Gas Transport 2 Lecture Notes PDF

Block 1.3 lectures 2024-2025 lecture Highlighter key Writer Reviewer...

Block 1.3 lectures 2024-2025 lecture Highlighter key Writer Reviewer Doctor explanation Abbreviation Key information Book >> >> Mazin Alfadhel Ghassan Alnasser Student explaintion 221-222-223 notes References Deleted  12/24/2024 Respiration: Gas Transport II Dr.TarekBENAMEUR Department of Biomedical Sciences College of Medicine King Faisal University Learning Objectives Definition of hematocrit Describe the various stages of blood cells synthesis & list the factors required for their production & maturation Definitions of some types of anemia, polycythemia & their physiological causes 1  12/24/2024 Hematocritdefinition & Normal Values Hematocrit (HCT) When we say hemotocrit of 40% that  The fraction of blood composed of RBCs (erythrocytes) means 40% of the blood volume is made up of RBCs, while the remaining 60% are e.g.HCT of 4040%are RBCs&the remainderis plasma. other components like plasma  Hematocrit normal values: Men: 40-54% averages42 % These values may differ slightly from one Women: 37-47% averages36 % place to another  The reference range varies depending on the methodology used. How HCT isdetermined ? Hematocrit Microhematocrit centrifuge HCT : hematocrit RBC : red blood cell Blood collection Micro-HCT Calibrated tubes: read directly the percentage of packed cells This is an old method to determine the HCT: Hematocrit reader First, we take a blood sample by micro-HCT calibrated tubes Second, putting the blood sample in the centrifuge and centrifuge the tube Third, we use the hematocrit reader to know the percentage of RBC 2  When you centrifuge the blood, there will be 12/24/2024 55% is plasma 45% erythrocytes reflected as hematocrit which Nowadays, we have automated is the most dense component hematology analyzer that give as a full 1% remaining is just leukocytes and platelets CBC called buffy coat Hematocrit CBC : complete blood count Add anticoagulants  Serum: plasma without fibrinogen and clotting factors e.g. HCT value of 45%means 45mLof RBCs in 100 mL of blood.  Modern automated hematology analyzers determines HCT values Hematocrit Hematocritvalues significance: "This is very important" to  know how these values can Abnormal HCT value Bone marrow is important affect the oxygen carrying because it is involved in blood capacity because: affects O 2carrying capacity &viscosity of blood cells synthesis abnormal values of HCT ---> affect oxygen carrying capacity of the hemoglobin -Anemia ;Severe bleeding and viscosity of the blood  Low HCT -Nutritional deficiencies, Living in mountains is not pathological cause of -Bone marrow problems,… high HCT but it cause mountain sickness ( an adaptive mechanism by the human body caused by lower atmospheric pressure) which can leads to fatigu, dizzines and lack of concentration -Living in mountains -Lungs & bone marrow disorders  High HCT -Dehydration Athletes use erythropoietin to increase the -Abuse of erythropoietin(athletes) production of red blood cells so their muscles will -Polycythemia… get more oxygentaed blood leading to increase their performance At mountains, atmospheric pressure decreases reducing the amount of of oxygen available in each breath ---> reduced oxygen causes hypoxia ---> hypoxia triggers the kidneys to release erythropoietin (EPO) ---> EPO stimulate the bone marrow to produce more and more red blood cells 3  12/24/2024 Learning Objectives Definition of hematocrit Describe the various stages of blood cells synthesis & list the factors required for their production & maturation Definitions of some types of anemia, polycythemia & their physiological causes Genesis of Blood Cells in the Bone Marrow  All cells of the circulating blood are derived from Pluripotent Hematopoietic Stem Cell (PHSC) The common source of blood is PHSC. We have to memorize Committed stem cells produce PHSC because it is very important specific type of blood cells  Committed stem cell that produces specifictype of blood cells Colony-Forming Unit–erythrocyte, CFU-E growth and differentiation  Factors: inducers is controlled by factors outside the bone marrow ( like low oxygen pressure in case of mountain -Growth inducers sickness ) Growth inducers: there