Physiology 28 PDF (2024)

28 JAWAD ALSHKIRAT Nadeen Ramadan Sama Shannak Ebaa Al Zayadneh  Blood Last lecture we talked about physical characteristics about RBCs and normal indices we look at to make sure we have normal erythropoiesis, erythrocytes and their number. The physical a...

28 JAWAD ALSHKIRAT Nadeen Ramadan Sama Shannak Ebaa Al Zayadneh  Blood Last lecture we talked about physical characteristics about RBCs and normal indices we look at to make sure we have normal erythropoiesis, erythrocytes and their number. The physical appearance of RBCs is biconcave discs. (Donut shape) Mean 7.8(diameter) x 2.5 microns (thickest) or x 1micron (center). Average volume 90-95 micrometers. The characteristic of the RBCs membrane is being flexible so they can squeeze in narrow vessels and narrow spaces such as capillaries. At the end of their life cycle, RBCs lose their flexibility. When they become deformed, they are destroyed and subsequently phagocytosed by macrophages. This process occurs in the reticular epithelial system, which includes organs like the liver and spleen, where small passageways facilitate the recycling of RBC components. RBC Count and Indices Men: 5,200,000 (± 300,000) / mm3 (micro meter) Women: 4,700,000 (± 300,000) / mm3 - When living at high altitudes for an extended period, such as in mountainous regions, the body adapts to the lower oxygen levels in the atmosphere. This adaptation includes increasing the production of red blood cells (RBCs) to enhance oxygen transport in the blood. This process occurs gradually over several weeks. 2 millions /sec RBCs are being produced è to compensate the RBCs loss due to aging.(normal) Remember that the life cycle of RBCs: 120 days. RBC indices: - MCV (Mean cell volume) =10^-15L or 9 (+-) 9 fL - MCH (Mean Cell Hgb): the average amount of Hgb inside cell = 32 ± 2 pg - MCHC (Mean cell Hgb conc) = 33 ± 3 % - RDW CV = 11.6-14.6 % - (SD of MCV/MCV) raw distribution width which identify variability in cell volume, like a standard deviation =39-46 fL -Increasing of RDW means increase in the variability of cells volumes and vice versa.  Hemoglobin and Hematocrit 280 million molecule of hemoglobin add /RBC The normal hemoglobin concentration within red blood cells (RBCs), or packed cells, is approximately 34 g per 100 mL. BUT the hemoglobin concentration in whole blood is lower because whole blood includes plasma and other cellular components, diluting the overall hemoglobin concentration. 