JOHN'S PIO NOTE Thursday, July 29, 2021 4:48 PM BLOOD Definition Red colored fluid that circulates the vascular system in human transporting nutrients and oxygen to and waste products out from all parts of the body. Properties Color - Red. Arterial scarlet and venous pale red Volume - adult - 5 L. newborn baby - 450 ml. females - 4.5 L PH - slightly alkaline 7.4 Specific gravity - 1.052 to 1.061 Viscosity: Stimes more viscous than water. Composition blood cells and liquid part plasma. « Plasma 55% ¢ Red blood cell 45% White blood cells and platelets = White buffy coat BLOOD CELLS ¢ Red blood cells or erythrocytes. ¢ White blood cells or leukocytes. e Platelets or thrombocytes. PLASMA Is a straw-colored clear liquid part of blood. It contains 91% to 92% of water and 8% to 9% of solids. SERUM Clear straw-colored fluid that oozes from blood clot. Serum = Plasma — Fibrinogen FUNCTIONS OF BLOOD ¢ Nutritive function ¢ Respiratory function ¢ Excretory function ¢ Transport function ¢ Regulation of water balance ¢ Regulation of acid-base balance ¢ Regulation of body temperature © Storage function ¢ Defense function PLASMA PROTEINS NORMAL VALUES Total proteins : 7.3 g/dL (6.4 to 8.3 g/dL) Serum albumin : 4.7 g/dL Serum globulin : 2.3 g/dL Fibrinogen : 0.3 g/dL PROPERTIES ¢ Colloidal osmotic (oncotic) pressure - 25mmHg ¢ Specific gravity - 1.026. ¢ Buffer action - 1/6 blood buffering action. ORIGIN IN EMBRYO - mesenchyme cells. IN ADULTS - mainly from reticuloendothelial cells of liver, spleen, bone marrow, disintegrating blood cells and general tissue cells. FUNCTIONS * Coagulation of blood (fibrinogen) * Defense mechanism of the body (y- globulin) © Transport mechanism (hormones & enzymes) ¢ Maintenance of osmotic pressure in blood ¢ Regulation of acid-base balance ¢ Role in viscosity of blood ¢ Role in erythrocytes sedimentation rate ¢ Suspension stability of RBC (globulin & fibrinogen) e Serve as reserve protein * Production of trephine substances N/B Albumin Hyper-albuminamia Hypo-albuminamia Globulin Hyper Hypo RED BLOOD CELLS Red blood cells (RBCs) are the non- nucleated formed elements in the blood. Properties ¢ Red color due to haem pigment ¢ Larger in no than other blood cells ¢ Non-nucleated ¢ Disc-shaped and biconcave, thin center and thick periphery Benefits of biconcave nature ¢ Large surface area for absorption or removal of substances ¢ Aids movement through capillaries without breaking ¢ Aid equal diffusion of oxygen and other substances through the cell ¢ Minimal tension on RBCs membrane when volume is altered Shape biconcave Diameter 7.8u Surface area 120sq u Volume 90 - 95um3 Thickness 2.5u and 1u or less at centre Avg life span 120 days FUNCTIONS ¢ Haem in RBC act as buffer ¢ Regulation of H+ conc. maintaining acid-base balance ¢ Transport of Oxygen from the Lungs to the Tissues (97%) * Transport of Carbon Dioxide from the Tissues to the Lungs (32%) ¢ Blood group determination PHYSIOLOGICAL VARIATIONS Increase in RBC Count - polycythemia Condition - age, sex, high altitude, muscle exercise, emotional condition, increased envt temp., after meal. Decrease in RBC Count - Anemia High barometric pressure, during sleep, pregnancy. ERYTHROPOIESIS Erythropoiesis is the process of the origin, development and maturation of erythrocytes. SITE OF ERYTHROPOIESIS IN FETAL LIFE Mesoblastic Stage - 1st 2 months - mesenchyme of yolk sac Hepatic Stage - from 3rd month - liver produces RBCs. Spleen and lymphoid organs are also involved in erythropoiesis. Myeloid Stage - last three months of intrauterine life - red bone marrow and liver. IN NEWBORN BABIES, CHILDREN AND ADULTS 1-20 years: RBCs are produced from red bone marrow of all bones (long bones and all the flat bones). Above 20 years: RBCs are produced from membranous bones like vertebra, sternum, ribs, scapula, iliac bones and skull bones and from the ends of long bones. Lifespan Leucocytes - 1 to 10 days Erythrocytes - 120 days RBCs are largest blood cells in no. PROCESS OF ERYTHROPOIESIS Hemopoietic stem cells are the primitive cells in the bone marrow, which give rise to the blood cells. Hemopoietic stem cells in the bone marrow are called uncommitted pluripotent hemopoietic stem cells (PHSC). PHSC is defined as a cell that can