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Blood Chapter 19 Functions of blood • Transportation – – – – Oxygen Carbon dioxide Nutrients & Hormones Wastes • Regulation – Fluid balance & Thermoregulation – pH & Electrolytes • Protection – Immune System & bodies defenses – Clotting and wound repair Physical characteristics of Blood • Yes, it is thicker than water • pH between 7.35 (venous) and 7.45 (arterial) • Volume – 5 to 6 liters in an average male (1.5 gal or 12 pints) – 4 to 6 liters in an average female (1.2 gal or 10 pints) • About 20% of the extracellular fluid • About 8% of the body mass Composition of Blood • Whole blood is divided into plasma and formed elements • Plasma: – 55% of whole blood volume – 91.5% water – 7% soluble proteins • Albumin = 54% (osmotic balance, buffering, transport of steroid hormones and fatty acids) • Globulins = 38% (antibodies, etc) • Fibrinogen = 7% (produced by liver, for clotting) • 1% other – Other solutes • Electrolytes, gases, nutrients, wastes, hormones Composition of Blood Extracellular Fluids • Interstitial fluid (IF) and plasma • Materials plasma and IF exchange across capillary walls: – water – ions – small solutes Plasma 3 Classes of Plasma Proteins • Albumins (60%) • Globulins (35%) • Fibrinogen (4%) Origins of Plasma Proteins • 90% made in liver • Antibodies made by plasma cells • Peptide hormones made by endocrine organs Formed Elements • Erythrocytes (a.k.a. red blood cells) 4 to 6 million per mm3 (mL) About 7 - 8 mm in diameter Anucleate Amitotic at maturity No mitochondria, centrioles, or much else in the way of cytoplasm. Mostly hemoglobin. – Live about 90 – 120 days – – – – – • Hematocrit – The total volume of blood occupied by erythrocytes. – 38 – 46 % for females, average 42% – 40 – 54% for males, average 47% Normal Blood Counts • RBC: – male: 4.5–6.3 million – female: 4.–5.5 million • Hematocrit: – male: 4–52 – female: 3–47 Fig.19.02 Formed elements An Erythrocyte Hemopoiesis: formation of blood cells • Also known as hematopoiesis • Occurs in the red marrow: – In adults, mostly in the proximal epiphysis of femur and bodies of the lumbar vertebrae – Originally from pluripotent stem cells from mesenchyme – In the fetus, hematopoiesis occurs in the liver, spleen, thymus, lymph nodes and yolk sac – Red marrow is found in the spaces of spongy bone • Erythropoietin from the kidneys stimulates hematopoiesis Erythrocyte development Stages of RBC Maturation • • • • • Myeloid stem cell Proerythroblast Erythroblasts Reticulocyte Mature RBC The structure of the hemoglobin molecule Hemoglobin (Hb) • Each RBC contains an average of 250 million Hb molecules • Each Hb molecule has 4 oxygen binding sites • That’s about 1 billion oxygen molecules per RBC! • CO (carbon monoxide) has approximately 200 times the affinity for Hb than oxygen and it fool O2 saturation detectors Erythrocyte catabolism • After roughly 120 days red blood cells are worn out and must be recycled • This occurs in the spleen and liver • Iron (Fe+++): – The Fe+++ is removed from the heme group and bound to transferrin – It is stored in the liver, muscle and spleen by transferring it to ferritin – It can be transported on demand to the bone marrow where it can be reincorporated into new Hb RBC catabolism continued • The rest of the heme molecule: – First converted to biliverdin (it is green) – Then to bilirubin (it is yellow-orange) – It’s carried in the blood to the liver where it is secreted into bile – Bile is stored in the gall bladder (if you have one) and then into the small intestine – When it reaches the large intestine it is converted by bacteria into urobilinogen – Some is reabsorbed and excreted in the urine (urobilin or urochrome). The rest is in the feces (stercobilin) RBC life cycle Recycling RBCs • 1% of circulating RBCs wear out per day: – about 3 million RBCs per second • Macrophages of liver, spleen, and bone marrow: – monitor RBCs – engulf RBCs before membranes rupture (hemolyze) Erythrocyte disorders Anemia & polycythemia Diagnosing Disorders • Hemoglobinuria: – hemoglobin breakdown products in urine due to excess hemolysis in blood stream • Hematuria: – whole red blood cells in urine due to kidney or tissue damage Anemia: