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Blood Everywhere: A Case Study in Blood
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Blood Everywhere: A Case Study in Blood An ambulance arrives at the scene of an automobile accident, having been summoned by an in-vehicle security system. What the emergency personnel find is like a scene from a horror film. Maggie Silvers, the apparent driver of the car, is sitting, slumped next to the vehicle, with blood covering her shirt and hands. Her car has clearly hit a tree: a branch is sticking into the driver’s window, and the airbag has been deployed. Maggie looks dazed, and as the paramedics approach she says with a mixture of panic and relief, “There’s blood everywhere!” Maggie is only semi-lucid as she babbles on about pushing out the broken glass in her car window. Maggie, a 48-year-old woman, is, indeed, bleeding profusely from multiple left-arm cuts and an especially deep laceration on her left upper arm. The paramedics stop the bleeding and move her quickly to the ambulance, after noting no other apparent injury. Her systolic blood pressure is 80 mm Hg (low), and her diastolic is not audible (too low to hear). Her heart rate is 122 bpm (very rapid), and her skin is pale and clammy, indicating peripheral vasoconstriction (narrowing of her blood vessels, particularly in the skin) and circulatory shock-like signs. On the way to the hospital, a paramedic begins transfusing normal saline solution (NSS; water with some NaCl, similar to body fluids, given directly into her vein). A fast hematocrit (HCT) test upon Maggie’s arrival to the emergency department (ED) indicates that her HCT is low, but normal. Several vials of Maggie’s blood are also sent to the lab for blood tests and typing. Two liters of NSS are transfused over the next hour while the ED physician sutures her deepest, left-upper-arm laceration. Despite no further bleeding since the paramedics treated her at the scene, Maggie’s next HCT, tested one hour after the original HCT, drops to below normal. Aside from her present health problem, Maggie is otherwise healthy. She is admitted to the hospital for overnight observation.
An Introduction to Blood and the Cardiovascular System • The CardiovascularSystem consists of: • A pump (the heart) • A conducting system (blood vessels) • A fluid medium (blood) • Is specialized fluid of connective tissue • Contains cells suspended in a fluid matrix
19-1 Physical Characteristics of Blood • Important Functions of Blood • Transportation of dissolved substances (to and from cells) • Regulation of pH and ions • Restriction of fluid losses at injury sites • Defense against toxins and pathogens • Stabilization of body temperature
19-1 Physical Characteristics of Blood • Whole Blood • Plasma • Fluid consisting of: • Water • Dissolved plasma proteins • Other solutes • Formed elements • All cells and solids
7% Figure 19-1 The Composition of Whole Blood (Part 3 of 8). Plasma Plasma Proteins 1% Other Solutes 55% (Range 46–63%) 92% Water Formed Elements Platelets .1% < 45% White Blood Cells (Range 37–54%) .1% < Red Blood Cells 99.9%
19-1 Physical Characteristics of Blood • Three Types of Formed Elements • Redbloodcells (RBCs) or erythrocytes • Transport oxygen • Whitebloodcells (WBCs) or leukocytes • Part of the immune system • Platelets • Cell fragments involved in clotting
19-1 Physical Characteristics of Blood • Hemopoiesis • Process of producing formed elements • By myeloid and lymphoid stem cells • Fractionation • Process of separating whole blood for clinical analysis • Into plasma and formed elements
19-1 Physical Characteristics of Blood • Three General Characteristics of Blood • 38C (100.4F) is normal temperature • High viscosity • Slightly alkaline pH (7.35–7.45)
19-1 Physical Characteristics of Blood • Characteristics of Blood • Blood volume (liters) 7 percent of body weight (kilograms) • Adult male: 5–6 liters • Adult female: 4–5 liters
19-2 Plasma • The Composition of Plasma • Makes up 50–60 percent of blood volume • More than 90 percent of plasma is water • Extracellular fluids • Interstitial fluid (IF) and plasma • Materials plasma and IF exchange across capillary walls • Water • Ions • Small solutes
19-2 Plasma • Plasma Proteins • Albumins (60 percent) • Globulins (35 percent) • Fibrinogen (4 percent)
19-2 Plasma • Albumins (60 percent) • Transport substances such as fatty acids, thyroid hormones, and steroid hormones • Globulins (35 percent) • Antibodies, also called immunoglobulins • Transport globulins (small molecules): hormone-bindingproteins, metalloproteins, apolipoproteins (lipoproteins), and steroid-bindingproteins • Fibrinogen (4 percent) • Molecules that form clots and produce long, insoluble strands of fibrin
19-2 Plasma • Serum • Liquid part of a blood sample • In which dissolved fibrinogen converts to solid fibrin • How can we isolate plasma from cells in whole blood? • How can we isolate serum? • If cells need to be analyzed in whole blood, how should the blood be handled?
