Chapter 11 The Red Blood Cell and Alterations in Oxygen Transport

Adult Hemoglobin 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? 1 2 3 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 Erythropoiesis oxygen Why would a man receiving chemotherapy for cancer develop anemia? Why would a man with renal failure develop anemia? kidneys secrete erythropoietin bone marrow stimulated creates new red blood cells

Red Blood Cells bone marrow creates new red blood cells: may release immature mature reticulocytes (RBCs RBCs RBCs that still have their (nucleated) endoplasmic reticulum)

mature RBCs circulate for 120 days become damaged RBCs Last About 120 Days RBCs Their membranes become weakened Because they have no nuclei, RBCs cannot make new membrane components Eventually, RBCs break as they squeeze through the capillaries circulate for 120 days become damaged

Most RBCs Break in the Spleen capillaries of the spleen White blood cells living in the spleen are ready to process RBCs Creating unconjugated bilirubin Question: Why would a man with defective red blood cells develop hepatosplenomegaly? eaten by white blood cells in the spleen, liver, bone marrow, or lymph nodes hemoglobin processed into bilirubin

The Fate of Bilirubin unconjugated bilirubin in blood bilirubinemia Unconjugated bilirubin is toxic Question: Why would a man with liver failure develop jaundice? bilirubinemia liver links it to gluconuride jaundice conjugated bilirubin bile

When RBCs Are Destroyed Outside the Spleen… break in When RBCs Are Destroyed Outside the Spleen… capillaries outside the spleen Hemoglobinemia makes the plasma turn red Hemoglobinuria makes the urine cola-colored Question: Why was malaria called “blackwater fever?” hemoglobin released into the blood hemoglobinemia hemoglobinuria

Question Red blood cells (erythrocytes) are made in the ________ and destroyed in the _________. kidneys, liver kidneys, spleen bone marrow, spleen bone marrow, liver

Answer 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.

Causes of Anemia Blood loss Hemolysis Impaired RBC production

Scenario A man had severe anemia and developed: Weakness Angina Fainting Tachycardia Sweating and pallor Pain in his bones and sternum Question: Which symptoms are caused by decreased RBCs, O2? By compensation using the GAS? By attempts to replace the RBCs?

Anemias of Deficient RBC Production Iron deficiency anemia (often caused by blood loss) Megaloblastic anemias Cobalamin (Vitamin B12) deficiency Pernicious anemia Folic acid deficiency Aplastic anemia (bone marrow depression) Chronic disease anemias Chronic inflammation Chronic renal failure

Iron-Deficiency Anemia Hypochromic and microcytic erythrocytes Poikilocytosis (irregular shape) Anisocytosis (irregular size) (Rubin E., Farber J.L. [1999]. Pathology [3rd ed., p. 1077]. Philadelphia: Lippincott-Raven.)

Vitamin B12 Deficiency (Pernicious Anemia) Megaloblastic anemia Erythrocytes are large, often with oval shape Poikilocytosis and teardrop shapes Neutrophils are hypersegmented (Rubin E., Farber J.L. [1999]. Pathology [3rd ed., p. 1076]. Philadelphia: Lippincott-Raven.)

Scenario A boy presents with: Pallor Weakness Increased respiratory and heart rates Enlarged spleen and liver Yellow skin Dark brown urine Low red blood cell count Question: Does he have a deficiency or hemolytic anemia? Which symptoms are caused by decreased RBC count and hypoxia? By GAS? By hemolysis?

Question Which type of deficiency is caused by pernicious anemia? Iron Vitamin B6 Vitamin B12 Folic acid

Answer Vitamin B12 Rationale: Pernicious anemia destroys the gastric mucosa, producing antibodies that block the binding of vitamin B12 to the intrinsic factor, blocking its absorption into the bloodstream.

Hemolytic Anemias Membrane disorders Hereditary spherocytosis Acquired hemolytic anemias and hemolytic disease of the newborn Hemoglobinopathies Sickle cell disease Thalassemia Alpha Beta G6PD deficiency

Sickle Cell Disease Mutation in beta chains of hemoglobin 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 Cerebral infarction  stroke Sickled cells more likely to be destroyed 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? In a population, the gene frequency of the sickle cell allele is 10% Assuming the gene is equally common in males and females and does not affect reproduction, what percentage of the next generation will have sickle trait?

Question Tell whether the following statement is 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

Thalassemias Alpha Beta Defective gene for alpha- chain synthesis May have 1–4 defective genes Affects both fetal and adult Hb In fetus, gamma4 Hb may form; in adult, beta4 Hb may form Defective gene for beta- chain synthesis May have 1–2 defective genes Affects only adult Hb Alpha4 Hb may form

Scenario A woman has 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 She has Heinz bodies 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?