Module 2.1: Oxygenation and Transport: Hematologic Disorders PDF

Oxygenation and Transport MODULE 2 PREPARED BY: MJ CABRALES, RN, LPT  Oxygen Transport in the Blood Even though oxygen is transported via the blood, you may recall that oxygen is not very soluble in liquids. A small amount of oxygen does dissolve in the blood and...

Oxygenation and Transport MODULE 2 PREPARED BY: MJ CABRALES, RN, LPT  Oxygen Transport in the Blood Even though oxygen is transported via the blood, you may recall that oxygen is not very soluble in liquids. A small amount of oxygen does dissolve in the blood and is transported in the bloodstream, but it is only about 1.5% of the total amount. The majority of oxygen molecules are carried from the lungs to the body’s tissues by a specialized transport system, which relies on the erythrocyte—the red blood cell. Erythrocytes contain a metalloprotein, hemoglobin, which serves to bind oxygen molecules to the erythrocyte. Heme is the portion of hemoglobin that contains iron, and it is heme that binds oxygen. One hemoglobin molecule contains iron-containing Heme molecules, and because of this, each hemoglobin molecule is capable of carrying up to four molecules of oxygen. As oxygen diffuses across the respiratory membrane from the alveolus to the capillary, it also diffuses into the red blood cell and is bound by hemoglobin. The following reversible chemical reaction describes the production of the final product, oxyhemoglobin (Hb–O2), which is formed when oxygen binds to hemoglobin. Oxyhemoglobin is a bright red-colored molecule that contributes to the bright red color of oxygenated blood. Hb + O2 ↔ Hb − O2 In this formula, Hb represents reduced hemoglobin, that is, hemoglobin that does not have oxygen bound to it. There are multiple factors involved in how readily heme binds to and dissociates from oxygen, which will be discussed in the subsequent sections. Function of Hemoglobin Hemoglobin is composed of subunits, a protein structure that is referred to as a quaternary structure. Each of the four subunits that make up hemoglobin is arranged in a ring-like fashion, with an iron atom covalently bound to the heme in the center of each subunit. Binding of the first oxygen molecule causes a conformational change in hemoglobin that allows the second molecule of oxygen to bind more readily. As each molecule of oxygen is bound, it further facilitates the binding of the next molecule, until all four heme sites are occupied by oxygen. The opposite occurs as well: After the first oxygen molecule dissociates and is “dropped off” at the tissues, the next oxygen molecule dissociates more readily. When all four heme sites are occupied, the hemoglobin is said to be saturated. When one to three heme sites are occupied, the hemoglobin is said to be partially saturated. Therefore, when considering the blood as a whole, the percent of the available heme units that are bound to oxygen at a given time is called hemoglobin saturation. Hemoglobin saturation of 100 percent means that every heme unit in all of the erythrocytes of the body is bound to oxygen. In a healthy individual with normal hemoglobin levels, hemoglobin saturation generally ranges from 95 percent to 99 percent.  Oxygen Dissociation from Hemoglobin Partial pressure is an important aspect of the binding of oxygen to and disassociation from heme. An oxygen–hemoglobin dissociation curve is a graph that describes the relationship of partial pressure to the binding of oxygen to heme and its subsequent dissociation from heme (Figure 22.5.2). Remember that gases travel from an area of higher partial pressure to an area of lower partial pressure. In addition, the affinity of an oxygen molecule for heme increases as more oxygen molecules are bound. Therefore, in the oxygen–hemoglobin saturation curve, as the partial pressure of oxygen increases, a proportionately greater number of oxygen molecules are bound by heme. Not surprisingly, the oxygen–hemoglobin saturation/dissociation curve also shows that the lower the partial pressure of oxygen, the fewer oxygen molecules are bound to heme. As a result, the partial pressure of oxygen plays a major role in determining the degree of binding of oxygen to heme at the site of the respiratory membrane, as well as the degree of dissociation of oxygen from heme at the site of body tissues. The mechanisms behind the oxygen–hemoglobin saturation/dissociation curve also serve as automatic control mechanisms that regulate how much oxygen is delivered to different tissues throughout the body. This is important because some tissues have a higher metabolic rate than others. Highly active tissues, such as muscle, rapidly use oxygen to produce ATP, lowering the partial pressure of oxygen in the