Chapter 10 Blood and the Circulatory System Disorders

Circulatory System The circulatory system consists of the cardiovascular system and lymphatic system. This chapter will cover the blood vessels, the blood, and associated disorders. Copyright © 2019 by Elsevier Inc. All rights reserved. 2

Anatomy of Major Arteries Copyright © 2019 by Elsevier Inc. All rights reserved. 3

Anatomy of Major Veins Copyright © 2019 by Elsevier Inc. All rights reserved. 4

Blood Vessels Arteries—arterioles Ø Veins—venules Ø Microcirculation within tissues Systemic circulation Ø Return blood back to the heart Capillaries Ø Transport blood away from heart Exchange of gases, nutrients, and wastes in tissues Pulmonary circulation Ø Gas exchange in lungs Copyright © 2019 by Elsevier Inc. All rights reserved. 5

Structural Comparison of Arteries and Veins Copyright © 2019 by Elsevier Inc. All rights

Histology of Arteries and Veins Tunica intima—endothelium (simple squamous epithelium) Tunica media—middle layer, mostly smooth muscle Tunica adventitia (externa)—connective tissue with fibrocytes, collagen (type I), and elastic fibers Copyright © 2019 by Elsevier Inc. All rights reserved. 7

Blood Copyright © 2019 by Elsevier Inc. All rights reserved. 8

Function Transport oxygen and nutrients to all tissues Remove waste products of cellular metabolism Play a critical role in the body's defenses/immune system, and Serve in maintaining body homeostasis Copyright © 2019 by Elsevier Inc. All rights reserved. 9

Composition of Blood Plasma Ø Plasma proteins Cellular component Erythrocytes Ø Leukocytes Ø Thrombocytes

Components of Blood and Their Functions Copyright © 2019 by Elsevier Inc. All rights

Hematopoiesis Copyright © 2019 by Elsevier Inc. All rights reserved. 12

Erythrocytes (Red Blood Cells) Biconcave flexible discs No nucleus in mature state Contains hemoglobin Globin portion Ø Heme group Ø Life span—approximately 120 days Erythropoietin produced in the kidney stimulates erythrocyte production. Copyright © 2019 by Elsevier Inc. All rights reserved. 13

Normal Red Blood Cells Copyright © 2019 by Elsevier Inc. All rights reserved. 14

Normal Blood Cells Copyright © 2019 by Elsevier Inc. All rights reserved. 15

Breakdown of Hemoglobin Copyright © 2019 by Elsevier Inc. All rights reserved. 16

Blood Clotting—Hemostasis Three steps Vasoconstriction or vascular spasm after injury Ø Platelet clot Ø Coagulation mechanism Ø Plasmin will eventually break down the blood clot. Copyright © 2019 by Elsevier Inc. All rights reserved. 17

Clot Formation Production of prothrombin factor due to tissue damage Prothrombin or factor II is converted into thrombin. Thrombin converts Fibrinogen (factor I) into fibrin threads. A fibrin mesh forms to trap cells. The clot gradually shrinks or retracts, pulling the edges of damaged tissue closer together and sealing the site. Copyright © 2019 by Elsevier Inc. All rights reserved. 18

Hemostasis and Anticoagulant Drugs Copyright © 2019 by Elsevier Inc. All rights reserved. 19

Blood Typing Blood typing is based on antigens in the plasma membrane of the erythrocytes. ABO system Based on the presence or absence of specific antigens Ø Antibodies in the blood plasma Ø Rh system Antigen D in plasma membrane: Rh+ Ø Absence of antigen D: Rh Ø Copyright © 2019 by Elsevier Inc. All rights reserved. 20

ABO Blood Groups Copyright © 2019 by Elsevier Inc. All rights reserved. 21

Diagnostic Tests Complete blood count (CBC) Includes total red blood cells (RBCs), white blood cells (WBCs), and platelets Ø Leukocytosis (increased WBCs) • Associated with inflammation or infection Ø Leukopenia (decreased WBCs) • Associated with some viral infections, radiation, Ø chemotherapy Ø Increased eosinophils • Common in allergic responses Differential count for WBCs Copyright © 2019 by Elsevier Inc. All rights reserved. 22

