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  • Speticemia(blood poisoning)
  • 1- wbcs are only formed elements that are complete cells 2- rbcs remain in blood stream while wbcs can slip out--- diapedesis (Leaping across) , Monocytes and Neutorphils can do this 3- mature cells– neutorphils– attack bacteria and viruses even in blood stream 4- Immature cells– monocytes—little ability to fight infections---but after entering tissues can change into Macrophages that are capable of combating pathogens
  • PHSC: a primitive, undifferentiated form of blood cell from which erythroblasts, lymphoblasts, myeloblasts, and other immature blood cells are derived, capable of self-renewal An early branching of the pathway divides the lymphoid stem cells which produce lymphocytes from the myeloid stem cells which give rise to all other formed elements.
  • 1-Thrombopoietin (leukemia virus oncogene ligand, megakaryocyte growth and development factor) , also known as THPO , is a glycoprotein hormone produced mainly by the liver and the kidney that regulates the production of platelets by the bone marrow . It stimulates the production and differentiation of megakaryocytes , the bone marrow cells that fragment into large numbers of platelets .[1] 2-In the liver it is produced by parenchymal cells and sinusoidal endothelial cells. In the kidney it is made by proximal convoluted tubule cells. Along with these it is made by striated muscle and stromal cells in the bone marrow . [1] In the liver, its production is augmented by interleukin 6 (IL-6). [1] Reference: Kaushansky K (2006). "Lineage-specific hematopoietic growth factors". N. Engl. J. Med. 354 (19): 2034–45. doi : 10.1056/NEJMra052706 . PMID 16687716 .
  • i- The Bone Marrow Doesn't Make Enough Platelets Bone marrow is the sponge-like tissue inside the bones. It contains stem cells that develop into red blood cells, white blood cells, and platelets. When stem cells are damaged, they don't grow into healthy blood cells. Several conditions or factors can damage stem cells. Cancer Cancer, such as leukemia (lu-KE-me-ah) or lymphoma (lim-FO-ma), can damage the bone marrow and destroy blood stem cells. Cancer treatments, such as radiation and chemotherapy, also destroy the stem cells. Aplastic Anemia Aplastic anemia is a rare, serious blood disorder in which the bone marrow stops making enough new blood cells. This lowers the number of platelets in your blood. Toxic Chemicals Exposure to toxic chemicals, such as pesticides, arsenic, and benzene, can slow the production of platelets. Medicines Some medicines, such as diuretics and chloramphenicol, can slow the production of platelets. Chloramphenicol (an antibiotic) is rarely used in the United States. Common over-the-counter medicines, such as aspirin or ibuprofen, also can affect platelets. Alcohol Alcohol also slows the production of platelets. A temporary drop in platelets is common among heavy drinkers, especially if they're eating foods that are low in iron, vitamin B12, or folate. Viruses Chickenpox, mumps, rubella, Epstein-Barr virus, or parvovirus can decrease your platelet count for a while. People who have AIDS often develop thrombocytopenia. Genetic Conditions Some genetic conditions, such as Wiskott-Aldrich and May-Hegglin syndromes, can cause low numbers of platelets in the blood. 2-The Body Destroys Its Own Platelets A low platelet count can occur even if the bone marrow makes enough platelets. The body may destroy its own platelets due to autoimmune diseases, certain medicines, infections, surgery, pregnancy, and some conditions that cause too much blood clotting. Autoimmune Diseases With autoimmune diseases, the body's immune system destroys its own platelets. One example of this type of disease is called idiopathic thrombocytopenic purpura , or ITP. In most cases, the body's immune system is thought to cause ITP. Normally, your immune system helps your body fight off infections and diseases. But if you have ITP, your immune system attacks and destroys its own platelets—for an unknown reason. Other autoimmune diseases that destroy platelets include lupus and rheumatoid arthritis. Medicines A reaction to some medicines can confuse your body and cause it to destroy its platelets. Any medicine can cause this reaction, but it happens most often with quinine, antibiotics that contain sulfa, and some medicines for seizures, such as Dilantin,® vancomycin, and rifampin. Heparin is a medicine commonly used to prevent blood clots. But an immune reaction may trigger the medicine to cause blood clots and thrombocytopenia. This condition is called heparin-induced thrombocytopenia (HIT). HIT rarely occurs outside of a hospital. In HIT, the body's immune system attacks a substance formed by heparin and a protein on the surface of the platelets. This attack activates the platelets and they start to form blood clots. Blood clots can form deep in the legs , or a clot can break loose and travel to the lungs . Infection A low platelet count can occur after blood poisoning from a widespread bacterial infection. A virus, such as mononucleosis or cytomegalovirus, also can cause a low platelet count. Surgery Platelets can be destroyed when they pass through man-made heart valves, blood vessel grafts, or machines and tubing used for blood transfusions or bypass surgery . Pregnancy About 5 percent of pregnant women develop mild thrombocytopenia when they're close to delivery. The exact cause isn't known for sure. Rare and Serious Conditions That Cause Blood Clots Some diseases can cause a low platelet count. Two examples are thrombotic thrombocytopenic purpura (TTP) and disseminated intravascular clotting (DIC). TTP is a rare blood condition. It causes blood clots to form in the body's small blood vessels, including vessels in the brains, kidneys, and heart. DIC is a rare complication of pregnancy, severe infections, or severe trauma. Tiny blood clots form suddenly throughout the body. In both conditions, the blood clots use up many of the blood's platelets. The Spleen Holds On to Too Many Platelets Usually, one-third of the body's platelets are held in the spleen. If the spleen is enlarged, it will hold on to too many platelets. This means that not enough platelets will circulate in the blood. An enlarged spleen is often due to severe liver disease—such as cirrhosis (sir-RO-sis) or cancer. Cirrhosis is a disease in which the liver is scarred. This prevents it from working properly. An enlarged spleen also may be due to a bone marrow condition, such as myelofibrosis (MI-eh-lo-fi-BRO-sis). With this condition, the bone marrow is scarred and isn't able to make blood cells.
  • 1- Males: Testosteron from leyding cells of testes, Increased BMR, increased oxygen demand, causes tissue hypoxia (low oxygen), this results in increased Erythropoietin release from kidneys (90%) (Juxta glumerular cells or mesangial cells) and liver (10%). Increased EPO, increased proerythroblasts formation from stem cells so increased RBCs. Females: Less testosteron so less RBCs. Infants: Greater need of oxygen as all their tissues are under a rapid growing process.
  • 1- Basophil- A cell, especially a white blood cell, having granules that stain readily with basic dyes. 2-Polycrhromatophil- A young or degenerated red blood cell staining with acid, neutral, or basic dyes. Also called polychromatic cell , polychromatocyte . adj. Staining readily with acid, neutral, or basic dyes. 3- Orthochromatic - Sensitive to all colors except red. Staining with the same color as that of the dye used. Used of a cell or tissue.
  • 1- Supravital dyes: Relating to or capable of staining living cells after their removal from a living or recently dead organism.
  • Other cells that arise from monocyte are Osteoclast, Microglia – CNS, Langerhans cells – Epidermis, Kupffer cells - Liver
  • Water soluble vitamins 1-Vitamin C (Ascorbic Acid) B1 (Thiamine), B2 (Riboflavin), B3 (Niacinamide, Niacin), B5 (Pantothenic acid), B6 (Pyridoxine), B7 (Biotin), B9 (Folic Acid (Folate) B12 (Cobolamine),
  • 1 -The heme of their hemoglobin is split off from globin. Its core of iron is salvaged, bound to protein (as ferritin or hemosiderin), and stored for reuse. The balance of the heme group is degraded to bilirubin (bil″i-roo′bin), a yellow pigment that is released to the blood and binds to albumin for transport. Bilirubin is picked up by liver cells, which in turn secrete it (in bile) into the intestine, where it is metabolized to urobilinogen. Most of this degraded pigment leaves the body in feces, as a brown pigment called stercobilin. The protein (globin) part of hemoglobin is metabolized or broken down to amino acids, which are released to the circulation. Disposal of hemoglobin spilled from red blood cells to the blood (as occurs in sickle-cell anemia or hemorrhagic anemia) takes a similar but much more rapid course to avoid toxic buildup of iron in blood. Released hemoglobin is captured by the plasma protein haptoglobin and the complex is phagocytized by macrophages.
  • 1- Hemostatic Imbalance: Rnal dialysis (Low EPO) Athletes Doping: 45%-65% , so blood becomes Thick, sticky sludge that can cause clotting, stroke, heart failure. Dehydration
  • 1- 10 AA of delta chain are different from beta chain. 2- 37 AA of gamma chain are different from beta chain in sequence. And has less positive charges as compared to beta chain so less reaction with 2,3-BPG or DPG. 2,3-bisphosphoglycerate reacts with Hb in adults and reduces its binding affinity to O2 Fetal hemoglobin's affinity for oxygen is substantially greater than that of adult hemoglobin. Notably, the P50 value for fetal hemoglobin (i.e., the partial pressure of oxygen at which the protein is 50% saturated; lower values indicate greater affinity) is roughly 19  mmHg , whereas adult hemoglobin has a value of approximately 26.8 mmHg. As a result, the so-called "oxygen saturation curve", which plots percent saturation vs. pO2, is left-shifted for fetal hemoglobin in comparison to the same curve in adult hemoglobin.
  • There are small amounts of hemoglobin A derivatives closely associated with hemoglobin A that represent glycated hemoglobins. One of these, hemoglobin A1c (HbA1c), has a glucose attached to the terminal valine in each β chain and is of special interest because the quantity in the blood increases in poorly controlled diabetes mellitus
  • 2,3-bisphosphoglycerate reacts with Hb in adults and reduces its binding affinity to O2 Fetal hemoglobin's affinity for oxygen is substantially greater than that of adult hemoglobin. Notably, the P50 value for fetal hemoglobin (i.e., the partial pressure of oxygen at which the protein is 50% saturated; lower values indicate greater affinity) is roughly 19 mmHg, whereas adult hemoglobin has a value of approximately 26.8 mmHg. As a result, the so-called "oxygen saturation curve", which plots percent saturation vs. pO2, is left-shifted for fetal hemoglobin in comparison to the same curve in adult hemoglobin.
  • 1-There are two copies of the α globin gene on human chromosome 16. In addition, there are five globin genes in tandem on chromosome 11 that encode β, γ, δ (Delta), ζ (zeeta), ε (epsilon) globin chains
  • When an abnormal gene inherited from one parent, when the individual is heterozygous—half the circulating hemoglobin is abnormal and half is normal. When identical abnormal genes are inherited from both parents,  homozygous all of the hemoglobin is abnormal. Many of the abnormal hemoglobins are harmless. However, some have abnormal O2 equilibriums. Others cause anemia. For example, hemoglobin S polymerizes at low O2 tensions, and this causes the red cells to become sickle-shaped, hemolyze, and form aggregates that block blood vessels. The result is the severe hemolytic anemia known as sickle cell anemia. Heterozygous individuals have the sickle cell trait and rarely have severe symptoms, but homozygous individuals develop the full-blown disease. The sickle cell gene is an example of a gene that has persisted and spread in the population. It originated in the black population in Africa, and it confers resistance to one type of malaria. This is an important benefit in Africa, and in some parts of Africa 40% of the population have the sickle cell trait. In the United States black population its incidence is about 10%. Hemoglobin F has the ability to decrease the polymerization of deoxygenated hemoglobin S, and hydroxyurea causes hemoglobin F to be produced in children and adults. It has proved to be a very valuable agent for the treatment of sickle cell disease. In patients with severe sickle cell disease, bone marrow transplantation has been carried out and the patients have generally done well, though more study is needed.