are at least 4 major growth -Differentiation inducers inducers. The major one is IL-3 which promotes growth for all types of committed stem cells. The others are committed to specific types of cells  What are the different stages of blood cells synthesis ? PHSC : can give rise to all types of blood cell Committed Stem Cell: Stem cells derived from PHSCs that are specialized and can give rise to specific types of blood cells 4  12/24/2024 Various Stages of Blood Cells Synthesis Committed stem cells This can be differentiated into: CFU-S (in the spleen) Neutrophil self-renewal Eosinophil lymphoid stem cell Basophil Monocyte Macrocphages Macrophage CFU-S give rise to different types of cells: 1. Erythrocytes ( after undergoing differentiation into CFU-B and CFU-E Bone marrow 2. CFU-GM which will differentiate into Adapted from figure 33-2-p446 Guyton Physiology 13hEdition. granulocyte monocytes ---> macrophages 3. Platelets ( after undergoing differentiation into CFU-M and megakaryocytes) CFU-S : Committed sten cell taht give rise to myeloid lineage Erythrocytes : Red Blood Cells One of the characteristics of these Shape and size cells, they have a flexible membrane -Biconcave discs ( they can change the shape) -Average volume 90-95 µm3 because these cells need to be squeezed through the capillaries -Changing shape (flexible membrane) RBC Count Men : 5.2 ±0.3 x 106/µL Women:4.7 ±0.3 x 106/µL Thickness: 2.5 µm This is how these cells look like Center :≤ 1 µm under the microscope in the blood smear test It is important for us to notice that Diameter 7.8 µm there is a variation in the RBC count between male and female. That's We will learn the importance of the why when you receive the CBC, you diameters when we will reach renal need to consider the gender before phsiology in this block because having the interpretation then compare these diameters give RBC the male to male's values and female to characteristic of not crossing the female's values capillaries and going outside secreted by the urine but it is not our objective today. 5  12/24/2024 Erythrocytes : Red Blood Cells Oxygen (O2) and carbon dioxide (CO2) transport In phsiology, we focus on the functions of RBC They are carrying this carbonic Anucleated(No nucleus) anhydrase which accelerates the convertion of CO2 and water to the carbonic acid and to wash out the cells from this toxic and harmful material (CO2) Enzymes : e.g.(Carbonic anhydrase) Carbonic anhydrase is an enzyme that catalyzes this reaction Resulting to carbonic acid which quickly dissociates Hemoglobin(binds O2, CO2& CO,…) into bicarbonate (HCO₃⁻) and hydrogen ion (H⁺). Erythrocytes : Red Blood Cells Average life span ≈ 120 days (4 months) RBC’s production in bone marrow (from PHSC) Already explained Erythropoietin (EPO) Major stimulator of RBCs production Filtered by the spleen& the liver. How are RBCs synthesized ? 6  12/24/2024 Stages of Erythropoiesis That's why any vitamin B12 deficiency will impair this stage and The transition of stem EPO Vitamin B12, intrinsic factor, Folic acid will affect the RBC count later on cells to committed cells required for maturation(DNA synthesis) leading to affected oxygen carrying requires EPO capacity of hemoglobin Stem cell Committed cell Developmental pathway Phase 1 Phase 2 Phase 3 Ribosome synthesis Hemoglobin accumulation Ejection of nucleus Hematopoietic stem B asophilic Polychromatic Orthochromatic cell Proerythroblast erythroblast erythroblast erythroblast Reticulocyte Erythrocyte (hemocytoblast) Pluripotent Normoblast hematopoietic Blood stream stem cell Hbsynthesis begins here 1-2days Bonemarrow4-5 days © 2013 Pearson Education, Inc. Reticulocytes can be found in the blood but it is not in high proportion compared to the erythrocytes Factors that regulate RBCs production Decreased oxygenation will It will go through a cascade of stimulate the production of diffrentiation. The synthesised EPO by the kidneys leading to RBCs will restore the tissue the differentiation of PHSC to oxygenation proerythroblasts Erythropoietin Tissue oxygenationlevel(hypoxia) In case of circulatory problems Pulmonary diseases will impair gas exchange leading to decreased oxygenation 7  12/24/2024 High altitude (Quiz) 1. How blood O2transport to the tissues is