Chapter 18 Cardiovascular System: Blood Blood functions • Transportation: circulates its components throughout the body (systemic and lungs) for cellular exchange (gases, nutrients, wastes) • Regulation: body temperature (98.6F) , pH(*7.3-7.4), fluid balance (colloid osmotic pressure) • Protection: immune components, platelets, plasma proteins *Bicarb (HCO3-) ion in blood, respiratory and urinary systems assist Blood Components 1 • Plasma – 55% of whole blood 92% Water, 7% plasma proteins; and 1% dissolved solutes (electrolytes, nutrients, wastes, gases) • plasma proteins: 58% albumin, 37% α, β and γ globulins; 4% fibrinogen and 1% regulatory proteins electrolytes: cations (Na+, K+, Ca2+, H+); anions (Cl-, OH-, HCO3-, HPO42-) Nutrients: Glucose, amino acids, lipids, lactic acid Wastes, gases: urea, ammonia, lactic acid, etc. Blood Components 2 • Formed elements – 45% of whole blood RBC: Erythrocytes - no nuclei, no organelles; filled with hemogloblin (O2 carrying capacity) Hematocrit: 38% - 56% (females-males) most numerous of formed elements: 4x106/ml6x106/ml *WBC: Leukocytes – immune cells; 4.5x103/ml11x103/ml; granulocytes, monocytes & lymphocytes Platelets: cellular particles formed from megakaryocytes; blood clotting functions. • Most WBC’s are in the tissues not the blood. Fig. 18.1 Blood Components 3 • Formed elements: RBC’s – erythrocytes (nonnucleated) 44%; biconcave disc shape; rouleau formation Hemoglobin (HGb) - red pigmented protein: two alpha (α) chains and two beta (β) chains: globins Each chain contains a porphyrin ring (lipid heme) with an Fe2+ molecule at its center. Each Fe2+ weakly binds an O2 molecule. CO2 binds to the globin molecules (not to heme) Fig. 18.5 Erythrocytes Hemoglobin Blood Components 4 • Formed elements RBC production is controlled by EPO (erythropoietin), a hormone produced by the kidney. The kidney detect low O2 levels in the blood & release EPO stimulating bone marrow production of RBC’s. Negative feedback mechanism: stimulus, receptor (kidney), control center (kidney), effector (red bone marrow), controls production of erythrocytes. Fig. 18.7 Plasma 1 • Plasma is a colloid with dispersed plasma proteins, and dissolved electrolytes, gases, nutrients, waste products. Serum is the solution portion of whole blood without the clotting proteins. • Plasma proteins Albumin – smallest & most numerous; most significant in exerting osmotic pressure in maintaining blood volume. Carrier protein for transport of hormones, lipids, medications Plasma 2 • Plasma proteins Globulins – globular proteins are the second most abundant; various size and forms: alpha (α) and beta (β) forms are carriers of ions, metals and hormones. β is larger than α. gamma (γ) globulins are the immune system’s humoral defense known also as antibodies or immunoglobulins. Fibrinogen – much less abundant than the previous listed plasma proteins; instrumental in blot clot formation (with other less abundant clotting factors). Plasma 3 • Plasma proteins Regulatory proteins – least numerous; enzymes, hormones • Electrolytes Cations and anions are instrumental in maintaining fluid balance between the tissues: cells and interstitial fluids, and blood volume. They actively regulate the function of nervous and muscular tissues. • Nutrients & wastes: nutrients absorbed by the body are used for building & repair; wastes are removed from the body. Both are transported by the blood. Hemopoiesis 1 • Hemocytoblast (red bone marrow): stem cell – produces all blood cell types (pluripotent) 1) myeloid line stimulated by multi-CSF (colony stimulation factors) growth factors: Megakaryocytes (platelets) : (Thrombopoietin) Erythrocytes (RBC’s): (*EPO, a hormone) Leukocytes (granulocytes, monocytes): GM-CSF (progenitor cell) , G-CSF (myeloblast), M-CSF (monoblast) *Blood O2 levels stimulate the kidneys to release erythropoietin; negative feedback control. Hemocytoblast Hemopoiesis 2 • Hemocytoblast (bone marrow): 2) lymphoid line: directly from stem cell (hemocytoblast) to lymphoid stem cell which generate: B-lymphoblast, T-lymphoblast and NK (Natural Killer) cell. • Erythropoeisis, recycling & destruction: atmospheric O2 levels help determine O2 blood levels by EPO stimulation regulated by neg. feedback loop. Lifespan of RBC ~120 days. Components – heme, iron and globulins metabolized and recycled or eliminated as wastes. Erythrocyte Formation (Erythropoiesis) Granulocytes & Agranulocytes Hemopoiesis 3 • Erythropoeisis, recycling & destruction: Iron – minor losses in wastes, it is stored in the liver by ferritin and hemosiderin. Heme – converted to biliverdin then to bilirubin by macrophages; transported to liver & excreted in bile, converted to urobilinogen in small intestines. Most is converted to stercobilin in large intestines (giving feces its characteristic color). Some is reabsorbed & converted to urobilin and excreted by the kidneys (giving urine its characteristic color). Globins – broken down to amino acids and recycled. Disorders of erythrocytes • Anemias: several types with diminished O2 carrying capacity of RBC/ # of RBC’s. Aplastic a.: defective