give rise to all types of blood cells. Committed PHSC - designed to form a particular type of blood cell. Types of committed PHSC Lymphoid stem cells (LSC) - lymphocytes and natural killer (NK) cells Colony forming blastocytes - myeloid cells. Myeloid cells are the blood cells other than lymphocytes. Different units of colony forming cells Colony forming unit-erythrocytes (CFU-E) — Erythrocytes Colony forming unit - granulocytes/monocytes (CFU-GM) — granulocytes (neutrophils, basophils and eosinophils) and monocytes Colony forming unit-megakaryocytes (CFU- M) — Platelets STAGES OF ERYTHROPOIESIS Proerythroblast Early normoblast Intermediate normoblast Late normoblast Reticulocyte Matured erythrocyte. Proerythroblast (Megaloblast) ¢ Nucleus and nucleoli present ¢ Diameter of about 20 u ¢ Basophilic cytoplasm ¢ Size - large Early Normoblast ¢ Diameter of about 15 u e Nucleoli disappears * Chromatin network condense ¢ Basophilic cytoplasm Intermediate Normoblast ¢ Diameter of 10to 12 py © Hemoglobin starts appearing ¢ Stains with both acidic and basic stains (polychromatic) Late Normoblast ¢ Diameter of about 8 to 10 u. ¢ Nucleus disintegrates and disappears ¢ Almost acidophilic The process by which nucleus disappears is called pyknosis Reticulocyte * Cytoplasm contains reticular network ¢ The reticulum of reticulocyte stains with supravital stain. © Cells enter the blood capillaries through capillary membrane from site of production by diapedesis ¢ Basophilic Matured Erythrocyte e Reticulum disappears © Cell attains biconcavity ¢ 7.2 diameter Development and maturation of RBC from proerythroblast = 7days Up to the stage of reticulocyte = 5 days Reticulocyte takes 2days to become the matured RBC. FACTORS NECESSARY FOR ERYTHROPOIESIS ¢ Stimulating factors ¢ Maturation factors ¢ Factors necessary for hemoglobin formation STIMULATING FACTORS e Erythropoietin ¢ Thyroxine ¢ Hemopoietic growth factors ¢ Vitamins. Erythropoietin Main Secretion - peritubular capillaries of kidney. small quantity - liver and brain. Secretion Stimulant - Hypoxia Duration - 4 to 5 days to show the action. Erythropoietin promotes ¢ Production of proerythroblasts from CFU-E of the bone marrow * Development of proerythroblasts into matured RBCs ¢ Release of matured erythrocytes into blood Thyroxine Accelerates the process of erythropoiesis Hemopoietic Growth Factors Are the interleukins and stem cell factor Induce the proliferation of PHSCs. Interleukins (IL) are glycoproteins, which belong to the cytokines family. interleukins involved in erythropoiesis: ¢ Interleukin-3 (IL-3) secreted by T-cells ¢ Interleukin-6 (IL-6) secreted by T-cells, endothelial cells and macrophages ¢ Interleukin-11 (IL-11) secreted by osteoblast. Vitamins Vitamins necessary for erythropoiesis: Vitamin B3 & B6: deficiency-anemia and pellagra Vitamin C: deficiency-anemia and scurvy Vitamin D: deficiency-anemia and rickets Vitamin E: deficiency-anemia and malnutrition MATURATION FACTORS Vitamin B12 (Cyanocobalamin) Absorption requires intrinsic factor of Castle. stored in liver and muscle. It is transported to the bone marrow to promote maturation of RBCs Action - synthesis of DNA in RBCs. Deficiency - failure in maturation of the cell and reduction in the cell division. Deficiency of vitamin B12 - pernicious anemia. Vitamin B12 is called antipernicious factor. Intrinsic Factor of Castle Production - gastric mucosa by the parietal cells of the gastric glands. Role - absorption of vitamin B12 from intestine. Absence - leads to pernicious anemia. Folic Acid Folic acid is also essential for maturation. Role - synthesis of DNA. Absence - Megaloblastic anemia FACTORS NECESSARY FOR HEMOGLOBIN FORMATION Amino acids - synthesis of protein part of hemoglobin, i.e. the globin. Iron - formation of heme part of the hemoglobin. Copper - absorption of iron from the gastrointestinal tract Cobalt and nickel - utilization of iron during hemoglobin formation Vitamins - Vitamin C, riboflavin B2, nicotinic acid B3 and pyridoxine B6 are also essential for the formation of hemoglobin. HEMOGLOBIN AND IRON METABOLISM HEMOGLOBIN Hemoglobin (Hb) is the iron containing coloring matter of red blood cell (RBC). Role - transport respiratory gases, oxygen and carbon