33% of RBC weight (which makes sense since the Hgb is the main molecule functioning in RBCs). Normal hematocrit (packed cell volume) is 40-45% (Slightly lower in women) because the number of RBCs is lower in women. Thus normal hemoglobin is 14-15 g per 100 ml of blood.‫اﻟرﻗم اﻟﻲ ﻓوق ھو ﻓﺣص ﻗوه اﻟدم و اﺣﻧﺎ ﺑﮭﻣﻧﺎ ﻓﯾﮫ ﻛﻣﯾﮫ اﻟﮭﯾﻣوﻏﻠوﺑﯾن ﺑس أﻛﯾد ﻋدد اﻟﺧﻼﯾﺎ ﺑﺄﺛر‬ O2 carrying capacity is 1.34 ml / g Hgb, or 19-20 ml O2/100ml blood. If the number is out of the range that means that there are an abnormality in Hgb or the number of cells. Transports 25% CO2 ( it binds on a different location than oxygen so it doesn’t compete with it). Erythropiesis It’s the formation process of the RBCs, starts before birth in the first weeks of pregnancy. Sites of Erythropoiesis: First few weeks of gestationè yolk sac Mid-trimesterèLiver (+ spleen, lymph nodes) Last month of gestation through adulthoodèbone marrow. The changes that may occur after birth in the site of erythropoiesis As we know the site of formation of RBCs after birth is bone marrow so which type of bones is responsible for this function? And what is the cellularity level of bone marrow? Cellularity level means how many cells that are responsible for the production of RBCs are present inside the bone marrow. The bone marrow either have stem cells that produce RBCs or adipose tissue (surely the adipose cells cannot produce RBCs) The cellularity level decreases with aging despite of the type of bone,and it’s replaced by adipose. ‫)ھذا طﺑﻌﺎ اﺷﻲ طﺑﯾﻌﻲ ﻻﻧﮫ اﺣﻧﺎ اﺧدﻧﺎ ﺑﺷﻛل ﻋﺎم اﻧﮫ ﻛل‬ ( ‫اﻻﻧﺳﺟﮫ ﻛﻣﯾﺗﮭﺎ ﺑﺗﻘل ﻛﻠﻣﺎ زاد اﻟﻌﻣر و ﺑﺣل ﻣﺣﻠﮭﺎ اﻧﺳﺟﮫ دھﻧﯾﮫ‬ One of the reasons why is because in the beginning of life the need of blood is more because the large amount of metabolic processes required for child growth. By looking to this chart: We know that in childhood the production process of RBCs take place in long and short bones. In (17-18)years we become dependent on short bones mainly for RBCs production. ‫ﯾﻌﻧﻲ ﻓﻲ ﺑداﯾﮫ اﻟﻌﻣر ﻋﻣﻠﯾﮫ ﺗﺻﻧﯾﻊ ﺧﻼﯾﺎ‬ ‫اﻟدم ﺑﺗﻛون ﻓﻲ اﻟﻌظم ﻛﻠﮫ ﺑﺷﻛل ﻋﺎم اﻟطوﯾل و اﻟﻘﺻﯾر ﺑﻌدﯾﮭﺎ ﺑﺗﻘل ﻋﻣﻠﯾﮫ اﻟﺗﺻﻧﯾﻊ ﺑﺷﻛل ﺗدرﯾﺟﺎ ﻣﻊ زﯾﺎده اﻟﻌﻣر ﻟﻛن ﺑﻔرق‬ ‫ ﺳﻧﮫ و رح ﯾﺻﯾر اﻻﻋﺗﻣﺎد ﻛﻠﮫ ﻋﻠﻰ ال ﻋظم اﻟﻘﺻﯾر‬25‫اﻟﻰ‬17 ‫اﻧﮫ اﻟﻌظم اﻟطوﯾل رح ﯾﺑطل ﯾﺻﻧﻊ ﻋﻠﻰ‬ ‫زي ﻣﺎ ﻋرﻓﻧﺎ اﻧﮫ ﺗﺻﻧﯾﻊ ﺧﻼﯾﺎ اﻟدم ﺑﻘل ﺑﺷﻛل ﻋﺎم ﻛﻠﻣﺎ زاد اﻟﻌﻣر ﻋﺷﺎن اﻻطﻔﺎل ﺑﺗﻛون ﻋﻧدھم ﻋﻣﻠﯾﺎت اﻻﯾض ﻧﺷطﮫ ﻻﻧﮭم‬ ‫ﻓﻲ طور اﻟﻧﻣو‬ Very important note: Cellularity decrease doesn’t mean that with age we will have less amount of RBCs , instead we get adequate number of RBCs for body demands. ‫ ﻟﻛل ﻋﻣر ﻓﻲ ﻋدد ﻣﻌﯾن ﻣن اﻟﺧﻼﯾﺎ ﻻزم‬,‫اﻟﻼزم ﯾﻛون ﻓﻲ ﻋدد ﻛﺎﻓﻲ ﻣن ﺧﻼﯾﺎ اﻟدم‬cellularity ‫ﯾﻌﻧﻲ ﺑﻐض اﻟﻧظر ﻋن‬. ‫ﯾﻛون ﻣوﺟود ﺑﺷﻛل طﺑﯾﻌﻲ و إﻻ ﺑﻛون ﻓﻲ ﻣرض‬ Hematopoiesis What is the source of hematic cells? Pluripotent