formation of RBC’s & HGb Pernicious a.: Intrinsic factor defect = Vit B12 deficiency. Sickle cell a.: autosomal recessive; misshapen cells @ low O2 tension, leads to hemolysis. • Polycythemia: various types; increased viscosity of blood due to an increased hematocrit. Disorders of leukocytes 1 • Leukopenia decreased number of WBC’s per unit of blood. Increases the risk of infection; decreases ability to fight an infection indicative of a pathological condition • Leukocytosis elevated number of WBC’s per unit of blood indicative of recent infection or stress • Differential count: the number of each type of WBC per unit of blood; the normal count of various types changes with the various causes of pathology. Disorders of leukocytes 2 • Differential count all values are in units: “x103/µl blood” WBC count norm: 4.5 - 11 neutrophils: 1.8 – 7.8 lymphocytes: 1 – 4.8 monocytes: 0.1 – 0.7 eosinophils: 0.1 – 0.4 basophils: 0.02 – 0.05 Acute ailments usually cause an increase in neutrophils (neutrophilia) with an increase of immature neutrophils (bands) in circulation (left shifted differential). A decrease in neutrophils (neutropenia) may be due to anemia, cancer therapy, etc. Disorders of leukocytes 3 • Differential count Lymphocytosis is an increase in lymphocyte count usually due to viral infections, chronic bacterial infections, multiple myeloma and some types of leukemias. Lymphocytopenia is a decrease in lymphocyte count below normal range. This may be due to HIV, other types of leukemias, or sepsis. Eosinophilia (increase in # of eosinophils) is seen in allergic reactions, parasite infection, autoimmune disorders. Disorders of leukocytes 4 • Differential count Monocyte #’s increase with chronic inflammatory conditions and Tuberculosis infection. They decrease with chronic steroid therapy. Basophils increase with disorders causing proliferation of formed elements by bone marrow overproduction. Cytoplasmic granules contain histamine (inflammatory) and heparin (anticoagulant) They decrease due to stress, and acute allergic reactions. Platelet formation (Thrombopoieses) 1 Platelet formation (Thrombopoieses) 2 • Thrombocytes membrane bound cell fragments. Circulate in blood for approx. 8 days then broken down & recycled. Numbers range from 150 x 103 to 400 x 103/ml Stress can increase the #’s. Decrease in platelet count, thrombocytopenia is due to drug therapy, TB, leukemia, metastatic cancer. Platelet formation (Thrombopoieses) 3 Platelet formation (Thrombopoieses) 4 Blood Types 1 Surface Antigens molecules present on the membrane of RBC’s. known also as agglutinogens two classifications: ABO and Rh groups • *ABO group: consists of two surface antigens, A & B; the presence or absence of either or both determines the blood type of this group. Types: A (only A present); B (only A present) AB (both present); O (neither present) • Plasma contains antibodies (agglutinins) which react with ‘non-self’ antigens. • *Important with blood transfusions Blood Types 2 • Plasma Agglutinins: Type A – anti B; Type B – anti A; Type AB – no antibodies Type O – anti A and anti B antibodies • *Rh group: consist of surface antigen D on RBC’s its the presence or absence determines the blood type of this group. Types: Rh+ (D is present); Rh– (absent D) • Plasma: Agglutinins: Type Rh+: no anti D antibodies Type Rh-: anti D antibodies only after exposure to Rh+ blood. • *Important during pregnancy. Hemostasis Blood clotting Cascade 1 • Intrinsic (tissue factor) pathway factors activated by damage to vessel wall: platelets adhere and release factor XII f. XII activates f. XI; f. XI activates f. IX; f. IX + Ca2+ & platelet factor 3 pf3 activates f. VIII. F. VIII activates f. X = Common pathway • Extrinsic (contact activation) pathway damaged tissues outside the vessel releases: (Tissue Thromboplastin)f. III; f. III + Ca2+ & f. VII activates f. X = Common pathway Blood clotting Cascade 2 • Common pathway f. X + f. II + f. V & Ca2+ & pf. 3 = prothrombin activator which activates prothrombin (f. II) to Thrombin which converts f. I (soluble fibrinogen) to fibrin (insoluble) fibrin + Ca2+ activates f. XIII which cross-links fibrin monomers into a fibrin polymer mesh stabilizing the clot. Fibrinolysis: within 2 days of clot formation, this process occurs by plasmin degrading the mesh. Clot retraction precedes this by actinomyosin (a platelet protein) contraction. Blood clotting disorders • Failure to clot: bleeding disorders; several variants genetic mutations: Hemophilias A & B (females usu. carriers: sex-linked) Vitamin K deficiency (usu. newborns) platelet deficiency: Thrombocytopenia • Hypercoagulation: genetic, environmental, drug related causes. Symptoms: DVT, embolus; life threatening • Which of the following is involved in all three phases of hemostasis? a) Ca+2 ion b) thrombin c)platelets d) fibrin • The myeloid line of blood cells does not include: a) monocytes b) basophils c)NK cells d) RBC’s • Blood typing includes all of the following except? a) RBC antigens b)agglutinins c)WBC antigens • Which is not present in plasma? a) fibrinogen b) albumin c) hemoglobin d) γ globulins