Erythrocytes 1 PDF

ERYTHROCYTES 1 Dr. Nisreen Daffa Alla M.B.B.S, PhD (Human Physiology), MSc health Profession Education  OBJECTIVES The student should be able to:  Identify the normal range of RBCs.  Enumerate different functions of hemoglobin.  Identify the sites of erythropoiesis in differen...

ERYTHROCYTES 1 Dr. Nisreen Daffa Alla M.B.B.S, PhD (Human Physiology), MSc health Profession Education  OBJECTIVES The student should be able to:  Identify the normal range of RBCs.  Enumerate different functions of hemoglobin.  Identify the sites of erythropoiesis in different stages of life.  Discuss the stages of erythropoiesis.  Discuss the requirements for erythropoiesis.  Explain the clinical conditions related to erythropoiesis.  ERYTHROCYTES Normal RBC count:. Male 5 – 5.5×106 /μL Female 4.5 – 5 106 /μL RBC has no nucleus, organelles contain hemoglobin which carries O2 & CO2. 3 ERYTHROCYTES (FEATURES) 1. RBC are biconcave discs 7.5 - 8 micrometer (µm) in diameter and 2µm thick at outer edge and 1µm thick at the center. 2. RBC membrane is flexible and can change as RBC pass through capillary with a narrow diameter of 5µm.  From AMBOSS Normal RBCs shape Abnormal RBCs  ERYTHROCYTES FEATURES 3. RBCs has no nucleus and organelle. 4. Enzymes in RBC: – Glycolytic enzyme, it generates energy ATP for active transport at membrane. – Carbonic anhydrase enzyme important in CO2 transport. 5. Average life of RBC is 120 days then old RBC are removed by spleen. New RBC generated by bone marrow. 6  HEMOGLOBIN Normal Hemoglobin concentration: Female14 g/dl Male 16g/dl. Structure of adult Hemoglobin(type A1) It has two parts 1. Globin: protein has 4 polypeptide chain 2 α chain [141 amino acid in each chain] 2 β chain [146 amino acid in each chain] 2. Heme: 4 iron containing groups, each is bound to one polypeptide chain. 7 8 Normal types of hemoglobin Adult hemoglobins:  HbA1  HbA2 Fetal hemoglobins  Hb F  Gower1 Hb  Gower2 Hb  HEMOGLOBIN For hemoglobin to bind iron present in heme, iron should be in ferrous state. 98.5% of O2 is carried in the blood bound to hemoglobin. Each subunit carry one oxygen molecules Hemoglobin appears reddish when combine with O 2, e.g. Arterial blood. Hemoglobin appears bluish when deoxygenated, e.g. venous blood. 11  Hemoglobin functions Transports O2. Transports CO2. Buffer: combines with H+ ion Combines with carbon monoxide (CO), therefore, can cause CO poisoning. The affinity of hemoglobin to CO is more than O 2. Combines with Nitric Oxide (NO) gas. 12  Site of synthesis of RBCs Fetus 1. First trimester: yolk sac 2. Second trimester: liver, spleen 3. Third trimester: bone marrow of all bones In children: bone marrow of all bones In adult: bone marrow of flat bones, proximal ends of humorous and femur. Red bone marrow in other bones is replaced by fatty yellow bone marrow that does not produce RBC.  Applied If we need bone marrow sample for examination, we usually take from iliac crest or sternum. MAJOR STEPS IN ERYTHROPOIESIS 17  Steps of erythropoiesis As RBC matures, it involves - reduction in size - disappearance of nucleus - acquiring of hemoglobin 19  Reticulocytes An immature red blood cell without a nucleus. Develop and mature in the bone marrow and then circulate for about a day in the blood stream before developing into mature red blood cells Having a granular or reticulated appearance when suitably stained due to a network of ribosomal RNA. Normal percentage (retic count) from total RBCs count is 0.5 – 1.5%. The number of reticulocytes is a good indicator of bone marrow activity because it represents recent production Reticulocytes  Requirements of erythropoiesis 1. Amino Acids – for synthesis of globin of hemoglobin. 2. Iron 3. Vitamins – Vitamin B12 and folic acid for synthesis of nucleo protein. 4. Trace elements – e.g. copper, zinc, cobalt 5. Hormones – erythropoietin, Cortisol, growth hormone. 22  Control of erythropoiesis Control of Erythropiesis: Controlled by Erythropoietin hormone. Erythropoietin is produced by the kidneys due to reduced O2 delivery to kidney. - Main stimulus for production of erythropoietin is hypoxia e.g. high altitude, anemia. List other pathological conditions increase erythropoeitin release? In people live in high altitude or any cause of hypoxia, what will be the hematocrit value? 23 24  Synthetic Erythropoietin Synthetic Erythropoietin: Synthetic erythropoietin is given to kidney failure patients or those patients undergoing chemotherapy for cancer as chemotherapy affects bone marrow and developing RBC. 25  Erythropoiesis after donation of blood During blood donation about 450 ml of blood is donated. Donated Plasma is replaced in 2-3 days. RBCs are replaced in 36 days [range 20–59 days], therefore, repeat donation of blood is recommended after 3 months. 26  ERYTHROPOIESIS Erythrocytes Breakdown: Average life of RBC is 120 days then it is destroyed. When RBC breakdown, they release hemoglobin. Hemoglobin is taken by macrophages. Hemoglobin is broken into heme + globin. Globin is degraded into amino acids which are used. From Hemoglobin, iron is released and passes back to blood. Porphyrin portion of hemoglobin molecule is converted into bilirubin. Bilirubin is carried to liver [bound with albumin] and secreted in bile by liver. 27  Destruction of red blood cells The spleen remove: - Old RBCs - Abnormal RBCs Destruction of RBCs  Applied Increase destruction of RBCs lead to …………… What is the name of this clinical sign?  Summary slide Sites and requirement of RBCs synthesis The most abundant type of adult hemoglobin The hormone that is released from the kidneys and control RBCs synthesis What happen to the RBCs as it mature in the bone marrow The importance of reticulocytes The site and products of RBCs breakdown Define jaundice  Case study An 18-year-old girl with sickle cell anemia was admitted with acute chest syndrome and was treated with intravenous fluid, analgesia and antibiotics. Her blood tests showed hemoglobin (Hb) level of 6.10 g/dL, hematocrit (Ht) of 19.2and bilirubin level of 5.95 mg/dL (unconjugated: 3.69 mg/dL). She received one unit of phenotypically matched packed RBCs, with no complications during the procedure. Laboratorial exams at discharge showed Hb level of 9.32 g/dL, Ht of 30.8%, LDH of 643 U/L and bilirubin level of 4.29 mg/dL.  Questions Why the patient had 1. Low hemoglobin 2. High bilirubin 3. What are the clinical symptoms and signs you expect this patient to have?  REFERENCES  Erythrocyte morphology and hemoglobin – AMBOSS  Human Physiology, Lauralee Sherwood, seventh edition.  Text book Physiology by Guyton &Hall,11th edition.  Text book of Physiology by Linda S. Contanzo, third edition.  Physiology by Berne and Levy, sixth edition. 34