Presentation on theme: "Chapter 13 The Red Blood Cell and Alterations in Oxygen Transport"— Presentation transcript:
1Chapter 13 The Red Blood Cell and Alterations in Oxygen Transport Essentials of PathophysiologyChapter 13 The Red Blood Cell and Alterations in Oxygen Transport
2PRE LECTURE QUIZ (True/false) 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.
3PRE LECTURE QUIZMature red blood cells are also known as ____________________.The function of red blood cells is to transport ____________________ 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 ______________________.Rh disease of the newborn is an example of ____________________ anemia.____________________ 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.AplasticErythrocytesHemolyticJaundiceoxygen
4Adult Hemoglobin Two alpha chains Two beta chains Each protein chain holds one iron-containing heme groupOxygen binds to the heme groups
5QuestionHow many molecules of oxygen can be carried by one molecule of hemoglobin?1234
6Answer4 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.
7ErythropoiesisWhy would a man receiving chemotherapy for cancer develop anemia?Why would a man with renal failure develop anemia?decreased bloodoxygenkidneys secreteerythropoietinbonemarrowstimulatedcreates newred blood cells
8Red Blood Cells bone marrow creates new red blood cells: may release immaturematurereticulocytes (RBCsRBCsRBCsthat still have their(nucleated)endoplasmic reticulum)
9mature RBCs circulate for 120 days become damaged RBCs Last About 120 DaysRBCsTheir membranes become weakenedBecause they have no nuclei, RBCs cannot make new membrane components, Why?Eventually, RBCs break as they squeeze through the capillariescirculatefor 120daysbecomedamaged
10Most RBCs Break in the Spleen capillariesof theWhite blood cells living in the spleen are ready to process RBCsCreating unconjugated bilirubinQuestion:Why would a man with defective red blood cells develop hepatosplenomegaly?Answer: Spleen & Liver have sluggish circulation subject to clotting causing ischemia with lack of circulation to carry away toxinsspleeneaten by white bloodcells in the spleen, liver,bone marrow, or lymphnodeshemoglobinprocessedintobilirubin
11Why would a man with liver failure develop jaundice? unconjugatedThe Fate of Bilirubinbilirubin inbloodXUnconjugated bilirubin is toxicQuestion:Why would a man with liver failure develop jaundice?bilirubinemialiver links ittogluconuridejaundiceconjugatedbilirubinbile
13When RBCs Are Destroyed Outside the Spleen… break incapillaries outsidethe spleenHemoglobinemia makes the plasma turn redHemoglobinuria makes the urine cola-coloredQuestion:Why was malaria called “blackwater fever?”hemoglobinreleased into thebloodhemoglobinemiahemoglobinuria
14QuestionRed blood cells (erythrocytes) are made in the ________ and destroyed in the _________.kidneys, liverkidneys, spleenbone marrow, spleenbone marrow, liver
15Answerbone marrow, spleenRationale: 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.
17Causes of AnemiaBlood lossHemolysisImpaired RBC production
18Question: Scenario A man had severe anemia and developed: Weakness AnginaFaintingTachycardiaSweating and pallorPain in his bones and sternumQuestion:Which symptoms are caused by decreased RBCs, O2?By compensation using the GAS?By attempts to replace the RBCs?
19Anemias of Deficient RBC Production Iron deficiency anemia (often caused by blood loss)Megaloblastic anemiasCobalamin (Vitamin B12) deficiency (Needed for DNA replication)Pernicious anemiaFolic acid deficiency (Needed for DNA replication)Aplastic anemia (bone marrow depression)Chronic disease anemiasChronic inflammationLymphocyte cytokines suppress erythropoietin productionChronic renal failureErythropoietin not produced
20Iron-Deficiency Anemia Hypochromic and microcytic erythrocytesPoikilocytosis (irregular shape) (poi'kə-lō-sī-tō'sĭs)Anisocytosis (irregular size) (ān-ī'sō-sī-tō'sĭs)(Rubin E., Farber J.L. . Pathology [3rd ed., p. 1077]. Philadelphia: Lippincott-Raven.)
21Vitamin B12 Deficiency (Pernicious Anemia) Megaloblastic anemiaErythrocytes are large, often with oval shapePoikilocytosis and teardrop shapesAnisocytosis (Irreg. size)Neutrophils are hypersegmented(Rubin E., Farber J.L. . Pathology [3rd ed., p. 1076]. Philadelphia: Lippincott-Raven.)