tissue to about 20 mm Hg. The partial pressure of oxygen inside capillaries is about 100 mm Hg, so the difference between the two becomes quite high, about 80 mm Hg. As a result, a greater number of oxygen molecules dissociate from hemoglobin and enter the tissues. The reverse is true of tissues, such as adipose (body fat), which have lower metabolic rates. Because less oxygen is used by these cells, the partial pressure of oxygen within such tissues remains relatively high, resulting in fewer oxygen molecules dissociating from hemoglobin and entering the tissue interstitial fluid. Although venous blood is said to be deoxygenated, some oxygen is still bound to hemoglobin in its red blood cells. This provides an oxygen reserve that can be used when tissues suddenly demand more oxygen. Factors other than partial pressure also affect the oxygen–hemoglobin saturation/dissociation curve. For example, a higher temperature promotes hemoglobin and oxygen to dissociate faster, whereas a lower temperature inhibits dissociation (see Figure 22.5.2, middle). However, the human body tightly regulates temperature, so this factor may not affect gas exchange throughout the body. The exception to this is in highly active tissues, which may release a larger amount of energy than is given off as heat. As a result, oxygen readily dissociates from hemoglobin, which is a mechanism that helps to provide active tissues with more oxygen. Certain hormones, such as androgens, epinephrine, thyroid hormones, and growth hormone, can affect the oxygen–hemoglobin saturation/disassociation curve by stimulating the production of a compound called 2,3-bisphosphoglycerate (BPG) by erythrocytes. BPG is a byproduct of glycolysis. Because erythrocytes do not contain mitochondria, glycolysis is the sole method by which these cells produce ATP. BPG promotes the disassociation of oxygen from hemoglobin. Therefore, the greater the concentration of BPG, the more readily oxygen dissociates from hemoglobin, despite its partial pressure. The pH of the blood is another factor that influences the oxygen–hemoglobin saturation/dissociation curve (see Figure 22.5.2). The Bohr effect is a phenomenon that arises from the relationship between pH and oxygen’s affinity for hemoglobin: A lower, more acidic pH promotes oxygen dissociation from hemoglobin. In contrast, a higher, or more basic, pH inhibits oxygen dissociation from hemoglobin. The greater the amount of carbon dioxide in the blood, the more molecules that must be converted, which in turn generates hydrogen ions and thus lowers blood pH. Furthermore, blood pH may become more acidic when certain byproducts of cell metabolism, such as lactic acid, carbonic acid, and carbon dioxide, are released into the bloodstream.  Hemoglobin of the Fetus The fetus has its own circulation with its own erythrocytes; however, it is dependent on the mother for oxygen. Blood is supplied to the fetus by way of the umbilical cord, which is connected to the placenta and separated from maternal blood by the chorion. The mechanism of gas exchange at the chorion is similar to gas exchange at the respiratory membrane. However, the partial pressure of oxygen is lower in the maternal blood in the placenta, at about 35 to 50 mm Hg, than it is in maternal arterial blood. The difference in partial pressures between maternal and fetal blood is not large, as the partial pressure of oxygen in fetal blood at the placenta is about 20 mm Hg. Therefore, there is not as much diffusion of oxygen into the fetal blood supply. The fetus’ hemoglobin overcomes this problem by having a greater affinity for oxygen than maternal hemoglobin (Figure 22.5.3). Both fetal and adult hemoglobin have four subunits, but two of the subunits of fetal hemoglobin have a different structure that causes fetal hemoglobin to have a greater affinity for oxygen than does adult hemoglobin. Carbon Dioxide Transport in the Blood Carbon dioxide is transported by three major mechanisms. The first mechanism of carbon dioxide transport is by blood plasma, as some carbon dioxide molecules dissolve in the blood. The second mechanism is transport in the form of bicarbonate (HCO3–), which also dissolves in plasma. The third mechanism of carbon dioxide transport is similar to the transport of oxygen by erythrocytes (Figure 22.5.4).  Dissolved Carbon Dioxide Although carbon dioxide is not considered to be highly soluble in blood, a small fraction—about 7 to 10 percent—of the carbon dioxide that diffuses into the blood from the tissues dissolves in plasma. The dissolved carbon dioxide then travels in the bloodstream and when the blood reaches the pulmonary capillaries, the dissolved carbon dioxide diffuses across the respiratory membrane into the alveoli, where it is then exhaled during pulmonary ventilation.  