90981 Ch 11 - Lippincott Williams & Wilkins

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PARTPARTDiseases of Organ Systems2The chapters in Part 2 focus on the pathologic anatomy and pathophysiology of diseases that originatein, or exert their primary effects on, particular organ systems.Chapter 11 Diseases of Blood Cells and BloodCoagulationChapter 20 Diseases of the Lower Urinary Tractand Male GenitaliaReviews the composition of normal blood and normal blood cellformation. Discusses anemia, leukemia, lymphoma, and coagulation dysfunction, as well as other disorders.Reviews the normal anatomy and physiology of the lower urinarytract and male genitalia. Discusses cystitis, urethritis, epididymitis, and other inflammations; erectile dysfunction and infertility;syphilis and other sexually transmitted diseases; prostate enlargement; cancers of the penis, prostate and bladder; and otherdisorders.Chapter 12 Diseases of Blood VesselsReviews normal vascular anatomy and blood flow and discussesatherosclerosis, hypertension, and other vascular diseases.Chapter 13 Diseases of the HeartReviews normal cardiac anatomy and cardiopulmonary blood flow,and discusses coronary artery disease, valvular disease, congestiveheart failure, congenital heart disease, and other disorders.Chapter 14 Diseases of the Respiratory SystemReviews normal pulmonary anatomy, ventilation, and gas exchange, and discusses asthma, cigarette smoking, chronic bronchitis, and emphysema. Also covers pulmonary edema andthromboembolism, pneumonia, tuberculosis, lung cancer, andother disorders.Chapter 15 Diseases of the Gastrointestinal TractReviews normal gastrointestinal anatomy and digestion.Discusses intestinal bleeding and obstruction; gastritis and pepticulcers; diarrhea, parasitic disease, and malabsorption syndromes;ulcerative colitis and Crohn disease; benign and malignant gastrointestinal tumors; and other disorders.Chapter 16 Diseases of the Liver and Biliary TractReviews the normal anatomy and physiology of the liver and biliary tract. Discusses cirrhosis, hepatitis, and alcoholic and metabolic liver disease; gallstones and other gallbladder disease; cancers of the liver and biliary tract; and other disorders.Chapter 17 Diseases of the PancreasReviews the normal anatomy and physiology of the digestive andendocrine functions of the pancreas. Discusses diabetes, pancreatitis, pancreatic cancer, and other disorders.Chapter 18 Diseases of Endocrine GlandsReviews the normal anatomy and physiology of the pituitary, thyroid, parathyroid, and adrenal glands, their interrelationships, andtheir role in homeostasis, as well as the importance of negativefeedback loops. Discusses overactivity and underactivity of theendocrine glands, as well as tumors and other disorders of each.Chapter 19 Diseases of the KidneyReviews the normal gross anatomy of the urinary tract, the microscopic anatomy of the glomerulus and renal tubules, the formation and flow of urine, the regulation salt and water balance,and normal urinalysis. Discusses glomerulonephritis and other inflammatory disease, the role of the kidney in hypertension, cancers of the kidney and bladder, and other disorders.Chapter 21 Diseases of the Female Genital Tractand BreastReviews the normal anatomy and physiology of the female genitalia and breast, including ovulation, fertilization, menstruation,pregnancy, lactation, and menopause. Discusses sexually transmitted disease, ectopic pregnancy, abortion, infertility, endometriosis, placental disease, dysplasia and cancer of the cervix,cancers and other tumors of the ovary, and other disorders.Chapter 22 Diseases of Bones, Joints, and SkeletalMuscleReviews the normal anatomy and physiology of bone and bonetypes, muscle and muscle types, and ligaments and tendons.Discusses bone infection and infarction, osteoporosis and fractures, arthritis and joint injury, tumors and tumor-like conditionsof bone and muscle, and other disorders.Chapter 23 Diseases of the Nervous SystemReviews the normal anatomy and physiology of the brain, spinalcord, peripheral nerves, and autonomic nervous system, their interconnections, and their connections to other cells. Discusses increased intracranial pressure, stroke, brain trauma, and brainhemorrhage; encephalitis and meningitis; degenerative diseasesand brain toxins; benign and malignant tumors of nerve cells;and other disorders.Chapter 24 Diseases of the SkinReviews the peculiar language of skin disease, the normal physiology and microscopic anatomy of skin, and the role of skin inbody defense against the environment. Discusses selected skinconditions, including the effects of systemic disease, sunlight,and pregnancy. Also covers hair loss, eczema, acne, allergies, autoimmune disease, infections and other inflammations, premalignant and malignant lesions including malignant melanoma, andother diseases.Chapter 25 Diseases of the Eye and EarReviews the normal anatomy of the eye and the optics and physiology of vision. Discusses refractive disorders, infections,cataract, glaucoma, chorioretinitis, and other inflammations;neoplasms of the eye; and other disorders. Also reviews the normal anatomy of the ear and the physiology of hearing and balance. Discusses acute otitis media, deafness, vertigo, and otherdisorders.233

