Pathophysiology of Blood Cells PDF

Dr Makinde Vincent OLUBIYI PATHOPHYSIOLOGY OF RED BLOOD AND WHITE BLOOD Dr Makinde Vincent OLUBIYI CELLS, AND PLATELETS Dr Makinde V. OLUBIYI Dr Makinde Vincent OLUBIYI Outline P...

Dr Makinde Vincent OLUBIYI PATHOPHYSIOLOGY OF RED BLOOD AND WHITE BLOOD Dr Makinde Vincent OLUBIYI CELLS, AND PLATELETS Dr Makinde V. OLUBIYI Dr Makinde Vincent OLUBIYI Outline Pathophysiology of red blood cells (Anaemia and Polycythaemia) Haemoglobinopathies Dr Makinde Vincent OLUBIYI Pathophysiology of white blood cells Pathophysiology of platelets Dr Makinde Vincent OLUBIYI ANAEMIA Anaemia is a condition in which the number of red blood cells (RBCs) or haemoglobin concentration within them is lower than normal The normal red blood count is 5.2 million (±300,000) per Dr Makinde Vincent OLUBIYI mm3 in men and 4.7 million (±300,000) per mm3 in women Types of anaemia include: 1) Blood loss anaemia 2) Aplastic anaemia 3) Megaloblastic anaemia 4) Haemolytic anaemia Dr Makinde Vincent OLUBIYI Blood loss anaemia This occurs after rapid haemorrhage. thus resulting in a low concentration of red blood cells. Usually, the body replaces the fluid portion of the plasma in 1 to 3 Dr Makinde Vincent OLUBIYI days, but red blood cell concentration usually returns to normal within 3 to 6 weeks. When chronic blood loss occurs, a person cannot absorb enough iron from the intestines to form haemoglobin as rapidly as it is lost. Thus the red blood cells produced are smaller than normal and contains too little haemoglobin. This further gives rise to microcytic, hypochromic anaemia.  Dr Makinde Vincent OLUBIYI Aplastic anaemia This is due to damage to or loss of the functional constituent of the bone marrow. Causes: Exposure to high-dose radiation or chemotherapy Dr Makinde Vincent forOLUBIYI cancer treatment High doses of some toxic chemicals like insecticides or benzene in gasoline, may also cause aplastic anaemia. Autoimmune disorders: the immune system begins attacking healthy cells such as bone marrow stem cells, which may lead to aplastic anemia. Idiopathic aplastic anaemia: in about half of aplastic anaemia cases the cause is unknown. Treatment: blood transfusion and bone marrow transplantation Dr Makinde Vincent OLUBIYI Dr Makinde Vincent OLUBIYI  Dr Makinde Vincent OLUBIYI Megaloblastic Anaemia This is usually occurs due to deficiency of vitamin B12, folic acid, and intrinsic factor from the stomach mucosa Megaloblastic anaemia often develops in patients who have intestinal sprue (a malabsorption disease), in whichDrfolic acid, vitamin B12, and Makinde Vincent OLUBIYI other vitamin B compounds are poorly absorbed. As Vitamin B12 and folic acid is essential for the maturation of red blood cells, thus in megaloblastic anaemia, the red blood cells (RBCs) grow too large, with odd shapes, and are called megaloblasts. Also, the megaloblasts have fragile membranes, thus they rupture easily, resulting in reduction in the number of normal RBCs. Dr Makinde Vincent OLUBIYI Pernicious anaemia It can be regarded as a type of megaloblastic anaemia that is caused by atrophy of the stomach mucosa or loss of the entire stomach after surgical gastrectomy. Intrinsic factor is produced by gastric glands andVincent Dr Makinde it is OLUBIYI important for the absorption of Vitamin B12 Thus loss of stomach mucosa thus compromises the adequate production of intrinsic factor which invariably reduces adequate absorption of Vitamin B12 Deficiency of B12 then causes the production of immature red blood cells referred to as megaloblasts.  Dr Makinde Vincent OLUBIYI Haemolytic Anaemia Different abnormalities of the RBCs make the cells fragile, so they rupture easily Even though the number of RBCs formed may be normal, the life span of the fragile RBC is so short that the cells areDrdestroyed Makinde Vincentfaster OLUBIYI than they can be formed, and thus anaemia results. For example: In hereditary spherocytosis, the RBCs are very small and spherical. These cells cannot withstand compression forces because they do not have the normal loose, bag-like, biconcave disk shaped cell membrane structure of normal RBCs. Upon passing through capillaries, especially through that of the spleen, they are easily ruptured by even slight compression. Dr Makinde Vincent OLUBIYI In sickle cell anaemia, the cells have an abnormal type of haemoglobin called haemoglobin S When haemoglobin S is exposed to low concentrations of oxygen, it precipitates into long crystals inside the RBC. These crystals elongate the cell and give it the appearance of a sickle rather than Dr Makinde Vincent OLUBIYI the normal biconcave disk. The precipitated haemoglobin also damages the cell membrane, so the cells become highly fragile leading to serious anaemia. Sickle cell patients often experience moments of “crisis,” in which low oxygen tension in the tissues causes sickling, which leads to ruptured RBCs, which causes a further decrease in oxygen tension and still more sickling and RBC destruction. Some moments of crisis can lead to death. Dr Makinde Vincent OLUBIYI Dr Makinde Vincent OLUBIYI Dr Makinde Vincent OLUBIYI In erythroblastosis foetalis, Rh-positive RBCs in the fetus are attacked by antibodies from an Rh-negative mother. These antibodies make the Rh-positive cells fragile, leading to rapid rupture and causing the child to be born with a serious case of anaemia. Dr Makinde Vincent OLUBIYI The extremely rapid formation of new RBCs to make up for the destroyed cells in erythroblastosis foetalis causes a large number of immature RBCs to be released from the bone marrow into the blood.  