  • Iron Metabolism and Erythropoiesis Roughly 2/3 of the body’s iron pool (ca. 2 g in women and 5 g in men) is bound to hemoglobin (Hb). About 1/4 exists as stored iron (ferritin, hemosiderin), the rest as functional iron (myoglobin, iron-containing enzymes). Iron losses from the body amount to about 1 mg/day in men and up to 2 mg/day in women due to menstruation, birth, and pregnancy. Iron absorption occurs mainly in the duodenum and varies according to need . The absorption of iron supplied by the diet usually amounts to about 3 to 15% in healthy individuals, but can increase to over 25% in individuals with iron deficiency. A minimum daily iron intake of at least 10–20 mg/day is therefore recommended (women > children > men). Iron absorption Heme-Fe++: Fe(II) supplied by the diet (hemoglobin,myoglobin found chiefly in meat and fish) is absorbed relatively efficiently as a heme-Fe(II) upon protein cleavage. With the aid of hemeoxygenase , Fe in mucosal cells cleaves from heme and oxidizes to Fe(III). The tri-ferric form either remains in the mucosa as a ferritin-Fe(III) complex and returns to the lumen during cell turnover or enters the bloodstream. Non-heme-Fe can only be absorbed as Fe2+. Therefore, non-heme Fe+++ must first be reduced to Fe2+ by ferrireductase (FR;) and ascorbate on the surface of the luminal mucosa . Fe2+ is probably absorbed through secondary active transport via an Fe2+-H+ symport carrier (DCT1) (competition with Mn2+, Co2+, Cd2+, etc.). A low chymous pH is important since it (a) increases the H+ gradient that drives Fe2+ via DCT1 into the cell and (b) frees dietary iron from complexes. The absorption of iron into the bloodstream is regulated by the intestinal mucosa . When an iron deficiency exists, aconitase (an iron-regulating protein) in the cytosol binds with ferritin- mRNA, thereby inhibiting mucosal ferritin translation. As a result, larger quantities of absorbed Fe(II) can enter the bloodstream.Fe(II) in the blood is oxidized to Fe(III) by ceruloplasmin (and copper). It then binds to apotransferrin , a protein responsible for iron transport in plasma . Transferrin (= apotransferrin loaded with 2 Fe +3 ), is taken up by endocytosis into erythroblasts and cells of the liver, placenta, etc. with the aid of transferrin receptors . Once iron has been released to the target cells, apotransferrin again becomes available for uptake of iron from the intestine and macrophages. Iron storage and recycling Ferritin ,( Ferritin is a globular protein complex consisting of 24 protein subunits and is the main intracellular iron storage protein in both prokaryotes and eukaryotes , keeping it in a soluble and non-toxic form. Ferritin which is not combined with iron is called apoferritin ). one of the chief forms in which iron is stored in the body, occurs mainly in the intestinal mucosa, liver, bone marrow, red blood cells, and plasma. It contains binding pockets for up to 4500 Fe3+ ions and provides rapidly available stores of iron (ca. 600 mg), whereas iron mobilization from hemosiderin is much slower (250mg Fe in macrophages of the liver and bone marrow). Hb-Fe and heme-Fe released from malformed erythroblasts (so-called inefficient erythropoiesis) and hemolyzed red blood cells bind to haptoglobin and hemopexin, respectively. They are then engulfed by macrophages in the bone marrow or in the liver and spleen, respectively, resulting in 97% iron recycling . An iron deficiency inhibits Hb synthesis, leading to hypochromic microcytic anemia: MCH "26 pg, MCV "70 fL, Hb "110 g/L. The primary causes are: ! blood loss (most common cause); 0.5mg Fe are lost with each mL of blood; ! insufficient iron intake or absorption; ! increased iron requirement due to growth, pregnancy, breast-feeding, etc.; ! decreased iron recycling (due to chronic infection); ! apotransferrin defect (rare cause). Iron overload most commonly damages the liver, pancreas and myocardium (hemochromatosis). If the iron supply bypasses the intestinal tract (iron injection),the transferrin capacity can be exceeded and the resulting quantities of free iron can induce iron poisoning. B12 vitamin (cobalamins) and folic acid are also required for erythropoiesis (! B ). Deficiencies lead to hyperchromic anemia (decreased RCC, increased MCH). The main causes are lack of intrinsic factor (required for cobalamin resorption) and decreased folic acid absorption due to malabsorption (see also p. 260) or an extremely unbalanced diet. Because of the large stores available, decreased cobalamin absorption does not lead to symptoms of deficiencyuntil many years later, whereas folic acid deficiency leads to symptoms within a few months.
  • Fucose is a hexose deoxy sugar with the chemical formula C6H12O5. It is found on N -linked glycans on the mammalian , insect and plant cell surface Ceramides are a family of lipid molecules.
  • It now appears that type O individuals have a single-base deletion in their corresponding gene. This creates an open reading frame, and consequently they produce a protein that has no transferase activity.
  • 1- An important problem related to the Rh factor occurs in pregnant Rh– women who are carrying Rh+ babies. The first such pregnancy usually results in the delivery of a healthy baby. But, when bleeding occurs as the placenta detaches from the uterus, the mother may be sensitized by her baby’s Rh+ antigens that pass into her bloodstream. If so, she will form anti-Rh antibodies unless treated with RhoGAM before or shortly after she has given birth. (The same precautions are taken in women who have miscarried or aborted the fetus.) RhoGAM is a serum containing anti-Rh agglutinins. Because it agglutinates the Rh factor, it blocks the mother’s immune response and prevents her sensitization. If the mother is not treated and becomes pregnant again with an Rh+ baby, her antibodies will cross through the placenta and destroy the baby’s RBCs, producing a condition known as hemolytic disease of the newborn, or erythroblastosis fetalis. The baby becomes anemic and hypoxic. In severe cases, brain damage and even death may result unless transfusions are done before birth to provide the fetus with more erythrocytes for oxygen transport. Additionally, one or two exchange transfusions (see Related Clinical Terms) are done after birth. The baby’s Rh+ blood is removed, and Rh– blood is infused. Within six weeks, the transfused Rh– erythrocytes have been broken down and replaced with the baby’s own Rh+ cells.
  • When an endothelial injury occurs, platelets adhere to subendothelial collagen fibers (! A1 ) bridged by von Willebrand’s factor (vWF), which is formed by endothelial cells and circulates in the plasma complexed with factor VIII. Glycoprotein complex GP Ib/IX on the platelets are vWF receptors. This adhesion activates platelets (! A2 ). They begin to release substances (! A3 ), some of which promote platelet adhesiveness (vWF). Others like serotonin, platelet- derived growth factor (PDGF) and thromboxane A2 (TXA2) promote vasoconstriction. Vasoconstriction and platelet contraction slow the blood flow. Mediators released by platelets enhance platelet activation and attract and activate more platelets: ADP, TXA2, platelet-activating factor (PAF). The shape of activated platelets change drastically (! A4 ). Discoid platelets become spherical and exhibit pseudopodia that intertwine with those of other platelets. This platelet aggregation (! A5 ) is further enhanced by thrombin and stabilized by GP IIb/IIIa. Once a platelet changes its shape, GP IIb/IIIa is expressed on the platelet surface, leading to fibrinogen binding and platelet aggregation. GP IIb/IIIa also increases the adhesiveness of platelets, which makes it easier for them to stick to subendothelial fibronectin.
  • Prothrombin and Thrombin. Prothrombin is a plasma protein, an alpha2-globulin, having a molecular weight of 68,700. It is present in normal plasma in a concentration of about 15 mg/dl. It is an unstable protein that can split easily into smaller compounds, one of which is thrombin , which has a molecular weight of 33,700, almost exactly one half that of prothrombin. Prothrombin is formed continually by the liver, and it is continually being used throughout the body for blood clotting. If the liver fails to produce prothrombin, in a day or so prothrombin concentration in the plasma falls too low to provide normal blood coagulation. Vitamin K is required by the liver for normal formation of prothrombin as well as for formation of a few other clotting factors. Therefore, either lack of vitamin K or the presence of liver disease that prevents normal prothrombin formation can decrease the prothrombin level so low that a bleeding tendency results.
  • DIC: Under homeostatic conditions, the body is maintained in a finely tuned balance of coagulation and fibrinolysis. The activation of the coagulation cascade yields thrombin that converts fibrinogen to fibrin; the stable fibrin clot being the final product of hemostasis. The fibrinolytic system then functions to break down fibrinogen and fibrin. Activation of the fibrinolytic system generates plasmin (in the presence of thrombin), which is responsible for the lysis of fibrin clots. The breakdown of fibrinogen and fibrin results in polypeptides called fibrin degradation products (FDPs) or fibrin split products (FSPs). In a state of homeostasis, the presence of thrombin is critical, as it is the central proteolytic enzyme of coagulation and is also necessary for the breakdown of clots, or fibrinolysis. In DIC, the processes of coagulation and fibrinolysis lose control, and the result is widespread clotting with resultant bleeding. Regardless of the triggering event of DIC, once initiated, the pathophysiology of DIC is similar in all conditions. One critical mediator of DIC is the release of a transmembrane glycoprotein called tissue factor (TF). TF is present on the surface of many cell types (including endothelial cells, macrophages, and monocytes) and is not normally in contact with the general circulation, but is exposed to the circulation after vascular damage. For example, TF is released in response to exposure to cytokines (particularly interleukin 1), tumor necrosis factor, and endotoxin. This plays a major role in the development of DIC in septic conditions. TF is also abundant in tissues of the lungs, brain, and placenta. This helps to explain why DIC readily develops in patients with extensive trauma. Upon activation, TF binds with coagulation factors that then trigger both the intrinsic and the extrinsic pathways of coagulation. The release of endotoxin is the mechanism by which Gram-negative sepsis provokes DIC. In acute promyelocytic leukemia, treatment causes the destruction of leukemic granulocyte precursors, resulting in the release of large amounts of proteolytic enzymes from their storage granules, causing microvascular damage. Other malignancies may enhance the expression of various oncogenes that result in the release of TF and plasminogen activator inhibitor-1 (PAI-1), which prevents fibrinolysis. Excess circulating thrombin results from the excess activation of the coagulation cascade. The excess thrombin cleaves fibrinogen, which ultimately leaves behind multiple fibrin clots in the circulation. These excess clots trap platelets to become larger clots, which leads to microvascular and macrovascular thrombosis. This lodging of clots in the microcirculation, in the large vessels, and in the organs is what leads to the ischemia, impaired organ perfusion, and end-organ damage that occurs with DIC. Coagulation inhibitors are also consumed in this process. Decreased inhibitor levels will permit more clotting so that a feedback system develops in which increased clotting leads to more clotting. At the same time, thrombocytopenia occurs because of the entrapment and consumption of platelets. Clotting factors are consumed in the development of multiple clots, which contributes to the bleeding seen with DIC. Simultaneously, excess circulating thrombin assists in the conversion of plasminogen to plasmin, resulting in fibrinolysis. The breakdown of clots results in excess amounts of FDPs, which have powerful anticoagulant properties, contributing to hemorrhage. The excess plasmin also activates the complement and kinin systems. Activation of these systems leads to many of the clinical symptoms that patients experiencing DIC exhibit, such as shock, hypotension, and increased vascular permeability. The acute form of DIC is considered an extreme expression of the intravascular coagulation process with a complete breakdown of the normal homeostatic boundaries. DIC is associated with a poor prognosis and a high mortality rate.
  • Vitamin K is required by the liver cells for production of the clotting factors, and because vitamin K is produced by bacteria that reside in the intestines, dietary deficiencies are rarely a problem. However, vitamin K deficiency can occur if fat absorption is impaired, because vitamin K is a fat-soluble vitamin that is absorbed into the blood along with fats. In liver disease, the nonfunctional liver cells fail to produce not only the procoagulants but also bile, which is required for fat and vitamin K absorption.
  • Sideroblastic Anemia: The body has iron available, but cannot incorporate it into hemoglobin. Sideroblasts are seen, which are nucleated erythrocytes with granules of iron in their cytoplasm. Cause: The common feature of these causes is a failure to completely form heme molecules, whose biosynthesis takes place partly in the mitochondrion . This leads to deposits of iron in the mitochondria that form a ring around the nucleus of the developing red blood cell . Sometimes the disorder represents a stage in evolution of a generalized bone marrow disorder that may ultimately terminate in acute leukemia. Toxins: lead or zinc poisoning Drug-induced: ethanol , isoniazid , chloramphenicol , cycloserine Nutritional: pyridoxine or copper deficiency Genetic: ALA synthase deficiency ( X-linked , associated with ALAS2 ) Myelophthisic anemia is a normocytic-normochromic anemia that occurs when normal marrow space is infiltrated and replaced by nonhematopoietic or abnormal cells. Causes include tumors, granulomatous disorders, and lipid storage diseases.
  • About Blood From Rtibloodinfo

    1. 1. Blood
    2. 2. Blood <ul><li>Blood is the “river of life” </li></ul><ul><li>Viscous fluid composed of cells and plasma </li></ul><ul><li>Blood is a specialized type of connective tissue in which living blood cells, (formed elements), are suspended in a non living fluid matrix called plasma. </li></ul><ul><ul><ul><li>Cellular Part (Formed Elements) </li></ul></ul></ul><ul><ul><ul><li>Non cellular part (Plasma) </li></ul></ul></ul>
    3. 3. Blood <ul><ul><ul><li>1/12 th of body weight </li></ul></ul></ul><ul><ul><ul><li>8 % of total body weight </li></ul></ul></ul><ul><li>Color range </li></ul><ul><ul><li>Oxygen-rich blood is scarlet red bright crimson </li></ul></ul><ul><ul><li>Oxygen-poor blood is dull red </li></ul></ul><ul><li>pH must remain between 7.35–7.45 </li></ul><ul><li>Temp 38 c or 100.4 F </li></ul>
    4. 4. Blood Composition <ul><li>Blood Composition </li></ul><ul><ul><li>Cellular Part (Formed Elements)--- 45% </li></ul></ul><ul><ul><ul><li>RBCs, Red blood cells or erythrocytes </li></ul></ul></ul><ul><ul><ul><li>WBCs, white blood cells or Leukocytes </li></ul></ul></ul><ul><ul><ul><li>Platelets (thromobocytes) </li></ul></ul></ul><ul><ul><li>Non cellular Portion (plasma)--- 55% </li></ul></ul><ul><ul><ul><li>Fluid part (91-92%)--- water </li></ul></ul></ul><ul><ul><ul><li>Solid part (8%-9%) </li></ul></ul></ul>
    5. 5. Composition of plasma <ul><li>Straw colourd fluid </li></ul><ul><li>Contains over 100 solutes </li></ul><ul><li>Organic substances </li></ul><ul><ul><li>Plasma Proteins (Approx 7%) </li></ul></ul><ul><ul><ul><li>Albumin </li></ul></ul></ul><ul><ul><ul><li>Globulin </li></ul></ul></ul><ul><ul><ul><li>Fibrinogin </li></ul></ul></ul><ul><ul><ul><li>Prothrombin </li></ul></ul></ul><ul><ul><ul><li>Plasma complement system, approx 20 proteins </li></ul></ul></ul><ul><ul><li>Nitrogenous substances </li></ul></ul><ul><ul><ul><li>Urea </li></ul></ul></ul><ul><ul><ul><li>Uric acid </li></ul></ul></ul><ul><ul><ul><li>Ammonia </li></ul></ul></ul><ul><ul><li>Non-nitrogenous substances </li></ul></ul><ul><ul><ul><li>carbohydrates </li></ul></ul></ul><ul><ul><ul><li>Lipids </li></ul></ul></ul><ul><ul><li>Enzymes </li></ul></ul><ul><ul><ul><li>Amylase </li></ul></ul></ul><ul><ul><ul><li>Carbonic Anhydrase </li></ul></ul></ul><ul><ul><li>Pigments (Biluribin) </li></ul></ul>
    6. 6. Composition of plasma <ul><li>Inorganic substances </li></ul><ul><ul><ul><li>Different ions </li></ul></ul></ul><ul><ul><ul><li>Sodium </li></ul></ul></ul><ul><ul><ul><li>Potassium </li></ul></ul></ul><ul><ul><ul><li>Bi-carbonate </li></ul></ul></ul>
    7. 7.