CHAPTER11Diseases of Blood Cells andBlood CoagulationThis chapter begins with a review of the composition of normal blood and normal blood cell formation. Latersections discuss anemia, leukemia, lymphoma, coagulation dysfunction, and other disorders.Section 1: Diseases of Blood CellsBACK TO BASICS Normal Blood Production (Hematopoiesis) Cell Compartments and Life Span Laboratory Assessment of Blood CellsTOO LITTLE HEMOGLOBIN (ANEMIA) The Anemia of Hemorrhage Anemia of Red Cell Destruction (Hemolytic Anemia) Anemia of Insufficient Red Cell ProductionTOO MANY RED CELLS—POLYCYTHEMIATOO FEW WHITE CELLS—LEUKOPENIA ANDAGRANULOCYTOSISTOO MANY WHITE CELLS—BENIGN AND MALIGNANTDISORDERS OF LEUKOCYTES Peripheral Leukocyte Responses to Infection or Injury Lymph Node Response to Injury or Infection Lymphoid Neoplasms Myeloid NeoplasmsDISORDERS OF THE SPLEEN AND THYMUSSection 2: Bleeding DisordersBACK TO BASICSBLEEDING DISORDERS Vascular or Platelet Deficiency Coagulation Factor Deficiency Disseminated Intravascular Coagulation (DIC)THROMBOTIC DISORDERSLearning ObjectivesAfter studying this chapter you should be able to:1. Give a reasonable estimate of the life span of blood cells and platelets2. Explain what is meant by red cell indices, and understand how to calculate them3. Define anemia, and list the major types of anemia4. Regarding sickle cell anemia, explain the cause and discuss what happens to red cells5. Explain blood and bone marrow ferritin, iron, transferrin, and iron binding capacity in iron deficiency anemia6. Explain the difference between relative and absolute erythrocytosis7. Explain the significance of a left shift in the white cell differential count in peripheral blood8. Name the two major groups of bone marrow malignancies, and list some of the diseases associated with each9. Explain the difference between acute and chronic leukemia10. Distinguish between leukemia and lymphoma11. Explain why patients with plasma cell proliferation have abnormal blood proteins12. Name the two major types of lymphoma13. Name the two types of non-Hodgkin lymphoma according to microscopic patterns, and explain why this distinction is important14. Define hypersplenism15. Name the elements of normal hemostasis16. Characterize bleeding associated with platelet disease17. Briefly characterize classic hemophilia (hemophilia A)18. Explain why patients with disseminated intravascular coagulation have bleeding problems234