Bicarbonate Buffer A large fraction—about 70 percent—of the carbon dioxide molecules that diffuse into the blood is transported to the lungs as bicarbonate. Most bicarbonate is produced in erythrocytes after carbon dioxide diffuses into the capillaries, and subsequently into red blood cells. Carbonic anhydrase (CA) causes carbon dioxide and water to form carbonic acid (H2CO3), which dissociates into two ions: bicarbonate (HCO3–) and hydrogen (H+). The following formula depicts this reaction: CO2 + H2O CA ↔ H2CO3↔H+ + HCO3− Bicarbonate tends to build up in the erythrocytes, so that there is a greater concentration of bicarbonate in the erythrocytes than in the surrounding blood plasma. As a result, some of the bicarbonate will leave the erythrocytes and move down its concentration gradient into the plasma in exchange for chloride (Cl–) ions. This phenomenon is referred to as the chloride shift and occurs because by exchanging one negative ion for another negative ion, neither the electrical charge of the erythrocytes nor that of the blood is altered. At the pulmonary capillaries, the chemical reaction that produced bicarbonate (shown above) is reversed, and carbon dioxide and water are the products. Much of the bicarbonate in the plasma re-enters the erythrocytes in exchange for chloride ions. Hydrogen ions and bicarbonate ions join to form carbonic acid, which is converted into carbon dioxide and water by carbonic anhydrase. Carbon dioxide diffuses out of the erythrocytes and into the plasma, where it can further diffuse across the respiratory membrane into the alveoli to be exhaled during pulmonary ventilation.  Carbaminohemoglobin About 20 percent of carbon dioxide is bound by hemoglobin and is transported to the lungs. Carbon dioxide does not bind to iron as oxygen does; instead, carbon dioxide binds amino acid moieties on the globin portions of hemoglobin to form carbaminohemoglobin, which forms when hemoglobin and carbon dioxide bind. When hemoglobin is not transporting oxygen, it tends to have a bluish-purple tone to it, creating the darker maroon color typical of deoxygenated blood. The following formula depicts this reversible reaction: CO2 + Hb ↔ HbCO2 Similar to the transport of oxygen by heme, the binding and dissociation of carbon dioxide to and from hemoglobin is dependent on the partial pressure of carbon dioxide. Because carbon dioxide is released from the lungs, blood that leaves the lungs and reaches body tissues has a lower partial pressure of carbon dioxide than is found in the tissues. As a result, carbon dioxide leaves the tissues because of its higher partial pressure, enters the blood, and then moves into red blood cells, binding to hemoglobin. In contrast, in the pulmonary capillaries, the partial pressure of carbon dioxide is high compared to within the alveoli. As a result, carbon dioxide dissociates readily from hemoglobin and diffuses across the respiratory membrane into the air. In addition to the partial pressure of carbon dioxide, the oxygen saturation of hemoglobin and the partial pressure of oxygen in the blood also influence the affinity of hemoglobin for carbon dioxide. The Haldane effect is a phenomenon that arises from the relationship between the partial pressure of oxygen and the affinity of hemoglobin for carbon dioxide. Hemoglobin that is saturated with oxygen does not readily bind carbon dioxide. However, when oxygen is not bound to heme and the partial pressure of oxygen is low, hemoglobin readily binds to carbon dioxide. Oxygen is primarily transported through the blood by erythrocytes. These cells contain a metalloprotein called hemoglobin, which is composed of four subunits with a ring-like structure. Each subunit contains one atom of iron bound to a molecule of heme. Heme binds oxygen so that each hemoglobin molecule can bind up to four oxygen molecules. When all of the heme units in the blood are bound to oxygen, hemoglobin is considered to be saturated. Hemoglobin is partially saturated when only some heme units are bound to oxygen. An oxygen–hemoglobin saturation/dissociation curve is a common way to depict the relationship of how easily oxygen binds to or dissociates from hemoglobin as a function of the partial pressure of oxygen. As the partial pressure of oxygen increases, the more readily hemoglobin binds to oxygen. At the same time, once one molecule of oxygen is bound by hemoglobin, additional oxygen molecules more readily bind to hemoglobin. Other factors such as temperature, pH, the partial pressure of carbon dioxide, and the concentration of 2,3- bisphosphoglycerate can enhance or inhibit the binding of hemoglobin and oxygen as well. Fetal hemoglobin has a different structure than