affectedin high altitude ? A- Decreased B- Increased C- Unchanged 2. Which one of the following conditions would be the main acclimatization responseof the body whenliving in high altitude ? A-Decreased RBC production B-IncreasedRBC production C-IncreasedRBC destruction Answer: 1) A 2) B Maturation of Red Blood Cells  Requiredfactorsfor RBC maturation: Cyanocobalamin is a synthetic, water- soluble form of vitamin B12. It is used to treat vitamin B12 deficiency -VitaminB12(Cyanocobalamin): 1-3 µg/day -Folic Acid Lackof VitaminB12orfolicacid These macrocytes, as you -Abnormal& diminished DNA can see, are larger than normal. They have -Failure of nuclear maturation & celldivision characteristics of fragility and a short lifespan. -Erythroblastic cells fail to proliferate rapidly Production of Macrocyte(larger, fragile, short-life) Deficiency of vitaminB12 or folicacid causes maturation failure in erythropoiesis 8  12/24/2024 Maturation of Red Blood Cells  Maturation failure caused by poor absorption of VitaminB 12 -Failure to absorb vitaminB12 from GI tract Pernicious anemia -Atrophic gastric mucosa Some GI diseases can lead to poor absorbtion of vitamin B12 leading to -Loss of parietal cells intrinsic factors defficiency pernicious anemia -Decreased availability of vitaminB12 (faultyabsorption) atrophic gastric mucosa fails to produce normal gastric secretion (like internsic factor) ------> parietal cells of the gastric glands will not secrete internsic factor [which bind to vitamin B12 to facilitate its absorption by the body and prevent it from digestive enzymes] ------> faulty absorption will occur { faulty absorption means impaired ability of the body to absorb vitamin B12 from the digestive tract, despite it being present in the diet } which lead to decreased availability of vitaminB12 3-4 years of defective vitaminB12 absorption can cause maturation failure anemia Learning Objectives Definition of hematocrit Describe the various stages of blood cells synthesis & list the factors required for their production & maturation Definitions of some types of anemia, polycythemia & their physiological causes 9  12/24/2024 What is Anemia ? Anemia: - Hb in the blood below the reference level for the age & sex of the individual which decrease the O2-carrying capacity of blood. Hb concentration erythrocytes count (RBCs) Here you can see, this is normal blood Normal values of Hbin the peripheral blood: compared to anemia which looks  yellow-pale Adult men: 13.5-17.5 (g/dL) Adult women: 11.5-16.0 (g/dL) Some Types of Anemia It could be due to Blood Loss Anemia hemorrhage AplasticAnemia Megaloblastic Anemia Hemolytic Anemia 10  12/24/2024 Some Types of Anemia (cont’d) Rapid hemorrhage will lead to Blood Loss Anemia RBCs loss, the plasma will be rplaced faster than the RBCs so we need to transfuge RBCs to the patients who lost more than 10% Rapid Hemorrhage of the blood volume because of a -RBCs loss trauma -Plasma replaced within 1-3 days The cells will be small in size and -RBCs return to normal within 3-6 weeks the color is different compared to normal red blood cells (hypochromic cells) due to the low hemoglobin level Chronic blood loss -Fails to absorb enough iron -Microcytic Hypochromic anemia -Smaller RBC - Hb concentration Ongoing blood loss due to ulcers or menstural periods decrease the RBCs -----> the body Microcytic hypochromic cells compensates by increasing the production of RBCs ------> continuous production of RBCs depletes the body's iron (which is essential for hemoglobin production) ------> due to the lack of iron, the bone marrow produces microcytic red blood cells that have low oxygen carrying capacity Some Types of Anemia (cont’d) Aplastic Anemia Bone marrow aplasia:dysfunctioning bone marrow The bone marrow is not able to produce the different cells -Radiation exposure/chemotherapy in sufficient numbers due to: -Toxic chemicals (insecticides, benzene,…) That's why the Food and Drug Administration tries to inspect food coming from outside to determine whether it contains insecticides above the allowed quantity. Also, we need to be careful while eating this food and wash it. -Autoimmune disorders (lupus erythematosus) Autoimmune disease which the body’s immune system mistakenly will attack the healthy