Chapter 11 Diseases of Blood Cells and Blood Coagulation235Key Terms and ConceptsBACK TO BASICS myeloid lymphoid hemoglobin hematocrit red cell indices mean cell volume macrocytic normocytic microcytic normochromic hypochromic reticulocyteTOO FEW WHITE CELLS—LEUKOPENIA ANDAGRANULOCYTOSIS leukopeniaTOO LITTLE HEMOGLOBIN (ANEMIA) anemia hemolysis hemoglobinopathy megaloblastic anemiaNORMAL HEMOSTASIS, COAGULATION, ANDLABORATORY TESTING hemostasis coagulation extrinsic coagulation pathway intrinsic coagulation pathwayTOO MANY WHITE CELLS—BENIGN AND MALIGNANTDISORDERS OF LEUKOCYTES leukemia lymphoma multiple myeloma Hodgkin lymphoma non-Hodgkin lymphomas (NHL) follicular lymphoma diffuse lymphoma chronic myeloproliferative disordersTOO MANY RED CELLS—POLYCYTHEMIA polycythemia veraBLEEDING DISORDERS hemorrhagic diathesis disseminated intravascular coagulation (DIC)Blood is thicker than water.THE SENTIMENT OF THIS PROVERB—THAT FAMILY TIES ARE THE CLOSEST OF ALL RELATIONSHIPS—IS AS OLD AS WRITING. IN ABOUT 1800 BC, THE SUMERIANS, INVENTORS OF WRITING WHO LIVED INWHAT IS MODERN-DAY IRAQ, WROTE IT THIS WAY: “FRIENDSHIP LASTS A DAY; KINSHIP IS FOREVER.”Section 1:Key Terms and ConceptsDiseases of Blood CellsBACK TO BASICSBlood is liquid tissue; a mixture of cells and water. Thewater contains protein, glucose, cholesterol, calcium,hormones, metabolic waste, and hundreds of othersubstances. Plasma is the liquid part of blood; the termrefers to blood circulating in vivo and to anticoagulatedblood in vitro (in a laboratory tube, for example).Serum, the fluid remaining after blood clots, differsfrom plasma in that serum contains no fibrinogen,which was consumed in formation of the clot. Whenblood clots it forms a gelatinous mass that traps cellsin a mesh of fibrin (Chapter 5). The clot shrinks andafter an hour is about half its original size. Serum isthe remaining fluid, which was squeezed from the clot.Serum contains no fibrinogen and cannot clot again,and for this reason is widely used for laboratory analyses because clots can interfere with the operation ofdelicate laboratory equipment. However, sometimestests are done on anticoagulated whole blood orplasma. When referring to concentrations of substances, the words “blood,” “serum,” and “plasma” areoften used interchangeably; as for example, when referring to blood or serum or plasma glucose. The composition of normal blood is detailed in Table 11-1 andFigure 11-1.