dioxide. It also acts as a buffer. Molecular weight - 68,000. NORMAL HEMOGLOBIN CONTENT Depending on age At birth - 25 g/dL After 3rd month - 20 g/dL After 1 year - 17 g/dL From puberty onwards - 14 to 16 g/dL Depending on sex Adult males - 15 g/dL Adult females - 14.5 g/dL FUNCTIONS OF HEMOGLOBIN ¢ Transport of Oxygen e Transport of Carbon Dioxide ¢ Acts asa buffer and plays an important role in acidbase balance STRUCTURE OF HEMOGLOBIN Consists of a protein combined with an iron containing pigment (heme) PORPHYRIN The pigment part of heme. Formation - four pyrrole rings (tetrapyrrole) called, |, Il, II and IV attached to one another by methane (CH4) bridges. The iron is attached to ‘N’ of each pyrrole ring and ‘N’ of globin molecule. TYPES OF NORMAL HEMOGLOBIN Adult hemoglobin — HbA Fetal hemoglobin — HbF Replacement of fetal hemoglobin by adult hemoglobin - immediately after birth and completed at about 10th to 12th week after birth. DIFFERENCES Adult hemoglobin - contains two a-chains and two £-chains. Fetal hemoglobin - two a chains and two y- chains instead of B-chains. Fetal hemoglobin has more affinity for oxygen than adult hemoglobin. ABNORMAL HEMOGLOBIN Mutant forms of hemoglobin produced because of structural changes in the polypeptide chains caused by mutation in the genes of the globin chains. CATEGORIES * Hemoglobinopathies ¢ Hemoglobin in thalassemia and related disorders. Hemoglobinopathies Hemoglobin S: found in sickle cell anemia. The a-chains are normal and B-chains are abnormal. Hemoglobin C: The B-chains are abnormal Hemoglobin E: Here also the B-chains are abnormal. Hemoglobin M: both in a and B chains abnormal Hemoglobin in Thalassemia and Related Disorders a-thalassemia - the a-chains are decreased, absent or abnormal 8-thalassemia - the B-chains are decreased, absent or abnormal SYNTHESIS OF HEMOGLOBIN Stages Synthesis of hemoglobin - starts in proerythroblastic stage and appears in the intermediate normoblastic stage only. Site of synthesis Heme portion - mitochondria. Protein part (globin) - ribosomes. Synthetic process Heme is synthesized from succinylCoA and the glycine. * Two molecules of succinylCoA combine with two molecules of glycine and condense to form 6- aminolevulinic acid (ALA) by ALA synthase (mitochondrion) * Two molecules of ALA combine to form porphobilinogen in the presence of ALA dehydratase (cytoplasm) ¢ Porphobilinogen is converted into uroporphobilinogen | by uroporphobilinogen | synthase e Uroporphobilinogen | is converted into uropor phobilinogen III by porphobilinogen III cosynthase ¢ From uroporphobilinogen Ill, a ring structure called coproporphyrinogen Ill is formed by uroporphobilinogen decarboxylase * Coproporphyrinogen Ill is transported back to the mitochondrion, where it is oxidized to form protoporphyrinogen IX by coproporphyrinogen oxidase ¢ Protoporphyrinogen IX is converted into protoporphyrin IX by protoporphyrinogen oxidase ¢ Protoporphyrin IX combines with iron to form heme in the presence of ferrochelatase. DESTRUCTION OF HEMOGLOBIN Lifespan - 120 days Site of destruction of RBC - reticuloendothelial system in spleen Porphyrin is converted into a green pigment called biliverdin. Biliverdin is converted into a yellow pigment called bilirubin. Bilirubin + biliverdin = bile pigments IRON METABOLISM IMPORTANCE OF IRON ¢ Oxygen transport. ¢ Fformation of hemoglobin and myoglobin. ¢ Formation of other substances like cytochrome, cytochrome oxidase, peroxidase and catalase. Total quantity of iron in the body - 4 g. ¢ Inthe hemoglobin : 65% to 68% ¢ Muscle as myoglobin : 4% ¢ As intracellular oxidative heme compound : 1% ¢ In Plasma as transferrin : 0.1% ¢ Stored in the reticuloendothelial system : 25% to 30% ABSORPTION OF IRON Site - small intestine through intestinal cells (enterocytes) by pinocytosis and into the blood. Bile is essential for the absorption of iron. TRANSPORT OF IRON Iron is transported in blood in the form of transferrin (iron combines with a B- globulin - apotransferrin - to form transferrin) STORAGE OF IRON Reticuloendothelial cells and liver hepatocytes. REGULATION OF TOTAL IRON IN THE BODY Factors © Stoppage of apotransferrin formation in the liver. ¢ Reduction in the release of iron from the transferrin.