TOO MUCH TIME. Cardiovascular System: Blood. Cell. Cell. Transport System of the Body: O 2 / Energy. Nutrients Waste O 2 CO 2.

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1 Transport System of the Body: 100 m 1 s 1 mm 100 s 1 cm s distance = time 2 O 2 / Energy O 2 CO 2 Nutrients Waste Source Cell TOO MUCH TIME External environment: CO 2 / Waste Sink O 2 / Nutrients CO 2 / Waste Transport System of the Body: O 2 CO 2 Nutrients Waste Diffusion O 2 / Energy Source Cell Bulk flow (pressure) External environment: CO 2 / Waste Sink O 2 / Nutrients CO 2 / Waste Cardiovascular System: Blood 1

2 Blood: Only fluid tissue in body (connective tissue) ph = (slightly alkaline) Temp. slightly higher than body temp. (38 C / 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 Maintains body temperature / ph Maintains fluid volumes 3) Protection Prevents blood loss (e.g., clot formation) Prevents infection (e.g., antibodies) Bloodletting a common medical treatment in the Middle Ages 1) Formed Elements (living cells) Erythrocytes (RBC s) Leukocytes (WBC s) Platelets Plasma Hematocrit: % of whole blood containing formed elements 2) Plasma Males ~ 47% Females ~ 42% Non-cellular fluid matrix (dissolved proteins) Formed elements Buffy Coat (~ 1%) Erythrocytes (~ 45%) A) Plasma Serum: Plasma minus clotting proteins Distributes materials / heat Composition: (precisely maintained) A) Water (~ 90%) (Primarily produced by liver) B) Protein (~ 8%) 60% 36% 4% Albumin Osmotic pressure Transport Globulins Transport ( / ) Antibodies ( ) Fibrinogen Clotting protein C) Other solutes (~ 2%; >100 different solutes present; Table 17.1) Organic nutrients (e.g., glucose) Electrolytes (e.g., sodium) Nitrogenous waste (e.g., urea) Respiratory gases (e.g., O 2) 2

3 Small (~ 7 m); biconcave ( certs ) Anucleate (lacking nucleus); few organelles Contain hemoglobin (O 2 / CO 2 transport protein) Shape maintained by network of proteins (e.g., spectrin) 250 million / cell 4 globins / hemoglobin (2 chains; 2 chains) = 4 molecules O 2 Why maintain hemoglobin in erythrocytes? 1) Leakage through capillary walls 2) Viscosity / osmotic pressure issues Heme (O 2-binding pigment w/ iron) + Globin (protein) Marieb & Hoehn (Human Anatomy and Physiology, 8 th ed.) Figures 17.3 / Structure complements function 1) Small size and shape equates to large surface area / volume Rapid respiratory gas loading / unloading 2) 97% of cell volume is hemoglobin (~ 250 million hemoglobin) Mass transport of respiratory gases 3) Lack mitochondria (don t burn oxygen) Efficient transport of respiratory gases Erythropoiesis (red blood cell formation): ~ 2 million RBCs produced per second Formation occurs in red bone marrow High Low Tibia Femur Long bones Vertebra Sternum Ribs Axial skeleton Young Age (years) Old 3

4 Entire process takes ~ 15 days Erythropoiesis (red blood cell formation): (ribosome factory) Hemocytoblast (stem cell) Myeloid stem cell Erythroblast Erythrocyte Reticulocyte Count: Provide rough index of RBC formation rate (enters blood stream) 1 2 % of RBCs Reticulocyte Normoblast (nucleus ejected) Erythropoiesis (red blood cell formation): Regulated hormonally by erythropoietin (~ 85%) (~ 15%) Hypoxia Produced by the kidney and liver 1) RBC loss 2) hemoglobin 3) Low O 2 (-) Normal Blood Oxygen Level Increased O 2 level in blood Reduced O 2 level in blood RBCs mature more rapidly Erythropoietin stimulates bone marrow Kidney releases erythropoietin Free iron ions toxic! Acts as a catalyst for the formation of free radicals Dietary requirements must be met for normal RBC formation Iron: (hemoglobin synthesis) Stored in liver & spleen in protein-iron complexes ferritin and hemosiderin Erythropoiesis (red blood cell formation): Ferritin (24 protein subunits) Transported in blood bound to transferrin Transferrin (Glycoprotein; 2 binding sites) Vitamin B 12 and folic acid necessary for proper DNA synthesis 4