Figure 29-1 The composition of blood. Plasma 55% Formed elements 45% Constituent Major Functions Number (per mm3 of blood) Solvent for carrying other substances; absorbs heat Functions Cell type Water Erythrocytes (red blood cells) Salts (electrolytes) 4 – 6 million Transport oxygen and help transport carbon dioxide Sodium Osmotic balance, pH buffering Potassium Calcium Magnesium Chloride Leukocytes (white blood cells) Defense and immunity Bicarbonate 4800 – 10,800 Plasma proteins Albumin Osmotic balance Lymphocyte Fibrinogen Clotting of blood Defense (antibodies) and lipid transport Globulins Basophil Eosinophil Substances transported by blood Monocyte Neutrophil Nutrients (glucose, fatty acids, amino acids, vitamins) Waste products of metabolism (urea, uric acid) Respiratory gases (O2 and CO2) Platelets 150,000 – 400,000 Blood clotting Hormones
19-2 Plasma • Other Plasma Proteins • 1 percent of plasma • Changing quantities of specialized plasma proteins • Peptide hormones normally present in circulating blood • Insulin, prolactin (PRL), and the glycoproteins thyroid-stimulating hormone (TSH), follicle-stimulating hormone (FSH), and luteinizing hormone (LH)
19-3 Red Blood Cells • Red blood cells (RBCs) • Make up 99.9 percent of blood’s formed elements • Hemoglobin • The red pigment that gives whole blood its color • Binds and transports oxygen and carbon dioxide
19-3 Red Blood Cells • Abundance of RBCs • Redbloodcellcount – the number of RBCs in 1 microliter of whole blood • Male: 4.5–6.3 million • Female: 4.2–5.5 million
19-3 Red Blood Cells • Abundance of RBCs • Hematocrit – (packed cell volume, PCV) percentage of RBCs in centrifuged whole blood • Male: 40–54 • Female: 37–47
19-3 Red Blood Cells • Abundance of RBCs • Hematocrit – (packed cell volume, PCV) percentage of RBCs in centrifuged whole blood • Male: 40–54 • Female: 37–47
19-3 Red Blood Cells • Structure of RBCs • Small and highly specialized discs • Thin in middle and thicker at edge
Figure 19-2c The Anatomy of Red Blood Cells. 0.45–1.16 μm 2.31–2.85 μm 7.2–8.4 μm c A sectional view of a mature RBC, showingthe normal ranges for its dimensions.
19-3 Red Blood Cells • Three Important Effects of RBC Shape on Function • High surface-to-volume ratio • Quickly absorbs and releases oxygen • Discs form stacks called rouleaux • Smooth the flow through narrow blood vessels • Discs bend and flex entering small capillaries • 7.8-µm RBC passes through 4-µm capillary
Red blood cell (RBC) Figure 19-2d The Anatomy of Red Blood Cells. Rouleau(stacked RBCs) Nucleus ofendothelial cell Blood vessels(viewed inlongitudinalsection) LM × 1430 Sectioned capillaries When traveling through relatively narrowcapillaries, RBCs may stack like dinner plates. d
Figure 19-2a The Anatomy of Red Blood Cells. Blood smear LM × 477 a When viewed in a standardblood smear, RBCs appear as two-dimensional objects,because they are flattenedagainst the surface of the slide.