    8. 8. Functions of plasma <ul><li>Helps in transport of substances in the body </li></ul><ul><li>Maintains colloid osmotic pressure of blood </li></ul><ul><li>Causes blood clotting because it contains the fibrinogen and prothrombin </li></ul><ul><li>Stores proteins for supply in needs </li></ul><ul><li>Helps in maintaining blood pressure and blood viscosity </li></ul><ul><li>Contains antibodies and antitoxins </li></ul>
    9. 9. Physical Properties of Blood and plasma <ul><li>Specific Gravity of plasma is 1.024 </li></ul><ul><li>Specific Gravity of blood is 1.055 - 1.062 </li></ul><ul><li>Male: 1.057 </li></ul><ul><li>Female: 1.053 </li></ul><ul><li>Blood is 5 times thicker or viscous than distilled water. </li></ul><ul><li>Blood----- blood cells </li></ul><ul><li>Plasma----Plasma Proteins </li></ul><ul><li>Relative viscosity of water, plasma and blood are </li></ul><ul><li>1, 1.8, 4.7 respectively. </li></ul><ul><li>Plsama-(clotting factor and fibrinogen) = serum </li></ul>
    10. 10. <ul><li>Blood performs a number of functions. </li></ul><ul><ul><li>Distribution </li></ul></ul><ul><ul><li>Regulation </li></ul></ul><ul><ul><li>Protection </li></ul></ul><ul><ul><ul><ul><ul><li>Distribution Functions </li></ul></ul></ul></ul></ul><ul><ul><ul><li>Nutritive Function: </li></ul></ul></ul><ul><ul><ul><ul><li>Nutrients from GIT to whole body </li></ul></ul></ul></ul><ul><ul><ul><li>Respiratory Function: </li></ul></ul></ul><ul><ul><ul><ul><li>O 2 and Co 2 Transport </li></ul></ul></ul></ul><ul><ul><ul><li>Excretory Function: </li></ul></ul></ul><ul><ul><ul><ul><li>Metabolic Wastes to kidneys </li></ul></ul></ul></ul><ul><ul><ul><li>Transport Function: </li></ul></ul></ul><ul><ul><ul><ul><li>Enzymes </li></ul></ul></ul></ul><ul><ul><ul><ul><li>Hormones </li></ul></ul></ul></ul><ul><ul><ul><ul><li>Vitamins </li></ul></ul></ul></ul>Functions of blood
    11. 11. Functions of blood <ul><ul><ul><ul><ul><li>Regulation Functions </li></ul></ul></ul></ul></ul><ul><ul><ul><li>Maintainance Functions </li></ul></ul></ul><ul><ul><ul><ul><li>Body Temperature maintenance through skin </li></ul></ul></ul></ul><ul><ul><ul><ul><li>Blood Volume, salts and blood proteins prevent excessive fluid loss. </li></ul></ul></ul></ul><ul><ul><ul><ul><li>Blood Pressure </li></ul></ul></ul></ul><ul><ul><ul><li>Buffering Functions </li></ul></ul></ul><ul><ul><ul><ul><li>Maintaining normal pH in body with the help of blood proteins </li></ul></ul></ul></ul><ul><ul><ul><ul><li>and other solutes </li></ul></ul></ul></ul><ul><ul><ul><ul><li>Acts as body’s alkaline reserve of HCO 3 - ions. </li></ul></ul></ul></ul><ul><ul><ul><ul><ul><li>Protection Functions </li></ul></ul></ul></ul></ul><ul><ul><ul><li>Preventing blood loss </li></ul></ul></ul><ul><ul><ul><ul><li>Platelets and plasma proteins initiate clot formation in case of damage </li></ul></ul></ul></ul><ul><ul><ul><li>Defensive function </li></ul></ul></ul><ul><ul><ul><ul><li>Prevents body from being infected from invaders eg bacteria and viruses with the help of antibodies, compliment proteins and WBCs </li></ul></ul></ul></ul>
    12. 12. Blood flow
    13. 13. Plasma Proteins <ul><li>Most are produced by liver, except for hormones and gamma globulins </li></ul><ul><li>Not used up by cells as fuels </li></ul><ul><li>Plasma proteins account for almost 7% by weight of plasma volume </li></ul><ul><ul><ul><li>6 - 8 grams of protein in a volume of 100 milliliters of blood (referred to as g/dl) </li></ul></ul></ul><ul><li>The plasma proteins include: </li></ul><ul><li>Albumins </li></ul><ul><li>Globulins </li></ul><ul><li>Fibrinogen & prothrombin </li></ul><ul><li>Regulatory proteins </li></ul><ul><ul><ul><li>Enzymes – coagulation enzymes, complement factors </li></ul></ul></ul><ul><ul><ul><li>C-reactive protein – acute phase reactant </li></ul></ul></ul>
    14. 14. Albumins <ul><ul><li>Smallest and most abundant of the plasma proteins almost 58% of total plasma proteins. </li></ul></ul><ul><ul><li>Soluble in distilled water </li></ul></ul><ul><ul><li>Precipitated by saturated ammonium sulphate </li></ul></ul><ul><ul><li>Coagulated by heat </li></ul></ul><ul><ul><li>20-Days half life </li></ul></ul><ul><ul><li>At pH 7.4 it is anionic with 20 negative charges per molecule </li></ul></ul><ul><ul><li>Highly polar </li></ul></ul><ul><li>Functions: </li></ul><ul><ul><ul><li>Regulate water movement between the blood and interstitial fluid. (Maintain osmotic pressure) </li></ul></ul></ul><ul><ul><ul><li>Albumins act as transport proteins that carry ions, hormones, and some lipids in the blood. </li></ul></ul></ul>
    15. 15. Albumin Structure Regulation of osmotic pressure
    16. 16. Causes of decreased plasma albumin: <ul><li>Decreased synthesis </li></ul><ul><li>A. malnutrtion </li></ul><ul><li>B. malabsorption </li></ul><ul><li>C. advanced chronic liver disease </li></ul><ul><li>Abnormal distribution or dilution </li></ul><ul><li>A. overhydration </li></ul><ul><li>B. increased capillary permeability like in </li></ul><ul><li> septicemia </li></ul><ul><li>Abnormal excretion or degradation </li></ul><ul><li>A. nephrotic syndrome </li></ul><ul><li>B. burns </li></ul><ul><li>C. hemorrhage </li></ul><ul><li>D. loss of protein from the digestive tract </li></ul><ul><li>Rare congenital defects </li></ul><ul><li>A. hypoalbuminemia </li></ul><ul><li>B. analbuminemia </li></ul>
    17. 17. Globulins <ul><li>Not soluble in distilled water </li></ul><ul><li>38 % of plasma proteins </li></ul><ul><li>More easily precipitated by saturated ammonium sulphate </li></ul><ul><li>They are coagulated by heat </li></ul><ul><li>Series of slightly different globulins may be separated by using different concentrations of alcohol. </li></ul><ul><li>Electrophoresis can also result in separation and identification of different globulins (alpha, beta, gamma) </li></ul><ul><li>Functions: </li></ul><ul><ul><ul><li>Alpha & beta: produced by liver; transport proteins that bind to lipids, metal ions, and fat – soluble vitamins </li></ul></ul></ul><ul><ul><ul><li>Gamma: Antibodies released primarily by plasma cells during immune response. </li></ul></ul></ul>
    18. 18. Fibrinogen & prothrombin <ul><li>Fibrinogen: </li></ul><ul><ul><ul><li>Produced by liver, </li></ul></ul></ul><ul><ul><ul><li>converted to web like substance of clot </li></ul></ul></ul><ul><li>Prothrombin: </li></ul><ul><ul><ul><li>produced by liver, </li></ul></ul></ul><ul><ul><ul><li>formation requires vitamin K, </li></ul></ul></ul><ul><ul><ul><li>converted to thrombin which enzymatically converts fibrinogen to fibrin </li></ul></ul></ul>
    19. 19. Blood Cells <ul><ul><li>RBCs, Red blood cells or erythrocytes </li></ul></ul><ul><ul><li>WBCs, white blood cells or Leukocytes </li></ul></ul><ul><ul><li>Platelets (thromobocytes) </li></ul></ul>
    20. 20. <ul><li>Cell Type </li></ul><ul><ul><ul><li>Erythrocytes (Red blood cells, RBCs) </li></ul></ul></ul><ul><li>Description </li></ul><ul><ul><ul><li>Bicancavae, anucleate disc, salmon-colored, sacs of hemoglobin,most organelles ejected, diameter 7-8 µm </li></ul></ul></ul><ul><li>Cells/mm 3 (µl) of blood </li></ul><ul><ul><ul><li>4-6 millions </li></ul></ul></ul><ul><li>Duration of development (D) & Life Span (LS) </li></ul><ul><ul><ul><li>D: 5-7 days </li></ul></ul></ul><ul><ul><ul><li>LS: 100-120 days </li></ul></ul></ul><ul><li>Function </li></ul><ul><ul><ul><li>Transport oxygen bound to hemoglobin and also small amount of CO 2 </li></ul></ul></ul>Erythrocytes
    21. 21. <ul><li>Cell Type </li></ul><ul><ul><ul><li>Leukocytes (lecuko- white) (White blood cells, WBCs) </li></ul></ul></ul><ul><li>Description </li></ul><ul><ul><ul><li>Spherical, nucleated cells </li></ul></ul></ul><ul><li>Cells/mm 3 (µl) of blood </li></ul><ul><ul><ul><li>4800-10,800 </li></ul></ul></ul><ul><li>Types </li></ul><ul><ul><ul><li>Granulocytes </li></ul></ul></ul><ul><ul><ul><ul><li>Neutrophils </li></ul></ul></ul></ul><ul><ul><ul><ul><li>Eosinophils </li></ul></ul></ul></ul><ul><ul><ul><ul><li>Basophils </li></ul></ul></ul></ul><ul><ul><ul><li>Agranulocytes </li></ul></ul></ul><ul><ul><ul><ul><li>Lymohocytes </li></ul></ul></ul></ul><ul><ul><ul><ul><li>Monocytes </li></ul></ul></ul></ul>Leuckocytes
    22. 22.
    23. 23.
    24. 24. Leukocytes <ul><li>General structural and functional characteristics </li></ul><ul><ul><li>Complete cells (nucleus and other organelles) </li></ul></ul><ul><ul><li>< 1 % of total blood volume </li></ul></ul><ul><ul><li>They form a mobile army of body’s protective system </li></ul></ul><ul><ul><li>Diapedesis (Leaping Across) </li></ul></ul><ul><ul><ul><li>The process of squeezing through the pores of blood vessels. </li></ul></ul></ul><ul><ul><li>Ameboid motion </li></ul></ul><ul><ul><ul><li>WBCs move through tissue spaces by Ameboid motion i.e. by forming flowing cytoplasmic extensions (throwing pseudopodia) </li></ul></ul></ul><ul><ul><li>Chemotaxis </li></ul></ul><ul><ul><ul><li>The ability of WBCs to locate areas of tissue damage and infection in body by responding to certain chemicals. </li></ul></ul></ul><ul><ul><li>Chemotactic substances </li></ul></ul><ul><ul><ul><li>Bacterial toxins </li></ul></ul></ul><ul><ul><ul><li>Degenerative products of inflammed tissues </li></ul></ul></ul><ul><ul><ul><li>Plasma clotting end products </li></ul></ul></ul>
    25. 25. Genesis of Formed Elements
    26. 26. Hematopoiesis <ul><li>Hematopoiesis or hemopoiesis (Hemato, hemo = blood, Poiesis = to make) </li></ul><ul><li>Process occurs in Red bone marrow </li></ul><ul><li>Red bone marrow composition </li></ul><ul><ul><ul><li>It is composed of a soft network of reticular connective tissue bordering on wide blood capillaries called blood sinusoids . With in this network are immature red blood cells, fat cells, reticular cells ( secrete the fibers). </li></ul></ul></ul><ul><ul><ul><li>On average, the marrow produces 1 ounce of new blood every day </li></ul></ul></ul><ul><ul><ul><li>Cells produced are about 100 billion </li></ul></ul></ul><ul><li>All cells arise from the same type of stem cells the PHSC or hemocytobalsts (Cyte = cell , blast = bud) that reside in red bone marrow. </li></ul><ul><li>But the maturation pathway is different form each other, once a cell is committed to a specific blood cell pathway, it can not change </li></ul><ul><li>This commitment is signaled by appearance of membrane surface receptors that respond to specific hormones or growth factors , which in turn push the cell towards further specialization. </li></ul>
    27. 27.
