Veterinary Physiology 1: Blood Lecture 2 PDF

LECTURE: BLOOD #2 Kavita R. Lall, B.Sc. (Hons.), D.V.M. (Hons.), M.Sc. (Dist.)  Learning objectives  Hemoglobin pigment in RBC  Hemostasis process of stopping blood  Understand the structure and function of hemoglobin  Explain the biosynthesis of hemoglobin  Describe the vari...

LECTURE: BLOOD #2 Kavita R. Lall, B.Sc. (Hons.), D.V.M. (Hons.), M.Sc. (Dist.)  Learning objectives  Hemoglobin pigment in RBC  Hemostasis process of stopping blood  Understand the structure and function of hemoglobin  Explain the biosynthesis of hemoglobin  Describe the various hemoglobin derivatives  Define hemostasis and the steps involved  Discuss blood coagulation and the two pathways (intrinsic and extrinsic)  Metalloprotein present in the RBCs of vertebrates  Transports oxygen and carbon dioxide  Functions as a buffer carbonic anhydrase  Hemoglobin contains four polypeptide chains (two α and two ß chains); each of the four chains unites with a heme group (pigment containing iron in ferrous state) resulting in a hemoglobin molecule  Hemoglobin biosynthesis  Hb is synthesized in a complex series of steps made  Heme - synthesized in a series of steps in the mitochondria and the cytosol of immature red blood cells separated then come together  Globin - synthesized by ribosomes in the cytosol fluid part of the cell not to be confused with cytoplasm which is everything in the cell aside from nucleus  Production of Hb continues in the cell throughout its early development from the proerythroblast to the reticulocyte in the bone marrow (at this point, the nucleus is lost in mammalian red blood cells, but not in birds and many other species); even after the loss of the nucleus in mammals, residual ribosomal RNA allows further synthesis of Hb until the reticulocyte loses its RNA soon after entering the vasculature Heme synthesis  Mitochondrion - condensation of succinyl CoA and glycine to form delta- amino levulinate  This molecule is transported to the cytosol where a series of reactions produce a ring structure called protoporphyrin IX  Many enzymes concerned with heme synthesis are intra-mitochondrial  The ALA synthetase is the rate-limiting enzyme of the Hb synthesis Globin synthesis  After heme is synthesized within the mitochondria, 4 heme molecules combine with 4 globin polypeptides to form one molecule of hemoglobin  The globin molecule of hemoglobin differs among the species, whereas there is no difference in the heme portion  fe++ comes from diet in this process a lack of fe can cause anemia process occurring glycine - amino acid in chickens' feed  Derivatives of hemoglobin  There are some derivatives of normal Hb that arise due to metabolic changes in RBCs 1. Oxyhemoglobin 2. Reduced hemoglobin 3. Carbaminohemoglobin 4. Methemoglobin 5. Carboxyhemoglobin  Oxyhemoglobin (HbO2)  Lungs: Partial pressure of oxygen is 100 mm Hg and hemoglobin is 97-98% saturated  On binding with O2 in the lungs, hemoglobin is converted into oxy- hemoglobin (Hb02)  O2 is bound to heme iron  Hb + O2 → HbO2 oxygen makes it brighter that why its brighter in arteries except pulmonary arteries  Reduced Hemoglobin (HHb)  Oxyhemoglobin moves into the tissue where the partial pressure of O2 is 26 mm of Hg and in turn H+ binds to Hb and forms reduced hemoglobin  HbO2 + H+ → HHb + O2  Carbaminohemoglobin  Hemoglobin also binds to CO2 in the tissues  CO2 is bound to the amine group at the N-terminal end of each of the four polypeptide chains of hemoglobin to form carbaminohemoglobin  As one CO2 binds O2 is released  Methemoglobin  In RBC the iron of hemoglobin is normally in ferrous (Fe2+) form, but it is readily oxidized to the ferric (Fe3+) form by hydrogen peroxide formed by RBC cell metabolism, to yield methemoglobin  Fe3+ is incapable of binding O2  Normally 1.7-2.4% of total hemoglobin will be in the form of methemoglobin  Increase in the percent of methemoglobin is prevented by the peroxidase action of a naturally occurring peptide known as glutathione present in the RBC  High levels (>20%) can cause hypoxia and shock high conc of methemoglobin  Clinical methemoglobinemia occurs when the RBC defense systems are overwhelmed and cannot reduce metHb back to Hb fast enough to keep up with the oxidative damage paracetamol  Caused by (animals): Acetaminophen, topical benzocaine formulations, phenazopyridine (a urinary tract analgesic), nitrites, nitrates and skunk musk don't give animals especially cats  Treatment involves augmentation of endogenous glutathione with N- acetylcysteine (NAC), antioxidant therapy, increased clearance or decreased metabolism of a toxin, blood transfusion if required and supportive care  Carboxyhemoglobin hb has a higher affinity for carbon monoxide which causes problems later with its oxygen carrying abilities  Hemoglobincan bind to carbon monoxide (CO) to form carboxyhemoglobin  CO has an affinity 200 times more than that of O2 towards Hb  Hb + CO → HbCO  Process of stopping blood loss erythropoietin is found in the kidney is a response to cellular hypoxia  Requires adequate:  Platelet numbers thrombocytes  Concentration of coagulation factors clotting factors[proteins] made in liver milk thistle / liv - 52 are supplements that are used to help the liver regenerate  Hemostasis involves three steps: vasoconstriction 1. Vascular spasm - constricts the flow of blood via reflex blood vessel constriction through the sympathetic branch or via local myogenic spasm through serotonin activity reseach more **autonomic nervous system : 1. symp and 2. parasympathetic nervous system 2. Platelet plug formation - temporarily seals small openings in the vessel 3. Coagulation - enables the repair of the vessel wall; the synthesis of fibrin in blood clots involves either an intrinsic pathway or an extrinsic pathway, both of which lead to a common pathway  Coagulation factors (made in the liver) circulate in the blood stream and become 'activated' when blood vessel or tissue injury occurs, and together with platelets, produce a clot at the site of injury  only released for 12 tissue damage  Intrinsic pathway 11 9  Sequence of reactions when the 8 blood comes into contact with complex activates factor 10 foreign surface (other than intact vascular endothelium) 5 activated thrombin activates  Extrinsic pathway  Sequence of reactions when the blood comes into contact with extra- vascular tissue factor, tissue factor III (thromboplastin), released from the surrounding tissues  Cofactor: Coagulation factor VII