hematopoietic stem cells give rise sequentially to committed stem cells and mature cells (which will differentiate to more differentiated cells until reaching the final destinationè the mature cells. (It is the source for all blood cells and fragment of cells)  These hematopoietic stem cells also undergo the process of proliferation (copying these stem cells to make more of them. This ensures we have enough stem cells throughout our life to produce all the different types of blood cells we need). Driven by: 1. Growth inducers (factors such as interleukin-3 or cytokines). (For proliferation) 2. Differentiation inducers. (For differentiation) The type of growth/differentiation inducers depends on the type of lineage. Hematopoiesis responds to changing conditions. - RBCs èthe number of RBCs is affected by a certain factor like tissue oxygenation so in Hypoxia the rate of erythropoiesis increase. - WBCs è when there is an Infection / inflammation it will increase the WBCs production(leukocyte). This image is very important ‫ھذه اﻟﺻوره ﻓﯾﮭﺎ ﻛل ﻣﺎ ﺗﺣﺗﺎﺟﮫ ﻣن اﻟﺗﻔﺎﺻﯾل وﺗﻌﺗﺑر ﻣراﺟﻌﮫ ﻧﻔس اﻟﮭﺳﺗو‬. Some notes: Every step occurs after a growth factor. Colony-forming unit-spleenèmyeloid stem cell Lymphoid cell and (MHSC) have the same appearance but they differ from each other by the proteins inside and the activated genes.  Blast means a big cell that will go farther modification. Platelets are fragments of megakaryocytes. Erythropoiesis The nucleus of proerythroblast is very large that’s because it will go in a lot of divisions so it must have a huge amount of DNA. In polychromatophil erythroblast Hgb begins to be synthesized so cytoplasm become reddish. As the cell differentiate its size reduces and the nucleus gets smaller and smaller until the ejection of it. Reticulocyte: immature erythrocytes (still having remains of polyribosomes) normally they exist the bone marrow and need (1-2) days to become fully mature. ‫ ﺑﺳﺎﻋدوﻧﻲ اﻋرف ﻋن أﺣوال ﻋﻣﻠﯾﮫ‬reticulocyte‫ ﻋدد ال‬:‫ﻣﮭم ﺟدا ﺟدا‬ 2days ‫ ﺗﺑﻌﺗﮫ‬life cycle ‫اﻟﺗﺻﻧﯾﻊ ﺑﺳﺑب‬ ‫طﺑﻌﺎ اﺣﻧﺎ ﻋﺎرﻓﯾن اﻧﮫ ﺧﻼﯾﺎ اﻟدم ﻣﺎ ﻓﯾﮭﺎ ﻧواه وﻻ اﻋﺿﺎء ﻓﻘط ﻣﻌﺑﯾﮫ‬ ‫ھﯾﻣوﻏﻠوﺑﯾن ﯾﻌﻧﻲ اي ﺿرر ﻓﯾﮭﺎ رح ﯾؤدي اﻟﻰ ﺗﺣطﯾﻣﮭﺎ ﻻﻧﮫ ﻣﺎ ﻋﻧدھﺎ اﻟﯾﮫ‬. ‫ﺗﺻﻧﯾﻊ اﻟﺑروﺗﯾﻧﺎت‬ Abnormal forms of RBCs 1. Hypochromic anemia: small size and low Hgb (iron deficiency). 2. Megaloblastic anemia: most of the cells are large, irregular shaped (having a problem in maturation). 