    28. 28. Production of Leukocytes <ul><li>Leukopoiesis </li></ul><ul><li>Hormonally stimulated </li></ul><ul><ul><li>T-Lymphocytes </li></ul></ul><ul><ul><li>Macrophages </li></ul></ul><ul><li>Hematopoietic Factors </li></ul><ul><ul><ul><li>Glycoproteins </li></ul></ul></ul><ul><ul><ul><ul><li>Interleukins </li></ul></ul></ul></ul><ul><ul><ul><ul><ul><li>IL-3, IL-5 </li></ul></ul></ul></ul></ul><ul><ul><ul><ul><li>CSFs (colony stimulating factors) </li></ul></ul></ul></ul><ul><ul><ul><ul><ul><li>Leukocyte population stimulated eg G-CSFs </li></ul></ul></ul></ul></ul><ul><ul><li>Functions </li></ul></ul><ul><ul><ul><li>Stimulation of WBCs precursors to divide and mature </li></ul></ul></ul><ul><ul><ul><li>Enhance protective potency of mature leukocytes </li></ul></ul></ul><ul><ul><ul><li>Clinically used (EPO) and other CSFs </li></ul></ul></ul><ul><ul><ul><ul><li>Stimulation of bone marrow in cancer patients </li></ul></ul></ul></ul><ul><ul><ul><ul><li>Marrow transplants </li></ul></ul></ul></ul><ul><ul><ul><ul><li>AIDS patients </li></ul></ul></ul></ul>
    29. 29. Production of Leukocytes
    30. 30.
    31. 31. <ul><li>Pluripotential hemopoietic stem cell (PHSC) (Hemocytoblasts) </li></ul><ul><ul><ul><li>A stem cell derived from the embryonic mesenchyme and considered to be capable of developing into any type of blood cell. </li></ul></ul></ul><ul><ul><ul><ul><li>Myeloid Stem cells </li></ul></ul></ul></ul><ul><ul><ul><ul><li>Lymphoid Stem cells </li></ul></ul></ul></ul><ul><li>Myeloid Stem cells </li></ul><ul><ul><ul><ul><li>Committed cells </li></ul></ul></ul></ul><ul><ul><ul><li>Myeloblast </li></ul></ul></ul><ul><ul><ul><li>Monoblast </li></ul></ul></ul><ul><li>Lymphoid Stem cells </li></ul><ul><ul><ul><ul><li>Committed cells </li></ul></ul></ul></ul><ul><ul><ul><li>Lymphoblast </li></ul></ul></ul>Production of Leukocytes
    32. 32. <ul><li>Myeloblasts accumulate lysosomes to become promyelocytes </li></ul><ul><li>Distinctive granules of each granulocyte appear in myelocyte stage  cell division stops </li></ul><ul><li>Band cells  nuclei become arc- like </li></ul><ul><li>Nuclear constriction & segmentation just before leaving bone marrow </li></ul><ul><li>Mature granulocytes are stored in bone marrow, 10-20 times more than in blood </li></ul><ul><li>Production ratio 3:1 (erythrocytes : granulocytes) </li></ul><ul><li>Shorter life span 0.5-9 days </li></ul>Production of Granulocytes
    33. 33. Production of Agranulocytes <ul><li>Monocytes diverge from pleuripotent myeloid stem cells  Monoblast  promonocyte  Monocytes  some cells form macrophages (in tissues) </li></ul><ul><li>Lymphocytes diverge from pleuripotent lymphoid stem cells  Lymphoblast  prolymphocyte  Lymphocytes  Plasma cells </li></ul><ul><li>Promonocytes and Prolymphocytes leave the bone marrow and travel to lymphoid tissue, where there further differentiation occur </li></ul><ul><li>Monocytes live for months </li></ul><ul><li>Lymphocytes  days to years </li></ul>
    34. 34. Leukocyte Disorders <ul><li>Leukocytosis </li></ul><ul><ul><li>Physiological cause </li></ul></ul><ul><ul><ul><li>Newborn </li></ul></ul></ul><ul><ul><ul><li>Pregnancy </li></ul></ul></ul><ul><ul><ul><li>Emotion </li></ul></ul></ul><ul><ul><ul><li>Stress </li></ul></ul></ul><ul><ul><li>Pathological Causes </li></ul></ul><ul><ul><ul><li>Infections </li></ul></ul></ul><ul><ul><ul><li>Burns </li></ul></ul></ul><ul><ul><ul><li>Malignancy </li></ul></ul></ul><ul><ul><ul><li>Allergic Reactions </li></ul></ul></ul>
    35. 35. Leukocyte Disorders <ul><li>Leukopenia </li></ul><ul><ul><ul><li>Exposure to Rays, e.g. Gamma rays </li></ul></ul></ul><ul><ul><ul><li>Chemicals e.g. Benzene </li></ul></ul></ul><ul><ul><ul><li>Drugs e.g. Chloramphenicol </li></ul></ul></ul><ul><li>Leukemias </li></ul><ul><ul><ul><li>An increased number of abnormal circulating WBCs due to uncontrolled over production as a result of mutation of myeloid or lymphoid cells. </li></ul></ul></ul><ul><ul><ul><li>Lymphocytic Leukemia </li></ul></ul></ul><ul><ul><ul><li>Myelocytic Leukemia </li></ul></ul></ul>
    36. 36. Platelets (Thrombocytes) <ul><li>Not cells </li></ul><ul><li>Cytoplasmic fragments of extraordinary large cells (60µm)  Megakaryocytes </li></ul><ul><li>Cytoplasm stain blue , granules Stain Purple </li></ul><ul><li>Essential for the clotting process when blood vessels are ruptured or their lining is injured. </li></ul><ul><li>Components of Granules </li></ul><ul><ul><ul><li>Seortonin </li></ul></ul></ul><ul><ul><ul><li>Ca 2+ </li></ul></ul></ul><ul><ul><ul><li>Different Enzymes </li></ul></ul></ul><ul><ul><ul><li>ADP </li></ul></ul></ul><ul><ul><ul><li>Platelets derived Growth Factors (PDGF) </li></ul></ul></ul><ul><li>When not involved in clotting mechanism, they are kept inactive by molecules (NO, PG I 2 ) secreted by endothelial cells lining blood vessels. </li></ul>
    37. 37. Genesis of Platelets <ul><li>Platelets formation is regulated by a Hormone Thrombopoietin 1 </li></ul><ul><li>Hemocytoblasts (PHSC) --> Myeloid Stem cells --> Megakaryoblasts </li></ul><ul><li>Megakaryoblasts under go repeated mitosis but cytokinesis does not occur, final result is MEGAKARYOCYTE. (A cell with a huge nucleus) </li></ul><ul><li>When formed the megakaryocyte presses up against a sinusoid (a specialized type of capillary in marrow) and sends cytoplasmic extensions through sinusoid wall into blood stream. </li></ul><ul><li>These extensions rupture, releasing the platelet fragment in blood stream. </li></ul><ul><li>150,000-400,000 </li></ul>
    38. 38. Platelets Disorders <ul><li>A number of factors can cause thrombocytopenia (a low platelet count). </li></ul><ul><ul><ul><li>Inherited (passed from parents to children), or it can develop at any age. </li></ul></ul></ul><ul><ul><ul><li>Sometimes the cause isn't known </li></ul></ul></ul><ul><li>Causes: (See Notes) </li></ul><ul><ul><ul><li>The body's bone marrow doesn't make enough platelets. </li></ul></ul></ul><ul><ul><ul><ul><li>Cancers </li></ul></ul></ul></ul><ul><ul><ul><ul><li>Aplastic Anemia </li></ul></ul></ul></ul><ul><ul><ul><ul><li>Toxic Chemicals - pesticides </li></ul></ul></ul></ul><ul><ul><ul><ul><li>Medicines – Chloramphenicol, Sulpha drugs </li></ul></ul></ul></ul><ul><ul><ul><ul><li>Viruses- Dengue </li></ul></ul></ul></ul><ul><ul><ul><li>The bone marrow makes enough platelets, but the body destroys them or uses them up. </li></ul></ul></ul><ul><ul><ul><ul><li>Autoimmune Disease </li></ul></ul></ul></ul><ul><ul><ul><ul><li>Surgery </li></ul></ul></ul></ul><ul><ul><ul><ul><li>Pregnancy- 5% </li></ul></ul></ul></ul><ul><ul><ul><li>The spleen holds onto too many platelets. </li></ul></ul></ul><ul><ul><ul><ul><li>Enlarged Spleen </li></ul></ul></ul></ul><ul><ul><ul><ul><ul><li>Cirrhosis </li></ul></ul></ul></ul></ul><ul><ul><ul><ul><ul><li>Liver Cancer </li></ul></ul></ul></ul></ul>
    39. 39. Erythrocytes (RBCs) <ul><li>Red, oxygen carrying, hemoglobin containing, non-nucleated cells, present in the blood </li></ul><ul><li>Shape  Bi-concave Discs </li></ul><ul><li>Size: </li></ul><ul><ul><ul><li>Dia  7.5 - 7.8 µm </li></ul></ul></ul><ul><ul><ul><li>Thickness: </li></ul></ul></ul><ul><ul><ul><ul><li>Thickest  2.5 µm </li></ul></ul></ul></ul><ul><ul><ul><ul><li>Thinnest  1 µm or <1 µm </li></ul></ul></ul></ul><ul><ul><ul><li>Thin centers appear lighter in colour than edges </li></ul></ul></ul><ul><li>Volume: 90-95 µm 3 </li></ul><ul><li>Life Span: </li></ul><ul><ul><ul><li>Adults: 100-120 Days </li></ul></ul></ul><ul><ul><ul><li>Neonates: 70-90 Days </li></ul></ul></ul><ul><li>Count: </li></ul><ul><ul><ul><li>Males: 5.2 million + 3,00,000 cells/mm 3 </li></ul></ul></ul><ul><ul><ul><li>Females: 4.7 million + 3,00,000 cells/mm 3 </li></ul></ul></ul><ul><ul><ul><li>Newborn: 6 – 6.5 million cells/mm 3 </li></ul></ul></ul><ul><ul><ul><li>Fetus: 7.8 million cells/mm 3 </li></ul></ul></ul><ul><ul><ul><ul><li>Why count is different? 1 </li></ul></ul></ul></ul>
    40. 40. <ul><li>Composition of RBCs: </li></ul><ul><li>The composition of RBCs is same as that of a normal cell except that mature RBCs contain Hb and don’t contain nucleus, mitochondria, and other important organelles . </li></ul><ul><ul><li>Water = 65 % </li></ul></ul><ul><ul><li>Solid and semisolids = 35 % </li></ul></ul><ul><ul><ul><ul><li>Hb (33 %) </li></ul></ul></ul></ul><ul><ul><ul><ul><li>Organic and inorganic substances (2%) </li></ul></ul></ul></ul><ul><ul><li>(Amino Acids, Cholesterol, Creatinine, Proteins, Phospholipids, Urea) </li></ul></ul><ul><li>How RBCs Change and Maintain Shape: </li></ul><ul><ul><ul><li>Main protein – Hb - 97 % </li></ul></ul></ul><ul><ul><ul><li>Other Proteins </li></ul></ul></ul><ul><ul><ul><ul><li>Anti-Oxidant Enzymes (Get rid body of harmful O 2 radicals) </li></ul></ul></ul></ul><ul><ul><ul><ul><li>Maintenance proteins </li></ul></ul></ul></ul><ul><li>Bi-concave shape of RBCs is maintained by network of proteins, especially one called spectrin , it is attached to the cytoplasmic side of the plasma membrane, as spectrin net is deformable, it gives erythrocytes the flexibility to change their shape as necessary- to twist, turn and become cup shaped when pass through small capillaries – and then resume their normal shape. </li></ul>Erythrocytes (RBCs)
    41. 41. Erythrocytes (RBCs) <ul><li>Energy Production: </li></ul><ul><li>For energy RBCs depend on plasma glucose, metabolic break down takes place through </li></ul><ul><ul><ul><li>Embden Meyerhof Glcolytic pathway </li></ul></ul></ul><ul><ul><ul><li>Pentose phosphate Pathway (PPP) or (Hexose Monophosphate shunt) </li></ul></ul></ul><ul><li>Structural Characterstics VS Function </li></ul><ul><ul><ul><li>Small size and Biconcave shape provides huge surface area (about 30 % more area than comparable spherical cells). </li></ul></ul></ul><ul><ul><ul><li>Excluding water content RBC is 97 % Hb that transports resp. gases. </li></ul></ul></ul><ul><ul><ul><li>Don’t use oxygen themselves as produce energy by anaerobic mechanisms. </li></ul></ul></ul><ul><li>Functions or RBCs: </li></ul><ul><ul><ul><li>O 2 Transport: </li></ul></ul></ul><ul><ul><ul><ul><li>Contains Hb, that carries oxygen bound to ‘Heme’ portion </li></ul></ul></ul></ul><ul><ul><ul><li>CO 2 Transport: </li></ul></ul></ul><ul><ul><ul><ul><li>CO 2 Transport takes place in combination with ‘globin’ protion. (20%) </li></ul></ul></ul></ul><ul><ul><ul><li>Acid-Base balance </li></ul></ul></ul><ul><ul><ul><ul><li>By buffering action of Hb </li></ul></ul></ul></ul><ul><ul><ul><li>Blood Viscosity </li></ul></ul></ul><ul><ul><ul><li>Ionic balance </li></ul></ul></ul>
    42. 42. Erythrocytes Production (Erythropoiesis) PHSC Myeloid Stem cells <ul><li>Hemocytoblasts: </li></ul><ul><li>Cell size large 20-25 mircon </li></ul><ul><li>Nucelus large </li></ul><ul><li>Less cytoplasm </li></ul><ul><li>Mitosis present </li></ul><ul><li>Proerythroblast: </li></ul><ul><li>Cell size decrease 15-17 mircon </li></ul><ul><li>Basophilic 1 Erythroblast: </li></ul><ul><li>Cell size 12-15 mircon </li></ul><ul><li>Nucelus Condensed </li></ul><ul><li>Mitosis present </li></ul><ul><li>Nucleoli Rudimentary </li></ul><ul><li>Produces huge number of Ribosomes </li></ul><ul><li>Hb synthesis starts </li></ul><ul><li>Polychromatophil 2 Erythroblast: </li></ul><ul><li>Cell size 10-12 mircon </li></ul><ul><li>Nucelus Condensed </li></ul><ul><li>Mitosis Absent </li></ul><ul><li>Orhochromatic 3 Erythroblast: </li></ul><ul><li>Cell size 8-10 mircon </li></ul><ul><li>Nucelus More Condensed </li></ul><ul><li>Reticulocyte: </li></ul><ul><li>Young Erythrocytes </li></ul><ul><li>Cell size 7-8 mircon </li></ul>
    43. 43. Erythrocytes Production (Erythropoiesis)
    44. 44. <ul><li>PHSC </li></ul><ul><li>Myeloid stem cells </li></ul><ul><li>Proerythroblast (Megaloblasts) </li></ul><ul><li>Basophilic Erythoroblasts (Early erythroblasts) (early Normoblast) </li></ul><ul><li>Polychromatophil Erythroblasts (Intermediate erythroblast or Normoblast) </li></ul><ul><li>Orhochromatic Erythroblasts (Late Erythroblast or Normoblasts) </li></ul><ul><li>Reticulocytes </li></ul><ul><ul><ul><li>Young erythrocytes </li></ul></ul></ul><ul><ul><ul><li>Contain a short network of clumped ribosomes and RER. </li></ul></ul></ul><ul><ul><ul><li>Enter the blood stream </li></ul></ul></ul><ul><ul><ul><li>Fully mature with in 2 days as their contents are degraded by intracellular enzymes. </li></ul></ul></ul><ul><ul><ul><li>Count = 1-2% of red cells </li></ul></ul></ul><ul><ul><ul><li>Provide an index of rate of RBC formation </li></ul></ul></ul><ul><li>Erythrocytes </li></ul>Erythrocytes Production (Erythropoiesis)
    45. 45. Proerythroblast or pronormoblast Basophilic erythroblast or Early Normoblast Polychromatophilic (or intermediate) Erythroblast or Normoblast Dividing Polychromatophilic Erythroblast or Normoblast Orthochromatic (Acidophilic) erythroblast Or Late Erythroblast Orthochromatic erythroblast Extruding Nucleus Reticulocyte Reticulocyte (brilliant cresyl blue dye) 1
    46. 46.