236Part 2 Diseases of Organ SystemsNormal (Reference) Ranges forTable 11-1 Blood Cells*ValueUnitsMenWomenRED –4933–43Red cell count(RBC)106 cells/cu mm4.3–5.93.5–5.0Red cell MCVfL76–100SameRed cell MCHCg/dL33–37“Red cell MCHpg27–33“Reticulocyte count%0.5–2.0“Total WBCWHITE CELLS103 cells/4.5–10.5cu mmSameNeutrophilsBands%%60–70 ocytes%20–25“Monocytes%3–8“Platelet countPLATELETS103 cells/150–350cu mmHemoglobin(HGB)Same*Ranges vary slightly from laboratory to laboratory. Most normal ranges areestablished by statistical technique to include 95% of healthy persons; therefore 5% of healthy persons have abnormally high or low values.NORMAL BLOOD PRODUCTION(HEMATOPOIESIS)The cells in blood are red cells (erythrocytes), whitecells (leukocytes), and platelets (cytoplasmic fragmentsof bone marrow platelet-producing cells, megakaryocytes). In the fetus, production of blood cells takes placein the liver, but by birth most blood cell production hasshifted to the bone marrow.As is depicted in Figure 11-2, all blood cells arisefrom a common ancestor, the totipotent stem cell. Thisprimitive stem cell gives rise to two other stem cells: amyeloid stem cell that in turn gives rise to red cells,megakaryocytes, monocytes and macrophages, andgranulocytes (neutrophils, basophils, eosinophils), anda lymphoid stem cell that give rise to lymphocytes.Bone marrow red cell production is stimulated byerythropoietin, a hormone synthesized by the kidney.Erythropoietin production is stimulated by low deliveryof oxygen to the kidney. Mild general hypoxia occurs inpeople living at high altitude. Their bone marrowmakes extra red cells to compensate, and they havehigher red blood cell counts than do people living atlower altitudes. General hypoxia also occurs in patientswith chronic lung disease; they, too, have high red cellcounts. Local kidney hypoxia can also stimulate erythropoietin production; for example, impaired renalblood flow (ischemia) owing to renal vascular diseasecan cause increased erythropoietin and very high redcell counts.Production of white blood cells and platelets is controlled by other hormones and factors.Red cells have no nucleus and no need for one. Theirrole is to carry oxygen, and a nucleus would take up unnecessary room. Leukocytes have a nucleus. There arethree kinds of leukocytes: granulocytes, lymphocytes,and monocytes. Monocytes are phagocytic: they ingestand digest foreign antigen and present it for action toimmune cells for immune response. Lymphocytes arethe main cells of the immune system: their task is toreact to foreign antigen. Granulocytes have cytoplasmicgranules of digestive enzymes and other substances thatplay an important role in inflammation (Chapter 3).The three granulocytes are: neutrophils, eosinophils,and basophils. Neutrophils are the most abundant granulocyte. Their task is to react to acute injury and infection by ingesting (phagocytosis) and digesting foreignagents, especially bacteria, and by cleaning up inflammatory debris. Basophils and eosinophils are the inflammatory cells of allergic reactions (Chapter 8) andreactions to parasites. Platelets are small fragments ofmegakaryocyte cytoplasm and have no nucleus. Theirtask is to stop bleeding by sticking together at points ofvascular injury to obstruct hemorrhage, and to initiatethe clotting process at the site of bleeding.CELL COMPARTMENTS AND LIFE SPANBlood cells exist in several body compartments (blood,bone marrow, spleen, lymph nodes and, to a great extentin the fetus and a lesser extent in adults, the thymus),and there is constant cell trafficking among them.How long cells live (and circulate) is critical.Compared to cells in most other tissues, the life span of

Chapter 11 Diseases of Blood Cells and Blood Coagulation2375% Fibrinogen: Clotting15% Immunoglobulins (gamma): Immune reactionsPlasmaWholeblood55%of bloodvolume7%Proteins60% Albumin: Transport; plasma osmotic pressure92% Water: Transport medium and solvent1%45%of bloodvolume20% Other globulins (beta): Transport; reactant proteinsOther: Amino nsProducts of metabolic processesRed bloodcells5% 99% Red bloodcellsMonocytes: Phagocytosis; immune reactions30% Lymphocytes: Immune reactions 1% Leukocytes65% Granulocytes97% Neutrophils: Acute inflammatory reactionsPhagocytosisDigestion of foreign andinflammatory debris2%Eosinophils: Allergic and antiparasitic reactions1%Basophils: Allergic reactionsFigure 11-1 The composition of blood.blood cells is short; therefore, cell turnover is rapid. Redcells have the longest life span of blood cells: about 120days. Neutrophils, basophils, and eosinophils live about4 days; lymphocytes and monocytes, a week or two;platelets, a day or two. Old (senescent) blood cells andplatelets are removed from circulation by the spleen.This rapid turnover means that it is critical that newcells be produced at a rate that equals the rate at whichcells are dying. Many diseases of blood cells are causedby production failure or early cell death or destruction;that is to say, by shortened cell life span. Anemia (toolittle hemoglobin) is usually attributable to too few redblood cells (anemia can also occur with normal numbers of red cells that do not contain enough hemoglobin). Some patients have low red blood cell count because bone marrow fails to produce enough red bloodcells (RBC); in other cases of anemia, RBC life span isshort because RBCs are destroyed (hemolysis). Thesame holds true for platelets and white blood cells—some conditions are attributable to failed cell or plateletproduction, others to early destruction or death.Hemoglobin is the compound in RBCs to which oxygen attaches for transport from lungs to tissues, there-fore the amount of hemoglobin in blood is critical.Hemoglobin cannot be synthesized without iron, vitamin B12, vitamin B6, and folic acid. The character ifhemoglobin is important. There are many types ofabnormal hemoglobin, most of them stemming fromgenetic defects of hemoglobin synthesis.LABORATORY ASSESSMENT OF BLOOD CELLSLaboratory assessment of blood cells is usually performed on a sample of blood collected from an armvein. Such a blood sample is typically referred to as “peripheral blood” to distinguish it from the pool of bloodin large vessels and the viscera, which is slightly moredilute than peripheral blood. Cellular elements typically are measured in anticoagulated whole blood.Conversely, chemical elements, such as glucose, aretypically measured in the liquid part of blood, usuallyserum obtained from a tube containing clotted blood.The most common standard laboratory study ofblood is referred to as a complete blood count (CBC).In modern laboratories the process is automated andconsists of a determination of white blood cells (white