22Scenario A boy presents with: Pallor Weakness Low red blood cell count Increased respiratory and heart ratesYellow skinDark brown urineEnlarged spleen and liverQuestion:What is your diagnosis?Is he lacking RBC production or hemolytic anemia?Which symptoms are caused by decreased RBC count?By GAS?By hemolysis?
23QuestionWhich type of deficiency causes pernicious anemia?IronVitamin B6Vitamin B12Folic acid
24AnswerVitamin B12Rationale: 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.
25Hemolytic Anemias Membrane disorders , RBC shape and fragility Hereditary spherocytosis (shape holding inner membrane)Acquired hemolytic anemias (chemicals drugs, antibodies) hemolytic disease of the newborn-Rh incompatibilityHemoglobinopathiesSickle cell diseaseThalassemiaAlphaBetaG6PD deficiency (Glucose 6 Phosphate Dehydrogenase enzyme deficiency- limits RBC’s ATP production)any of a group of inherited hypochromic anemias and especially Cooley's anemia controlled by a series of allelic genes that cause reduction in or failure of synthesis of one of the globin chains making up hemoglobin and that tend to occur especially in individuals of Mediterranean, African, or southeastern Asian ancestry —sometimes used with a prefix (as alpha-, beta-, or delta-) to indicate the hemoglobin chain affected.
26G6PDG6PD Easily mistaken for malaria.Heinz bodies on the periphery
27Sickle 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”
28Sickle Cell Disease Mutation in beta chains of hemoglobin At a single location in the protein chain valine is substituted for glutamic acidWhen hemoglobin is deoxygenated, beta chains link together, forming long protein rods that make the cell “sickle”ValineGlutamic acid
29Problems Caused by Sickle Cell Disease Sickled cells block capillariesAcute painInfarctions cause chronic damage to liver, spleen, heart, kidneys, eyes, bonesPulmonary infarction acute chest syndrome (Pneumonia)Cerebral infarction strokeSickled cells more likely to be destroyedReleasing excess bilirubin Jaundice
30Sickle Cell Disease Inheritance Scenario:A man has sickle trait (heterozygous for sickle cell)His wife has sickle cell diseaseQuestion: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’s population will have sickle trait?Use the Hardy-Wienberg Equilibrum equations: p+q=1 ; p= probability of normal gene and q = prob. of Sickleq2 + 2pq + p2 =1 ; 2pq= freq of occurrence of father’s genotype, heterozygous
31Possible Children’s Genotype Sickle Cell Disease Inheritances = Sickle GeneS= nonSicklepercentage of their childrenMothers sFatherMother has the disease, ssSsSsssSsssPossible Children’s Genotype50% have the disease, ss50% are Heterozygous, SsFather has the Trait, Ss
32Solve for frequency HETEROZYGOTES IN THE POPULATION Use the Hardy-Wienberg Equilibrum equations: p+q=1 ; p= probability of normal gene and q = prob. of Sickleq2 + 2pq + p2 =1 ; 2pq= freq of occurrence of father’s genotype, heterozygousGiven: Frequency of Sickle gene = 10%In the Hardy-Wienberg equation q=.1Therefore p= 1-.1=.9 or 90% of genes are normalq2 = percent with sickle disease = (.1)2 = .01 =1% Question: What is the % heterozygousFrom equations 2pq= 2(.1*.9) =.18 or 18% have the trait without the disease
33QuestionTrue or False. Patients with sickle cell disease who also suffer from lung diseases are more prone to sickling.
34AnswerTrue Rationale: Hypoxia, which is more likely to occur in lung/pulmonary disease, is an important exacerbating factor associated with increased sickling and vessel occlusion.
35Fetal Hemoglobin Has No Beta Chains It has alpha chains and gamma chainsThis means it cannot sicklePersons with some fetal hemoglobin are partially protected from sickle cell diseaseSome treatments include inducing HbF production
36Thalassemias Alpha Beta Defective gene for alpha- chain synthesis May have 1–4 defective genesAffects both fetal and adult HbIn fetus, gamma4 Hb may form; in adult, beta4 Hb may formDefective gene for beta- chain synthesisMay have 1–2 defective genesAffects only adult HbAlpha4 Hb may form
37Scenario A woman has β thalassemia. p219 She has pale skin and gums, fatigue, and headachesShe has been treated with transfusions since childhoodHer jaw is enlarged; she has had two leg fractures in the past year(Thin cortical bone w/ 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 failureQuestion:Which of these signs and symptoms are due to anemia, which to compensatory erythropoiesis, and which to treatment?