    47. 47.
    48. 48. Factor needed of Erythropoiesis <ul><li>Erythropoietin ( Released in response to Hypoxia) </li></ul><ul><li>Vitamin B 6 (Pyridoxine) </li></ul><ul><li>Vitamin B 9 (Folic Acid) </li></ul><ul><li>Vitamin B 12 (Cobolamin) </li></ul><ul><ul><ul><li>Essential for DNA synthesis and RBC maturation </li></ul></ul></ul><ul><li>Vitamin C  Helps in iron absorption (Fe+++  Fe++) </li></ul><ul><li>Proteins  Amino Acids for globin synthesis </li></ul><ul><li>Iron & copper  Heme synthesis </li></ul><ul><li>Intrinsic factor  Absorption of Vit B 12 </li></ul><ul><li>Hormones </li></ul>Physiological Variations in RBC count <ul><li>Diurnal Variation (During 24 hours) </li></ul><ul><ul><ul><li>5 % </li></ul></ul></ul><ul><ul><ul><li>Lowest - Sleep and early morning hours </li></ul></ul></ul><ul><ul><ul><li>Highest - Evening </li></ul></ul></ul><ul><li>Temperature </li></ul><ul><li>High Altitude </li></ul><ul><li>Hypoxia </li></ul><ul><li>Radiations </li></ul><ul><ul><ul><li>X-rays </li></ul></ul></ul>
    49. 49. <ul><li>Anucleate  certain limitations. </li></ul><ul><ul><ul><li>No synthesis of new proteins, No growth, No division. </li></ul></ul></ul><ul><li>However they do have Cytoplasmic enzymes (hexokinase, Glu-6-phosphate dehydrogenase) that are capable of metabolizing glucose and forming small amounts of ATP. These enzymes also perform following actions </li></ul><ul><ul><ul><li>maintain pliability of the cell membrane, </li></ul></ul></ul><ul><ul><ul><li>maintain membrane transport of ions, </li></ul></ul></ul><ul><ul><ul><li>keep the iron of the cells’ hemoglobin in the ferrous form rather than ferric </li></ul></ul></ul><ul><ul><ul><li>Prevent oxidation of the proteins in the red cells. </li></ul></ul></ul><ul><li>Erythrocytes become “old” as they lose their flexibility and become pikilocytes (spherical), increasingly rigid and fragile. Once the cell become fragile, they easily destruct during passage through tight circulation spots, especially in spleen, where the intra-capillary space is about 3 micron as compared to 8 micron of cell size </li></ul><ul><ul><ul><li>RBCs useful life span is 100 to 120 days,After which they become trapped and fragment in smaller circulatory channels, particularly in those of the spleen. For this reason, the spleen is sometimes called the “red blood cell graveyard.” </li></ul></ul></ul><ul><li>Dying erythrocytes are engulfed and destroyed by macrophages. </li></ul>Fate and destruction of RBCs 1
    50. 50. Fate and destr-uction of RBCs
    51. 51. Regulation of RBCs production <ul><li>Control of rate of erythropoiesis is based on ability of RBCs to transport sufficient oxygen to tissues as per demand, not the number </li></ul><ul><li>Tissue Oxygenation </li></ul><ul><ul><li>Drop in normal blood oxygen levels may result due to </li></ul></ul><ul><ul><ul><li>Reduced number of RBCs </li></ul></ul></ul><ul><ul><ul><ul><li>Hemorrhage </li></ul></ul></ul></ul><ul><ul><ul><ul><li>Excess RBC Destruction </li></ul></ul></ul></ul><ul><ul><ul><li>Reduced Availability of Oxygen </li></ul></ul></ul><ul><ul><ul><ul><li>High Altitude </li></ul></ul></ul></ul><ul><ul><ul><ul><li>Lung Diseases </li></ul></ul></ul></ul><ul><ul><ul><li>Increase Tissue demands of Oxygen </li></ul></ul></ul><ul><ul><ul><ul><li>Aerobic Exercises </li></ul></ul></ul></ul><ul><li>Erythropoietin (Formation & role) 1 </li></ul><ul><ul><ul><li>Glycoprotein, Mol wt= 34,000. </li></ul></ul></ul><ul><ul><ul><li>Erythropoietin , a hormone, produced mainly by the kidneys(90%) and also by liver(10%), stimulates erythropoiesis   by   acting   on committed stem cells to induce proliferation and differentiation of erythrocytes in bone marrow. </li></ul></ul></ul><ul><ul><ul><li>Site of Action: BONE Marrow </li></ul></ul></ul>
    52. 52. Regulation of RBC production A negative Feed back mechanism
    53. 53. Hemoglobin (Hb) <ul><li>Red, oxygen carrying pigment present in RBCs. </li></ul><ul><ul><ul><li>Heme (4%) </li></ul></ul></ul><ul><ul><ul><li>Globin (96%) </li></ul></ul></ul><ul><li>Quantity </li></ul><ul><ul><ul><li>700-900g in body </li></ul></ul></ul><ul><ul><ul><li>29-32 peco gram/RBC </li></ul></ul></ul><ul><li>RBCs </li></ul><ul><ul><ul><li>Male= 36g/100ml </li></ul></ul></ul><ul><ul><ul><li>Female = 34g/100ml </li></ul></ul></ul><ul><li>Whole Blood </li></ul><ul><ul><ul><li>Newborn = 14-20g/100ml </li></ul></ul></ul><ul><ul><ul><li>Male= 14-16g/100ml </li></ul></ul></ul><ul><ul><ul><li>Female = 12-14g/100ml </li></ul></ul></ul><ul><li>Molecular Weight </li></ul><ul><ul><ul><li>64,450 </li></ul></ul></ul><ul><li>Types </li></ul><ul><ul><ul><li>4 types of poly peptide chains based on amino acid composition and sequence. </li></ul></ul></ul><ul><ul><ul><li>alpha, beta, gamma, delta </li></ul></ul></ul><ul><ul><li>Adult Hb </li></ul></ul><ul><ul><ul><li>Hb A = 2 alpha (141 AA)+ 2 beta (146 AA) chains (α 2 β 2 ) </li></ul></ul></ul><ul><ul><ul><li>Hb A 2 = 2 alpha (141 AA)+ 2 delta (146 AA) chains (2.5%) 1 (α 2 δ 2 ) (10 AA differ) </li></ul></ul></ul><ul><ul><li>Fetal Hb </li></ul></ul><ul><ul><ul><li>Hb F = 2 alpha (141 AA)+ 2 gamma (146 AA) chains 2 ( α 2 γ 2 ) (37 AA differ) </li></ul></ul></ul><ul><ul><ul><li>99% replaced with adult Hb with in a year of birth. </li></ul></ul></ul>
    54. 54. <ul><li>250 million Hb molecules / RBC </li></ul><ul><li>So carry 1 billion oxygen molecules / RBC </li></ul><ul><li>Synthesis of Hb </li></ul><ul><ul><ul><li>Starts at proerythroblastic stage </li></ul></ul></ul><ul><li>Synthesis steps: </li></ul><ul><ul><ul><li>Heme is made from acetic acid and glycine in mitochondria </li></ul></ul></ul><ul><ul><ul><li>Acetic Acid  α-ketoglutaric Acid  Succinyl Co A (Krebs Cycle) </li></ul></ul></ul><ul><ul><ul><li>Globin (polypeptide chain) is synthesized by Ribosomes </li></ul></ul></ul><ul><li>Reactions of Hb: </li></ul><ul><ul><ul><li>Oxyhemoglobin (oxygen + Hb) Ruby Red (in lungs) (Co-ordination bonds) </li></ul></ul></ul><ul><ul><ul><li>Deoxyhemoglobin (Reduced Hb) Dark Red (in tissues) </li></ul></ul></ul><ul><ul><ul><li>Carbaminohemoglobin (Co 2 + Hb) (Globin’s amino acids) (20 %) </li></ul></ul></ul><ul><ul><ul><li>Caroboxyhemoglobin (Co + Hb) </li></ul></ul></ul><ul><ul><ul><li>Methemoglobin (Fe+++ instead of Fe++) </li></ul></ul></ul>Hemoglobin (Hb)
    55. 55. Reactions of Hb: <ul><li>Hemoglobin binds O 2 to form oxyhemoglobin, O 2 attaching to the Fe 2+ in the heme. The affinity of hemoglobin for O 2 is affected by </li></ul><ul><ul><ul><li>pH, </li></ul></ul></ul><ul><ul><ul><li>Temperature, </li></ul></ul></ul><ul><ul><ul><li>The concentration of 2,3-diphosphoglycerate (2,3-DPG) in the red cells. </li></ul></ul></ul><ul><li>2,3-DPG and H+ compete with O 2 for binding to deoxygenated hemoglobin, decreasing the affinity of hemoglobin for O 2 by shifting the positions of the four peptide chains (quaternary structure). </li></ul><ul><li>Each of the four iron atoms can bind reversibly to one O 2 molecule. The iron stays in the ferrous state, so that the reaction is an oxygenation, not an oxidation. It has been customary to write the reaction of hemoglobin with O 2 as </li></ul><ul><ul><ul><li>Hb + O 2 ↔ HbO 2 </li></ul></ul></ul><ul><li>Since it contains four Hb units, the hemoglobin molecule can also be represented as Hb 4 , and it actually reacts with four molecules of O 2 to form Hb 4 O 8 as following. </li></ul><ul><li>The reaction is rapid, requiring less than 0.01 s. </li></ul><ul><li>The deoxygenation (reduction) of Hb 4 O 8 is also very rapid. </li></ul>
    56. 56. Hb Abnormalities <ul><li>Globin Genes 1 determine the AA sequence in Hb. </li></ul><ul><li>Two types of Abnormalities: </li></ul><ul><ul><li>Hemoglobinopathy </li></ul></ul><ul><ul><ul><li>Abnormal polypeptide chains are produced </li></ul></ul></ul><ul><ul><ul><ul><li>Sickle cell disease due to Hb-S </li></ul></ul></ul></ul><ul><ul><li>Thalassemia </li></ul></ul><ul><ul><ul><li>In which the chains are normal in structure but produced in decreased amounts or absent because of defects in the regulatory portion of the globin genes. </li></ul></ul></ul><ul><ul><ul><ul><li>The α and β thalassemias are defined by decreased or absent α and β polypeptides, respectively. </li></ul></ul></ul></ul><ul><li>1000 Abnormal Hbs due to mutant genes in humans. usually identified by letter—Hb-C, E, I, J, S, etc. </li></ul><ul><li>Mostly, the abnormal Hbs differ from normal Hb-A in the structure of the polypeptide chains. </li></ul><ul><li>For example, In hemoglobin S, </li></ul><ul><ul><ul><li>α chains normal </li></ul></ul></ul><ul><ul><ul><li>β chains abnormal, among the 146 AA residues in each β polypeptide chain, one glutamic acid residue has been replaced by a valine residue. </li></ul></ul></ul>
    57. 57. <ul><li>Heterozygous  Half the circulating hemoglobin is abnormal and half is normal. </li></ul><ul><ul><ul><li>Have sickle cell trait </li></ul></ul></ul><ul><li>Homozygous  all of the hemoglobin is abnormal. </li></ul><ul><ul><ul><li>Develop the full blown disease </li></ul></ul></ul><ul><li>Results of abnormality </li></ul><ul><ul><li>Many of the abnormal hemoglobins are harmless. </li></ul></ul><ul><ul><li>Abnormal O2 equilibriums. </li></ul></ul><ul><ul><li>Anemia. </li></ul></ul><ul><ul><ul><li>Hb-S polymerizes at low O 2 tensions, and this causes the red cells to become sickle-shaped, hemolyze, and form aggregates that block blood vessels. </li></ul></ul></ul><ul><ul><ul><li>The result is the severe hemolytic anemia known as sickle cell anemia. </li></ul></ul></ul><ul><li>The sickle cell gene is an example of a gene that has persisted and spread in the population. </li></ul><ul><li>It originated in the black population in Africa, and it confers resistance to one type of malaria. </li></ul><ul><li>Africa = 40% of the black population have the sickle cell trait. </li></ul><ul><li>In United States 10 % </li></ul><ul><li>Treatment: </li></ul><ul><ul><ul><li>Bone marrow Transplatation </li></ul></ul></ul><ul><ul><ul><li>Hb-F production by hydroxyurea. </li></ul></ul></ul>Hb Abnormalities
    58. 58. Hb Abnormalities
    59. 59. Hemoglobin Metabolism <ul><li>The heme of the hemoglobin is split off from globin. </li></ul><ul><ul><li>Its core of iron is saved, bound to protein (as ferritin or hemosiderin), and stored for reuse. </li></ul></ul><ul><ul><li>The heme is converted to biliverdin. In humans, most of the biliverdin is converted to bilirubin, a yellow pigment that is released to the blood and binds to albumin for transport. </li></ul></ul><ul><ul><li>Bilirubin is picked up by liver cells, which in turn secrete it (in bile) into the intestine, where it is metabolized to urobilinogen. </li></ul></ul><ul><ul><li>Most of this degraded pigment leaves the body in feces, as a brown pigment called stercobilin. </li></ul></ul><ul><ul><li>Exposure of the skin to white light converts bilirubin to lumirubin, which has a shorter half-life than bilirubin. </li></ul></ul><ul><ul><li>Phototherapy (exposure to light) is of value in treating infants with jaundice due to hemolysis. </li></ul></ul><ul><li>The protein (globin) part of hemoglobin is metabolized or broken down to amino acids, which are released to the circulation. </li></ul>