Diagnostic Tests (Cont. ) Morphology Observed with blood smears Ø Shows size, shape, uniformity, maturity of cells • Different types of anemia can be distinguished. Ø Hematocrit Ø Percent by volume of cellular elements in blood Hemoglobin Amount of hemoglobin per unit volume of blood Ø Mean corpuscular volume (MCV) • Indicates the oxygen-carrying capacity of blood Ø Copyright © 2019 by Elsevier Inc. All rights reserved. 23

Diagnostic Tests (Cont. ) Reticulocyte count Ø Assessment of bone marrow function Chemical analysis Ø Determines serum levels of components, such as iron, vitamin B 12, folic acid, cholesterol, urea, glucose Bleeding time Ø Measures platelet function Prothrombin time (PT) and partial thromboplastin time (PTT) Measure function of various factors in coagulation process Ø International normalized ratio (INR) is a standardized version. Ø Copyright © 2019 by Elsevier Inc. All rights reserved. 24

Blood Therapies Whole blood, packed red blood cells, packed platelets Ø Plasma or colloid volume-expanding solutions Ø For severe anemia or thrombocytopenia To maintain blood volume Artificial blood products Compatible with all blood types Ø None of them can perform all the complex functions of normal whole blood. Ø Copyright © 2019 by Elsevier Inc. All rights reserved. 25

Blood Therapies (Cont. ) Epoetin alpha Ø Bone marrow or stem cell transplantation Ø Artificial form of erythropoietin • Before certain surgical procedures • Anemia related to cancer • Chronic renal failure Close tissue match necessary • Treatment of some cancers • Severe immunodeficiency • Severe blood cell diseases Drug treatment Ø Aids in the clotting process Copyright © 2019 by Elsevier Inc. All rights reserved. 26

Blood Dyscrasias Copyright © 2019 by Elsevier Inc. All rights reserved. 27

The Anemias Anemia causes a reduction in oxygen transport. Basic problem is hemoglobin deficit. Oxygen deficit leads to: Less energy production in all cells • Cell metabolism and reproduction diminished Ø Compensation mechanisms • Tachycardia and peripheral vasoconstriction Ø General signs of anemia • Fatigue, pallor (pale face), dyspnea, tachycardia Ø Copyright © 2019 by Elsevier Inc. All rights reserved. 28

The Anemias (Cont. ) Oxygen deficit leads to: Ø Decreased regeneration of epithelial cells • Digestive tract becomes inflamed and ulcerated, leading to stomatitis. • Inflamed and cracked lips • Dysphasia • Hair and skin may show degenerative changes. Ø Severe anemia may lead to angina or congestive heart failure (CHF). Copyright © 2019 by Elsevier Inc. All rights reserved. 29

Iron Deficiency Anemia Insufficient iron impairs hemoglobin synthesis. Ø Microcytic, hypochromic RBCs • Result of low hemoglobin concentration in cells Very common Ranges from mild to severe Ø Occurs in all age groups, but more common in women of childbearing age Ø Estimated that one in five women is affected • Proportion increases for pregnant women. Ø Frequently sign of an underlying problem Copyright © 2019 by Elsevier Inc. All rights reserved. 30

Iron Deficiency Anemia—Blood Smear Copyright © 2019 by Elsevier Inc. All rights reserved. 31

Causes Dietary intake of iron below minimum requirement Chronic blood loss Ø Impaired duodenal absorption of iron Ø As from bleeding, ulcer, hemorrhoids, cancer In many disorders, malabsorption syndromes Severe liver disease Ø May affect iron absorption as well as storage Copyright © 2019 by Elsevier Inc. All rights reserved. 32

