Red Blood Cells, Anemia and Polycythemia

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Red Blood Cells, Anemia and Polycythemia. Prof. dr. Zoran Vali Department of Physiology University of Split School of Medicine. Red Blood Cells (Erythrocytes). functions: transport of hemoglobin (O 2 ) in some animals it circulates as free protein - PowerPoint PPT Presentation


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Red Blood Cells, Anemia and PolycythemiaProf. dr. Zoran ValiDepartment of PhysiologyUniversity of Split School of MedicineRed Blood Cells (Erythrocytes)functions:transport of hemoglobin (O2)in some animals it circulates as free proteinin humans within RBC loss by filtration 3%large quantity of carbonic anhydrase (CO2 and H2O)an excelent acid-base buffer (proteins)yolk sac (few early weeks)liver; spleen and lymph nodes(middle trimester of gestation)bone marrowbeyond the age of 20 most RBC are produced in membranous bones (vertebrae, sternum, ribs and ilia)biconcave discs (=7,8 m; V=90-95 m3)shape can change remarkably (squeeze through capillaries, excess of membrane)M = 5,2x1012F = 4,7x1012chemoglobin in RBC < 340 g/LHt = 40-45%chemohlobin in blood = 160-140 g/L

growth inducers proteins which control growth and reproduction of stem cellsinterleukin-3 promotes growth and reproduction of virtually all stem cellsdifferentiation inducers (low oxygen, infectious diseases)

1%bone marrow

tissue oxygenation most essential regulator (viscosity)hemorrhage, x-ray therapy, high altitudes, cardiac failure, lung diseaseserythropoietin (glycoprotein; 34000)90% is formed in kidneys (unknown, liver)fibroblast-like interstitial cells surrounding the tubules?renal tissue hypoxia (and some other) HIF-1 erythropoietinquick secretion (min 24 h), RBC in 5 daysproduction of proerythroblasts, speeding uperythropoietic cells are among the most rapidly growing and reproducing cellspersons nutritional statusvitamin B12 and folic acid (thymidine)macrocytes flimsy membrane and irregular, large shape shorten life span (1/2-1/3 normal)B12 pernicious anemia (atrophic gastric mucosa; parietal cells intrinsic factor)folic (pteroylglutaminic) acid widely spread but destroyed during cooking sprueFormation of Hemoglobinbegins in proerythroblasts and continues even into the reticulocyte stagesuccinyl-CoA from Krebs metabolic cyclealpha, beta, gamma and delta chainsmost common hemoglobin A (2 alpha, 2 beta chains)each hemoglobin molecule transports 4 molecules of oxygen

sickle cell anemia the amino acid valine is substituted for glutamic acid at one point in each of the two beta chains15 m elongated crystals in low oxygen environmentloosely and reversibly combining with O2coordination bond, molecular oxygen

Iron Metabolismhemoglobin, myoglobin, cytochrome-oksidase, peroxidase and catalasetotal iron in the body 4-5g (65% in hemoglobin, 4% in myoglobin, 15-30% in reticuloendothelial system and liver parenchymal cells)

transferrin molecule binds strongly with receptors in the cell membrane s of erythroblasts in bone marrow endocytosisinadequate quantities of transferrin failure to transport iron to the erythroblasts hypochromic anemiaAbsorption of Ironliver secretes moderate amounts of apotransferrin into the bile transferrin (with the iron, pinocytosis into enterocyts, plasma transferrin)absorption is slow and limited; total body iron is regulated mainly by altering the rate of absorptionLife Span of RBCaverage circulating time 120 dayscytoplasmic enzymes:maintaining pliability of the cell membranemaintain membrane transport of ionskeep the iron in ferrous, rather than ferric formprevent oxidation of the RBC proteinsmany RBC self-destruct in the spleen (when squeezing through the red pulp)hemoglobin is phagocytized by macrophages (Kupffer cells of the liver) iron and bilirubin (from porphyrin portion)Anemias (deficiency of hemoglobin)microcytic hypochromic anemia blood loss anemia (acute and chronic)aplastic anemia bone marrow aplasia (high-dose radiation, chemotherapy, drugs, toxic chemicals insecticides or benzene)megaloblastic anemia (lack of B12 (pernicious) or folic acid)hemolytic anemia (abnormalities (hereditary) of RBC)hereditary spherocytosis (small and spherical RBC)sickle cell anemia (hemoglobin S, crisis)erythroblastosis fetalisEffects of Anemia on Circulationviscosity of blood depends largely on RBCfall in blood viscosity decrease in total resistance (added tissue hypoxia vasodilation) increase in CO (3-4x) increased pumping workload on the heartproblems during exercise acute cardiac failurePolycythemiasecondary polycythemia due to hypoxia (at high altitude, cardiac failure) 6-7 x 1012 (30%)polycythemia vera (erythremia) 7-8 x 1012 (Ht = 60-70%) genetic aberration in the hemocytoblastic cellsincreased viscosity CO almost normal (decreased venous return, but increased blood volume), ruddy complexion with a bluish (cyanotic) tint to the skin)Blood Types; Transfusion; Tissue and Organ TransplatationAntigenicityfirst attempts were unsuccessfultransfusion reaction and deathblood posses antigenic and immune propertiesat least 30 commonly occurring, and hundreds of other antigensmost of antigens are week, used to establish parentagesystems: O-A-B and RhOAB system is discovered by Austrian scientist Karl Landsteiner 1900. (three types, awarded Nobel prize 1930; simultaneously with Czech serologist Jan Jansk)also with Alexander S Wiener identified Rh factor 1937.O-A-B Blood Typesantigens A i B (also called agglutinogens cause blood cell agglutination) occur on the surface of the RBCbecause of the way of inheritance people may have neither of them on their cells, they may have one or they may have both simultaneouslywhen neither A or B agglutinogen is present blood (person) is blood type Oonly agglutinogen A blood is type Aonly agglutinogen B blood is type Bwhen both agglutinogens are present blood is type AB

