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- 1. Chapter 19 The Cardiovascular System: Blood
- 2. Blood is a connective tissue made up of two parts: -Cells (formed elements) and matrix (plasma) Overview Transport • Oxygen & nutrients to body (main function) • Metabolic wastes to lungs and kidneys • Hormones Defense • Preventing blood loss (clotting) • Immunity • White blood cells • Antibodies • Complement proteins Homeostasis • Body temperature • pH using buffers; reserve of bicarbonate ions • Fluid volume
- 3. Overview • The only fluid tissue • Oxygenate bright red, deoxygenated dusky red • pH 7.35-7.45 • Temperature 38oC (100.4oF) • 5X more viscous than water • Adult males 5-6 liters • Females 4-5 liters Oxygenated De-Oxygenated • Components – Matrix = plasma (non-living) – Cells = formed elements (living) – Erythrocytes (RBC) – Leukocytes (WBC) – Platelets
- 4. Hematocrit - measures RBC Overview Plasma is the liquid matrix. • 55% of blood volume Formed elements are the cells and cell fragments. • 45% of blood volume Hematocrit - Spinning blood to calculate the volume percentage of red blood cells in blood • 40.7–50.3% for males • 36.1–44.3% for females
- 5. • Plasma (92% water) – Albumin - most abundant protein, binding proteins, aids in blood pressure – Globulin - transporting molecules, antibodies/immunoglobulins – Fibrinogen - important in blood clotting – 1% include various electrolytes & organic nutrients Overview
- 6. • totipotent stem cell (zygote) • differentiates into any cell • pluripotent stem cell • differentiates into multiple body cell within the 3 embryonic layers, differentiate has begun • multipotent stem cell • can also be called adult stem cells, cells will differentiate into specific cells within tissue types • hemopoietic stem cell • differentiates into blood components (hemopoiesis - the process of making blood components) Formed Elements hemocytoblast
- 7. Formed Elements platelet RBC WBC Red blood cells (erythrocytes). 95% of the volume of formed elements. White blood cells (leukocytes). • Granulocytes: cytoplasm contains large granules • neutrophils • eosinophils • basophils. • Agranulocytes: cytoplasm contains small granules • lymphocytes • monocytes. Platelets (thrombocytes). Cell fragment. Form platelet plugs.
- 8. Formed Elements • Hematopoiesis or hemopoiesis: Process of blood cell production. • Occurs in bone marrow • When a hemocytoblast divides, one cell remains a hemocytoblast, the other differentiates into either a myeloid stem cell or a lymphoid stem cell. platelets RBC WBC Hemopoiesis • myeloid stem cell - give rise to platelets (thrombocytes), RBC (erythrocytes), some WBC (leukocytes) • lymphoid stem cell - give rise to WBC (lymphocytes) • Cytokines - controlling glycoproteins, act as signals to drive cell differentiation
- 9. Erythrocytes (RBC) Structural Characteristics • Main function is to transport oxygen and carbon dioxide • Spectrin: protein provides flexibility • NEVER leaves blood vessel • Enucleated as it matures • Small-diameter cells (larger than capillaries) • Bi-concave increases surface area • Filled with hemoglobin (Hb) Exemplary of structure complementing function
- 10. • Hemoglobin binds oxygen (reversibly) • Four polypeptide chains (globulin proteins) • 2 alpha, 2 beta in adults • 2 alpha, 2 gamma in fetus • red colored (pigmented) heme that has an iron • iron binds one O2, CO2 is not usually bound but transported as bicarbonate (HCO3) • degrades to yellow pigment bilirubin • 250 million Hb/cell – oxyhemoglobin (ruby red) – deoxyhemoglobin (dark red) • CO will bind irreversibly resulting in carboxyhemoglobin Function of Erythrocytes molecular oxygen carbon monoxide
- 11. Hemoglobin Breakdown 1. Macrophages in spleen and liver ruptured RBC and take hemoglobin. Lysosomal enzymes digest the hemoglobin to yield amino acids, iron, and bilirubin. 2. Amino acids are reused to make proteins. 3. Heme broken down, releasing iron. 4. Iron reused in new hemoglobin molecules. 5. Heme is converted to biliverdin (green color) and then to bilirubin (yellow color). Bilirubin binds to albumin and transported to liver. 6. Bilirubin is conjugated and becomes part of the bile. If liver cannot conjugate then a build up of bilirubin occurs in body causing jaundice. 7. Bacteria convert bilirubin into the pigments that give feces its color. 8. Bilirubin contributes to characteristic yellow color of urine.
