Essentials of Pathophysiology CHAPTER 13 THE RED BLOOD CELL AND ALTERATIONS IN OXYGEN TRANSPORT COMPOSITION OF BLOOD ➤ Blood is a liquid that fills the vascular compartment and serves to transport dissolved materials and blood cells throughout the body. ➤ The most abundant of the blood cells, the erythrocytes or red blood cells, function in oxygen and carbon dioxide transport. ➤ The leukocytes, or white blood cells, serve various roles in immunity and inflammation. ➤ Platelets are small cell fragments that are involved in blood clotting. COMPOSITION OF BLOOD BLOOD CELLULAR COMPONENT RBCS WBCS PLATELETS FLUID COMPONENT PLASMA PRE LECTURE QUIZ Aplastic Erythrocytes Mature red blood cells are also known as ____Erythrocytes________________. The function of red blood cells is to transport _oxygen___________________ from the lungs to the tissues. If red blood cell destruction is excessive, bilirubin production is increased, causing a yellow discoloration of the skin called Jaundice______________________. Rh disease of the newborn is an example of ____Aplastic________________ anemia. Hemolytic Jaundice oxygen ____Hemolytic________________ anemia describes a primary condition of bone marrow stem cells that results in a reduction of all three hematopoietic cell lines—red blood cells, white blood cells, and platelets. RED BLOOD CELLS Main carrier or transporter of Oxygen to the body tissues. Matured forms are biconcave discs in shape with no nucleus Oxygen transport is facilitated by an iron containing molecule-HAEMOGLOBIN Life span of RBCS-120 days Production is in the Bone marrowErythropoiesis ADULT HEMOGLOBIN (Hb A) Two alpha chains Two beta chains Each protein chain holds one iron-containing heme group Oxygen binds to the heme groups QUESTION How many molecules of oxygen can be carried by one molecule of hemoglobin? a. 1 b. 2 c. 3 d. 4 ANSWER 4 Rationale: Each hemoglobin molecule has 2 alpha and 2 beta protein chains. Each chain contains 1 heme group. Each heme group (4 chains = 4 heme groups) is capable of carrying 1 molecule of oxygen. decreased blood oxygen ERYTHROPOIESIS kidneys secrete erythropoietin bone marrow stimulated creates new red blood cells RED BLOOD CELLS bone marrow creates new red blood cells: may release immature RBCs (nucleated) reticulocytes (RBCs that still have their endoplasmic reticulum) mature RBCs CLINICAL SCENARIO RBCS LAST ABOUT 120 DAYS Their membranes become weakened Because they have no nuclei, RBCs cannot make new membrane components Eventually, RBCs break as they squeeze through the capillaries mature RBCs circulate for 120 days become damaged MOST RBCS BREAK IN THE SPLEEN White blood cells living in the spleen are ready to process RBCs Creating unconjugated bilirubin break in capillaries of the spleen eaten by white blood cells in the spleen, liver, bone marrow, or lymph nodes hemoglobin processed into bilirubin THE FATE OF BILIRUBIN Unconjugated bilirubin is toxic unconjugated bilirubin in blood X bilirubinemia liver links it to gluconuride jaundice conjugated bilirubin bile CLINICAL SCENARIO Why would a man with liver failure develop jaundice? WHEN RBCS ARE DESTROYED OUTSIDE THE SPLEEN(IN CIRCULATION)-HAEMOLYSIS Hemoglobinemia occurs-Free Hb Excreted in the urine(Hemoglobinuria) makes the urine cola-colored break in capillaries outside the spleen hemoglobin released into the blood hemoglobinemia hemoglobinuria MALARIA PARASITES Question: Why was malaria called “blackwater fever?” QUESTION Red blood cells (erythrocytes) are made in the ________ and destroyed in the _________. a. b. c. d. kidneys, liver kidneys, spleen bone marrow, spleen bone marrow, liver ANSWER c. bone marrow, spleen Rationale: Erythropoietin, made in the kidneys, stimulates the bone marrow to produce RBCs. Eventually, RBCs break up in the capillaries of the spleen and their hemoglobin is processed as bilirubin in the liver. ANAEMIA It is the deficiency of red blood cells or haemoglobin or both, resulting in diminished oxygen-carrying capacity. CAUSES OF ANAEMIA Blood loss Hemolysis Impaired RBC production SCENARIO A man had severe anemia and developed: Weakness - Tissue Hypoxia Angina - Tissue Hypoxia Fainting - Brain Hypoxia Headache – Brain Hypoxia Tachycardia - Increase Cardiac Output Sweating - Increase Cardiac Output Pallor - Redistribution of blood from peripheral tissues/low Hb levels Pain in his bones and sternum – Acceleration of Erythropoiesis TYPES OF ANAEMIAS Impaired RBC Production Megaloblastic anaemias Cobalamin (Vitamin B12) deficiency (Needed for DNA replication) º Pernicious anemia-malabsorption of vit B12 from gastric mucosa Folic acid deficiency (Needed for DNA replication) Chronic inflammation-TB,AIDS Chronic renal failure Aplastic anaemia (bone marrow depression) Deficiency in Iron- For Hb synthesis Chronic disease anaemias Lymphocyte cytokines suppress erythropoietin production Erythropoietin not produced IRON-DEFICIENCY ANAEMIA Hypochromic and microcytic erythrocytes Poikilocytosis (irregular shape) (poi'kə-lō-sī-tō'sĭs) Anisocytosis (irregular size) (ān-ī'sō-sī-tō'sĭs) (Rubin E., Farber J.L. [1999]. Pathology [3rd ed., p. 1077]. Philadelphia: Lippincott-Raven.) VITAMIN B12 DEFICIENCY (PERNICIOUS