnancy, Hyperlipidemia. Aplastic anemia, Acute blood loss.
• Blood film: Macrocytic RBCs


  • Normal, Macrocytic RBCS
• Macrocytic RBCs


  Most RBCs larger than nucleus of normal lymphocytes. The causes of increased MCV are: Folate or Vit. B12 deficiencies, hyperlipidemia, alcoholism, liver disease
• Anemia: Diagnosis


  • case history, 2. clinical examination, 3. assessment of the FBC and blood film
• Anemia: Diagnosis - History

  I. Blood loss: Gastrointestinal blood loss, Menorrhagia. Dietary history should assess the intake of iron and folate which may become deficient in comparison to needs; B12 deficiency may be seen in pure vegetarians. II. Past medical history: can reveal a disease associated with anemia. III. Family history: Haemolytic anemias (haemoglobinopathies and hereditary spherocytosis), Pernicious anaemia. IV. Drug history: Aspirin, anti-inflammatory drugs, drugs that may cause haemolysis or aplasia.
• Anemia: Diagnosis - Clinical examination


  On clinical examination, as well as the general physical findings of anaemia (clinical exam blood) there may be specific findings related to the etiology of the anaemia. For example: 1. A patient may be found to have a right iliac fossa mass due to an underlying caecal carcinoma. 2. Haemolytic anaemias can cause jaundice. 3. Vitamin B12 deficiency may be associated with neurological signs, including peripheral neuropathy, dementia and signs of subacute combined degeneration of the cord. 4. Sickle-cell anaemia may result in leg ulcers, stroke or features of pulmonary hypertension.
• Anemia: Diagnosis - Symptoms & Signs

  The clinical features of anaemia reflect diminished oxygen supply to the tissues. Symptoms and signs help to indicate the clinical severity of anaemia. A full history and examination is needed to identify the underlying cause. A rapid onset of anaemia (e.g. due to blood loss) causes more profound symptoms than a gradually developing anaemia. Individuals with cardiorespiratory disease are more susceptible to symptoms of anaemia.
• Anemia: Diagnosis - FBC and blood film

  Schemes for the investigation of anaemias are often based on the size of the red cells, which is most accurately indicated by the MCV in the FBC. In the presence of anemia: 1. A normal MCV (normocytic anemia) suggests either acute blood loss or the anemia of chronic disease (ACD). 2. A low MCV (microcytic anemia) suggests iron deficiency or thalassemia. 3. A high MCV (macrocytic anemia) suggests vitamin B12 or folate deficiency.