- 12. Regulation of Erythropoiesis homeostatic imbalance Kidney releases erythropoietin More RBC to carry O2 • When low blood O2 levels (hypoxia) are detected the hormone erythropoietin (EPO) is released by the kidneys. Erythropoiesis is the formation of red blood cells. It takes about 4 days. • Always small amount of EPO in blood • Kidney (JGC) triggers synthesis of EPO
- 13. Regulation of Erythropoiesis • When low blood O2 levels (hypoxia) are detected the hormone erythropoietin (EPO) is released by the kidneys. Erythropoiesis is the formation of red blood cells. It takes about 4 days. • Always small amount of EPO in blood • Kidney (JGC) triggers synthesis of EPO
- 14. Erythrocyte Disorders • Anemia – Low RBC concentration – Low O2 -carrying capacity – Symptoms: fatigue, pallor (paleness), dyspnea, chills – Cause • Blood loss • Not enough RBCs • Too many RBCs destroyed (sickle cell) • Polycythemia – High RBC concentration – Increases blood viscosity, sluggish flow Normal Polycythemia
- 15. Erythrocyte Disorders • Sickle-cell anemia – Crescent shaped when O2 low – Block small vessels – Prevalent in people of African decent – Benefit - not susceptible to malaria – Treatment: acute crisis treated with transfusions, nitric oxide – Crisis Prevention: » Hydroxyurea induces formation of fetal hemoglobin » Stem cell transplants » Gene therapy » Nitric oxide for vasodilation
- 16. Leukocytes • Leukocytes: only formed element that is complete cell with nuclei and organelles • Function: Defense against disease – each WBC type has different function – Leave capillaries via emigration – Positive chemotaxis - “911” signal released from injury site that signals to WBC for help – Short life fighting microbes
- 17. Leukocytes • Leukocytes: only formed element that is complete cell with nuclei and organelles • Function: Defense against disease – each WBC type has different function – Leave capillaries via emigration – Positive chemotaxis - “911” signal released from injury site that signals to WBC for help – Short life fighting microbes
- 18. Leukocytes • Two major categories: – Granulocytes (3): contain visible granules • Neutrophils • Eosinophils • Basophils – Agranulocytes (2): do not contain visible granules • Lymphocytes • Monocytes Neutrophil Eosinophil Basophil Lymphocyte Monocyte Abundance Never Let Monkeys Eat Bananas
- 19. Leukocytes Neutrophil Eosinophil Basophil - Larger and shorter-lived than RBCs - Lobed nuclei - Granules stain specific - All phagocytic to some degree (Micrographs provided by the Regents of University of Michigan Medical School © 2012) • Two major categories: – Granulocytes (3): contain visible granules • Neutrophils • Eosinophils • Basophils
- 21. Granulocytes • Neutrophils – Arise from myloid stem cell – Most numerous WBCs – First and most rapid responders – Prefer bacteria – Polymorphonuclear - nucleus has 3-6 lobes – Granules contain: • defensin: pierce holes in membrane of ingested microbe • lysozyme: breaks down cell wall • cytoplasm appear pinkish due to acidic nature – high or low count signals infection or disease
- 22. Granulocytes • Eosinophils – Arise from myloid stem cell – Nucleus has two lobe nucleus (ear muffs) – Granules contain: • antihistamine • digestive enzymes: released on parasitic worms, digesting surface • acidic in nature and stain pinkish to dark pink – Phagocytosis particularly effective when antibodies bind antigen on pathogen – Role in allergies, asthma, and immune response modulators
- 23. Granulocytes • Basophils – Arise from myloid stem cell – Rarest for WBC – Nucleus is bi-lobed but difficult to see because of granule stain – Granules contain: • histamine: intensify inflammatory response • heparin: opposes blood clotting • cytoplasm appears bluish to purple due to basic environment – Functionally similar to mast cells
- 25. Agranulocytes - no visible granules • Lymphocytes – Form from lymphoid stem cell – Mostly in lymphoid tissue – Crucial to immunity – Live a few hours to decades – Types: • T lymphocytes (T cells) • mature in thymus • act against virus-infected cells and tumor cells, • B lymphocytes (B cells) • mature within bone marrow • give rise to plasma cells, which produce antibodies • Natural killers • attack cells that do not express “self” proteins on membrane
- 26. Agranulocytes - no visible granules • Overproduction of lymphocytes: • leukemias • infectious mononucleosis • Under production lymphocytes: • immunesuppression • usually causes increase in eosinophils leukemia leukopenia
- 27. Agranulocytes - no visible granules • Monocytes – Only agranulocyte from myloid stem cell – Largest of all leukocytes – Nucleus is kidney-shaped – Differentiate into macrophages • Active phagocytic cells against • viruses • bacterial parasites • chronic infections – Activate lymphocytes to mount immune response – Live for several months
- 28. Platelets • Fragments of megakaryocyte (myeloid line) • Regulated by hormone thrombopoietin • Function is to form temporary plug to stop bleeding • Exist ~10 days • Thrombocytosis - excess platelets • Thrombocytopenia - platelet deficiency Thrombopoietin released from kidney and liver https://www.researchgate.net/figure/The-platelet-activation-mechanism-When-the- platelets-are-activated-they-release-growth_fig1_338345510 activated platelet
