CHAPTER 30: ERYTHROCYTIC PROTECTION FROM O2 TOXICITY
Chapter 30: Erythrocytic Protection from O2 Toxicity Erythrocytes, or red blood cells (RBCs), carry oxygen (O2) from the lungs to tissues, and are involved in the transport of carbon dioxide (CO2) from tissues to the lungs. The mature erythrocyte is a highly specialized cell. Hemoglobin (Hb), which constitutes about one-third of its weight, contributes red color and gas-carrying capacity. Although RBCs of primates may have a 120-day life-span (traveling some 175 miles through the circulation), the life-span of RBCs among domestic animal species varies considerably (e.g., 65 days in the pig and 150 days in the horse). In smaller animals with a high metabolic rate, the survival time is generally shorter than in larger animals, and red cell survival time generally increases with hibernation. On average, approximately 1% of circulating erythrocytes are replaced daily. As erythrocytes age, they are removed from the circulation by cells of the reticuloendothelial (RE) system (predominantly macrophages in the spleen). To balance this degradation, there is a constant need for hematopoiesis (production of new RBCs in bone marrow). The primary stimulatory factor for red blood cell production is erythropoietin (EPO), a protein hormone produced largely by vascular endothelial cells of the kidney. Erythrocytes carry on their surface antigenic determinants commonly known as blood groups. These determinants are commonly, but not always, identified with specific carbohydrate elements of glycoproteins on the cell surface. Oxygen Toxicity: Although O2 is essential for mammalian life, breathing 100% oxygen for several hours can be toxic, with damage to the lungs, brain, and retina occurring. At one time this was a major cause of blindness among premature human infants with respiratory distress syndrome. Now, such infants are administered air containing no more than 40% oxygen. The toxicity of O2 is due to the production of highly reactive products derived from it. Even under normal circumstances, small amounts of these reduced products are produced; however, RBCs and other tissues are specialized for their removal. These reactive products are the superoxide anion (O2 –., a free radical), hydrogen peroxide (H2O2), and the hydroxyl radical (OH). The O2 –. normally has a short half-life (milliseconds), and arises from the acquisition of a single electron (e-) by a molecule of O2. It can be generated by the action of ionizing radiation on O2 (thus causing tissue radiation damage), from xanthine oxidase (an enzyme which catalyzes the oxidation of xanthine to uric acid), from flavoprotein oxidases (e.g., aldehyde oxidase), from auto-oxidation of reduced quinones, catecholamines and thiols (i.e., oxidations in the absence of an enzyme), and when O2 combines with Hb or myoglobin. In contrast to the recent appreciation of the role of superoxide anions, generation of H2O2 in cellular oxidations (and the need to reduce the concentration of this toxic metabolite) has been known for many years. Enzymes known to generate H2O2 include D-amino acid oxidase and amine oxidase, as well as superoxide dismutase. The hydroxyl radical (OH. ) can be generated in erythrocytes from H2O2 in both the HaberWeiss and Fenton reactions. It is considerably more reactive, and therefore more toxic than either H2O2 or O2 –. . It affects proteins and DNA, as well as unsaturated fatty acids in cell membrane phospholipids. Hydroperoxidation of membrane lipids has two consequences:
It increases the hydrophilic nature of the lipid, which changes membrane structure so that normal function is disturbed.
It inhibits some enzymes, thus compromising metabolic processes within the membrane and within the cell.
For example, when red blood cell membranes are sufficiently damaged by hydroperoxidation, cells are more rapidly degraded with resultant anemia. A further problem is that iron atoms in Hb are readily oxidized (even by H2O2), and the resulting methemoglobin is unable to properly transport O2. Cellular Protection Against Free Radicals At least four cellular mechanisms appear to play a role in reducing harmful effects of these oxidants. Indeed, at normal oxygen tensions they usually eliminate the problem entirely.
The enzyme SOD serves to lower normal intracellular O2 –. concentrations to extremely low levels (<10^-11). The H2O2 produced is then removed by the action of catalases, or glutathione peroxidase. SOD, a zinc- and copper-containing enzyme, is present in all aerobic tissues, as well as RBCs.
