TOO MUCH TIME Cardiovascular System: Blood
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100 m 1 s 1 mm 100 s distance = time2 Transport System of the Body: 1 cm 10000 s Transport System of the Body: O2 / Energy O2 Nutrients O2 Nutrients O2 / Energy CO2 Waste CO2 Waste Diffusion Source Source Cell Cell TOO MUCH Bulk flow (pressure) TIME External environment: External environment: Sink CO2 / Waste Sink CO2 / Waste O2 / Nutrients O2 / Nutrients CO2 / Waste CO2 / Waste Cardiovascular System – Blood Cardiovascular System: Blood: Blood • Only fluid tissue in body (connective tissue) • pH = 7.35 – 7.45 (slightly alkaline) • Temp. slightly higher than body temp. (38°C / 100.4°F) • ~ 8% body weight (♂ = 5-6 L; ♀ = 4-5 L) Function (“River of Life”): 1) Distribution • Delivers oxygen / nutrients • Carries away metabolic wastes • Transports hormones 2) Regulation Bloodletting a common medical • Maintains body temperature / pH treatment in the • Maintains fluid volumes Middle Ages 3) Protection • Prevents blood loss (e.g., clot formation) • Prevents infection (e.g., antibodies) Cardiovascular System – Blood Cardiovascular System – Blood Blood Components: Blood Components: Serum: Plasma minus 1) Formed Elements (living cells) A) Plasma clotting proteins • Erythrocytes (RBC’s) • Distributes materials / heat • Leukocytes (WBC’s) • Platelets Composition: (precisely maintained) Plasma A) Water (~ 90%) (Primarily produced Hematocrit: by liver) % of whole blood containing formed elements Buffy Coat Males ~ 47% (~ 1%) B) Protein (~ 8%) Females ~ 42% 60% 36% 4% Formed Albumin Globulins Fibrinogen elements Erythrocytes • Osmotic pressure • Transport ( / ) • Clotting protein (~ 45%) • Transport • Antibodies () 2) Plasma C) Other solutes (~ 2%; >100 different solutes present; Table 17.1) • Non-cellular fluid matrix (dissolved proteins) • Organic nutrients (e.g., glucose) • Electrolytes (e.g., sodium) • Nitrogenous waste (e.g., urea) • Respiratory gases (e.g., O2) 1 Cardiovascular System – Blood Cardiovascular System – Blood Blood Components: Blood Components: B) Erythrocytes (red blood cells – RBCs) B) Erythrocytes (red blood cells – RBCs) • Small (~ 7 m); biconcave (“certs”) • Anucleate (lacking nucleus); few organelles Structure complements function • Contain hemoglobin (O2 / CO2 transport protein) Shape maintained by network of proteins (e.g., spectrin) 1) Small size and shape equates to large 250 million / cell surface area / volume Rapid respiratory gas loading / unloading 4 globins / hemoglobin 2) 97% of cell volume is hemoglobin (2 chains; 2 chains) (~ 250 million hemoglobin) = 4 molecules O2 Mass transport of respiratory gases Why maintain hemoglobin 3) Lack mitochondria (don’t burn oxygen) in erythrocytes? Efficient transport of respiratory gases 1) Leakage through capillary walls 2) Viscosity / osmotic pressure issues Heme (O2-binding pigment w/ iron) + Globin (protein) Marieb & Hoehn (Human Anatomy and Physiology, 8th ed.) – Figures 17.3 / 17.14 Cardiovascular System – Blood Cardiovascular System – Blood Blood Components: Blood Components: Entire process takes ~ 15 days B) Erythrocytes (red blood cells – RBCs) B) Erythrocytes (red blood cells – RBCs) Erythropoiesis (red blood cell formation): Erythropoiesis (red blood cell formation): • ~ 2 million RBCs produced per second (ribosome factory) • Formation occurs in red bone marrow High Hemocytoblast Myeloid stem cell Erythroblast Vertebra (stem cell) Sternum Axial skeleton Ribs Femur Reticulocyte Count: Provide rough index of RBC Long bones formation rate Tibia Low (nucleus ejected) Young Old (enters blood stream) 1 – 2 % of RBCs Age (years) Erythrocyte Reticulocyte Normoblast Cardiovascular System – Blood Cardiovascular System – Blood Blood Components: Blood Components: Free iron ions toxic! (~ 85%) (~ 15%) • Acts as a catalyst for B) Erythrocytes (red blood cells – RBCs) B) Erythrocytes (red blood cells – RBCs) the formation of Produced by the kidney free radicals and liver Erythropoiesis (red blood cell formation): Erythropoiesis (red blood cell formation): • Regulated hormonally by erythropoietin • Dietary requirements must be met for normal RBC formation 1) RBC loss 2) hemoglobin Iron: Hypoxia (hemoglobin synthesis) 3) Low O2 • Stored in liver & spleen in protein-iron (-) Normal Blood Oxygen Level complexes ferritin and hemosiderin Increased O2 Reduced O2 Ferritin level in blood level in blood (24 protein subunits) • Transported in blood bound to transferrin Vitamin B12 and folic acid RBCs mature Erythropoietin stimulates Kidney releases necessary for proper DNA synthesis Transferrin more rapidly bone marrow erythropoietin (Glycoprotein; 2 binding sites) 2 Cardiovascular System – Blood Cardiovascular System – Blood Pathophysiology: Blood Components: Jaundice: Blood Components: Yellowing of skin due to Anemia