3. Sickle cell anemia: genetic problem in Hgb. 4. erythroblastosis fetalis: blood type unmatching between the mother and baby. We will take it later J  Regulation of Red Cell Production Red blood cell mass is regulated within a relatively narrow range to maintain adequate oxygen carrying capacity. Avoid excessive blood viscosity because if the viscosity increases that will increase the load on the heart..‫ﺟﺳم اﻻﻧﺳﺎن داﯾﻣﺎ ﺑﻌﻣل ﻋﻠﻰ ﺗﻧظﯾم اﻻﺷﯾﺎء اﻟﻣﮭﻣﮫ واﻛﯾد اﻟدم وﻋدد اﻟﺧﻼﯾﺎ ﻓﯾﮫ ﻣن اﻻﺷﯾﺎء اﻟﻛﺛﯾر ﻣﮭﻣﮫ‬ If the bone marrow is damaged or if the demand for erythropoiesis is extreme, other parts of the bone marrow may become hyperplastic (as a compensation) , or extramedullary hematopoiesis may occur. ‫إذا ﺻﺎر اي ﺿرر ﻓﻲ ﻣﻧطﻘﮫ ﻣﻌﯾﻧﮫ ﻣن ﻧﺧﺎع اﻟﻌظم اﺳﺗﺟﺎﺑﮫ اﻟﺟﺳم ﺑﺗﻛون ﻋن طرﯾق اﻧﮫ ﯾزﯾد اﻟﺗﺻﻧﯾﻊ ﻓﻲ ﻣﻧﺎطق اﺧرى‬ ‫ﻣن ﻧﺧﺎع اﻟﻌظم او ﺑﺻﯾر ﯾﺻﻧﻊ دم ﺑﺄﻋﺿﺎء اﺧرى‬ Tissue O2 and Erythropoietin Erythropoietin is the growth factor for RBCs. The level of erythropoietin is controlled by the kidneys. Tissue oxygenation is the main trigger for erythropoiesis. Here the type of feedback is negative feedback. Like: bleeding Number of RBCs is not enough. Iron deficiency Thrombus blocking the blood reaching to specific site or heart failure. Weak lungs ‫ﻣﮭم‬ ‫ﯾﻌﻧﻲ ھون ﻛﻣﯾﮫ اﻻﻛﺳﺟﯾن ﻓﻲ اﻻﻏﺷﯾﮫ ﻟﻣﺎ ﺗﻘل ھﻲ اﻟﻲ ﺑﺗﺣﻔز اﻧﺗﺎج اﻟﺧﻼﯾﺎ و ﺑﺎﻟﺗﺎﻟﻲ زﯾﺎده اﻧﺗﺎج اﻟدم و ﻟﻣﺎ ﺗرﺟﻊ و ﺗزﯾد‬.‫ﻛﻣﯾﮫ اﻻﻛﺳﺟﯾن ﻓﻲ اﻟﻐﺷﺎء ﻋﺷﺎن ﺗﺻﻧﻌت ﺧﻼﯾﺎ اﻟدم ﺑﻘل ﺗﺻﻧﯾﻊ ال و ﺑﺎﻟﺗﺎﻟﻲ ﺑﺗﻘل ﺧﻼﯾﺎ اﻟدم ﺑﺎﻟﻛﻣﯾﮫ اﻟﻣﻧﺎﺳﺑﮫ‬  Polycythemia Sustained hypoxia can result in red cell mass above the usual normal range (more than 5000000 RBCs) Polycythemia can occur either due to disease (where there is no low O₂ in the atmosphere, but RBC count is high) or physiological conditions such as prolonged stay at high altitude, lung disease, or heart failure (chronic factors) è Compensatory Polycythemia. Erythropoietin (EPO) A circulating hormone with a molecular weight of approximately 34 kilodaltons. Produced 90% in the kidneys and 10% in the liver. In individuals without functional kidneys, the liver cannot compensate fully for EPO production. As a result, RBC production decreases significantly, reducing blood capacity by half. Such individuals require external EPO supplementation. Essential for erythropoiesis in response to hypoxia. Hypoxia → HIF-1 (Hypoxia-Inducible Factor-1) → Binds to the hypoxia response element (binds to DNA) → EPO transcription (in kidney cells). Even if hypoxia occurs in tissues far from the kidneys, EPO is still released. This is because other hormones activated by hypoxia, such as epinephrine, norepinephrine, and certain prostaglandins, also exert a positive stimulatory effect on EPO production. ‫ﺗﻣت ﻛﺗﺎﺑﺔ ھذا اﻟﺷﯾت ﺻدﻗﺔ ﺟﺎرﯾﺔ ﻋن روح واﻟدة زﻣﯾﻠﻧﺎ ﻋﻣرو راﺋد ﻣن دﻓﻌﺔ ﺗﯾﺟﺎن‬ ‫دﻋواﺗﻛم ﻟﮭﺎ ﺑﺎﻟرﺣﻣﺔ واﻟﻣﻐﻔرة‬ Thank you