pathology - hematology

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  1. 1. 77 Lecture 4: Alterations in hematologic function Introduction The cardiovascular system consists of three interrelated components: Blood, the heart, and blood vessels. Blood is composed of two main components: a liquid portion called Plasma and a cellular portion containing red blood cells (erythrocytes), white blood cells (leukocytes) and platelet (thrombocytes). Blood contributes to homeostasis by transporting respiratory gasses (Oxygen & CO2), nutrients,ions and hormones to and from bodys cells. It helps regulate body pH and temperature, and provides protection through its clotting mechanisms and immune defenses
  2. 2. 78 Components of Blood Plasma (55%) 91 % Water 9 % Solutes : Plasma proteins 7% largest proportion of solutes
  3. 3. 79 Albumins 58 % of the proteins maintain osmotic (oncotic) pressure hold water in the blood Globulins 38 % - antibodies synthesized by plasma cells Clotting factors fibrinogen 4 % 2 % mineral salts, sugars, fats, hormones and vitamins. Blood Cells (45%) Three types Erythrocytes/RBCs Leukocytes/WBCs Thrombocytes/Platelets Plasma vs. Serum If the liquid part of blood is allowed to coagulate it is called serum - serum is just plasma without the clotting factors Serum is stable at room temperature and can be stored on a shelf. It is also used for diagnostic testing because it wont coagulate in the machine and mess it up (!) Physical Characteristics of Blood Heavier, thicker, and 3-4 X more viscous than water 38o C (100.4o F) pH : 7.35 7.45 4-6 liters in an adult Varies with electrolyte concentration and amount of adipose tissue Blood Volume Blood volume is about 8% of body weight. 1 kg of blood 1 L of blood 70 kg X 0.08 = 5.6 Kg = 5.6 L Plasma (~55% of volume). Cellular portion ( R.B.C ,W.B.C and Platelets) (~45% of volume) Hematopoiesis Hematopoiesis is the process by which blood cells are formed. All of the cellular components in blood are derived from a common precursor called a stem cell. In the maturing fetus, early production of erythrocytes (R.B.Cs) takes place in developing blood vessels.
  4. 4. 80 As gestation continues, the production of both red and white blood cells shifts to the fetal liver and spleen and eventually is localized primarily in the bone marrow. Hematopoiesis continues in the bone marrow after birth and is a lifelong process. A number of growth factors and cytokines are involved in regulating the process of hematopoiesis. A major regulator of red blood cell production is the hormone erythropoietin that is produced by the adult kidney. Erythropoietin is a glycoprotein released by cells of the kidney in response to the presence of hypoxia. The erythropoietin that is produced acts directly on stem cells in the bone marrow to promote the proliferation, maturation and release of new erythrocytes. Red Blood Cells Red blood cells are bi-concave discs. Mature RBCs don't have a nucleus or any protein making machinery and are destined to die in about 120 days. In a sense they are not really cells, but remnants of cells with a very specific purpose to carry O2 to the tissues of the body. The unique shape of the mature erythrocyte maximizes surface area and facilitates diffusion of oxygen across the cell membrane. Their shape also allows them to deform and fit in small capillary beds The cell membranes of normal red blood cells must be strong enough to survive transport under high pressure yet be flexible enough to fit through narrow and winding capillaries. A protein cytoskeleton provides a framework of support to the red blood cell membrane.
  5. 5. 81 Erythropoiesis Erythropoiesis is the part of hematopoiesis that deals with the production of RBCs. Erythropoiesis increases when states of hypoxia (O2 deficiency) stimulates the kidneys to release the hormone Erythropoietin (EPO) EPO circulates to the red marrow and speeds up the maturation and release of immature red cells (Reticulocytes) The rate of erythropoiesis is measured by the number of immature RBCs (called reticulocytes or retics) in the peripheral circulation A low retic count (2%) indicates a high rate of erythropoiesis Red Blood Cells & Glycolysis The characteristic RBC shape increases the cell surface area and gives them a high oxygen carrying capacity; because they lack mitochondria, they dont use any of the oxygen they carry. They rely primarily on glycolysis to meet their metabolic needs. Glycolysis (from glucose + -lysis degradation) is the metabolic pathway that converts glucose into pyruvate. The free energy released in this process is used to form the high- energy compounds ATP (adenosine triphosphate) and NADH (reduced nicotinamide adenine dinucleotide).
