ANP 1105A Lecture 11 - Revised 2022 PDF

ANP 1105A - Anatomy & Physiology I Basic Cellular Physiology & the Anatomy and Physiology of the Cardiovascular, Lymphatic & Respiratory Systems Lecture 11 – Blood (Part 1) Presented by: Dr. Stephen Gee Faculté de médecine | Faculty o...

ANP 1105A - Anatomy & Physiology I Basic Cellular Physiology & the Anatomy and Physiology of the Cardiovascular, Lymphatic & Respiratory Systems Lecture 11 – Blood (Part 1) Presented by: Dr. Stephen Gee Faculté de médecine | Faculty of Medicine uOttawa.ca  Readings – Marieb and Hoehn 11th Ed. Chapter 17 (pp. 642-666) 17.1 The functions of blood are transport, regulation and protection 17.2 Blood consists of plasma and formed elements 17.3 Erythrocytes play a crucial role in oxygen and carbon dioxide transport 17.5 Platelets are cell fragments that help stop bleeding 17.6 Hemostasis prevents blood loss 17.7 Transfusion can replace lost blood Overview: Chapter 17 Blood  Blood – Internal Transport System Life-sustaining transport vehicle of the cardiovascular system Functions of Blood Transport O2, nutrients, metabolic wastes (CO2 and urea) Hormones: from endocrine glands → targets Regulation Body temp: absorbing, distributing heat pH buffering; alkaline reserve of bicarbonate Fluid volume in circulatory system Protection Proteins, platelets initiate clot formation to prevent blood loss Prevents infection: Antibodies, complement proteins, white blood cells are ‘agents of immunity’  Composition of Blood Fluid connective tissue Matrix Plasma Cells Enclosed in PM, definite structure and shape Suspended in plasma Formed elements: Erythrocytes (RBCs); Leukocytes (WBCs); Platelets  Composition of Blood Centrifugation of a tube of blood yields three layers: Hematocrit - Normal values: M: 47 ± 5%; F: 42 ± 5% Buffy coat - Thin, whitish layer between RBCs & plasma Plasma - ~55%  Physical Characteristics and Volume Sticky, opaque fluid, metallic taste Color varies with O2 content: O2 rich: scarlet red O2 poor: dark red pH 7.35–7.45 (slightly alkaline) Denser than water; 5 x viscosity (due mainly to RBCs) ~8% body weight Average volumes: 5-6 L 4-5 L Blood Plasma Blood plasma straw-colored, sticky fluid (90% H20) >100 dissolved solutes Nutrients, gases, hormones, wastes, proteins, inorganic ions Plasma proteins most abundant – Remain in blood; not taken up by cells; produced by liver Albumin: 60% plasma protein – carrier of other molecules, blood buffer, contributes to plasma osmotic pressure, which helps to keep water in the bloodstream Formed Elements RBCs, WBCs, platelets Only WBCs are complete cells RBCs: no nuclei or organelles Platelets: cell fragments Survive in bloodstream only few days Most originate in bone marrow, do not divide  Erythrocytes – Structural Characteristics Small-diameter (7.5 μm) cells - gas transport Biconcave disc shape, anucleate, no organelles Contains hemoglobin (Hb) for gas transport RBC diameters are larger than some capillaries – Spectrin and other PM proteins - flexibility to change shape Complementarity of structure and function: Features for efficient gas transport: 1. Biconcave shape - huge surface area to volume ratio for gas exchange 2. 97% Hb cell volume (excluding H20) 3. No mitochondria. ATP production anaerobic, do not consume O2  Erythrocyte Function Respiratory gas transport Hemoglobin (Hb) binds reversibly with O 2 Normal values: M: 13–18g/100ml; F: 12–16 g/100ml Hb: heme pigment bound to protein globin – Globin is composed of four polypeptide chains Two  and two  chains – A heme pigment is bonded to each globin chain Gives blood its red color Each heme’s central iron atom binds one O2 Each Hb molecule can transport four O 2 Each RBC contains 250 million Hb molecules (Why is Hb contained within RBCs and not in the plasma?) O2 loading in lungs produces oxyhemoglobin O2 unloading in tissues produces deoxyhemoglobin, or reduced hemoglobin CO2 loading in tissues (carbonic anhydrase) – 20% of CO 2 in blood binds to Hb, producing carbaminohemoglobin  Hematopoiesis Formation of blood cells in red bone marrow: reticular connective tissue, sinusoids – Adult - in axial skeleton, girdles, proximal epiphyses of humerus, femur Hematopoietic stem cell (HSC)(a.k.a. hemocytoblast) – All formed elements – Hormones, growth factors SC → specific pathways – Committed SCs cannot change lineage New blood cells enter blood sinusoids  Erythropoiesis Stages (15 days) 1. Hematopoietic stem cell; transforms into myeloid stem cell 2. Myeloid stem cell (not shown); transforms into proerythroblast 3. Pro-erythroblast; divides often, transforming into basophilic erythroblasts 4. Basophilic erythroblasts; synthesize many ribosomes, which stain blue 5. Polychromatic erythroblasts; synthesize large amounts of red-hued hemoglobin; cell now shows both pink and blue areas 6. Orthochromatic erythroblasts; contain mostly hemoglobin, so appear just pink; eject most organelles; nucleus degrades, causing concave shape 7. Reticulocytes; still contain small amount of ribosomes. Reticulocyte count (1-2% of all erythrocytes) indicates rate of RBC formation. 