antigen H essential precursor of OAB blood antigenslocated on chromosome 19, posses 3 exons which are coding enzyme fucosyltransferaseenzyme creates H antigen on RBCcarbohydrate chain: -D-galactose, -D-N-acetilglucosamine, -D-galactose i -L-fucose (connection with protein or ceramid)OAB locus is on chromosome 9, has 7 exonsexon 7 is the biggest and contains the greatest portion of coding sequenceOAB locus has 3 allele types: O, A, Ballele A codes glycosyltransferase which bindes N-acetylgalactosamine on D-galactose end of H antigenallele B codes glycosyltransferase which bindes -D-galactose on D-galactose end of H antigenallele 0 has deletion in exon 6 loss of enzimatic activity only H antigen is present

Relative Frequencies of the Different Blood Types:047%A41%B9%AB3%there are 6 different allele types among white population: (A1, A2, B1, O1, O1v i O2), in Asian population B type is more frequent

Agglutininsantibodies directed at agglutinogensimmediately after birth not presentthey are formed 2-8 month after the birthmaximum titer is reached 8-10 years of agegamma-globulins (IgM i IgG)why are they produced?environmental antigens (bacteria, viruses, plants, foods)

for anti-A agglutinins influenzafor anti-B agglutinins gram-negative bacteria (E. coli)

light in the dark theory viruses during replication process incorporate parts of host membraneAgglutination Processagglutinins have 2 (IgG) or 10 (IgM) binding sites for agglutinogensattaching to two or more RBC bounding together (clump of cells) agglutinationplugging of small blood vessels throughout the circulation physical distortion of the cells or phagocytosis hemolysis of the RBCAcute Hemolysison rare occasionhemolysis occurs immediately in circulating bloodactivation of the complement system release of proteolytic enzymes (the lytic complex) rupture of the cell membranes (existence of high titer of IgM antibodies hemolysins)Blood Typingblood typing and blood matchingRBC are separated from the plasma and diluted with saline; mixing with anti-A and anti-B agglutinins

Rh Blood Typesspontaneous agglutinins almost never occur (difference)person must first be massively exposed (transfusion)six common types of Rh antigens (C, D, E, c, d, e; one of each pair in every person) most prevalent is type D antigen (Rh +)about 85 percent of white people are Rh +in reality two genes: RHCE i RHDproteins which carry Rh antigens are transmembranic proteins (ion channel?)RHD gene codes RhD protein with D antigen (on chromosome 1p)RHCE gene codes RhCE protein with C, E, c, e antigensthere is no d antigen, d means lack of D antigen

Rh Immune Responsemaximum concentration of anti-Rh agglutinins develop about 2 to 4 months after transfusiondelayed, mild transfusion reactionerythroblastosis fetalis (mother Rh -, father Rh +, child inherits Rh from father; mother develops agglutinins for Rh which diffuse through the placenta into the fetus and cause red blood cell agglutination) firstborn usually doesnt develop, second born in 3%, third born in 10%agglutination of the fetus's blood hemolysis release of hemoglobin (jaundice)newborn baby is usually anemic, liver and spleen become greatly enlarged, early forms of RBC are passed from the baby's bone marrow into the circulatory system, permanent mental impairment or damage to motor areas of the brain because of precipitation of bilirubin in the neuronal cells kernicterus treatment replacing the neonate's blood with Rh-negative blood (400 ml during 1,5 hours)RBC are replaced by infant's own at the time anti-Rh agglutinins that had come from the mother are destroyedPrevention of Erythroblastosis Fetalisdevelopment of Rh immunoglobulin globin, an anti-D antibody administered to the expectant mother starting at 28 to 30 weeks of gestation or after deliveryTransfusion Reactionsusually agglutination of the RBC from the donor, rarely agglutination of cells in recipient (dilution of plasma)hemolysis (immediate hemolysins, later phagocytosis)jaundice (more than 400 milliliters of blood is hemolyzed in less than a day)acute kidney failure release of toxic substances renal vasoconstrictionloss of circulating RBC circulatory shockhemoglobin precipitates and blocks many of the kidney tubules patient dies within a week to 12 daysTransplantation of Tissues and Organsbeside RBC antigens each tissue posses additional set of antigens which are responsible for immunological reactionsresisting invasion by foreign bacteria or red cellsType of Transplantautograft tissue or whole organ from one part of the same animal to another partisograft from one identical twin to anotherallograft from one human being to another or from any animal to another animal of the same speciesxenograft from a lower animal to a human being or from an animal of one species to one of another speciesxenografts immune reactions almost always occur, causing death of the cells in the graft within 1 day to 5 weeks after transplantationskin, kidney (5 to 15 years), heart, liver, glandular tissue, bone marrow, and lung most important antigens for causing graft rejection are a complex called the HLA antigens (6 of these antigens are present on the tissue cell membranes of each person, but there are about 150 different HLA antigens to choose from more than a trillion possible combinations; on the white blood cells, as well as on the tissue cells tissue typing)Prevention of Graft Rejectionsuppressing the immune system T cells are mainly the portion of the immune system important for killing grafted cellsglucocorticoid hormones and similar drugsdrugs that have a toxic effect on the lymphoid system azathioprinecyclosporine specific inhibitory effect on the formation of helper T cellsinfectious disease, incidence of cancer!


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