Insufficient Erythrocytes • Hemorrhagic anemia – result of acute or chronic loss of blood • Hemolytic anemia – prematurely ruptured erythrocytes • Aplastic anemia – destruction or inhibition of red bone marrow Anemia: Decreased Hemoglobin Content • Iron-deficiency anemia results from: – A secondary result of hemorrhagic anemia – Inadequate intake of iron-containing foods – Impaired iron absorption • Pernicious anemia results from: – Deficiency of vitamin B12 – Lack of intrinsic factor needed for absorption of B12 • Treatment is intramuscular injection of B12 Anemia: Abnormal Hemoglobin • Thalassemias – absent or faulty globin chain in hemoglobin – Erythrocytes are thin, delicate, and deficient in hemoglobin • Sickle-cell anemia – results from a defective gene coding for an abnormal hemoglobin called hemoglobin S (HbS) – HbS has a single amino acid substitution in the beta chain – This defect causes RBCs to become sickleshaped in low oxygen situations Polycythemia • Polycythemia – excess RBCs that increase blood viscosity • Three main polycythemias are: – Polycythemia vera – Secondary polycythemia – Blood doping Sickle Cell Disease RBC homeostasis Leukocytes • White blood cells are important for bodily defenses and immunity • 2 General categories: – Granulocytes • Neutrophils • Eosinophils • Basophils – Agranulocytes • Lymphocytes • Monocytes Granulocytes • Granulocytes – neutrophils, eosinophils, and basophils – Contain cytoplasmic granules that stain specifically (acidic, basic, or both) with Wright’s stain – Are larger and usually shorter-lived than RBCs – Have lobed nuclei – Are all phagocytic cells Neutrophils • Neutrophils have two types of granules that: – Take up both acidic and basic dyes – Give the cytoplasm a lilac color – Contain peroxidases, hydrolytic enzymes, and defensins (antibiotic-like proteins) • Neutrophils are our body’s bacteria slayers Eosinophils • Eosinophils account for 1–4% of WBCs – Have red-staining, bilobed nuclei connected via a broad band of nuclear material – Have red to crimson (acidophilic) large, coarse, lysosome-like granules – Lead the body’s counterattack against parasitic worms – Lessen the severity of allergies by phagocytizing immune complexes Basophils • Account for 0.5% of WBCs and: – Have U- or S-shaped nuclei with two or three conspicuous constrictions – Are functionally similar to mast cells – Have large, purplish-black (basophilic) granules that contain histamine • Histamine – inflammatory chemical that acts as a vasodilator and attracts other WBCs (antihistamines counter this effect) Agranulocytes • Agranulocytes – lymphocytes and monocytes: – Lack visible cytoplasmic granules – Are similar structurally, but are functionally distinct and unrelated cell types – Have spherical (lymphocytes) or kidney-shaped (monocytes) nuclei Lymphocytes • Account for 25% or more of WBCs and: – Have large, dark-purple, circular nuclei with a thin rim of blue cytoplasm – Are found mostly enmeshed in lymphoid tissue (some circulate in the blood) • There are two types of lymphocytes: T cells and B cells – T cells function in the immune response – B cells give rise to plasma cells, which produce antibodies Monocytes • Monocytes account for 4–8% of leukocytes – They are the largest leukocytes – They have abundant pale-blue cytoplasms – They have purple-staining, U- or kidney-shaped nuclei – They leave the circulation, enter tissue, and differentiate into macrophages Monocytes • Macrophages: – Are highly mobile and actively phagocytic – Activate lymphocytes to mount an immune response Leukocytes WBC Production Figure 19–10 4 Colony-Stimulating Factors (CSFs) • Hormones that regulate blood cell populations: 1. M-CSF: • stimulates monocyte production 2. G-CSF: • stimulates granulocyte production • neutrophils, eosinophils, and basophils 4 Colony-Stimulating Factors (CSFs) 3. GM-CSF: • stimulates granulocyte and monocyte production 4. Multi-CSF: • accelerates production of granulocytes, monocytes, platelets, and RBCs Chemotaxis of neutrophils Leukocyte Disorders • Leukemia – Acute: uncontrolled production of immature WBCs. – Chronic: accumulation of mature WBCs in the blood Leukocytes Disorders: Leukemias • Leukemia refers to cancerous conditions