    60. 60. Iron metabolism <ul><li>Iron = 4-5g Per person </li></ul><ul><li>Hb  65 % of total iron </li></ul><ul><li>Reticuloendothelial system + liver = 15-30 % </li></ul><ul><li>Myoglobin = 4% </li></ul><ul><li>Intracellular oxidating heme compounds = 1% </li></ul><ul><li>Transferrin = 0.1 % </li></ul><ul><li>Absorption of Iron: </li></ul><ul><ul><ul><li>Mianly from Duodenum. </li></ul></ul></ul><ul><ul><ul><li>Heme-Fe +2 from Meat (Myoglobin, hemoglobin) </li></ul></ul></ul><ul><ul><ul><li>Fe +2 from small intestine (Fe +3 reduced by Vit C & ferrireductase (FR) to Fe +2 for absorption) </li></ul></ul></ul><ul><li>Transport of Iron: </li></ul><ul><ul><ul><li>Iron + Apotransferrin [protein from liver]  Transferrin (Bound)  is taken up by endocytosis into erythroblasts and cells of the liver, placenta, etc. with the aid of transferrin receptors. </li></ul></ul></ul><ul><li>Storage & Recycling: </li></ul><ul><ul><ul><li>Ferritin  one of the chief forms in which iron is stored in the body, storage occurs mainly in the intestinal mucosa, liver, bone marrow, red blood cells, and plasma. (4500 Fe +3 ions i.e. 600mg as readily available store). </li></ul></ul></ul><ul><ul><ul><li>Hemosidrin  In marcophages of liver and bone marrow (250mg) slow release. </li></ul></ul></ul><ul><ul><ul><li>97 % recycled by phagocytes of liver, spleen and bone marrow </li></ul></ul></ul>Ferritin
    61. 61. FR= ferrireductase Daily Iron Loss Male: 1mg/day Females: 2mg/day Daily Iron Requirement Male: 1mg/day Females: 2mg/day
    62. 62. Blood Transfusion <ul><li>Whole blood transfusions are routine when blood loss is rapid and substantial. </li></ul><ul><li>In all other cases, infusions of packed red cells (whole blood from which most of the plasma has been removed) are preferred for restoring oxygen-carrying capacity. </li></ul><ul><li>The usual blood bank procedure involves collecting blood from a donor and then mixing it with an anticoagulant, such as certain citrate or oxalate salts, which prevents clotting by binding with calcium ions. </li></ul><ul><li>The shelf life of the collected blood at 4°C is about 35 days. </li></ul><ul><li>Because blood is such a valuable commodity, it is most often separated into its component parts so that each component can be used when and where it is needed. </li></ul>
    63. 63. ABO Blood Group <ul><li>BLOOD TYPES </li></ul><ul><ul><li>The membranes of human red cells contain a variety of blood group antigens , which are also called agglutinogens . </li></ul></ul><ul><ul><li>Antibodies against red cell antigens are called agglutinins . </li></ul></ul><ul><ul><ul><li>When the plasma of a type A individual (containing Anti-B antibodies) is mixed with type B red cells, the anti-B antibodies cause the type B red cells to clump (agglutinate). </li></ul></ul></ul><ul><ul><li>The most important and best known of these are the A and B antigens, but there are many more. eg </li></ul></ul><ul><ul><ul><li>MNSs, Lutheran, Kell, Kidd, </li></ul></ul></ul>
    64. 64.
    65. 65. <ul><li>The individuals are divided into four major blood types on this basis of presence of these antigens. </li></ul><ul><ul><li>Type A individuals have the A antigen, </li></ul></ul><ul><ul><li>Type B have the B, </li></ul></ul><ul><ul><li>Type AB have both, and </li></ul></ul><ul><ul><li>Type O have neither. </li></ul></ul><ul><ul><ul><li>These antigens are found in many tissues in addition to blood: </li></ul></ul></ul><ul><ul><ul><li>E.g.. salivary glands, saliva, pancreas, kidney, liver, lungs, testes, semen, and amniotic fluid. </li></ul></ul></ul><ul><li>Chemsitry of Anitgens: </li></ul><ul><ul><ul><li>The A and B antigens are complex oligosaccharides that differ in their terminal sugar. </li></ul></ul></ul><ul><ul><ul><li>On red cells they are mostly glycosphingolipids, </li></ul></ul></ul><ul><ul><ul><li>whereas in other tissues they are glycoproteins. </li></ul></ul></ul><ul><ul><ul><li>An H gene codes for a fucose transferase that puts a fucose 1 (hexose dexoy sugar) on the end of these glycolipids or glycoproteins, forming the H antigen </li></ul></ul></ul><ul><ul><ul><li>H-antigen is usually present in individuals of all blood types. </li></ul></ul></ul>ABO Blood Group
    66. 66. <ul><ul><li>Individuals who are type A have a gene which codes for a transferase that catalyzes placement of a terminal N -acetylgalactosamine on the H antigen, </li></ul></ul><ul><ul><li>Individuals who are type B have a gene which codes for a transferase that places a terminal galactose. </li></ul></ul><ul><ul><li>Individuals who are type AB have both transferases. </li></ul></ul><ul><ul><li>Individuals who are type O have neither, so the H antigen persists. </li></ul></ul>ABO Blood Group
    67. 67. ABO Blood Group <ul><li>Subgroups of blood types A and B </li></ul><ul><ul><li>Most important being A1 and A2. </li></ul></ul><ul><ul><ul><li>A1 cell has about 1,000,000 copies of the A antigen on its surface, </li></ul></ul></ul><ul><ul><ul><li>A2 cell has about 250,000 copies of the A antigen on its surface </li></ul></ul></ul><ul><li>Antibody Development: </li></ul><ul><ul><ul><li>Antigens very similar to A and B are common in intestinal bacteria and possibly in foods to which newborn individuals are exposed. </li></ul></ul></ul><ul><ul><ul><li>Therefore, infants rapidly develop antibodies against the antigens not present in their own cells. </li></ul></ul></ul><ul><ul><li>Thus, </li></ul></ul><ul><ul><ul><li>type A individuals develop anti-B antibodies, </li></ul></ul></ul><ul><ul><ul><li>type B individuals develop anti-A antibodies, </li></ul></ul></ul><ul><ul><ul><li>type O individuals develop both, </li></ul></ul></ul><ul><ul><ul><li>and type AB individuals develop neither. </li></ul></ul></ul><ul><li>Blood Typing Test: </li></ul><ul><ul><li>Blood typing is performed by mixing an individual's red blood cells with antisera containing the various agglutinins on a slide and seeing whether agglutination occurs. </li></ul></ul>
    68. 68. Missing H-gene so no fucose tranferase so no fucose and no H-antigen that Forms the base for A and B Antigen. Bombay phenotype No fucose
    69. 69. Bombay Phenotype <ul><li>This blood phenotype was first discovered in Bombay, now known as Mumbai , in, by Dr. Y.M. Bhende. </li></ul><ul><li>hh is a rare blood group also called Bombay Blood group . Individuals with the rare Bombay phenotype ( hh ) do not express H antigen (the antigen which is present in blood group O). </li></ul><ul><li>So whatever alleles they may have of the A and B blood-group genes, they cannot make A-anitgen or B-antigen on their red blood cells ,because A antigen and B antigen are made from H antigen. </li></ul><ul><li>As a result, people who have Bombay phenotype can donate to any member of the ABO blood group system (unless some other gene , such as Rhesus , is checked for compatibility), but they cannot receive any member of the ABO blood group system 's blood (which always contains one or more of A and B and H antigens), but only from other people who have Bombay phenotype. </li></ul><ul><li>The usual tests for ABO blood group system would show them as group O, unless the hospital worker involved has the means and the thought to test for Bombay group. </li></ul>
    70. 70. Rh Blood Groups <ul><li>45 different types of Rh agglutinogens, each called an Rh factor. </li></ul><ul><li>Three, the C, D, and E antigens, are fairly common. </li></ul><ul><li>Rh antigen  first identified in rhesus monkeys. </li></ul><ul><li>As a rule, ABO and Rh blood groups reported together eg, O+, A–, and so on. </li></ul><ul><li>If an Rh– person receives Rh+ blood, the immune system becomes sensitized and begins producing anti-Rh antibodies against the foreign antigen soon after the transfusion. </li></ul><ul><li>Hemolysis does not occur after the first such transfusion because it takes time for the body to react and start making antibodies. </li></ul><ul><li>But the second time, and every time thereafter, a typical transfusion reaction occurs in which the recipient’s antibodies attack and rupture the donor RBCs. eg Erythorblastosis fetalis 1 </li></ul><ul><li>Prevention: </li></ul><ul><ul><ul><li>Anit-Rh antibodies given after every Rh+ birth. [RhoGAM] </li></ul></ul></ul>
    71. 71. Rh Factor
    72. 72. Blood Transfusion Reactions <ul><li>When mismatched blood is infused, a transfusion reaction occurs </li></ul><ul><li>Donor’s red blood cells  attacked by the recipient’s plasma agglutinins. </li></ul><ul><li>Donor’s plasma antibodies may also agglutinate the host’s RBCs, but they are so diluted that this does not usually present a serious problem. </li></ul><ul><li>Initially, agglutination clogs small blood vessels throughout the body. </li></ul><ul><li>During the next few hours, the clumped red blood cells begin to rupture or are destroyed by phagocytes, and their hemoglobin is released into the bloodstream. </li></ul><ul><li>These events lead to two easily recognized problems: </li></ul><ul><ul><ul><li>The oxygen-carrying capability of the transfused blood cells is disrupted </li></ul></ul></ul><ul><ul><ul><li>The clumping of red blood cells in small vessels hinders blood flow to tissues beyond those points. </li></ul></ul></ul><ul><li>Less apparent, but more devastating, is the consequence of hemoglobin escaping into the bloodstream. </li></ul><ul><li>Circulating hemoglobin passes freely into the kidney tubules, causing cell death and renal shutdown. If shutdown is complete (acute renal failure), the person may die. </li></ul>
    73. 73. Blood Transfusion Reactions <ul><li>Transfusion reactions can also cause </li></ul><ul><ul><ul><li>fever, </li></ul></ul></ul><ul><ul><ul><li>chills, </li></ul></ul></ul><ul><ul><ul><li>low blood pressure, </li></ul></ul></ul><ul><ul><ul><li>rapid heartbeat, </li></ul></ul></ul><ul><ul><ul><li>nausea, </li></ul></ul></ul><ul><ul><ul><li>vomiting, and general toxicity; </li></ul></ul></ul><ul><ul><li>but in the absence of renal shutdown, these reactions are rarely lethal. </li></ul></ul><ul><li>Treatment of transfusion reactions is directed toward preventing kidney damage by administering fluid and diuretics to increase urine output, diluting and washing out the hemoglobin. </li></ul><ul><li>Some laboratories are developing methods to enzymatically convert other blood types to type O by clipping off the extra (A- or B-specific) sugar residue. </li></ul><ul><li>Autologous (auto = self) transfusions. </li></ul><ul><li>The patient predonates his or her own blood, and it is stored and immediately available if needed during or after the operation. . </li></ul><ul><li>Iron supplements are given, and as long as the patient’s preoperative hematocrit is at least 30%, one unit (400–500 ml) of blood can be collected every 4 days, with the last unit taken 72 hours prior to surgery. </li></ul>
    74. 74. Hemostatis <ul><li>Hemostasis or stoppage of bleeding (stasis = halting). </li></ul><ul><li>No hemostasis  No sealing  bleed to death from minor wounds </li></ul><ul><li>The hemostasis response is </li></ul><ul><ul><ul><li>fast </li></ul></ul></ul><ul><ul><ul><li>localized and </li></ul></ul></ul><ul><ul><ul><li>carefully controlled </li></ul></ul></ul><ul><li>Involves many blood coagulation factors normally present in plasma as well as some substances that are released by platelets and injured tissue cells. </li></ul><ul><li>During hemostasis, following steps occur: </li></ul><ul><ul><li>Vascular spasms, </li></ul></ul><ul><ul><li>Platelet plug formation, </li></ul></ul><ul><ul><li>Coagulation, or blood clotting. </li></ul></ul><ul><ul><li>Growth of fibrous tissue in clot to close the hole in vessel. </li></ul></ul><ul><li>Blood loss at the site is permanently prevented when fibrous tissue grows into the clot and seals the hole in the blood vessel. </li></ul>
    75. 75.