adult hemoglobin, which results in fetal hemoglobin having a greater affinity for oxygen than adult hemoglobin. Carbon dioxide is transported in blood by three different mechanisms: as dissolved carbon dioxide, as bicarbonate, or as carbaminohemoglobin. A small portion of carbon dioxide remains. The largest amount of transported carbon dioxide is as bicarbonate, formed in erythrocytes. For this conversion, carbon dioxide is combined with water with the aid of an enzyme called carbonic anhydrase. This combination forms carbonic acid, which spontaneously dissociates into bicarbonate and hydrogen ions. As bicarbonate builds up in erythrocytes, it is moved across the membrane into the plasma in exchange for chloride ions by a mechanism called the chloride shift. At the pulmonary capillaries, bicarbonate re- enters erythrocytes in exchange for chloride ions, and the reaction with carbonic anhydrase is reversed, recreating carbon dioxide and water. Carbon dioxide then diffuses out of the erythrocyte and across the respiratory membrane into the air. An intermediate amount of carbon dioxide binds directly to hemoglobin to form carbaminohemoglobin. The partial pressures of carbon dioxide and oxygen, as well as the oxygen saturation of hemoglobin, influence how readily hemoglobin binds carbon dioxide. The less saturated hemoglobin is and the lower the partial pressure of oxygen in the blood is, the more readily hemoglobin binds to carbon dioxide. This is an example of the Haldane effect. Hematologic Disorders Anemia is an abnormally low amount of circulating RBCs, Hgb concentration, or both. It is an indicator of an underlying disease or disorder. Anemia results in diminished oxygen-carrying capacity and delivery to tissues and organs. The goal of treatment is to restore and maintain adequate tissue oxygenation. Iron-deficiency anemia due to inadequate intake is the most common cause of anemia in children, adolescents, and pregnant clients. Iron-deficiency anemia due to blood loss (such as from a gastrointestinal ulcer) is the most common cause of anemia in clients who are postmenopausal, as well as males. Clients who are menstruating can develop anemia secondary to menorrhagia.  Relative Polycythemia It is an increase in RBC numbers without an increase in total RBC mass. usually., this is caused by loss of plasma volume with resultant hemo-concentration, as seen in severe dehydration relate to vomiting and diarrhea.  Primary Polycythemia Primary occurs when excess RBC are produced as a result of an abnormality in the bone marrow. Often, excess WBC and platelets are also produced.  Secondary Polycythemia It is usually due to increased erythropoietin (EPO) production either in response to chronic hypoxia (low oxygen level) or from erythropoietin secreting tumor.  Complications Patients with polycythemia vera are at increased risk for thromboses that may be either venous or arterial. Thromboses can result in strokes or myocardial infarctions; thrombotic complications are the most common cause of death. Patients older than 60 years of age, those with a prior history of thrombosis, or those with an elevated platelet count (exceeding 1 million/mm3) are at greater risk for developing thrombotic complications. Bleeding is also a complication, possibly because the platelets are often very large and somewhat dysfunctional. The bleeding can be significant and can occur in the form of nosebleeds, ulcers, frank GI bleeding, hematuria, and intracranial hemorrhage.  Nursing Management The nurse focuses on symptom management Monitor for peripheral and cerebral thrombosis. Assist the patient for ambulation Perform phlebotomy as per doctors order Administer IV fluids and encourage to take oral fluids.  Administer pain medications as ordered. Advice to do regular exercise Instruct to avoid tobacco us. Advise to maintain skin hygiene. Avoid extreme temperatures. Provide psychological support to the patient.  Coagulation Disorders Coagulation disorders occur secondary to an alteration in platelets, clotting factors, or both. Coagulopathy is the term for any condition that affects an individual’s ability to coagulate. Coagulopathies are suspected when the usual measures used to stop bleeding fail. Coagulopathy can occur secondary to an autoimmune disorder or extensive blood loss in which platelets and clotting factors are lost. In some cases, the development of microemboli in the circulatory system paradoxically uses up the clotting factors that cause hemorrhages to occur at the same time intravascular clotting occurs.  Idiopathic or immune thrombocytopenic purpura (ITP) It is a coagulopathy that is an autoimmune disorder in which the life span of platelets is decreased by antiplatelet antibodies although platelet production is normal. This can result in severe hemorrhage following a cesarean birth or lacerations.  