19-3 Red Blood Cells • Life Span of RBCs • Lack nuclei, mitochondria, and ribosomes • Means no repair and anaerobic metabolism • Live about 120 days
19-3 Red Blood Cells • Hemoglobin (Hb) • Protein molecule that transports respiratory gases • Normal hemoglobin (adult male) • 14–18 g/dL whole blood • Normal hemoglobin (adult female) • 12–16 g/dL whole blood
19-3 Red Blood Cells • Hemoglobin Structure • Complex quaternary structure • Four globular protein subunits • Each with one molecule of heme • Each heme contains one iron ion
19-3 Red Blood Cells • Hemoglobin Structure • Iron ions • Associate easily with oxygen (oxyhemoglobin, HbO2) • Dissociate easily from oxygen (deoxyhemoglobin)
β chain 1 α chain 1 Heme Figure 19-3 The Structure of Hemoglobin. β chain 2 Heme α chain 2 Hemoglobinmolecule
19-3 Red Blood Cells • FetalHemoglobin • Strong form of hemoglobin found in embryos • Takes oxygen from mother’s hemoglobin
19-3 Red Blood Cells • Hemoglobin Function • Carries oxygen • With low oxygen (peripheral capillaries): • Hemoglobin releases oxygen • Binds carbon dioxide and carries it to lungs • Forms carbaminohemoglobin
19-3 Red Blood Cells • RBC Formation and Turnover • 1 percent of circulating RBCs wear out per day • About 3 million new RBCs per second • Hemoglobin Conversion and Recycling • Macrophages of liver, spleen, and bone marrow • Monitor RBCs • Engulf RBCs before membranes rupture (hemolyze)
19-3 Red Blood Cells • Hemoglobin Conversion and Recycling • Phagocytes break hemoglobin into components • Globular proteins to amino acids • Heme to biliverdin • Iron
19-3 Red Blood Cells • Hemoglobin Conversion and Recycling • Hemoglobinuria • Hemoglobin breakdown products in urine due to excess hemolysis in bloodstream • Hematuria • Whole red blood cells in urine due to kidney or tissue damage
19-3 Red Blood Cells • Breakdown of Biliverdin • Biliverdin (green) is converted to bilirubin (yellow) • Bilirubin • Is excreted by liver (bile) • Jaundice is caused by bilirubin buildup • Converted by intestinal bacteria to urobilins and stercobilins
19-3 Red Blood Cells • Iron Recycling • Iron removed from heme leaving biliverdin • To transport proteins (transferrin) • To storage proteins (ferritin and hemosiderin)
Events Occurring in the Red Bone Marrow Events Occurring in Macrophages Macrophages monitor the condition of circulating RBCs, engulfing them before they hemolyze (rupture), or removing Hb molecules, iron, and cell fragments from the RBCs that hemolyze in the bloodstream. Developing RBCs absorb amino acids and Fe2+ from the bloodstream and synthesize new Hb molecules. RBC formation Macrophages in spleen, Liver, and red bone marrow Fe2+ transported in bloodstream by transferrin Fe2+ Amino acids Heme Figure 19-4 Recycling of Red Blood Cell Components. Average life span of RBC is 120 days 90% Biliverdin New RBCs released into bloodstream Old and damaged RBCs Bilirubin 10% In the bloodstream, The rupture of RBCs Is called hemolysis. Bilirubin bound to albumin in bloodstream Hemoglobin that is not phagocytized breaks down, and the alpha and beta chains are eliminated in urine. Kidney Liver Hb Bilirubin Absorbed into the bloodstream Urobilins Excreted in bile Eliminated In urine Urobilins, stercobilins Bilirubin Events Occurring in the Kidney Eliminated in feces Events Occurring in the Liver Events Occurring in the Large Intestine The kidneys excrete some hemoglobin, as well as urobilins, which gives urine its yellow color. Bilirubin released from macrophages binds to albumin and is transported to the liver for excretion in bile. Bacteria convert bilirubin to urobilins and stercobilins. Feces are yellow-brown or brown due to the presence of urobilins and stercobilins in varying proportions.