    76. 76.
    77. 77. <ul><li>The immediate response to blood vessel injury is constriction of the damaged blood vessel (vasoconstriction). </li></ul><ul><li>Factors that trigger this vascular spasm include </li></ul><ul><ul><ul><li>Direct injury to vascular smooth muscle, </li></ul></ul></ul><ul><ul><ul><li>Chemicals released by endothelial cells and platelets, </li></ul></ul></ul><ul><ul><ul><li>Reflexes initiated by local pain receptors. </li></ul></ul></ul><ul><ul><li>spasm mechanism becomes more and more efficient as the amount of tissue damage increases, and is most effective in the smaller blood vessels. </li></ul></ul><ul><li>Advantage: </li></ul><ul><ul><ul><li>A strongly constricted artery can significantly reduce blood loss for 20–30 minutes, allowing time for platelet plug formation and blood clotting to occur. </li></ul></ul></ul><ul><ul><ul><li>It is claimed that for a time after being divided transversely, arteries as large as the radial artery constrict and may stop bleeding. </li></ul></ul></ul><ul><ul><ul><li>But arterial walls cut longitudinally or irregularly do not constrict in such a way that the lumen of the artery is occluded, and bleeding continues. </li></ul></ul></ul>1-Vascular Spasms
    78. 78. 2 - Platelet Plug Formation <ul><li>Platelets play a key role in hemostasis by forming a plug that temporarily seals the break in the vessel wall. </li></ul><ul><ul><li>They also help to initiate subsequent events that lead to blood clot formation. </li></ul></ul><ul><ul><ul><li>As a rule, platelets do not stick to each other or to the smooth endothelial linings of blood vessels. </li></ul></ul></ul><ul><ul><li>But, when the endothelium is damaged and underlying collagen fibers are exposed, platelets, with the help of a large plasma protein called von Willebrand factor (VWF) synthesized by endothelial cells, adhere to the collagen fibers and undergo some remarkable changes. </li></ul></ul><ul><ul><ul><li>Swell, </li></ul></ul></ul><ul><ul><ul><li>Form spiked processes or pseudipodia, </li></ul></ul></ul><ul><ul><ul><li>Become sticky. </li></ul></ul></ul>
    79. 79. <ul><ul><li>Once attached, the platelets are activated and their granules begin to break down and release several chemicals. </li></ul></ul><ul><ul><ul><li>serotonin, enhance the vascular spasm. </li></ul></ul></ul><ul><ul><ul><li>Adenosine diphosphate (ADP), (potent aggregating agents that attract more platelets to the area and cause them to release their contents). </li></ul></ul></ul><ul><ul><ul><li>Thromboxane A2 , a short-lived prostaglandin derivative, stimulates both events (Vasoconstriction & Activation). </li></ul></ul></ul><ul><ul><li>So a positive feedback cycle begins that activates and attracts greater and greater numbers of platelets to the area </li></ul></ul><ul><ul><li>within one minute, a platelet plug is built up, which further reduces blood loss. </li></ul></ul><ul><ul><li>Limiting the platelet plug to the immediate area where it is needed is the task of prostacyclin (also called PG I 2 ), a prostaglandin produced by intact endothelial cells that is a strong inhibitor of platelet aggregation. </li></ul></ul><ul><ul><li>Platelet plugs are loosely knit, but when helped by fibrin threads they are quite effective in sealing the small tears in a blood vessel that occur with normal activity. </li></ul></ul><ul><ul><li>Once the platelet plug is formed, the next stage, coagulation, comes into play. </li></ul></ul>2 - Platelet Plug Formation
    80. 80.
    81. 81. <ul><li>Coagulation or blood clotting </li></ul><ul><ul><li>Complicated process, Liquid Blood  becomes gel, </li></ul></ul><ul><ul><li>Over 50 Substances are involved </li></ul></ul><ul><ul><li>Factors that enhance clot formation are called clotting factors or procoagulants . </li></ul></ul><ul><ul><li>Factors that inhibit clotting are called anticoagulants. </li></ul></ul><ul><ul><li>Balance between these two groups of factors. Normally, anticoagulants dominate and clotting is prevented; but when a vessel is ruptured, procoagulant activity in that area increases dramatically and clot formation begins. </li></ul></ul><ul><ul><li>The procoagulants are numbered I to XIII according to the order of their discovery; hence the numerical order does not reflect the reaction sequence. </li></ul></ul><ul><ul><li>Most of these factors are plasma proteins made by the liver that circulate in an inactive form in blood until mobilized. </li></ul></ul>3-Coagulation
    82. 82.
    83. 83. <ul><li>Three Phases of Coagulation: </li></ul><ul><ul><ul><li>A complex substance called prothrombin activator is formed. </li></ul></ul></ul><ul><ul><ul><li>Prothrombin activator converts prothrombin (a plasma protein) into thrombin, (an enzyme). </li></ul></ul></ul><ul><ul><ul><li>Thrombin catalyzes the joining of fibrinogen molecules present in plasma to a fibrin mesh. </li></ul></ul></ul><ul><li>Role of Vitamin K in coagulation. </li></ul><ul><ul><li>Vitamin K not directly involved in coagulation, this fat-soluble vitamin is required for the synthesis of four of the procoagulants made by the liver i.e (II, VII, IX and X). </li></ul></ul>3-Coagulation
    84. 84.
    85. 85. <ul><li>Clotting may be initiated by either the </li></ul><ul><ul><ul><li>Intrinsic Pathway </li></ul></ul></ul><ul><ul><ul><li>Extrinsic pathway </li></ul></ul></ul><ul><li>Both pathways are usually triggered by the tissue-damaging events. Clotting of blood outside the body (such as in a test tube) is initiated only by the intrinsic mechanism.     </li></ul><ul><ul><li>Critical components in both mechanisms are negatively charged membranes, particularly those on platelets that contain phosphatidylserine (platelets phospholipids), also known as PF 3 (platelet factor 3). </li></ul></ul><ul><ul><li>Many intermediates of both pathways can be activated only in the presence of PF 3 . </li></ul></ul>Phase 1- Formation of prothrombin Activator
    86. 86. <ul><li>Intrinsic Pathway </li></ul><ul><ul><li>In the slower intrinsic pathway, all factors needed for clotting are present in (intrinsic to) the blood. </li></ul></ul><ul><li>Extrinsic Pathway </li></ul><ul><ul><li>By contrast, when blood is exposed to an additional factor in tissues underneath the damaged endothelium called tissue factor (TF), factor III, or tissue thromboplastin , the “shortcut” extrinsic mechanism, which bypasses several steps of the intrinsic pathway, is triggered. </li></ul></ul><ul><li>Role of calcium </li></ul><ul><ul><li>Each pathway requires ionic calcium and involves the activation of a series of procoagulants, each functioning as an enzyme to activate the next procoagulant in the sequence. </li></ul></ul><ul><ul><li>The intermediate steps of each pathway cascade toward a common intermediate, factor X. </li></ul></ul><ul><ul><li>Activated factor X complexes with calcium ions, PF3, and factor V to form prothrombin activator. </li></ul></ul><ul><ul><li>Slowest step of the blood clotting process, but once formed, the clot forms in 10 to 15 seconds. </li></ul></ul>Phase 1- Formation of prothrombin Activator
    87. 87. Intrinsic Pathway Blood Trauma or contact with collagen XII (Hageman) Activated XII (XII a ) HMW Kininogen, Prekellikerein XI (PTA) Activated XI (XI a ) IX (PTC) Activated IX (IX a ) Ca ++ X (SPF) Activated X (X a ) Ca ++ VIII (AHF-A) VIIIa Thrombin Ca ++ Thrombin V Prothrombin Activator V a Prothrombin Thrombin or PF 3 Ca ++ (1) (2) (3) (4) (5)
    88. 88. Extrinsic Pathway Tissue trauma VII (Proconvertin) Activated VII (VII a ) X (SPF) Activated X (X a ) Ca ++ Ca ++ Thrombin V Prothrombin Activator V a Prothrombin Thrombin or PF 3 Ca ++ (1) (2) (3)
    89. 89. Phase 2: Common Pathway to Thrombin <ul><li>Prothrombin activator catalyzes the transformation of the plasma protein prothrombin to the active enzyme thrombin . </li></ul>Prothrombin Activator complex Prothrombin Thrombin Extrinsic pathway Intrinsic pathway
    90. 90. Phase 3: Common Pathway to the Fibrin Mesh <ul><li>Thrombin catalyzes the polymerization of fibrinogen (another plasma protein made by the liver). </li></ul><ul><li>Thrombin is a protein enzyme with weak proteolytic capabilities. It acts on fibrinogen to remove four low-molecular weight peptides from each molecule of fibrinogen, forming one molecule of fibrin monomer. </li></ul><ul><li>Fibrin monomers has the automatic capability to polymerize with other fibrin monomer molecules to form fibrin fibers . </li></ul><ul><li>Many fibrin monomer molecules polymerize within seconds into long fibrin fibers. </li></ul>
    91. 91. <ul><li>During early polymerization, fibrin fibers are held together by weak non covalent hydrogen bonding, No cross-linkage with one another. </li></ul><ul><li>fibrin-stabilizing factor causes the cross linkage of fibrin fibers (Released from platelets entrapped in the clot). </li></ul><ul><li>Activated by thrombin </li></ul><ul><li>This activated substance operates as an enzyme to form covalent bonds between fibrin monomer molecules, as well as multiple cross linkages between adjacent fibrin fibers. </li></ul>Lets watch it
    92. 92. <ul><li>Within 30 to 60 minutes, the clot is stabilized further by a platelet-induced process called clot retraction. </li></ul><ul><li>Platelets contain contractile proteins (actin and myosin), and they contract in much the same manner as muscle cells. </li></ul><ul><li>As the platelets contract, they pull on the surrounding fibrin strands, squeezing serum (plasma minus the clotting proteins) from the mass, compacting the clot and drawing the ruptured edges of the blood vessel more closely together. </li></ul><ul><li>Even as clot retraction is occurring, vessel healing is taking place. </li></ul><ul><li>Platelet-derived growth factor (PDGF) released by platelet degranulation stimulates smooth muscle cells and fibroblasts to divide and rebuild the wall. </li></ul><ul><li>As fibroblasts form a connective tissue patch in the injured area, endothelial cells, stimulated by vascular endothelial growth factor (VEGF), multiply and restore the endothelial lining. </li></ul>4-Clot Retraction and Repair
    93. 93. <ul><li>A process called fibrinolysis removes unneeded clots when healing has occurred. </li></ul><ul><li>Because small clots are formed continually in vessels, this cleanup is important. Without fibrinolysis, blood vessels would gradually become completely blocked. </li></ul><ul><li>The critical natural “clot buster” is a fibrin-digesting enzyme called plasmin , which is produced when the plasma protein plasminogen is activated. </li></ul><ul><li>Large amounts of plasminogen are incorporated into a forming clot, where it remains inactive until appropriate signals reach it. </li></ul><ul><ul><ul><li>The presence of a clot in and around the blood vessel causes the endothelial cells to secrete </li></ul></ul></ul><ul><ul><ul><ul><li>tissue plasminogen activator (tPA). </li></ul></ul></ul></ul><ul><ul><ul><li>Along with that </li></ul></ul></ul><ul><ul><ul><ul><li>Activated factor XII and </li></ul></ul></ul></ul><ul><ul><ul><ul><li>thrombin </li></ul></ul></ul></ul><ul><ul><ul><li>released during clotting also serve as plasminogen activators. As a result, most plasmin activity is confined to the clot, and any plasmin that strays into the plasma is quickly destroyed by circulating enzymes. </li></ul></ul></ul><ul><li>Fibrinolysis begins within two days and continues slowly over several days until the clot is finally dissolved. </li></ul>Fibrinolysis