Thrombotic thrombocytopenic purpura (TTP) It is a coagulopathy in which platelets abnormally clump together in capillaries due to an autoimmune reaction from platelet aggregation, resulting in an insufficient quantity in circulation. Inappropriate clotting occurs, and clotting fails to occur with trauma. This can lead to kidney failure, myocardial infarction, and stroke, and can be fatal within 3 months if untreated.  Heparin-induced thrombocytopenia (HIT) It is an immunity-mediated clotting disorder that causes unexplained low blood platelet count as a result of treatment with heparin. Disseminated Intravascular Coagulation Disseminated intravascular coagulation (DIC) is not an actual disease but a sign of an underlying condition. DIC may be triggered by sepsis, trauma, cancer, shock, abruptio placentae, toxins, allergic reactions, and other conditions; the vast majority (two thirds) of cases of DIC are initiated by an infection or a malignancy. The severity of DIC is variable, but it is potentially life-threatening. RISK FACTORS  Risk factors in patients with Idiopathic or immune thrombocytopenic purpura (ITP) Female sex (ages 20 to 50 years) Secondary conditions (medications, viruses [HIV, hepatitis C) Other autoimmune disorders Recent virus (children only)  Risk factor in Thrombotic thrombocytopenic purpura (TTP) Other autoimmune disorders  Risk factor in Heparin-induced thrombocytopenia (HIT) Female sex Receiving heparin longer than 1 week Exposure to unfractionated heparin Postsurgical thromboprophylaxis (prevention of thromboembolic disease) PATIENT-CENTERED CARE NURSING CARE  Hemophilia Hemophilia is a genetic bleeding disorder where blood doesn’t clot properly Hemophilia is usually hereditary and can be passed down from parent to child In people with hemophilia bleeding continues for longer but it is not faster than someone else There are effective treatments to manage and prevent bleeding There is support and advice available at all stages of life if issues arise With knowledge and planning most people live well with hemophilia and lead active and independent lives. There are two types of hemophilia. Both have the same symptoms Hemophilia A is the most common form and is caused by having low levels of clotting factor VIII (8). It is also called factor VIII deficiency. Hemophilia B, also known as Christmas Disease, is caused by having low levels of clotting factor IX (9). It is also called factor IX deficiency  Acquired hemophilia A Acquired hemophilia A is a very rare condition where a person’s immune system (a system that protects your body from diseases) develops antibodies, also known as inhibitors, that mistakenly target the body’s own clotting factors, most commonly factor VIII. It is not hereditary. People with acquired hemophilia A would previously have been well with no history of bleeding and would have had normal blood clotting tests. In some cases, there is an underlying medical condition that can trigger acquired hemophilia A, for example, autoimmune conditions and certain cancers. In other cases, no cause of acquired hemophilia A is found.  There are several differences between acquired and hereditary forms of hemophilia. These include: How severe the bleeding is can be variable. Some people with acquired hemophilia A may have very little bleeding while others have significant life threatening bleeding. The pattern of bleeding is different. In acquired hemophilia A it often includes skin, gastrointestinal and muscle bleeds rather than joint bleeds. However, bleeding can occur at any site in the body.  The age when people with acquired hemophilia A first seek medical care for their condition is different to hereditary forms of hemophilia. Although acquired hemophilia A can occur at any age, it most often occurs in older people and in some women in late pregnancy or who have recently given birth. In acquired hemophilia A both males and females are affected equally.  A person with hemophilia will usually have the same level of severity over their lifetime, eg a person with severe hemophilia will always have severe hemophilia. Within a family, males with hemophilia will also nearly always have the same level of severity, eg if a grandfather has severe hemophilia and his grandson has inherited hemophilia, his grandson will also have severe hemophilia. However, factor levels in females affected by hemophilia are unpredictable and severity can vary between females and other family members. Inheritance Pattern https://open.oregonstate.education/aandp/chapter/22-5-transport-of-gases/ https://www.haemophilia.org.au/HFA/media/Documents/Haemophilia/Haemophilia-booklet.pdf