Totipotent Stem CellBone marrowMyeloidcellLymphoidcellCells in bone marrowMyeloid stem egakaryocyteFunctionCells in bloodRelease frombone ReticulocyteMyelocyteMyelocyteMetamyelocyte MetamyelocyteBand cellBand cellBand cellMonocyteRed blood osisAntigen inflammationAllergic gure 11-2 Hematopoiesis. There are two main groups of blood cells: myeloid and lymphoid, each derived from a primitive stem cell.238

Chapter 11 Diseases of Blood Cells and Blood Coagulationblood cell count), red blood cells (red blood cellcount), the percentage of white cells that are neutrophils, eosinophils, or basophils (the white celldifferential count), the amount of hemoglobin, and thehematocrit. The hematocrit is the percent of blood volume occupied by red blood cells (RBC). It is measuredby centrifuging whole blood to compact red blood cellsand observing the percentage of whole blood volumeoccupied by red blood cells. The number of white cellsand platelets is so small that their volume is negligible.Also important in a complete blood count is determination of the red cell indices, which are measures of thesize and hemoglobin content of the average RBC. The average size of an RBC is the mean cell volume (MCV); theaverage amount of hemoglobin in an average RBC is themean cell hemoglobin (MCH); and the average concentration of hemoglobin per unit of volume in an averageRBC is the mean cell hemoglobin concentration(MCHC). As is indicated in Figure 11-3, each of the indices can be calculated using hemoglobin, hematocrit,and red blood cell count. Red cell indices are importantin the diagnosis of diseases of red blood cells—in anemiared blood cells may be too large (macrocytic), normalsize (normocytic)m or too small (microcytic). Additionally, diseased RBCs may have a normal amount ofhemoglobin per cell (normochromic) or too littlehemoglobin (hypochromic). There is no such thing as ared cell with too much hemoglobin.239Visual examination of blood cells is an importanttool, but it is ordinarily not necessary unless there aresignificant abnormalities in the measurements obtainedon a complete blood count. Every laboratory has criteria defining when visual examination is necessary. Forexample, visual examination may be required if the hemoglobin is below 10 gm/dL, or the WBC count isabove 15,000 cells/cu mm. Additionally, the clinicianmay know of signs and symptoms that indicate need forvisual examination of blood cells and can request visualexamination. Among the important things detectable byvisual examination are the presence of malignant whitecells in leukemia, abnormally shaped RBCs, malariaparasites in RBC, RBCs with nuclei, and giant platelets.Laboratories also seek to identify nor

11. Explain why patients with plasma cell proliferation have abnormal blood proteins 12. Name the two major types of lymphoma 13. Name the two types of non-Hodgkin lymphoma according to microscopic patterns, and explain why this distinc-tion is important 14. Define hypersplenism 15. Name the elements of normal hemostasis 16.

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