    94. 94. <ul><li>Normally, two homeostatic mechanisms prevent clots from becoming unnecessarily large: </li></ul><ul><ul><ul><li>swift removal of clotting factors, and </li></ul></ul></ul><ul><ul><ul><li>inhibition of activated clotting factors. </li></ul></ul></ul><ul><li>Limiting the Activity of Thrombin </li></ul><ul><ul><li>As a clot forms, almost all of the thrombin produced is bound onto the fibrin threads. </li></ul></ul><ul><ul><li>This is an important safeguard because thrombin also exerts positive feedback effects on the coagulation process prior to the common pathway. </li></ul></ul><ul><ul><ul><li>It speed up the production of prothrombin activator by acting through factor V, </li></ul></ul></ul><ul><ul><ul><li>It also accelerates the earliest steps of the intrinsic pathway by activating platelets. </li></ul></ul></ul><ul><ul><li>Thus, fibrin effectively acts as an anticoagulant to prevent enlargement of the clot and prevents thrombin from acting elsewhere. </li></ul></ul><ul><ul><li>Thrombin not bound to fibrin is quickly inactivated by antithrombin III , a protein present in plasma. It inactivates the protease activity of thrombin and factors IXa, Xa, XIa and XIIa by forming complexes with them. </li></ul></ul><ul><ul><li>Heparin , the natural anticoagulant contained in basophil and mast cell granules, inhibits thrombin by enhancing the activity of antithrombin III. </li></ul></ul>Factors Limiting Normal Clot Growth
    95. 95. <ul><li>Thromboembolic disorders </li></ul><ul><ul><ul><li>Resulting from conditions that cause undesirable clot formation. </li></ul></ul></ul><ul><li>Disseminated intravascular coagulation (DIC) </li></ul><ul><ul><ul><li>Involving both wide spread clotting and severe bleeding. </li></ul></ul></ul><ul><li>Bleeding disorders </li></ul><ul><ul><ul><li>Arising from abnormalities that prevent normal clot formation. </li></ul></ul></ul><ul><li>-Thromboembolic Conditions </li></ul><ul><ul><li>A clot that develops and persists in an unbroken blood vessel is called a thrombus . It may block circulation to the cells beyond the occlusion and lead to death of those tissues. </li></ul></ul><ul><ul><ul><li>eg coronary thrombosis. </li></ul></ul></ul><ul><ul><li>Free Floating thrombus in the bloodstream is called an embolus (plural: emboli). Casue embolism by obstructing the vessel. </li></ul></ul><ul><ul><ul><li>For example, emboli that become trapped in the lungs (pulmonary embolisms). </li></ul></ul></ul><ul><ul><ul><li>A cerebral embolism may cause a stroke. </li></ul></ul></ul><ul><ul><li>Conditions that roughen the vessel endothelium, like atherosclerosis or inflammation, cause thromboembolic disease by allowing platelets to clump. </li></ul></ul><ul><ul><li>Slowly flowing blood or blood stasis is another risk factor, eg in bedridden patients (No quick washing away of clotting factors). </li></ul></ul>Disorders of Hemostasis
    96. 96. <ul><li>Disorders of Hemostasis </li></ul><ul><li>Disseminated Intravascular Coagulation </li></ul><ul><li>DIC is a situation in which widespread clotting occurs in intact blood vessels and the residual blood becomes unable to clot. </li></ul><ul><ul><ul><li>Blockage of blood flow </li></ul></ul></ul><ul><ul><ul><li>Severe bleeding follows </li></ul></ul></ul><ul><li>DIC is most commonly encountered as a complication of pregnancy or a result of septicemia or cancers. </li></ul>
    97. 97. <ul><li>The most common causes are </li></ul><ul><ul><li>Platelet deficiency (thrombocytopenia) </li></ul></ul><ul><ul><li>Deficiencts of some procoagulants, (which can result from impaired liver function) </li></ul></ul><ul><ul><li>Hemophilias (certain genetic conditions.) </li></ul></ul><ul><li>Thrombocytopenia     </li></ul><ul><ul><li>A condition in which the number of circulating platelets is deficient, evidenced by many small purplish blotches, called petechiae (pe-te′ke-e), on the skin. </li></ul></ul><ul><ul><li>Cause: </li></ul></ul><ul><ul><ul><li>Condition that suppresses or destroys the bone marrow, such as bone marrow malignancy, </li></ul></ul></ul><ul><ul><ul><li>exposure to ionizing radiation, or certain drugs. </li></ul></ul></ul><ul><li>A platelet count of under 50,000/µl of blood is usually diagnostic for this condition. </li></ul><ul><li>Impaired Liver Function   </li></ul><ul><ul><li>When the liver is unable to synthesize its usual supply of procoagulants, abnormal, and often severe, bleeding occurs. </li></ul></ul><ul><ul><li>Cause: </li></ul></ul><ul><ul><ul><li>Vitamin K deficiency (common in newborns or after taking systemic Antibiotics) </li></ul></ul></ul><ul><ul><ul><ul><li>Destruction of Intestinal flora </li></ul></ul></ul></ul><ul><ul><ul><ul><li>Intestinal malabsorption </li></ul></ul></ul></ul><ul><ul><ul><li>Impairment of liver function (as in hepatitis or cirrhosis). </li></ul></ul></ul><ul><li>Bleeding Disorders </li></ul>
    98. 98. <ul><li>Hemophilias     </li></ul><ul><li>The term hemophilia refers to several different hereditary bleeding disorders that have similar signs and symptoms. </li></ul><ul><li>Hemophilia A, or classical hemophilia, </li></ul><ul><ul><ul><li>Results from a deficiency of factor VIII (antihemophilic factor). </li></ul></ul></ul><ul><ul><ul><li>It accounts for 77% of cases. </li></ul></ul></ul><ul><li>Hemophilia B </li></ul><ul><ul><ul><li>Results from a deficiency of factor IX. </li></ul></ul></ul><ul><li>Both types are X-linked conditions occurring primarily in males. </li></ul><ul><li>Hemophilia C, </li></ul><ul><li>A less severe form of hemophilia seen in both sexes, is due to a lack of factor XI. The relative mildness of this form, as compared to the A and B forms, reflects the fact that the procoagulant (factor IX) that factor XI activates may also be activated by factor VII </li></ul><ul><li>Symptoms: </li></ul><ul><ul><ul><li>Symptoms of hemophilia begin early in life; </li></ul></ul></ul><ul><ul><ul><li>even minor tissue trauma causes prolonged bleeding into tissues that can be life threatening. </li></ul></ul></ul><ul><ul><ul><li>Commonly, the person’s joints become seriously disabled and painful because of repeated bleeding into the joint cavities after exercise or trauma. </li></ul></ul></ul><ul><li>Treatment: </li></ul><ul><ul><ul><li>Transfusions of fresh plasma or injections of the appropriate purified clotting factor. These therapies provide relief for several days but are expensive and inconvenient. </li></ul></ul></ul>Bleeding Disorders
    99. 99. <ul><li>Blood Sample </li></ul><ul><ul><li>Complete Blood Count (CBC) </li></ul></ul><ul><ul><ul><li>WBC’s (4000-10800 cells/mm 3 ) </li></ul></ul></ul><ul><ul><ul><li>Plateltes (150,000-400,000 cells/mm 3 ) </li></ul></ul></ul><ul><ul><ul><li>RBC’s (Male: 4.6–5.9, Female: 4.2–5.4 million cells/mm 3 ) </li></ul></ul></ul><ul><ul><ul><ul><li>Direct measurements </li></ul></ul></ul></ul><ul><ul><ul><ul><ul><li>RCC (Red cells Count) </li></ul></ul></ul></ul></ul><ul><ul><ul><ul><ul><li>Hb Concentration (g/dl) </li></ul></ul></ul></ul></ul><ul><ul><ul><ul><ul><li>Hematocrit (Hct) (Vol of RBC’s / Vol of whole blood) </li></ul></ul></ul></ul></ul><ul><ul><ul><ul><li>Calculated from direct measurements </li></ul></ul></ul></ul><ul><ul><ul><ul><ul><li>MCH (Mean Corpuscular Hb Mass / RBC) </li></ul></ul></ul></ul></ul><ul><ul><ul><ul><ul><li>MCV (Mean Corpuscular volume/RBC) </li></ul></ul></ul></ul></ul><ul><ul><ul><ul><ul><li>MCHC (Mean Corpsucular Hb Conc. per Liter (RBC) </li></ul></ul></ul></ul></ul>Blood Testing
    100. 100. Blood Testing
    101. 101. <ul><li>Diagnostic Classification </li></ul><ul><ul><li>Kinetic Approach </li></ul></ul><ul><ul><ul><li>Production vs. destruction or loss </li></ul></ul></ul><ul><ul><ul><ul><li>Reticulocyte Production Index (RPI) </li></ul></ul></ul></ul><ul><ul><li>Morphological Approach </li></ul></ul><ul><ul><ul><li>Red blood cell size </li></ul></ul></ul><ul><ul><ul><ul><li>Microcytic (Cells Smaller than normal size i.e. MCV< 80 fl) </li></ul></ul></ul></ul><ul><ul><ul><ul><li>Normocytic (Cells Normal sized i.e. MCV = 80-00 fl) </li></ul></ul></ul></ul><ul><ul><ul><ul><li>Macrocytic (Cells bigger than normal size i.e. > 100 fl) </li></ul></ul></ul></ul><ul><ul><ul><li>Concentration of Hb </li></ul></ul></ul><ul><ul><ul><ul><li>Hyperchromic (Increased Hb Concentration) </li></ul></ul></ul></ul><ul><ul><ul><ul><li>Normochromic (Normal Hb Concentration) </li></ul></ul></ul></ul><ul><ul><ul><ul><li>Hypochromic (Decreased Hb Concentration- cells paler than normal) </li></ul></ul></ul></ul>Anemias
    102. 102. <ul><li>Anemia means deficiency of hemoglobin in the blood </li></ul><ul><ul><li>Cause </li></ul></ul><ul><ul><ul><li>Too few red blood cells or </li></ul></ul></ul><ul><ul><ul><li>Too little hemoglobin in the cells. </li></ul></ul></ul><ul><li>Aplastic Anemia </li></ul><ul><ul><li>Anemia due to lack of functioning of Bone Marrow or bone marrow aplasia. Aplastic anemia patients have lower counts of all three blood cell types: termed pancytopenia. </li></ul></ul><ul><ul><li>Causes </li></ul></ul><ul><ul><ul><li>Hereditary </li></ul></ul></ul><ul><ul><ul><ul><li>Congenital hypoplastic anemia (or constitutional aplastic anemia) refers to a type of aplastic anemia which is primarily due to a congenital disorder (defects or damage to a developing fetus). </li></ul></ul></ul></ul><ul><ul><ul><ul><li>Examples include: </li></ul></ul></ul></ul><ul><ul><ul><ul><ul><li>Fanconi anemia (Caused by short Stature, Skeletal Abnormalities) </li></ul></ul></ul></ul></ul><ul><ul><ul><ul><ul><li>Diamond-Blackfan anemia (Congenital Erythroid Aplasia- Characterized by anemia with decreased erythroid progenitors in bone marrow) </li></ul></ul></ul></ul></ul>Anemias
    103. 103. <ul><ul><ul><li>Acquired </li></ul></ul></ul><ul><ul><ul><ul><li>Pure Red cell Aplasia (PRCA) </li></ul></ul></ul></ul><ul><ul><ul><ul><li>Sideroblastic anemia (Sideroachrestic anemia) 1 The body has iron available, but cannot incorporate it into hemoglobin </li></ul></ul></ul></ul><ul><ul><ul><ul><li>Myelophthisic anemia 2 (Normal marrow space is replaced by nonhematopoietic or abnormal cells). Cause e.g. tumors </li></ul></ul></ul></ul><ul><li>Nutritional Anemia </li></ul><ul><li>Hemolytic Anemia </li></ul>Anemias