8. Mature erythrocyte; in 2 days, ribosomes degrade, transforming into mature RBC 1 3 4 5 6 7 8  Regulation of Erythropoiesis by Erythropoietin Balance between RBC production (> 2 million RBC/sec) and destruction → constant # circulating erythrocytes Some athletes use artificial EPO increases hct → increases stamina, performance BUT … EPO can increase hct from 45 to 65%, with dehydration concentrating blood even more → increased blood viscosity, which can cause clotting, stroke, or heart failure Erythropoiesis Dietary Requirements Amino acids, lipids, carbohydrates Iron: available from diet 65% in Hb; 35% liver, spleen, bone marrow Plant sources high in iron: Beans and lentils. Free iron ions toxic so iron is bound with Tofu. proteins: Baked potatoes. Cashews – Stored in cells as ferritin and Dark green leafy vegetables such as spinach hemosiderin Fortified breakfast cereals Whole-grain and enriched breads – Transported in blood bound to transferrin Small amounts of iron lost in feces, urine, sweat (and menstrual flow). Vitamin B12, folic acid necessary for DNA synthesis for rapidly dividing cells like developing RBCs  Erythrocyte Fate Life span: 100–120 days Anucleate, cannot synthesize new proteins, grow or divide Old RBCs fragile, Hb begins to degenerate Trapped in smaller circulatory channels, especially in spleen Macrophages in spleen engulf, breakdown dying RBCs Breakdown: heme, Fe, globin separated – Fe binds ferritin or hemosiderin, stored for reuse – Heme degraded to bilirubin; liver secretes bilirubin (in bile) into intestines, transformed into brown pigment stercobilin → feces – Globin: metabolized into amino acids → circulation Erythrocyte Disorders Anemia (too few), polycythemia (too many) Anemia (”lacking blood”) O2-carrying capacity too low to support normal metabolism - sign rather than cause conjunctival pallor Symptoms: fatigue, pallor, dyspnea, and chills 3 classes: 1. Blood loss 2. Not enough produced 3. Too many destroyed Anemia – Blood Loss Acute Hemorrhagic anemia - Rapid blood loss (e.g. wound) – Treated by blood replacement Chronic hemorrhagic anemia – Slight, persistent blood loss (e.g. hemorrhoids, bleeding ulcer) – Primary problem must be treated to stop blood loss Monty Python Fight Scene Anemia – RBC Production Defects Iron-deficiency anemia Hemorrhage, low Fe intake, impaired absorption; can’t make Hb - lack of Fe → small, pale RBCs (microcytes). Treatment: Fe supplements Pernicious anemia Autoimmune - destroys stomach mucosa →intrinsic factor; needed to absorb B12,→developing RBCs enlarge, cannot divide (macrocytes). Also, low B12 dietary intake Treatment: Intramuscular B12 injections, nasal gel Renal anemia Renal disease - kidneys cannot produce enough EPO Treatment: synthetic EPO Eleanor_Roosevelt_cph.3b16000 (1).jpg Aplastic Anemia Destruction/inhibition bone marrow function (e.g. drugs, chemicals, radiation, viruses) All formed elements affected – anemia; clotting and immunity defects Treatment: short-term: transfusions; long-term: HSCs  Anemia – RBC Destruction Hemolytic anemia - Premature RBC lysis → Incompatible transfusions, infections Hb Abnormalities: Genetic → abnormal globin Thalassemia (α, β) - Mediterranean ancestry, 1 globin chain absent/faulty, RBCs thin, delicate, Hb-deficient; mild to severe; blood transfusions Sickle-cell Anemia HbS: mutant Hb - 1 aa change in  chain RBCs crescent shaped when O 2 low (e.g. exercise) RBCs rupture, block small BVs → poor O2 delivery, pain Sub-Saharan Africa, descendants Benefit? People with sickle cell do not contract malaria - infectious disease kills 1 million/yr – Plasmodium parasites - transmitted by Anopheles mosquito, contaminated needle, transfusion. – 2 HbS alleles: develop sickle-cell anemia; 1 HbS - milder disease, better chance to survive malaria Treatment: acute crisis - transfusions; inhaled NO for vasodilation – Prevention of sickling: Hydroxyurea induces formation of fetal hemoglobin (does not sickle); SC transplants; gene therapy  Polycythemia Excess RBCs; increases blood viscosity, causing sluggish blood flow Polycythemia vera: Bone marrow cancer leading to excess RBCs – Hematocrit may go as high as 80% – Treatment: therapeutic phlebotomy Secondary polycythemia: caused by low O2 levels (example: high altitude) or increased EPO production Blood doping: athletes remove, store, and reinfuse RBCs before an event to increase O2 levels for stamina  Platelets (thrombocytes) Megakaryocyte fragments Light blue-staining outer region; purple granules Contain chemicals involved in clotting: – Serotonin, Ca2+, enzymes, ADP, platelet- derived growth factor (PDGF) Form temporary plug - helps seal breaks in BVs Circulating platelets kept inactive, mobile by nitric oxide (NO) and prostacyclin from endothelial cells lining BVs  Platelet Formation – Thrombopoiesis Regulated by thrombopoietin - glycoprotein hormone produced by liver, kidney. (HSCs) → blood cells. Myeloid (bone marrow) cells include monocytes, macrophages, neutrophils, basophils, eosinophils, erythrocytes, megakaryocytes to platelets. Formed in myeloid line from megakaryoblast (stage I megakaryocyte) – Mitosis occurs, but not cytokinesis, → large stage IV cell with multilobed nucleus  Platelets Stage IV megakaryocyte contacts sinusoid in bone marrow Sends cytoplasmic projections (podosomes) into capillary lumen – Projections break off into platelet fragments Age quickly, degenerate in about 10 days Normal = 150,000– 400,000 platelets/l blood Summary of Formed Elements