BMS 300 1st edition Lecture 35Outline of Last Lecture I. Smooth muscle effects in anterioles-alpha receptors—no epinephrine/epinephrine-contraction -effect on RII. Components of blood -plasma 1. protein solution -buffy coat 1. cells of immunity (proper cells)2. platelets (self-fragments)  blood clotting -hematocrit -concept of reformed element III. Blood as connective tissue -hematopoietic stem cells 1. mesularyocytes 2. cells of immunity >monocytes >granulocytes These notes represent a detailed interpretation of the professor’s lecture. Grade Buddy is best used as a supplement to your own notes, not as a substitute.>lymphocytes IV. Erythrocytes -structure and function 1. hemoglobinOutline of Current Lecture V. Erythrocyte structure and hormonal control of production -hormonal regulation1. erythropoietin >glycoprotein hormone >kidney as “sensing” and production organ >site of hormonal regulation -proerythrocytes-growth factor -structure and function of erythrocytes 1. biconcave disk2. 250,000,000 hemoglobin molecules >2 alpha, 2 beta -contraction -effect on RVI. Fate of erythrocyte -spleen-red pulp>role of macrophagesVII. Recycle FeVIII. Porphyrin rinsas waste IX. Hemodynamics and lymph production Current LectureRecap last lecture:-proerythrocytes gave rise to normoblasts which then gave rise to enterocytes which then gave rise to the blood vascular compartment-up to the point of the reticulocytes all the other cells were confined to the red bone marrow -hormonal control that regulates the production: erythropoietia (EPO) which is a protein/peptide hormone secreted by cells in the kidney -the kidney receives a tremendous amount of blood -at the top is the descending aorta -there are two blood vessels called the renal arteries which provide the blood supply to the two kidneys -the blood flow from the descending aorta into the kidneys is 20-25% of the blood leaving the left ventricle is destined for the kidney -the kidney receives an enormous amount of blood supply-one of the roles of the kidney is to monitor O2 levels in blood -if the oxygen levels of blood begin to drop there are kidney cells (endothelial cells) which respond to low oxygen by secreting EPO -the target for the EPO is destined to bind to receptors on cells in the red bone marrow -the proerythrocytes contain transmembrane protein receptors for EPO >receptor tyrosine kinase receptor >these tend to be growth factor receptors >as a growth factor EPO on the receptor leads to greater cell survival among the proerythrocytes (also may increase the rate of cell division) -EPO is a highly glycolated protein -Lance Armstrong was using EPO Erythrocytes as highly elaborated cells carrying hemoglobin (as highly specialized “cells” for carrying hemoglobin)-we talked about this the other day when we talked about the volume of the cell was increased by getting rid of everything in the cells except for hemoglobin -specialized as bags of hemoglobin -in fact every one of the cells contains 250,000,000 hemoglobin molecules -in the adult the hemoglobin is composed of 4 protein chains -there are 2 alpha chains -there are 2 beta chains-the alpha globin chain (the 2 alpha chains) contains an atom of iron -there are also 2 beta chains which each contain an atom of iron -there are a billion iron atoms in the 250,000,000 hemoglobin >each one of the irons can bind a molecule of oxygen -the erythrocytes containing these are thin structures-the binding of hemoglobin to the oxygen requires a short diffusion distance which is why they are structured that way The organization of the porphyrin ring in hemoglobin **don’t have to memorize the structure -each of the iron as seen above are coordinated by 5 member rings with nitrogen -whenever we have a metal ion in a protein we always put it in a porphyrin ring -one of the most common in our bodies because we have so much hemoglobin -the nitrogen’s are bound to the iron which helps make it a positive charge so that oxygen can bind to it-hemoglobin is a really really important oxygen carrying molecule -when you are in utero, you are dependent on your mother’s hemoglobin >the are 2 alphas and the betas are replaces by gammas -the reason new born babies may turn yellow is because they can’t handle getting rid of the porphyrin rings -ultraviolet light works to get rid of this (breaks the ring structures) -the beta subunits can be changed in response to certain pressures >sickle cell anemia (there’s a single slight mutation in the beta subunits) The fate of worn out erythrocytes-erythrocytes lack protein synthesis machinery -90-120 days -if we look at them in the process as being generated there are some characteristics that are true of all cells -they contain transmembrane proteins (glycolated) -as the erythrocytes move the sugars become oxidized-the change in the structure of the sugars on the outside become a signal for macrophages -erythrocytes meet their end primarily in the spleen Spleen as the site of erythrocyte disposal -the spleen is an organ which contains a ton of blood -fed by the splenic artery and drained by the splenic vein -between these there are capillaries called splenic capillaries -there are large gaps between adjacent endothelial cells which are so large that cells can actually move out of the compartment -they end up in the red pulp and they are erythrocytes -associated with macrophages (the big eaters)-in the red pulp there are macrophages with transmembrane proteins that will recognizethe oxidized sugars on the erythrocyte and begin the process of endocytosis -they are put in a compartment and then sent to a lysosome where they are broken down into its separate