involving white blood cells • Leukemias are named according to the abnormal white blood cells involved – Myelocytic leukemia – involves myeloblasts – Lymphocytic leukemia – involves lymphocytes • Acute leukemia involves blast-type cells and primarily affects children • Chronic leukemia is more prevalent in older people Leukemia • Immature white blood cells are found in the bloodstream in all leukemias • Bone marrow becomes totally occupied with cancerous leukocytes • The white blood cells produced, though numerous, are not functional • Death is caused by internal hemorrhage and overwhelming infections • Treatments include irradiation, antileukemic drugs, and bone marrow transplants Hemostasis & clotting • Involves: – platelets (fragments of megakaryocytes) – Proteins & Fibers (Thrombin & Fibrin) – Clotting factors Platelets • Cell fragments involved in human clotting system • Nonmammalian vertebrates have thrombocytes (nucleated cells) Platelet Circulation • Circulates for 9–12 days • Are removed by spleen • 2/3 are reserved for emergencies Platelet Counts • 150,000 to 500,000 per microliter (mm3) • Thrombocytopenia: – abnormally low platelet count • Thrombocytosis: – abnormally high platelet count Hormonal Controls • Thrombopoietin (TPO) • Inteleukin-6 (IL-6) • Multi-CSF Hemostasis The Platelet Phase • Platelet aggregation (stick together): – forms platelet plug – closes small breaks The Platelet Phase • Platelet adhesion (attachment): – to sticky endothelial surfaces – to basal laminae – to exposed collagen fibers • Platelet aggregation (stick together): – forms platelet plug – closes small breaks Platelet plug formation Plug formation Clotting The Coagulation Phase Figure 19–12a Plasma Clotting Factors Table 19–4 Hemostasis Disorders: Thromboembolytic Conditions • Thrombus – a clot that develops and persists in an unbroken blood vessel – Thrombi can block circulation, resulting in tissue death – Coronary thrombosis – thrombus in blood vessel of the heart Hemostasis Disorders: Thromboembolytic Conditions • Embolus – a thrombus freely floating in the blood stream – Pulmonary emboli can impair the ability of the body to obtain oxygen – Cerebral emboli can cause strokes Prevention of Undesirable Clots • Substances used to prevent undesirable clots include: – Aspirin – an antiprostaglandin that inhibits thromboxane A2 – Heparin – an anticoagulant used clinically for pre- and postoperative cardiac care – Warfarin – used for those prone to atrial fibrillation Hemostasis Disorders: Bleeding Disorders • Thrombocytopenia – condition where the number of circulating platelets is deficient – Patients show petechiae (small purple blotches on the skin) due to spontaneous, widespread hemorrhage – Caused by suppression or destruction of bone marrow (e.g., malignancy, radiation) – Platelet counts less than 50,000/mm3 is diagnostic for this condition – Treated with whole blood transfusions Hemostasis Disorders: Bleeding Disorders • Inability to synthesize procoagulants by the liver results in severe bleeding disorders • Causes can range from vitamin K deficiency to hepatitis and cirrhosis • Inability to absorb fat can lead to vitamin K deficiencies as it is a fat-soluble substance and is absorbed along with fat • Liver disease can also prevent the liver from producing bile, which is required for fat and vitamin K absorption Hemostasis Disorders: Bleeding Disorders • Hemophilias – hereditary bleeding disorders caused by lack of clotting factors – Hemophilia A – most common type (83% of all cases) due to a deficiency of factor VIII – Hemophilia B – results from a deficiency of factor IX – Hemophilia C – mild type, caused by a deficiency of factor XI Hemostasis Disorders: Bleeding Disorders • Symptoms include prolonged bleeding and painful and disabled joints • Treatment is with blood transfusions and the injection of missing factors Blood typing – ABO groups Cross-Reaction (a.k.a. transfusion reaction) Figure 19–6b Blood Type Test Figure 19–7 ABO groups by frequency in US population Rh factor Blood Transfusions • Whole blood transfusions are used: – When blood loss is substantial – In treating thrombocytopenia • Packed red cells (cells with plasma removed) are used to treat anemia