Catalase is a rather ubiquitous enzyme, that selectively converts H2O2 to O2 and H2O. Patients deficient in this enzyme, however, show few toxic symptoms, presumably because of the redundant actions of glutathione peroxidase. The tripeptide glutathione is present at high concentrations in RBCs. The reduced form of glutathione is represented by the abbreviation GSH, thus highlighting the importance of the sulfhydryl (-SH) group contributed by cysteine. This group is highly reactive, and may also act non-enzymatically as a free radical scavenger (as well as protecting against H2O2 via conversion to H2O). This vitally important enzyme contains selenium (Se), an essential mineral in the diet. In normal RBCs, GSH is constantly being oxidized to GSSG, but GSSG accounts for less than 1% of total erythrocyte glutathione. Continual reduction of GSSG to GSH is accomplished by the FAD-containing enzyme, glutathione reductase, and NADPH (produced in the HMS); reduced glutathione (GSH) again becomes available to protect against oxidizing agents. The liver also produces GSH, and exports it into blood and bile for use by other tissues. Methemoglobin reductase does not use NADPH, instead it makes use of NADH generated during anaerobic glycolysis in the RBC.
Methemoglobin (metHb Fe+++) is an inactive form of Hb in which the iron has been auto-oxidized from the ferrous (Fe++) to ferric (Fe+++) state by superoxides. Methemoglobin is dark-colored, and when present in large quantities in the circulation causes a dusky discoloration of the skin resembling cyanosis. Only heme iron in the ferrous state can carry oxygen reversibly (HbFe++ + O2 HbFe++-O2), but small amounts of Hb-Fe++ still undergo slow auto-oxidation (even in the absence of oxidative stress) to metHb-Fe+++. Methemoglobin reductase converts it back to its functional form. Methemoglobinemia due to methemoglobin reductase deficiency may be inherited or acquired (by ingestion of certain drugs and/or other chemicals).
Excessive oxidative stress may result in the formation of Heinz bodies (large rigid structures that distort the RBC membrane). Heinz bodies are formed when the SH groups of Hb become oxidized, and the globin precipitates. Horses that feed on red maple leaves, for example, sometimes develop an acute hemolytic anemia that is characterized by the formation of Heinz bodies and methemoglobin in erythrocytes. The oxidizing agent in red maple leaves has not been clearly elucidated.
Heinz body formation will generally occur within 24 hours of toxin exposure, and may occur with or without methemoglobinemia. Oxidative injury to erythrocytic membranes may also occur, with changes usually being irreversible, thus altering membrane deformability. The spleen generally functions to remove Heinz bodies from erythrocytes; consequently, if the spleen is removed, Heinz bodies persist in the circulation for longer periods of time. Compared to other domestic animals, the spleen of the cat is generally less capable of removing Heinz bodies from erythrocytes. Therefore, these inclusions may be seen in the blood of normal cats. Acetaminophen toxicity is a common cause of Heinz body anemia in cats. Because acetaminophen is normally detoxified in the liver via glucuronidation, and cats are less capable of glucuronidating xenobiotics, the circulating half-life of this drug increases, thus exacerbating the toxicity.
Onion ingestion is known to precipitate Heinz body formation in cattle, horses, dogs, and cats. The toxic agent is reported to be n-propyl disulfide, a compound which decreases erythrocytic glucose-6-phosphate dehydrogenase activity, thus decreasing NADPH generation and GSH production. Vitamin antioxidants available to the body include tocopherol (vitamin E), and ascorbate (vitamin C). Several problems associated with red cell glucose 6-phosphate dehydrogenase deficiency have reportedly improved following vitamin E administration. Uric acid is also reported to possess antioxidant activity, and may contribute to longevity in certain vertebrate species (Hediger MA, 2002; and Simoyi MF, et al, 2002).
SUMMARY
Chapter 30 discusses erythrocytic protection from oxygen (O2) toxicity. Erythrocytes, or red blood cells (RBCs), carry oxygen from the lungs to tissues and are involved in the transport of carbon dioxide from tissues to the lungs. The chapter explains the lifespan of RBCs in different animal species and the process of erythrocyte degradation and hematopoiesis. It also discusses the antigenic determinants on the surface of erythrocytes known as blood groups. The toxicity of oxygen is explained, including the production of reactive products such as superoxide anion, hydrogen peroxide, and hydroxyl radical. The chapter explores the effects of oxygen toxicity on proteins, DNA, and cell membranes. It also discusses cellular protection mechanisms against free radicals, including the enzymes superoxide dismutase, catalase, and glutathione peroxidase. Methemoglobin and Heinz body formation are also discussed, along with their causes and effects. The chapter concludes by mentioning vitamin antioxidants and uric acid as potential contributors to cellular protection against oxidative stress.
