Medical brain notes 30

  DISORDERS OF THE BLOOD  INTRODUCTION Blood is a protein-rich fluid called  plasma  in which erythrocytes and leukocytes, sometimes called red and white blood cells respectively, and platelets are suspended ( Figure 13.1 ). The cells constitute about 40–45% of the volume of the blood. The blood is pumped around the body by the heart through the arteries that supply the capillaries and is returned to the heart in the veins . The main functions of the blood are to distribute oxygen, nutrients and hormones and other signaling molecules between tissues and to remove carbon dioxide and other waste products. Plasma contains the proteins of the clotting system and of the immune systems. Plasma is blood from which the cells have been removed. It contains a range of plasma proteins in addition to the clotting and immune system proteins mentioned above, nutrients, such as glucose, waste materials, for example urea, and a range of electrolytes in solution. If it is allowed to ...

  BLOOD CELLS AND PLATELETS All of the cells of the blood originate from pluripotent stem cells in the bone marrow ( Figure 13.2 ). Chemical signals, such as cytokines , direct primordial stem cells to develop in different ways to produce  erythrocytes ,  leukocytes  of various types, and  megakaryocytes , which are the precursorsof  platelets . Normoblasts are erythroid cells that arise from divisions of pluripotent stem cells. Eventually these lose their nuclei giving rise to  reticulocytes,  which contain mRNAs for globins and are still able to synthesize hemoglobin (Hb), and which are the precursors of the erythrocytes. The reticulocytes circulate in the blood for 1 2 days before maturing to erythrocytes, and normally constitute 1   2% of the circulating red cells. Erythrocytes are the most numerous cells in the blood. Adult males and females have erythrocyte counts of about 5.5 and 4.8  s  10 12  dm –3 , respectively. The ...

  HEMOGLOBINS Hemoglobin is the red-colored, oxygen-transporting protein in erythrocytes. Its  M r  is about 64 000 and it is made up of four subunits, each containing an iron-containing heme group ( Figure 13.6 ). Each molecule can carry up to four O 2  molecules. Oxygen is taken up as the blood passes through the lungs and is transported to all parts of the body allowing respiration, the oxidation of fuels, to occur in the mitochondria. The iron in the heme group of Hb remains in the ferrous (Fe(II)) state throughout. Should the iron become oxidized to Fe(III),  methemoglobin  is formed, which is incapable of carrying oxygen. This oxidation happens to a small extent continuously, so that normal blood always contains a few percent of methemoglobin. However, methemoglobin reductase, present in erythrocytes, constantly catalyzes its reduction back to Hb. The rare individuals with a genetic deficiency of this enzyme have severe problems and tend to be cyanose...

  HEMOSTASIS AND BLOOD CLOTTING The circulatory system is self-sealing. Hemostasis rapidly stops all but the most catastrophic bleeding in normal individuals. If the lining of a blood vessel is damaged, eventually a platelet plug is formed that prevents further blood loss. Blood clotting is then initiated leading to the deposition of fibrin and the formation of a clot to seal the wound. Wound healing can then begin.   Blood clotting occurs in one of two pathways, the so-called intrinsic and extrinsic pathways. These pathways each have a number of unique reactions but, in the end, both pathways activate the final clotting stage, which is the formation of fibrin. The clotting pathways involve a group of plasma proteins that act in sequence, each activating the next in line. The end result is the conversion of soluble fibrinogen to the insoluble fibrin, which polymerizes to form a clot at the site of the damage and critically not elsewhere ( Figure 13.10 ). About 20 plasma protei...

  ANEMIAS Anemia develops when the amount of Hb in the blood falls below the reference levels for an individual’s age and sex ( Table 13.4 ) and there is insufficient iron for Hb synthesis. Anemia may be caused by major blood loss, or as a consequence of defects with Hb, the hemoglobinopathies, and by deficiencies of, for example, iron or some vitamins. The characteristic signs of anemia are pallor, tachycardia, a fast heart rate, cardiac failure and epithelial changes including brittle nails, spoon-shaped nails, atrophy of the tongue papillae, angular stomatitis and brittle hair. Other signs specific to the type of anemia may also be present. However, anemic patients may be asymptomatic, even when the anemia is quite severe, or may present with various nonspecific symptoms, such as fatigue, headache, breathlessness, angina on effort or palpitations . Rapid onset of anemia tends to cause more symptoms than slow onset, and the elderly tolerate anemia less well than the young when th...

  MICROCYTIC ANEMIAS The major causes of microcytic anemias are iron deficiency, thalassemias, sideroblastic anemia and the anemia of chronic disease. Iron is difficult to absorb because of problems connected with the low solubility of its salts, its oxidation state, and interaction with other components of the diet. Loss of iron also occurs in hemorrhage and menstruation. Iron deficiency anemia, the commonest cause of anemia worldwide, shows a number of characteristic features. The erythrocytes ( Figure 13.16 ) are microcytic, with an MCV of less than 80 fdm 3 , and hypochromic, the MCH being less than 27 pg. There is variation in, cell sizes, anisocytosis and poikilocytosis, that is abnormal shapes, and a reduced reticulocyte count. There are also changes in the bone marrow, for example erythroid hypoplasia and decreased iron deposits. The serum iron decreases while the serum iron binding capacity increases compared with their normal concentration ( Table 13.4 ). The transferrin ...

  MACROCYTIC ANEMIA Macrocytic anemias are characterized by the presence of anemia and erythrocytes of variable shapes but with diameters in excess of 9  L m and MCVs characteristically greater than 96 fdm 3  ( Table 13.4 ). The condition may be caused by certain liver diseases, including alcoholism, that produces large rounded cells or by megaloblastic anemia, which is associated with enlarged oval cells. The latter is also indicated by the presence of the erythrocyte precursors, erythroblasts (megaloblasts) in blood. The increased proportion of immature forms of all cell lines reflects the premature death of cells in the process of development ( Figure 13.17 ). The cells are large, although there is a substantial variation in size, and they have large, immature nuclei. The basis of the problem is the inability to synthesize deoxythymidine monophosphate from methylated deoxyuridine monophosphate. The methyl group is supplied by the folate coenzyme, methylene tetrahydrofo...