5 Jaundice: Yellowing of skin due to bilirubin deposition Destruction of Erythrocytes Lose flexibility Iron salvages; stored for re-use Heme group degraded to bilirubin (captured by liver; released via gallbladder) Bilirubin (yellow pigment) Old RBCs engulfed by macrophages in spleen / liver (metabolized in Urobilinogen large Intestine) (exits in feces) Stercobilin (brown pigment) Globins recycled to amino acids Pathophysiology: Anemia ( oxygen carrying capacity of blood) Decreased number of RBCs Hemorrhagic anemia (blood loss) Hemolytic anemia (RBC rupture) Aplastic anemia (red marrow destruction) Microcytes Decreased hemoglobin content Iron-deficiency anemia (inadequate intake of iron) Macrocytes Pernicious anemia (deficiency of vitamin B 12) Abnormal hemoglobin Sickle-cell anemia (genetic mutation abnormal globin) Thalassemias (genetic mutation missing globin) Pathophysiology: Polycythemia ( red blood cell number) Polycythemia increases blood viscosity, causing it to flow sluggishly Whole blood EPO Polycythemia vera (bone marrow cancer) Artificial polycythemia (blood doping) Secondary polycythemia (high altitude living) 5

6 C) Leukocytes (white blood cells WBCs) Only complete cell in blood (e.g., nucleus / organelles) Function in defense against disease ONLY utilize blood for transport ~ ,800 WBCs / l Rolling Margination Migration Diapedesis Inflamed endothelial cells sprout cell-adhesion molecules (CAMs) Tight adherence Amoeboid movement leaping across Carman, C.V., Journal of Cell Science. 2009;122: C) Leukocytes (white blood cells WBCs) Categories of Leukocytes: Granulocytes (contain granules) 1) Neutrophils (50 70%) Small granules (hydrolytic enzymes/defensins) Multi-lobed nucleus Engulfs bacteria / fungi 2) Eosinophils (2 4%) Large granules (lysosomes) Bi-lobed nucleus Kills parasitic worms 3) Basophils (< 1%) Large granules (histamines) U-shaped nucleus Vasodilator / attracts WBCs Lifespan = hours days C) Leukocytes (white blood cells WBCs) Categories of Leukocytes: Agranulocytes (lack granules) 1) Lymphocytes (15 45%) Large nucleus (spherical) Function in immunity T lymphocytes B lymphocytes Lifespan = hours decades 2) Monocytes (3 8%) Largest of WBCs U-shaped nucleus Function as macrophages (differentiate in tissues) Lifespan = hours months 6

7 C) Leukocytes (white blood cells WBCs) Hormones: Interleukins Colony-stimulating factors Leukopoiesis (white blood cell formation): migrate to lymphoid tissue Lymphoblast Lymphocyte (+) Lymphoid stem cell Monoblast Monocyte Granules appear Nuclei arc Hemocytoblast (stem cell) Neutrophilic myelocyte Neutrophilic band cell Neutrophil Myeloid stem cell Myeloblast Basophilic myelocyte Eosinophilic myelocyte Basophilic band cell Eosinophilic band cell Basophil Eosinophil C) Leukocytes (white blood cells WBCs) Mononucleosis: Epstein-Barr Pathophysiology: virus Leukemia: Uncontrolled proliferation of WBCs (cancerous) Excessive number of agranulocytes Named according to abnormal cell line involved Lymphocytic leukemia Myelocytic leukemia Acute leukemia: Derived from blast-type cells Rapid advancement Often observed in children Symptoms: Anemia / bleeding problems Fever / weight-loss Frequent infections Chronic leukemia: Derived from later cell stages Slow advancement Often observed in elderly Treatment: Irradiation Chemotherapy Bone marrow transplant D) Platelets (thrombocytes) Cytoplasmic fragments (anucleate) Function in blood clotting (contain clotting chemicals) Thrombopoiesis (platelet formation): (+) Hormone: Thrombopoietin Myeloid stem cell Hemocytoblast (stem cell) ~ 150, ,000 / l Lifespan = ~ 10 days Repeat mitosis; no cytokinesis Megakaryoblast Megakaryocyte Platelets 7