OUTLINE
I. Introduction to Erythrocytes
A. Function of erythrocytes in oxygen and carbon dioxide transport
B. Specialized characteristics of mature erythrocytes
C. Lifespan and replacement of erythrocytes
II. Erythrocyte Degradation and Hematopoiesis
A. Removal of aged erythrocytes by reticuloendothelial system
B. Constant need for hematopoiesis
C. Role of erythropoietin in red blood cell production
III. Blood Groups and Antigenic Determinants
A. Identification of blood groups on erythrocyte surface
B. Association of blood groups with specific carbohydrate elements
IV. Oxygen Toxicity
A. Toxic effects of breathing 100% oxygen
B. Production of reactive products from oxygen
C. Superoxide anion, hydrogen peroxide, and hydroxyl radical as reactive products
D. Sources of superoxide anion and hydrogen peroxide in erythrocytes
V. Consequences of Oxygen Toxicity
A. Hydroperoxidation of membrane lipids and its effects on membrane structure and function
B. Inhibition of enzymes and compromised metabolic processes
C. Oxidation of iron in hemoglobin and formation of methemoglobin
VI. Cellular Protection Against Free Radicals
A. Role of superoxide dismutase in lowering intracellular superoxide anion concentrations
B. Removal of hydrogen peroxide by catalase and glutathione peroxidase
C. Importance of glutathione as a free radical scavenger and protection against oxidizing agents
D. Methemoglobin reductase and conversion of methemoglobin back to functional form
VII. Heinz Body Formation and Oxidative Injury
A. Formation of Heinz bodies due to oxidation of hemoglobin SH groups
B. Factors contributing to Heinz body formation, including red maple leaves and onion ingestion
C. Role of the spleen in removing Heinz bodies from erythrocytes
VIII. Vitamin Antioxidants and Uric Acid
A. Role of tocopherol (vitamin E) and ascorbate (vitamin C) as antioxidants
B. Improvement of red cell glucose 6 P
QUESTIONS
Qcard 1:
Question: What is the primary function of erythrocytes?
Answer: Erythrocytes carry oxygen from the lungs to tissues and transport carbon dioxide from tissues to the lungs.
Qcard 2:
Question: What is the main component of erythrocytes that contributes to their red color and gas-carrying capacity?
Answer: Hemoglobin (Hb) constitutes about one-third of the weight of erythrocytes and contributes to their red color and gas-carrying capacity.
Qcard 3:
Question: How are aging erythrocytes removed from circulation?
Answer: Aging erythrocytes are removed from circulation by cells of the reticuloendothelial (RE) system, predominantly macrophages in the spleen.
Qcard 4:
Question: What is the primary stimulatory factor for red blood cell production?
Answer: Erythropoietin (EPO), a protein hormone produced largely by vascular endothelial cells of the kidney, is the primary stimulatory factor for red blood cell production.
Qcard 5:
Question: What are the reactive products derived from oxygen that contribute to its toxicity?
Answer: The reactive products derived from oxygen that contribute to its toxicity are the superoxide anion (O2 –.), hydrogen peroxide (H2O2), and the hydroxyl radical (OH).
Qcard 6:
Question: What are the consequences of hydroperoxidation of membrane lipids in erythrocytes?
Answer: Hydroperoxidation of membrane lipids increases the hydrophilic nature of the lipid, which changes membrane structure and inhibits some enzymes, compromising normal function and leading to anemia.
Qcard 7:
Question: What are the four cellular mechanisms that protect against the harmful effects of oxidants?
Answer: The four cellular mechanisms that protect against the harmful effects of oxidants are superoxide dismutase (SOD), catalase, glutathione peroxidase, and glutathione reductase.
Qcard 8:
Question: What is the inactive form of hemoglobin in which the iron has been oxidized?
Answer: Methemoglobin (metHb Fe+++) is the inactive form of hemoglobin in which the iron has been oxidized from the ferrous (Fe++) to ferric (Fe+++) state.
Qcard 9:
Question: What are Heinz bodies and how are they formed?