- 29. Hemostasis • Hemostasis is the fast series of reactions to stop bleeding • Clotting factors and substances released by platelets and injured tissues • Three steps involved Step 1: Vascular spasm Step 2: Platelet plug formation Step 3: Coagulation (blood clotting) https://my.clevelandclinic.org/health/ symptoms/21999-hemostasis Vascular spasm Platelet plug formation Coagulation
- 30. Step 1: Vascular spasm • Vasoconstriction - smooth muscle contract which significantly reduce blood flow until other mechanisms can kick in Step 2: Platelet plug formation • Platelets stick to collagen fibers • Activated platelets swell, become spikey and sticky, release chemical messengers: – ADP – Serotonin and thromboxane A2 • Positive feedback cycle Hemostasis Vascular spasm Platelet plug formation
- 31. Hemostasis Vascular spasm Platelet plug formation Coagulation Anticoagulant drugs: used to prevent undesirable clotting (aspirin, heparin, warfarin) Step 3: Coagulation • A network of threadlike fibers, trapped blood cells, platelets and fluid. • Three pathways: • Extrinsic pathway - triggered by trauma. • Intrinsic pathway - begins in bloodstream and triggered by internal damage to the wall of the vessel. • Common pathway - converging of both pathway to form fibrin • 12 clotting factors
- 32. Hemostasis https://diapharma.com/coagulation/ Step 3: Coagulation • A network of threadlike fibers, trapped blood cells, platelets and fluid. • Three pathways: • Extrinsic pathway - triggered by trauma. • Intrinsic pathway - begins in bloodstream and triggered by internal damage to the wall of the vessel. • Common pathway - converging of both pathway to form fibrin • 12 clotting factors
- 33. Disorders of Hemostasis • Thrombus: clot develops and persists in unbroken blood vessel • Embolus: thrombus free in bloodstream • Risk factors: • atherosclerosis • inflammation • slowly flowing blood • blood stasis from immobility https://my.clevelandclinic.org/health/diseases/22242-thrombosi https://www.nhs.uk/conditions/blood-clots/ https://ksi.uconn.edu/emergency-conditions/ internal-trauma/deep-vein-thrombosis/
- 34. Disorders of Hemostasis - Bleeding condition (hemophilia) where an individual can not clot to stop bleeding. • Hereditary disorders – Hemophilia A: Factor VIII deficiency, most common – Hemophilia B: Factor IX deficiency, also known as Christmas disease – Hemophilia C: Factor XI deficiency, usually found in Ashkenazi Jews • Prolonged bleeding, especially joint cavities • Treatment: injections of engineered factors; eliminated transfusion Queen Victoria
- 35. • Blood groups are determined by the presence or absence of specific surface marker molecules on the plasma membranes of erythrocytes • Important for the transfusion of blood Blood Typing Blood Typing
- 36. • Human blood groups – RBC membranes bear ~30 different antigens – Mismatched blood may agglutinate (clumps of erythrocytes) – Hemolysis: the rupturing of cells and releasing cell content – ABO and Rh blood groups are major groups typed Blood Typing The surface of a human cell has on average about 2800 surface proteins. agglutination
- 37. • Human blood groups – RBC membranes bear ~30 different antigens – Mismatched blood may agglutinate (clumps of erythrocytes) – Hemolysis: the rupturing of cells and releasing cell content – ABO and Rh blood groups are major groups typed Blood Typing – ABO blood groups • Presence or absence of agglutinogens – Type A only A – Type B only B – Type AB both A and B – Type O neither A nor B • Anti-A or anti-B antibodies act on RBCs with ABO antigens • Antibodies form at ~2 months of age agglutination
- 38. – Rh blood groups • Not part of ABO blood group • Discovered in rhesus macaque monkey • 52 different named Rh factors • Rh+ indicates presence of D antigen – 85% Americans Rh+ • Anti-Rh antibodies not formed until antigen is encountered first time • Second exposure results in transfusion reaction Blood Typing https://www.kindpng.com/imgv/wobTRT_blood- types-rh-abo-blood-type-red-blood/
- 39. Clinical – Homeostatic Imbalance • Mother is Rh - and fetus is Rh+ • First pregnancy: • Rh– mom exposed to Rh+ blood during delivery • baby healthy • mother makes anti-Rh antibodies • Second pregnancy: • Mom’s anti-Rh antibodies cross placenta and destroy RBCs of Rh+ baby • Baby treated with pre-birth transfusions and exchange transfusions after birth • RhoGAM serum containing anti-Rh can prevent Rh– mother from making anti-Rh antibodies Hemolytic disease of newborn (erythroblastosis fetalis)
- 40. Transfusing Red Blood Cells Type AB Type A Type B Type O Serum Anti-A Anti-B • Blood typing determines ABO and Rh blood types. Red cells tested against antibodies. • Crossmatch: donor blood cells mixed with recipient’s serum and vice versa; look for agglutination. • Type O- universal donor, no A or B antigens present universal • Type AB+ universal recipient; no anti- bodies present
- 41. Transfusing Red Blood Cells • Transfusion reactions: – Donor’s cells attacked by recipient’s agglutinins – Symptoms: fever, chills, low blood pressure, rapid heartbeat, nausea, vomiting – Treatment: fluids and diuretics to wash out hemoglobin