Dr. Shaikh Mujeeb Ahmed Assistant Professor AlMaarefa College ERYTHROCYTES [RBCs] HMIM BLOCK 224 Dr. Shaikh Mujeeb Ahmed Assistant Professor AlMaarefa College

Objectives Know the normal range of RBCs. Enumerate different functions of hemoglobin. Know the sites of erythropoiesis in different stages of life. Stages of erythropoiesis & the requirements. Explain the clinical conditions related to erythropoiesis.

ERYTHROCYTES Normal RBC count - 5 million per cubic millimeter (mm3) of blood. Male – 5 – 5.5 / mm3 Female 4.5 – 5 / mm3 RBC contain hemoglobin which carries O2. Main function of RBC – O2 transport, also CO2 transport.

STRUCTURE OF RBC RBC are biconcave discs 7.5 - 8 micrometer (µm) in diameter and 2µm thick at outer edge and 1µm thick at the center. RBC membrane is flexible and can change as RBC pass through capillary with a narrow diameter of 5µm.

HEMOGLOBIN Hemoglobin is found only in RBC. Normal Hemoglobin – 15 gram / dl . Structure of Hemoglobin 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.

HEMOGLOBIN[cont] Each iron atom present in Heme [iron is in ferrous state] can combine reversibly with one molecule of O2, therefore, each hemoglobin molecule can take four O2 molecules in the lungs. 98.5% of O2 is carried in the blood bound to hemoglobin. Hemoglobin is a pigment naturally colored because of iron content.

HEMOGLOBIN[cont] It appears reddish when combine with O2, e.g. Arterial blood. It appears bluish when deoxygenated, e.g. venous blood.

HEMOGLOBIN FUNTIONS Transports O2. Also transports CO2. Combines with H+ ion, therefore, plays part as buffer. Combines with carbon monoxide (CO), therefore, can cause CO poisoning. Nitric Oxide (NO) gas combines with hemoglobin and this NO is released at the tissues and causes vasodilation.

IMPORTANT NOTE RBC is mainly a plasma membrane having hemoglobin. RBC has no nucleus and organelle. Enzyme in RBC - Glycolytic enzyme, it generates energy ATP for active transport at membrane. - Carbon anhydrase enzyme for CO2 transport.

ERYTHROPOIESIS Formation and maturation of RBCs. In adult RBC are formed in bone marrow. [Bone marrow is cellular tissue that fills the internal cavities of bones]. Bone marrow normally generates new RBC to replace old ruptured cells. In the fetus – RBC formation takes place in yolk sac during first 03 months of life then liver and spleen up to 7th month of intrauterine life. Bone marrow starts from 4th month till birth of baby.

ERYTHROPOIESIS In children, most bones produce RBC by red bone marrow then red bone marrow is replaced by fatty yellow bone marrow that does not produce RBC. In adults, red bone marrow remains in sternum, ribs, vertebrae, pelvis, upper end of long bones e.g. femur, humerus.

IMPORTANT If we need bone marrow sample for examination, we usually take from iliac crest or sternum.

MAJOR STEPS IN ERYTHROPOIESIS

ERYTHROPOIESIS As RBC matures, it involves - reduction in size - disappearance of nucleus - acquiring of hemoglobin

NUTRIONAL REQUIREMENT OF RBC PRODUCTION 1. Amino Acids – for synthesis of globin of hemoglobin. 2. Iron – If iron deficiency, it causes microcytic hypochromic anemia [small RBC with less Hb]. 3. Vitamins – Vitamin B12 and folic acid for synthesis of nucleo protein. If less DNA metabolism affected and results in megloblastic anemia [mega means large]. 4. Trace elements – e.g. copper, zinc, cobalt 5. Hormones – Cortisol, growth hormone.

CONTROL OF ERYTHROPOIESIS It is done by Erythropoietin hormone. Source of Erythropoietin – mainly kidney. 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. Hormone erythropoietin is secreted in blood and stimulates erythropoiesis in the bone marrow by acting on committed RBC.

IMPORTANT Normal RBC count 5 millions / mm3. In every person, 25 trillion – 30 trillion RBC are moving through our blood vessels. Average life of RBC is 120 days. RBC are replaced at average rate of 2 millions to 3 millions / sec.

TEST YOUR KNOWLEDGE Q . In case of hemorrhage [blood loss], what will happen to rate of Erythropoiesis ? Answer: Rate of Erythropoiesis can be increased more than 6 times.

TEST YOUR KNOWLEDGE Q. When you donate blood, your circulating RBC supply is replaced in how much time? During blood donation about 450ml of blood is donated. Donated Plasma is replaced in 2-3 days. RBC are replaced in 36 days [range 20–59 days], therefore, repeat donation of blood is recommended after 3 months.

RETICULOCYTES It is immature erythrocyte. Normal reticulocyte count 0.5 – 1.5% in blood. Increased reticulocyte count in blood indicates high rate of erythropoietic activity.

SYNTHETIC ERYTHROPOIETIN Synthetic erythropoietin is given to kidney failure patients or those patients under going chemotherapy for cancer as chemotherapy affects bone marrow and developing RBC.

RBC 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.

WHAT YOU SHOULD KNOW FROM THIS LECTURE ? Normal RBC count, Size, Shape and Function Life Span of RBC Erythropoiesis in Adults & Children Nutritional Requirement for Erythropoiesis Erythropoietin Functions of Hemoglobin Importance of Reticulocyte count in blood Hemoglobin Breakdown

I Thank Dr. Zahoor for this lecture