Answer: Heinz bodies are structures that are formed from the breakdown of hemoglobin in red blood cells. They occur due to oxidative damage from toxins, medications, or as a result of underlying G6PD deficiency or thalassemia12. Heinz bodies look like small dark spots inside red blood cells. They form when hemoglobin molecules in the red blood cells break down due to oxidative damage1. Hemoglobin is a red blood cell protein that binds to and carries oxygen to cells throughout the body
Erythrocyte Structure and Function
Oxygen Toxicity
Cellular Protection Against Free Radicals
Hemoglobin (Hb)
Lifespan of RBCs
Blood Groups
Reactive products derived from O2
Superoxide anion (O2 –.)
Hydrogen peroxide (H2O2)
Hydroxyl radical (OH.)
Effects of oxygen toxicity on tissues
Prevention of oxygen toxicity in premature infants
Mechanisms to reduce harmful effects of oxidants
Superoxide dismutase (SOD)
Catalase
Glutathione peroxidase
Glutathione reductase
Methemoglobin and methemoglobin reductase
Formation of Heinz bodies and oxidative injury to erythrocytic membranes
Factors affecting cellular protection against free radicals
Vitamin antioxidants (E and C)
Uric acid
Note: The mind map is not exhaustive and may not include all sub-branches or details.
Read and understand the introduction to Chapter 30.
Focus on the role of erythrocytes in oxygen and carbon dioxide transport.
Study the structure of mature erythrocytes, including the composition of hemoglobin and its contribution to the cell's function.
Take notes on the lifespan of erythrocytes in different animal species and the process of their removal from circulation.
Review the concept of hematopoiesis and its importance in maintaining a balance between erythrocyte degradation and production.
Understand the role of erythropoietin (EPO) in stimulating red blood cell production.
Focus on the source of EPO production and its regulation.
Take note of any factors that can influence erythropoiesis.
Study the concept of blood groups and their significance in erythrocytes.
Understand the antigenic determinants present on the surface of erythrocytes and their association with specific carbohydrate elements.
Take note of any exceptions or variations in blood group identification.
Learn about the toxicity of oxygen and its potential damage to various organs.
Focus on the production of reactive products, including the superoxide anion, hydrogen peroxide, and the hydroxyl radical.
Understand the sources of these reactive products and their effects on proteins, DNA, and cell membrane lipids.
Take note of the consequences of hydroperoxidation of membrane lipids and its impact on cellular function.
Study the four cellular mechanisms involved in reducing the harmful effects of oxidants.
Focus on the role of superoxide dismutase (SOD) in lowering intracellular superoxide anion concentrations.
Understand the actions of catalase and glutathione peroxidase in removing hydrogen peroxide.
Learn about the importance of glutathione and its role as a free radical scavenger.
Take note of the role of methemoglobin reductase in converting methemoglobin back to its functional form.
Note: Throughout the study plan, make sure to review and reinforce the key
Chapter 30: Erythrocytic Protection from O2 Toxicity Erythrocytes, or red blood cells (RBCs), carry oxygen (O2) from the lungs to tissues, and are involved in the transport of carbon dioxide (CO2) from tissues to the lungs. The mature erythrocyte is a highly specialized cell. Hemoglobin (Hb), which constitutes about one-third of its weight, contributes red color and gas-carrying capacity. Although RBCs of primates may have a 120-day life-span (traveling some 175 miles through the circulation), the life-span of RBCs among domestic animal species varies considerably (e.g., 65 days in the pig and 150 days in the horse). In smaller animals with a high metabolic rate, the survival time is generally shorter than in larger animals, and red cell survival time generally increases with hibernation. On average, approximately 1% of circulating erythrocytes are replaced daily. As erythrocytes age, they are removed from the circulation by cells of the reticuloendothelial (RE) system (predominantly macrophages in the spleen). To balance this degradation, there is a constant need for hematopoiesis (production of new RBCs in bone marrow). The primary stimulatory factor for red blood cell production is erythropoietin (EPO), a protein hormone produced largely by vascular endothelial cells of the kidney. Erythrocytes carry on their surface antigenic determinants commonly known as blood groups. These determinants are commonly, but not always, identified with specific carbohydrate elements of glycoproteins on the cell surface. Oxygen Toxicity: Although O2 is essential for mammalian