Dr Makinde Vincent OLUBIYI POLYCYTHAEMIA (ERYTHROCYTOSIS) Polycythaemia is a condition characterized by an abnormal increase in the number of red blood cells or haemoglobin concentration in the blood There are two types of polycythaemia: polycythaemia vera and secondary polycythaemia Dr Makinde Vincent OLUBIYI 1) Polycythaemia vera (primary polycythaemia) It is a pathological condition caused by a mutation in the bone marrow cells that produce red blood cells leading to an uncontrolled production of red blood cells There is also excess production of white blood cells and platelets Due to increased haematocrit, there is an increase in blood viscosity, leading to sluggish blood flow There is also an increase in the total blood volume. Dr Makinde Vincent OLUBIYI Dr Makinde Vincent OLUBIYI  Dr Makinde Vincent OLUBIYI 2) Secondary Polycythaemia This occurs whenever the tissues become hypoxic because of too little oxygen in the breathed air (such as at high altitudes), or because of failure of oxygen delivery to the tissues (such as in cardiac failure) This triggers an increased production of red blood cells (RBC) Dr Makinde Vincent OLUBIYI above normal The RBC count commonly rises to about 30 percent above normal. A common type of secondary polycythaemia is called physiological polycythaemia This occurs in natives who live at high altitudes where the atmospheric oxygen is very low. The low atmospheric oxygen tension causes an increased in RBC count which allows the efficient performance of the inhabitants inspite of the little availability of oxygen in the air.  Dr Makinde Vincent OLUBIYI HAEMOGLOBINOPATHIES Haemoglobinopathies are genetic disorders affecting the structure or production of the haemoglobin molecule Haemoglobinopathies can be broadly divided into: structural Dr Makinde Vincent OLUBIYI haemoglobinopathies and thalassemia 1) Thalassemia This is a condition caused by a reduced production of haemoglobin. The chains are normal in structure but produced in decreased amounts or absent There are two main types of thalassemia: Alpha thalassemia: reduction in the production of alpha globin chains Beta thalassemia: reduction in the production of beta globin chains. Dr Makinde Vincent OLUBIYI 2) Structural hemoglobinopathies These are caused by production of abnormal globin polypeptide chains Examples include: Sickle Cell Disease (HbS): it is Dr the Makindemost common structural Vincent OLUBIYI hemoglobinopathy. the α chains are normal but in the β chain valine is substituted for glutamic acid. This leads to to sickle-shaped red blood cells, causing vaso-occlusion and haemolysis. Haemoglobin C (HbC): it is due to a substitution of lysine for glutamic acid in the β-globin chain. It can lead to mild haemolytic anaemia. Haemoglobin E (HbE): it is caused by a substitution of lysine for glutamic acid at in the β-globin chain. It is common in Southeast Asia and can cause mild anaemia. Dr Makinde Vincent OLUBIYI PATHOPHYSIOLOGY OF WHITE BLOOD CELLS The normal white blood cell count is 4000–11,000 per mL Dr Makinde Vincent OLUBIYI Leukopenia Also called leukocytopenia, is a condition in which the body has a lower-than-normal number of white blood cells (WBCs) in its blood. This condition leaves the body unprotected against many bacteria and other agents that might invade the tissues. Irradiation of the body by x-rays or gamma rays, or exposure to drugs and chemicals that contain benzene or anthracene nuclei, is likely to cause aplasia of the bone marrow thus leading to leukopenia Dr Makinde Vincent OLUBIYI Dr Makinde Vincent OLUBIYI Dr Makinde Vincent OLUBIYI Leukaemia It is a condition characterized by increased numbers of abnormal white blood cells (WBCs) in the circulating blood. There are two types of leukaemia viz: lymphocytic and myelogenous. Dr Makinde Vincent OLUBIYI Lymphocytic leukaemia: caused by cancerous production of lymphoid cells, usually beginning in a lymph node or other lymphocytic tissue and spreading to other areas of the body. Myelogenous leukaemia: begins by cancerous production of young myelogenous cells in the bone marrow and then spreads throughout the body so that WBCs are produced in many extramedullary tissues— especially in the lymph nodes, spleen, and liver. Dr Makinde Vincent OLUBIYI Dr Makinde Vincent OLUBIYI Dr Makinde Vincent OLUBIYI In myelogenous leukaemia, the cancerous process occasionally produces partially differentiated cells, resulting in what might be called neutrophilic, eosinophilic, basophilic or monocytic leukemia. The first effect of leukemia is metastatic growth of leukemic cells in abnormal areas of the body. Dr Makinde Vincent OLUBIYI Leukemic cells from the bone marrow may reproduce so greatly that they invade the surrounding bone, causing pain and, eventually, a tendency