8 Series of fast, localized reactions to halt blood loss Phase 1: Vascular spasm Phase 2: Platelet plug formation Vasoconstriction of damaged vessel (significantly reduces blood loss) Activated by: 1) Direct injury to smooth muscle 2) Chemical release (endothelial cells) 3) Nociceptors Temporarily seals vessel break (positive feedback loop) Intact endothelial cells release nitric oxide and prostacyclin which prevent platelet aggregation in undamaged tissue Marieb & Hoehn (Human Anatomy and Physiology, 8 th ed.) Figures17.13 Platelet plug formation: Rupture of vessel von Willebrand factor: Large plasma protein; links platelets to collagen fibers Collagen exposed Platelets swell and form spiked processes Attracts more platelets (+) Platelets stick to collagen Vascular spasms Platelets release contents Adenosine diphosphate (ADP) Aspirin Thromboxane A 2 Serotonin Series of fast, localized reactions to halt blood loss Step 1: Formation of prothrombin activator Phase 3: Coagulation (blood clotting) Blood converted from liquid to gel (3 6 minutes) Requires clotting factors (procoagulants) Activation turns clotting factors into enzymes Marieb & Hoehn (Human Anatomy and Physiology, 8 th ed.) Figures

9 Series of fast, localized reactions to halt blood loss Intrinsic pathway: triggered by negatively charged surfaces (platelets / collagen / glass) Slow due to many intermediate steps (all factors found within blood) Step 1: Formation of prothrombin activator (requires factor outside blood) Extrinsic pathway: triggered by factor found in tissues under the damaged endothelium (tissue factor) Rapid due to few intermediate steps Severe trauma: 15 seconds Both pathways cascade to activation of Factor X which combines with Platelet Factor 3 (PF 3 ), Ca ++, and Factor V to form Prothrombin Activator Activation turns clotting factors into enzymes Found on surface of platelets Marieb & Hoehn (Human Anatomy and Physiology, 8 th ed.) Figures17.14 Series of fast, localized reactions to halt blood loss Anticoagulants: Factors that inhibit clotting (e.g., heparin) Step 2: Formation of thrombin Inactivated by antithrombin III Step 3: Formation of fibrin mesh Factor XIII (fibrin stabilizing factor): Cross-linking enzyme that binds fibrin strands together Marieb & Hoehn (Human Anatomy and Physiology, 8 th ed.) Figures17.14 = requires vitamin K for synthesis Marieb & Hoehn (Human Anatomy and Physiology, 8 th ed.) Table

10 Series of fast, localized reactions to halt blood loss (2 days following damage) Clot Retraction / Repair: Fibrinolysis: (30 60 minutes following damage) Process of removing clot once healing has occurred Platelets contain actin / myosin fibers; contract in manner of muscle fibers (draws ruptured edges of blood vessel closer together) Plasmin: Fibrin-digesting enzyme ( clot buster ) Platelet-derived growth factor: Released by platelets; stimulates smooth muscle cells and fibroblasts to divide and rebuild vessel wall (incorporated into clot) Plasminogen tissue plasminogen activator (tpa) (released by endothelial cells) Plasmin Disorders of Hemostasis: Thromboembolic Disorders (undesirable clot formation) Bleeding Disorders (abnormal bleeding due to inability to clot) Petechiae Thrombus: A clot develops in an unbroken blood vessel Embolus: A free-floating clot in the bloodstream (may lead to embolism) Thrombocytopenia Deficiency in platelets Marrow destruction Impaired Liver Function Vitamin K deficiency Cirrhosis / hepatitis Causes: Roughened endothelium (e.g., atherosclerosis) Slowly flowing blood (e.g., airlines - economy class) Hemophilia Missing clotting factor(s) Genetic (e.g., X-linked) Hemophilia: (less severe) Hemophilia C Factor XI deficiency Hemophilia B Factor IX deficiency Hemophilia A Factor VIII deficiency 77% of cases Symptoms: Prolonged bleeding Disabled / painful joints Treatment: Plasma transfusions Injection of clotting factor(s) 10