ANAEMIA) Megaloblastic anemia Erythrocytes are large, often with oval shape Poikilocytosis and teardrop shapes Anisocytosis (Irreg. size) Neutrophils are hypersegmented (Rubin E., Farber J.L. [1999]. Pathology [3rd ed., p. 1076]. Philadelphia: LippincottRaven.) QUESTION Which type of deficiency causes pernicious anemia? a. Iron b. Vitamin B6 c. Vitamin B12 d. Folic acid ANSWER c. Vitamin B12 Rationale: Intrinsic factor produced by cells of the gastric mucosa binds vitamin B12 and assists absorption of B12. When gastric mucosa cells are lacking often due to autoimmune antibodies attacking gastric mucosa production of IF is reduced and B12 is not absorbed. HAEMOLYTIC ANEMIAS Membrane disorders , RBC shape and fragility Hereditary spherocytosis (deficiency in membrane proteins) Acquired hemolytic anemias (chemicals, drugs, antibodies) hemolytic disease of the newborn-Rh incompatibility Hemoglobinopathies Sickle cell disease Thalassemia º Alpha º Beta G6PD deficiency (Glucose 6 Phosphate Dehydrogenase enzyme deficiency) SCENARIO A boy presents with: Pallor Weakness Low red blood cell count Increased respiratory and heart rates Yellow skin Dark brown urine Enlarged spleen and liver Question: What is your diagnosis? Is he lacking RBC production or haemolytic anaemia? Which symptoms are caused by decreased RBC count? Tissue Hypoxia? Cardiac compensation? By haemolysis? G6PD G6PD Heinz bodies on the periphery Heinz bodies are inclusions within red blood cells composed of denatured haemoglobin. SICKLE CELL DISEASE Mutation in beta chains of hemoglobin Sickle hemoglobin (HbS) is transmitted by recessive inheritance – heterozygote (trait – 1 HbS gene) or sickle cell disease (i.e., homozygote with 2 HbS genes) When haemoglobin is deoxygenated, beta chains link together Forming long protein rods that make the cell “sickle” SICKLE CELL DISEASE Mutation in beta chains of hemoglobin At a single location in the protein chain valine is substituted for glutamic acid Valine Glutamic acid When hemoglobin is deoxygenated, beta chains link together, forming long protein rods that make the cell “sickle” PROBLEMS CAUSED BY SICKLE CELL DISEASE Sickled cells block capillaries Acute pain Infarctions cause chronic damage to liver, spleen, heart, kidneys, eyes, bones Pulmonary infarction acute chest syndrome (Pneumonia) Cerebral infarction stroke Sickled cells more likely to be destroyed Releasing excess bilirubin Jaundice SICKLE CELL DISEASE INHERITANCE Scenario: A man has sickle trait (heterozygous for sickle cell) His wife has sickle cell disease Question: What percentage of their children will have the disease? SICKLE CELL DISEASE INHERITANCE s = Sickle Gene S= nonSickle percentage of their children s s S Ss Ss s ss ss Father has the Trait, Ss Mother has the disease, ss Possible Children’s Genotype 50% have the disease, ss 50% are Heterozygous, Ss QUESTION True or False. Patients with sickle cell disease who also suffer from lung diseases are more prone to sickling. ANSWER True Rationale: Hypoxia, which is more likely to occur in lung/pulmonary disease, is an important exacerbating factor associated with increased sickling and vessel occlusion. FETAL HEMOGLOBIN HAS NO BETA CHAINS It has alpha chains and gamma chains This means it cannot sickle Persons with some fetal hemoglobin are partially protected from sickle cell disease Some treatments include inducing HbF production THALASSEMIAS Due to absent or defective synthesis of the α or the β chains of adult hemoglobin. The β-thalassemias result from one of nearly 200 point mutations in the β-globin gene causing a defect in β-chain synthesis. The α-thalassemias are caused by a gene deletion that results in defective α-chain synthesis. A person may be heterozygous for the trait and have a mild form of the disease or be homozygous and have the severe form of the disease. THALASSEMIAS Alpha Beta • Defective gene for alphachain synthesis • Defective gene for betachain synthesis • May have 1–4 defective genes • May have 1–2 defective genes • Affects both fetal and adult Hb • Affects only adult Hb • More common in Asians • Also called Cooleys or Mediterranean anaemia. • Common in Greece and Italy SCENARIO A woman has β thalassemia. She has pale skin and gums, fatigue, and headaches She has been treated with transfusions since childhood Her jaw is enlarged; she has had two leg fractures in the past year(Thin cortical bone with enlarged marrow. Bone deposition on jaw) She has Heinz bodies (precipitate aggregate of excess α chains in RBC) Her liver is enlarged; she has jaundice and liver failure Question: Which of these signs and symptoms are due to anemia, which to compensatory erythropoiesis, and which to treatment? PRE LECTURE QUIZ (TRUE/FALSE) T F F F F There are two major types of hemoglobin—adult hemoglobin (HbA) and fetal hemoglobin (HbF). Sickle cell disease is a chronic disorder that results from changes in the size of red blood cells, not their shape. Iron-deficiency anemia affects only infants and toddlers. Hyperbilirubinemia is an increased level of serum bilirubin and very often causes cyanosis in the neonate. Thalassemias are inherited disorders of platelet synthesis that cause severe bruising and bleeding.