Signs and Symptoms Pallor of skin and mucous membranes Fatigue, lethargy, cold intolerance Irritability Degenerative changes Stomatitis and glossitis Menstrual irregularities Delayed healing Tachycardia, heart palpitations, dyspnea, syncope Copyright © 2019 by Elsevier Inc. All rights reserved. 33

Pernicious Anemia: Vitamin B 12 Deficiency Basic problem is lack of absorption of vitamin B 12 because of lack of intrinsic factor. Intrinsic factor secreted by gastric mucosa Ø Required for intestinal absorption of vitamin B 12 Ø Characterized by very large, immature, nucleated erythrocytes Carry less hemoglobin Ø Shorter life span Ø Copyright © 2019 by Elsevier Inc. All rights reserved. 34

Pernicious Anemia: Vitamin B 12 Deficiency (Cont. ) Dietary insufficiency is very rarely a cause. Genetic factors have been implicated. Ø More common in light-skinned women of northern European ancestry Often accompanies chronic gastritis May also be an outcome of gastric surgery Copyright © 2019 by Elsevier Inc. All rights reserved. 35

Development of Pernicious Anemia Copyright © 2019 by Elsevier Inc. All rights reserved. 36

Vitamin B 12 and Nerve Cells Vitamin B 12 is needed for the function and maintenance of neurons. Significant deficit of the vitamin will cause symptoms in the peripheral nerves. These may be reversible. Copyright © 2019 by Elsevier Inc. All rights reserved. 37

Vitamin B 12 Deficiency Copyright © 2019 by Elsevier Inc. All rights reserved. 38

Additional Manifestations Tongue is typically enlarged, red, sore, and shiny. Digestive discomfort, often with nausea and diarrhea Feeling of pins and needles, tingling in limbs Copyright © 2019 by Elsevier Inc. All rights reserved. 39

Diagnostic Test Microscopic examination (erythrocytes) Bone marrow examination (hyperactive) Vitamin B 12 serum levels below normal Presence of hypochlorhydria or achlorhydria Presence of gastric atrophy Copyright © 2019 by Elsevier Inc. All rights reserved. 40

Aplastic Anemia Impairment or failure of bone marrow May be temporary or permanent Often idiopathic but possible causes include: Myelotoxins • Radiation, industrial chemicals, drugs Ø Viruses • Particularly hepatitis C Ø Genetic abnormalities • Myelodysplastic syndrome • Fanconi anemia Ø Copyright © 2019 by Elsevier Inc. All rights reserved. 41

Aplastic Anemia (Cont. ) Blood counts indicate pancytopenia. Anemia, leukopenia, thrombocytopenia Ø Bone marrow biopsy may be required. Ø Erythrocytes often appear normal. Ø Identification of cause and prompt treatment needed for bone marrow recovery Removal of any bone marrow suppressants Ø Failure to identify cause and treat effectively is lifethreatening! Ø Copyright © 2019 by Elsevier Inc. All rights reserved. 42

Hemolytic Anemia Results from excessive destruction of RBCs Causes Genetic defects Ø Immune reactions Ø Changes in blood chemistry Ø Infections such as malaria Ø Toxins in the blood Ø Antigen–antibody reactions • Incompatible blood transfusion • Erythroblastosis fetalis Ø Copyright © 2019 by Elsevier Inc. All rights reserved. 43

Sickle Cell Anemia Genetic condition Autosomal Ø Incomplete dominance Ø Anemia occurs in homozygous recessive. Ø Diagnostic testing is available. Ø More common in individuals of African ancestry • Heterozygous condition is somewhat protective against Ø malaria. • One in ten African Americans is heterozygous for the trait. Copyright © 2019 by Elsevier Inc. All rights reserved. 44

Sickle Cell Anemia (Cont. ) Copyright © 2019 by Elsevier Inc. All rights reserved.