B) Erythrocytes (red blood cells – RBCs) bilirubin deposition B) Erythrocytes (red blood cells – RBCs) ( oxygen carrying capacity of blood) Destruction of Erythrocytes Decreased • Lose flexibility number of RBCs Hemorrhagic anemia Hemolytic anemia Aplastic anemia (blood loss) (RBC rupture) (red marrow destruction) Microcytes • Iron salvages; stored for re-use Decreased • Heme group degraded to bilirubin hemoglobin content Macrocytes (captured by liver; Iron-deficiency anemia Pernicious anemia Bilirubin (yellow pigment) released via gallbladder) (inadequate intake of iron) (deficiency of vitamin B12) (metabolized in Urobilinogen large Intestine) • “Old” RBCs engulfed by macrophages Abnormal in spleen / liver (exits in feces) Stercobilin (brown pigment) hemoglobin • Globins recycled to amino acids Sickle-cell anemia Thalassemias (genetic mutation – abnormal globin) (genetic mutation – missing globin) Cardiovascular System – Blood Cardiovascular System – Blood Pathophysiology: Blood Components: Blood Components: B) Erythrocytes (red blood cells – RBCs) Polycythemia C) Leukocytes (white blood cells – WBCs) ( red blood cell number) • Only complete cell in blood (e.g., nucleus / organelles) Polycythemia increases blood viscosity, • Function in defense against disease ~ 4800 – 10,800 WBCs / l causing it to flow sluggishly • ONLY utilize blood for transport Whole blood EPO Rolling Margination Migration Diapedesis Polycythemia vera Artificial polycythemia (bone marrow cancer) (blood doping) Amoeboid Tight movement adherence “leaping across” Secondary polycythemia Inflamed endothelial cells sprout (high altitude living) cell-adhesion molecules (CAMs) Carman, C.V., Journal of Cell Science. 2009;122:3025-3035 Cardiovascular System – Blood Cardiovascular System – Blood Blood Components: Blood Components: C) Leukocytes (white blood cells – WBCs) C) Leukocytes (white blood cells – WBCs) Categories of Leukocytes: Categories of Leukocytes: Granulocytes (contain granules) Agranulocytes (lack granules) 1) Neutrophils (50 – 70%) 2) Eosinophils (2 – 4%) 3) Basophils (< 1%) 1) Lymphocytes (15 – 45%) 2) Monocytes (3 – 8%) • Small granules • Large granules • Large granules • Large nucleus (spherical) • Largest of WBCs (hydrolytic enzymes/defensins) (lysosomes) (histamines) • Function in immunity • U-shaped nucleus • Multi-lobed nucleus • Bi-lobed nucleus • U-shaped nucleus T lymphocytes • Function as macrophages • Engulfs bacteria / fungi • Kills parasitic worms • Vasodilator / attracts WBCs B lymphocytes (differentiate in tissues) Lifespan = hours – decades Lifespan = hours – months Lifespan = hours – days 3 Cardiovascular System – Blood Cardiovascular System – Blood Mononucleosis: Blood Components: Blood Components: C) Leukocytes (white blood cells – WBCs) C) Leukocytes (white blood cells – WBCs) Hormones: Leukopoiesis (white blood cell formation): Epstein-Barr Interleukins Pathophysiology: virus Colony-stimulating factors migrate to Excessive number of lymphoid tissue Leukemia: agranulocytes Lymphocyte Lymphoblast • Uncontrolled proliferation of WBCs (cancerous) Lymphoid • Named according to abnormal (+) stem cell Monoblast Monocyte cell line involved Granules appear Nuclei arc Acute leukemia: Chronic leukemia: Derived from blast-type cells Derived from later cell stages Neutrophilic Neutrophilic • Rapid advancement • Slow advancement myelocyte band cell Hemocytoblast Neutrophil • Often observed in children • Often observed in elderly (stem cell) Lymphocytic leukemia Basophilic Basophilic Symptoms: Treatment: Myeloblast myelocyte band cell • Anemia / bleeding problems • Irradiation Basophil Myeloid • Fever / weight-loss • Chemotherapy stem cell Eosinophilic Eosinophilic • Frequent infections • Bone marrow transplant myelocyte band cell Myelocytic leukemia Eosinophil Cardiovascular System – Blood Cardiovascular System – Blood Blood Components: Hemostasis (“stoppage of bleeding”): D) Platelets (thrombocytes) • Series of fast, localized reactions to halt blood loss • Cytoplasmic fragments (anucleate) Phase 1: Phase 2: • Function in blood clotting (contain clotting chemicals) Vascular spasm Platelet plug formation Thrombopoiesis (platelet formation): Hormone: Thrombopoietin (+) Myeloid stem cell Hemocytoblast (stem cell) • ~ 150,000 – 400,000 / l • Lifespan = ~ 10 days Vasoconstriction of damaged vessel Temporarily seals vessel break Repeat mitosis; (significantly reduces blood loss) (positive feedback loop) no cytokinesis Activated by: Intact endothelial cells release nitric oxide 1) Direct injury to smooth muscle and prostacyclin which prevent platelet aggregation in undamaged tissue Megakaryoblast 2) Chemical release (endothelial cells) Megakaryocyte Platelets 3) Nociceptors Marieb & Hoehn (Human Anatomy and Physiology, 8th ed.) – Figures17.13 Cardiovascular System – Blood Cardiovascular