tissues in many parts of the body. The sign and symptoms are Bauer’s individuals. It could be mild or severe. Idiopathic aplastic anemia:  50%, (unknown cause) 11  12/24/2024 Some Types of Anemia (cont’d)  Megaloblastic Anemia -Slow erythroblast proliferation Large, odd shaped, fragile (megaloblasts) -Deficiency:Vitamin B12 , folic acid, intrinsic factor from the stomach mucosa -GI disorders -Total gastrectomy M egaloblast Patients who underwent gastrectomy will develop this type of anemia because of the loss of parietal cells and internsic factor required for the maturation of RBCs. That's why we should monitor properly these patients to prevent this condition Some Types of Anemia (cont’d) Hemolytic Anemia 1. Hereditary spherocytosis -Small, fragile, Spherical-not biconcave discs -Destroyed in : spleen/tight vascular beds This will impair the oxygen carrying Spherocytes capacity in hemoglobin 2. Sickle cell anemia (Sickle shaped RBCs : Hemoglobin S (HbS) It will take the form of -HbS precipitates into long crystals when sickle. It is due to exposed to O2levels defect in hemoglobin S It will lead to abdominal pain and problems with breathing Sickle cell anemia 12  12/24/2024 Link:https://youtu.be/R4-c3hUhhyc?si=2Hj2t--3EnjVE_X_ Sickle cell anemia (video) Some Types of Anemia (cont’d) 3. Erythroblastosis fetalis Rh(+)RBCs in the fetusattacked by antibodies from Rh(-)mother -Antibodies (abs) fragilize the Rh(+) cells New born with serious anemia 13  12/24/2024 Polycythemia Polycythemia -Overproduction of RBCs - Elevated Hematocrit Two forms of Polycythemia:  Secondary Polycythemia This just an example for illustration: PolycythemiaVera (Erythremia) In normal condition : 45% anemia: has lower packed volume of RBCs 30% polycythemia: has higher packed volume of RBCs 70% Polycythemia (cont’d)  Secondary Polycythemia -Occurs with hypoxic tissues : -Insufficient O2in the air (high altitude) -Failure of O2delivery to tissues (cardiac failure, pulmonary diseases) -RBCs production = 6 -7 millions cells/μL -Normal or higher levels of EPO Physiologic polycythemia It is an adaptive mechanism to the high altitudes -Living at high altitudes of 14,000-17,000 ft -Atmospheric O2 very low 14  12/24/2024 Polycythemia (cont’d) PolycythemiaVera (Erythremia) -RBCs overproduction 7 -8 million/mm3 -Hematocrit 60 -70%; -Genetic aberrationin hemocytoblast -Excessproduction of WBCs& platelets - blood volume & viscosity - Lowlevel of EPO  Vascular system becomes intensely engorged It is a consequence of A mutation of JAK2 gene in the bone marrow causes high production of RBCs ------> polycythemia vera high numbers of RBCs lead to increased oxygen carrying capacity -----> high oxygen level signal the kidneys to reduce EPO ------> the production of RBCs will not be rduced because in JAK2 mutation there is high production of RBCs regardless the levels of EPO Anemia : Summary Anemia Some causes A↓ in circulating Hb which ↓ O2-carrying  Decreased production capacity of the blood Iron deficiency (↓Hb synthesis)hypochromic microcytic  anemia Low Aplastic anemia dysfunctioning bone marrow Low Hb RBCsconcentration count Megaloblastic anemiadeficiency of vit B12, Folate slow reproduction erythroblastsmegaloblasts  Increased destruction Sickle cell anemia(“S” hemoglobin; βchains faulty This is a point that I would like to highlight: precipitates in RBC) Erythroblastosis Fetalis Fetal RBCs damaged by the in case of anemia it can be both mother antibodies Decreased production or  Bleeding increased destruction Acute chronicmicrocytic anemia (small RBCs, low MCH values) 15  12/24/2024 Summary HCT: The fraction of blood composed of RBCs Abnormalvalues of HCT affect the O2-carrying capacityof Hb RBCs: producedin the Bonemarrow& derivedfromHematopoieticstem cells Growth& differentiationinducerscontrol the growth& differentiationof stem cells Vitam B12, folicacidand intrinsic factorsare requiredfor RBCsmaturation EPO, O2 level, … regulateerythropoiesis Polycythemia: characterized by overproduction of RBC, high HCT,… 31 References Email: [email protected] (Chapter 33, 14, 25) Guyton & Hall. 14thEdition Next lecture : Regulation of respiration 16  12/24/2024 Anyquestions ? THANK YOU 17 https://youtu.be/R4-c3hUhhyc?si=NaY_4epmBMFTqFO2  team Wishes you the best