Sickle Cell Anemia (Cont. ) Abnormal hemoglobin (Hb. S) Sickle cell crisis occurs whenever oxygen levels are lowered. Altered hemoglobin is unstable and changes shape in hypoxemia. Sickle-shaped cells are too large to pass through the microcirculation. Obstruction leads to multiple infarctions and areas of necrosis. Copyright © 2019 by Elsevier Inc. All rights reserved. 46

Sickle Cell Anemia (Cont. ) Multiple infarctions affect brain, bones, organs. In addition to basic anemia: Ø Hyperbilirubinemia, jaundice, gallstones • Caused by high rate of hemolysis Clinical signs Ø Do not usually appear until the child is about 12 months old Copyright © 2019 by Elsevier Inc. All rights reserved. 49

Signs and Symptoms Severe pain because of ischemia of tissues and infarction Pallor, weakness, tachycardia, dyspnea Hyperbilirubinemia—jaundice Splenomegaly Vascular occlusions and infarctions Ø In lungs • Acute chest syndrome Ø Smaller blood vessels • Hand-foot syndrome Delay of growth and development Congestive heart failure Copyright © 2019 by Elsevier Inc. All rights reserved. 50

Diagnostic Tests Blood test—determine abnormal RBC morphology Hemoglobin electrophoresis Prenatal DNA analysis Copyright ©

Treatment Hydroxyurea has reduced the frequency of this crisis. Dietary supplementation with folic acid Bone marrow transplantation Immunization in children Ø Against pneumonia, influenza, meningitis Copyright © 2019 by Elsevier Inc. All rights reserved. 52

Comparison of Selected Anemias Copyright © 2019 by Elsevier Inc. All rights reserved. 53

Polycythemia Primary polycythemia—polycythemia vera Increased production of erythrocytes and other cells in the bone marrow Ø Neoplastic disorder Ø Serum erythropoietin levels are low. Ø Secondary polycythemia—erythrocytosis Increase in RBCs in response to prolonged hypoxia Ø Increased erythropoietin secretion Ø Compensation mechanism to provide increased oxygen transport Ø Copyright © 2019 by Elsevier Inc. All rights reserved. 54

Signs and Symptoms Distended blood vessels, sluggish blood flow Increased blood pressure Hypertrophied heart Hepatomegaly Splenomegaly Dyspnea Headaches Visual disturbances Thromboses and infarctions Copyright © 2019 by Elsevier Inc. All rights reserved. 55

Diagnostic Tests to determine: Increased cell counts Increased hemoglobin and hematocrit values Hypercellular bone

Treatment Identify specific cause Drugs or radiation Suppression of bone marrow activity Periodic phlebotomy

Indications of Blood-Clotting Disorders Persistent bleeding from gums Repeated epistaxis Petechiae Ø Frequent purpura and ecchymosis More than normal bleeding in trauma Bleeding into joint—hemarthroses Ø Pinpoint, flat, red spots on skin and mucous membrane Swollen, red, painful Hemoptysis Copyright © 2019 by Elsevier Inc. All rights reserved. 58

Blood-Clotting Disorders Hematemesis Ø Blood in feces Ø Coarse brown particles (coffee ground emesis)in vomit Black or occult Anemia Feeling faint and anxious Low blood pressure Rapid pulse Copyright © 2019 by Elsevier Inc. All rights reserved. 59

Petechiae Copyright © 2019 by Elsevier Inc. All rights reserved. 60

Hemophilia A Classic hemophilia Ø Deficit or abnormality of factor VIII Most common inherited clotting disorder X-linked recessive trait Ø Manifested in men, carried by women Ø Varying degrees of severity Prolonged bleeding after minor tissue trauma Spontaneous bleeding into joints Possible hematuria or blood in feces Copyright © 2019 by Elsevier Inc. All rights reserved. 61

Hemophilia A (Cont. ) Diagnostic tests Bleeding time and PT normal Ø PTT, activated PTT (a. PTT), coagulation time prolonged Ø Serum levels of factor VIII are low. Ø Treatment Desmopressin (DDAVP) Ø Replacement therapy for factor VIII Ø Copyright © 2019 by Elsevier Inc. All rights reserved. 62