  6. 6. 82
  7. 7. 83 Hematopoiesis (The role of erythropoietin and hypoxia) Analysis of Blood Cells
  8. 8. 84 R.B.C & O2 The function of red blood cells is to transport oxygen to tissues. This is accomplished by the intracellular protein hemoglobin. The quaternary hemoglobin protein ( Globin portion) is composed of two and two subunits. Each of the subunits contains a central iron containing protein called a Heme protein (the pigment). It is the iron atom in the heme protein that binds to molecular oxygen. Oxygen binds to iron in heme (also CO) 23 % of CO2 is bound to globin portion As a result of the four iron-containing heme groups, each molecule of hemoglobin can carry four atoms of oxygen. Hemoglobin Types In the normal adult, hemoglobin A, which is composed of two alpha and two beta globins (a2 b2 ), is the most prevalent, comprising about 95% of all hemoglobin. Two minor hemoglobins also occur: Hemoglobin A2, composed of two alpha and two delta globins (a2 d2 ) comprises 2-3.5% of hemoglobin, while Hemoglobin F, composed of two alpha and two gamma globins (a2 g2 ), comprises less than 2% of hemoglobin. Hemoglobin F, or fetal hemoglobin, is produced by the fetus in uterus and until about 48 weeks after birth. Hgb F has a high oxygen-affinity in order to attract oxygen from maternal blood and deliver it to the fetus. After birth, the production of adult hemoglobin rapidly increases and fetal hemoglobin production drops off.
  9. 9. 85 RBC breakdown Healthy RBCs live about 120 days; the person breaks down about 174 million per minute RBCs are removed from circulation by the liver and spleen Broken down into heme and globin portions Globin is broken down into amino acids Iron is removed from heme and stored or recycled Heme is broken down into biliverdin and then into bilirubin Bilirubin is produced when the liver breaks down old red blood cells. Usually eliminated in bile. Bilirubin is then removed from the body through the stool (feces) and gives stool its normal brown color. Also it is responsible for the yellow color of bruises. To produce more RBCs, the body needs sufficient iron and amino acids as well as the vitamins folate (folic acid) and vitamin B12
  10. 10. 86 Anemia Anemia is a condition in which there is a reduced number of red blood cells or decreased concentration of hemoglobin in those cells or both. Anemia is often a manifestation of some disease process or abnormality within the body. Although there are many causes of anemia, the actual mechanism by which the anemia results is generally due to : 1- Decreased red cell production, which may be due to lack of nutrient (B12, folic acid, iron) or bone marrow failure. 2- Increased red cell destruction secondary to hemolysis. 3- Increased red cell loss caused by acute or chronic bleeding. Anemias may be classified according to cause or effect on red cell morphology Terms that end with cytic refer to cell size, and those that end in chromic refer to hemoglobin content. Additional terms: Anisocytosis various sizes Poikilocytosis various shapes General manifestations of anemia A major feature of anemia is a reduced capacity for the transport of oxygen to tissues. This reduced oxygen delivery can result in the following:
  11. 11. 87 Ischemia Fatigability Breathlessness upon exertion Exercise intolerance Pallor Increased susceptibility to infection Classification of Anemia Based on Red Cell Morphology
  12. 12. 88 Iron Lab Studies Ferritin : Storage protein of iron Transferrin : o Plasma protein that transports iron to the bone marrow o What is measured with serum iron TIBC : Total Iron Binding Capacity o What degree of transferrin is open for binding of iron Iron Studies in Various Disease States
  13. 13. 89 Morphological classification of anemia Types of Anemia We will study: 1) Hemolytic anemia 2) Blood loss anemia 3) Iron-deficiency anemia 4) Cobalamin-deficiency or folate-deficiency anemia 5) Inherited anemia a. sickle cell anemia and b. thalassemia
  14. 14. 90 6) Aplastic anemia 7) Sideroblastic anemia Hemolytic anemia Anemia that results from excess destruction of red blood cells (hemolysis) Factors that may cause hemolysis include the following: o Autoimmune destruction of red blood cells o Certain drugs (example: quinine) or toxins o Cancers such as lymphoma and leukemia o Rheumatoid arthritis o Certain viral infections (parvovirus) o Parasitic infections (malaria) Blood loss anemia Anemia that results from acute blood loss. With acute loss of large amounts of blood, shock is the major concern. With chronic loss of smaller amounts of blood, iron deficiency is a chief concern. Causes of acute and chronic blood loss may include the following: o Trauma and hemorrhage o Malignancy o Peptic ulcers Iron-deficiency anemia Iron-deficiency anemia is a major cause of anemia worldwide. It can occur as a result of iron-deficient diets. Vegetarians are at particular risk for iron deficiency as are menstruating or pregnant women due to increased requirement for iron. Iron-deficiency anemia may also result from poor absorption of iro

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