19-3 Red Blood Cells • RBC Production • Erythropoiesis • Occurs only in myeloidtissue (redbonemarrow) in adults • Stem cells mature to become RBCs
RED BONE MARROW Day 1:Proerythroblast Erythroblasts Day 2:Basophilicerythroblast Figure 19-5 Stages of RBC Maturation. Day 3:Polychromatophilicerythroblast Day 4:Normoblast Ejection ofnucleus Days 5–7:Reticulocyte Enters bloodstream Mature redblood cell
19-3 Red Blood Cells • Regulation of Erythropoiesis • Building red blood cells requires: • Amino acids • Iron • Vitamins B12, B6, and folic acid • Perniciousanemia • Low RBC production • Due to unavailability of vitamin B12
19-3 Red Blood Cells • Stimulating Hormones • Erythropoietin (EPO) • Also called erythropoiesis-stimulatinghormone • Secreted when oxygen in peripheral tissues is low (hypoxia) • Due to disease or high altitude
19-4 Blood Typing • SurfaceAntigens • Are cell surface proteins that identify cells to immune system • Normal cells are ignored and foreign cells attacked • BloodTypes • Are genetically determined • By presence or absence of RBC surface antigens A, B, Rh (or D)
Blood Everywhere Case Questions (Continued): 5. Why might a physician be reluctant to order a blood transfusion for Maggie, or for any patient for that matter, unless absolutely necessary? Blood is sometimes (and in some communities) in short supply and should be used only when absolutely necessary. Any blood transfusion carries with it an increased risk of transfusion reaction, though crossmatch screening processes are strict when followed. Though rare (due to thorough screening procedures), blood may carry blood-borne diseases such as hepatitis, human immunodeficiency virus, malaria, etc. Given time, an otherwise healthy body has the ability to replace its own red blood cells. Blood is more expensive to obtain, process, and store than saline solution. 6. Despite no blood transfusion, Maggie’s hematocrit improves by the time she visits her physician for the removal of her sutures a week later. [See multiple choice question 3 for the calculation.] She is adequately hydrated. Explain the physiological mechanism for the improvement in her hematocrit. When RBCs are lost, HCT drops, and this leads to low oxygen delivery to the tissues (hypoxia). Hypoxia is a signal for the kidney to secrete erythropoietin (EPO). EPO is a hormone that targets red bone marrow to produce more red blood cells, which then restores HCT to normal. This is a negative feedback mechanism. 7. Besides the HCT, what other component of blood could be measured to give a better understanding of oxygen-carrying capacity? Explain your answer. Hemoglobin (Hb) is an index of oxygen-carrying capacity; it is the actual molecule within an RBC that binds oxygen. A normal Hb value for healthy females is 12-16 g/100 ml of blood, and for healthy males it is 13-18 g/100 ml. Typically, HCT and Hb are measured and evaluated together to give a fuller hematological understanding.
19-4 Blood Typing • Four Basic Blood Types • A (surface antigen A) • B (surface antigen B) • AB (antigens A and B) • O (neither A nor B)
19-4 Blood Typing • Agglutinogens • Antigens on surface of RBCs • Screened by immune system • Plasma antibodies attack and agglutinate (clump) foreign antigens
19-4 Blood Typing • Blood Plasma Antibodies • Type A • Type B antibodies • Type B • Type A antibodies • Type O • Both A and B antibodies • Type AB • Neither A nor B antibodies
Type AB Type B Type A Type O Type AB blood has RBCs withboth A and B surface antigens. Type O blood has RBCs lackingboth A and B surface antigens. Type B blood has RBCs withsurface antigen B only. Type A blood has RBCs withsurface antigen A only. Figure 19-6a Blood Types and Cross-Reactions. Surfaceantigen A Surfaceantigen B If you have type A blood, yourplasma contains anti-Bantibodies, which will attacktype B surface antigens. If you have type B blood, yourplasma contains anti-Aantibodies, which will attacktype A surface antigens. If you have type O blood, your plasma contains both anti-Aand anti-B antibodies. If you have type AB blood,your plasma has neitheranti-A nor anti-B antibodies. Blood type depends on the presence of surface antigens (agglutinogens) on RBC surfaces. Theplasma contains antibodies (agglutinins) that will react with foreign surface antigens. a
19-4 Blood Typing • The RhFactor • Also called D antigen • Either Rhpositive (Rh) or Rhnegative (Rh) • Only sensitized Rh blood has anti-Rh antibodies
Rh−mother Figure 19-8 Hemolytic Disease of the Newborn (Part 3 of 6). Rh+fetus 1 During First Pregnancy Problems seldomdevelop during a firstpregnancy, becausevery few fetal cellsenter the maternalbloodstream then,and thus the mother’simmune system is notstimulated to produceanti-Rh antibodies. Maternal blood supplyand tissue Rh− Rh− Rh− Rh− Placenta Rh+ Rh+ The most commonform of hemolyticdisease of the newborndevelops after an Rh−woman has carried aRh+ fetus. Fetal blood supplyand tissue Rh+ Rh+