Von Willebrand Disease Most common hereditary clotting disorder Three major types Signs and symptoms include: Skin rashes Ø Frequent nosebleeds Ø Easy bruising Ø Bleeding of gums Ø Abnormal menstrual bleeding Ø Treatment based on type and severity Copyright © 2019 by Elsevier Inc. All rights reserved. 63

Disseminated Intravascular Coagulation (DIC) Involves both excessive bleeding and clotting Excessive clotting in circulation Ø Thrombi and infarcts occur. Clotting factors are reduced to a dangerous level. Widespread, uncontrollable hemorrhage results. Very poor prognosis, with high fatality rate Complication of many primary problems Obstetrical complications, such as abruptio placentae Ø Infections Ø Carcinomas Ø Major trauma Ø Copyright © 2019 by Elsevier Inc. All rights reserved. 64

Disseminated Intravascular Coagulation (DIC) (Cont. ) Copyright © 2019 by Elsevier Inc. All rights

Thrombophilia Group of inherited or acquired disorders Risk of abnormal clots in veins or arteries Blood testing for clotting factor levels and abnormal antibody levels Causative condition should be treated. Copyright © 2019 by Elsevier Inc. All rights reserved. 66

Myelodysplastic Syndromes Diseases that involve inadequate production of cells by the bone marrow Signs and symptoms include anemia; dependent on type of deficiencies that occur. May be idiopathic or occur after chemotherapy or radiation treatment Treatment depends on deficiency type. Transfusion replacement Ø Chelation therapy to reduce iron overload Ø Bone marrow transplantation Ø Copyright © 2019 by Elsevier Inc. All rights reserved. 67

The Leukemias Group of neoplastic disorders involving white blood cells Uncontrolled WBC production in bone or lymph nodes Other hemopoietic tissues are reduced. One or more types of leukocytes are undifferentiated, immature, and nonfunctional. Large numbers released into general circulation Infiltrate lymph nodes, spleen, liver, brain, other organs Copyright © 2019 by Elsevier Inc. All rights reserved. 68

Copyright © 2019 by Elsevier Inc. All rights reserved. 69

The Leukemias (Cont. ) Acute leukemias (ALL and AML) High proportion of immature nonfunctional cells in bone marrow and peripheral circulation Ø Onset usually abrupt , marked signs of complications • Occurs primarily in children and younger adults Ø Chronic leukemias (CLL and CML) Higher proportion of mature cells but with reduced function Ø Insidious onset Ø Mild signs and better prognosis • Common in older adults Ø Copyright © 2019 by Elsevier Inc. All rights reserved. 70

Acute Lymphocytic Leukemia Copyright © 2019 by Elsevier Inc. All rights reserved. 71

Signs and Symptoms of Acute Leukemia Usual signs at onset Frequent or uncontrolled infections Ø Petechiae and purpura Ø Signs of anemia Ø Severe and steady bone pain Weight loss, fatigue, possible fever Enlarged lymph nodes, spleen, liver Headache, visual disturbances, drowsiness, vomiting Copyright © 2019 by Elsevier Inc. All rights reserved. 72

The Leukemias (Cont. ) Diagnostic tests Ø Peripheral blood smears • Immature leukocytes and altered numbers of WBCs • Numbers of RBCs and platelets decreased • Bone marrow biopsy for confirmation Treatment Chemotherapy Ø ALL in young children responds well to drugs Ø Biologic therapy (interferon) • May be used to stimulate the immune system Ø Copyright © 2019 by Elsevier Inc. All rights reserved. 73

Complications of Leukemia Opportunistic infections, including pneumonia Sepsis Congestive heart failure Hemorrhage Liver failure Renal failure CNS depression and coma Copyright © 2019 by Elsevier Inc. All rights reserved. 74

Multiple Myeloma Neoplastic disease that involves increased production of plasma cells in bone marrow Unknown cause Occurs in older adults Production of other blood cells is impaired. Multiple tumors in bone Loss of bone Ø Severe bone pain Ø Prognosis poor, with short life expectancy Copyright © 2019 by Elsevier Inc. All rights reserved. 75