for bones to fracture easily. Almost all leukemias eventually spread to the spleen, lymph nodes, liver, and other vascular regions, regardless of whether the origin of the leukemia is in the bone marrow or the lymph nodes. Common effects in leukemia are the development of infection, severe anaemia, and a bleeding tendency caused by thrombocytopenia (lack of platelets). Dr Makinde Vincent OLUBIYI These effects result mainly from displacement of the normal bone marrow and lymphoid cells by the nonfunctional leukemic cells. Another effect of leukaemia is excessive use of metabolic substrates by the growing cancerous cells. Thus, while the leukemic tissues grow, other tissues become debilitated. Dr Makinde Vincent OLUBIYI After metabolic starvation has continued long enough, this factor alone is sufficient to cause death. Dr Makinde Vincent OLUBIYI Allergy and hypersensitivity In some conditions, there are some undesirable side effects of immunity which is referred to as allergy or immune hypersensitivity. There are several types of allergy and other hypersensitivities broadly Dr Makinde Vincent OLUBIYI classified as: 1) Delayed-reaction allergy 2) Atopic allergies  Dr Makinde Vincent OLUBIYI 1) Delayed-reaction allergy It is caused by activated T cells. For example: the toxin of poison ivy in itself does not cause much harm to the tissues. However, upon repeated exposure, it causes the formation of activated helper and cytotoxic T cells. Dr Makinde Vincent OLUBIYI The activated T cells diffuse from the circulating blood in large numbers into the skin to respond to the poison. T-cells trigger cell-mediated type of immune reaction, which involves the release of many toxic substances from the activated T cells, as well as invasion of the tissues by macrophages causing serious tissue damage. The damage normally occurs in the tissue area where the antigen is present, such as in the skin in the case of poison ivy, in the lungs to cause lung edema or asthmatic attacks in the case of some airborne antigens.  Dr Makinde Vincent OLUBIYI 2) Atopic allergies This is associated with excess IgE antibodies These allergies are called atopic allergies because they are caused by a non-ordinary response of the immune system (an unnecessary, excessive or abnormal immune response). Dr Makinde Vincent OLUBIYI This allergic tendency is genetically passed from parent to child and is characterized by the presence of large quantities of IgE antibodies in the blood. These antibodies are called reagins or sensitizing antibodies When an allergen enters the body, an allergen-reagin reaction takes place and a subsequent allergic reaction occurs. A special characteristic of the IgE antibodies (the reagins) is a strong propensity to attach to mast cells and basophils  Dr Makinde Vincent OLUBIYI A single mast cell or basophil can bind a lot of IgE antibodies, thus, when an antigen (an allergen) binds with several IgE antibodies that are already attached to a mast cell or basophil, this causes immediate change in the membrane of the mast cell or basophil Many of the mast cells and basophils rupture and thus release substances like histamine, protease, slow-reacting substance Dr Makinde of anaphylaxis, Vincent OLUBIYI eosinophil chemotactic substance, neutrophil chemotactic substance, heparin, and platelet activating factors. These substances causes a number of responses e.g. dilation of the local blood vessels; attraction of eosinophils and neutrophils to the reactive site; increased permeability of the capillaries with loss of fluid into the tissues; and contraction of local smooth muscle cells. The tissue responses that occurs depends on the type of tissue in which the allergen-reagin reaction occurs.  Dr Makinde Vincent OLUBIYI Pathophysiology of platelets The normal platelet count is 300,000/μL Thrombocytopenia It is defined as the presence of very low numbers Dr Makinde Vincent OLUBIYI in the of platelets circulating blood. Causes: Decreased production of platelets due to bone marrow suppression in aplastic anemia or leukemia Increased destruction of platelets (e.g. immune thrombocytopenia). Trapping of platelets caused by splenomegaly Liver cirrhosis: due to reduced production of thrombopoietin Drug-induced thrombocytopenia (e.g., from heparin or chemotherapy). Dr Makinde Vincent OLUBIYI People with thrombocytopenia have a tendency to bleed, as seen in hemophilia, except that the bleeding is usually from many small venules or capillaries, rather than from larger vessels Small punctate haemorrhages occur throughout all the body tissues. Dr Makinde Vincent OLUBIYI The skin displays many small, purplish blotches, giving the disease the name thrombocytopenic purpura. Dr Makinde Vincent OLUBIYI Thrombocytosis (High Platelet Count): A condition caused by increased platelet count above normal Causes: Primary (essential) thrombocythemia: it is due to a rare blood Dr Makinde Vincent OLUBIYI cancer (myeloproliferative disorder) in which excess blood cells including platelets are produced Secondary (reactive): Occurs as a physiological response to an underlying condition e.g. inflammation, infection, iron deficiency, or splenectomy. It can result in thrombosis