life, breathing 100% oxygen for several hours can be toxic, with damage to the lungs, brain, and retina occurring. At one time this was a major cause of blindness among premature human infants with respiratory distress syndrome. Now, such infants are administered air containing no more than 40% oxygen. The toxicity of O2 is due to the production of highly reactive products derived from it. Even under normal circumstances, small amounts of these reduced products are produced; however, RBCs and other tissues are specialized for their removal. These reactive products are the superoxide anion (O2 –., a free radical), hydrogen peroxide (H2O2), and the hydroxyl radical (OH). The O2 –. normally has a short half-life (milliseconds), and arises from the acquisition of a single electron (e-) by a molecule of O2. It can be generated by the action of ionizing radiation on O2 (thus causing tissue radiation damage), from xanthine oxidase (an enzyme which catalyzes the oxidation of xanthine to uric acid), from flavoprotein oxidases (e.g., aldehyde oxidase), from auto-oxidation of reduced quinones, catecholamines and thiols (i.e., oxidations in the absence of an enzyme), and when O2 combines with Hb or myoglobin. In contrast to the recent appreciation of the role of superoxide anions, generation of H2O2 in cellular oxidations (and the need to reduce the concentration of this toxic metabolite) has been known for many years. Enzymes known to generate H2O2 include D-amino acid oxidase and amine oxidase, as well as superoxide dismutase. The hydroxyl radical (OH. ) can be generated in erythrocytes from H2O2 in both the HaberWeiss and Fenton reactions. It is considerably more reactive, and therefore more toxic than either H2O2 or O2 –. . It affects proteins and DNA, as well as unsaturated fatty acids in cell membrane phospholipids. Hydroperoxidation of membrane lipids has two consequences:
It increases the hydrophilic nature of the lipid, which changes membrane structure so that normal function is disturbed.
It inhibits some enzymes, thus compromising metabolic processes within the membrane and within the cell.
For example, when red blood cell membranes are sufficiently damaged by hydroperoxidation, cells are more rapidly degraded with resultant anemia. A further problem is that iron atoms in Hb are readily oxidized (even by H2O2), and the resulting methemoglobin is unable to properly transport O2. Cellular Protection Against Free Radicals At least four cellular mechanisms appear to play a role in reducing harmful effects of these oxidants. Indeed, at normal oxygen tensions they usually eliminate the problem entirely.
The enzyme SOD serves to lower normal intracellular O2 –. concentrations to extremely low levels (<10^-11). The H2O2 produced is then removed by the action of catalases, or glutathione peroxidase. SOD, a zinc- and copper-containing enzyme, is present in all aerobic tissues, as well as RBCs.
Catalase is a rather ubiquitous enzyme, that selectively converts H2O2 to O2 and H2O. Patients deficient in this enzyme, however, show few toxic symptoms, presumably because of the redundant actions of glutathione peroxidase. The tripeptide glutathione is present at high concentrations in RBCs. The reduced form of glutathione is represented by the abbreviation GSH, thus highlighting the importance of the sulfhydryl (-SH) group contributed by cysteine. This group is highly reactive, and may also act non-enzymatically as a free radical scavenger (as well as protecting against H2O2 via conversion to H2O). This vitally important enzyme contains selenium (Se), an essential mineral in the diet. In normal RBCs, GSH is constantly being oxidized to GSSG, but GSSG accounts for less than 1% of total erythrocyte glutathione. Continual reduction of GSSG to GSH is accomplished by the FAD-containing enzyme, glutathione reductase, and NADPH (produced in the HMS); reduced glutathione (GSH) again becomes available to protect against oxidizing agents. The liver also produces GSH, and exports it into blood and bile for use by other tissues. Methemoglobin reductase does not use NADPH, instead it makes use of NADH generated during anaerobic glycolysis in the RBC.
Methemoglobin (metHb Fe+++) is an inactive form of Hb in which the iron has been auto-oxidized from the ferrous (Fe++) to ferric (Fe+++) state by superoxides. Methemoglobin is dark-colored, and when present in large quantities in the circulation causes a dusky discoloration of the skin resembling cyanosis. Only heme iron in the ferrous state can carry oxygen reversibly (HbFe++ + O2 HbFe++-O2), but small amounts of Hb-Fe++ still undergo slow auto-oxidation (even in the absence of oxidative stress) to metHb-Fe+++. Methemoglobin reductase converts it back to its functional form. Methemoglobinemia due to methemoglobin reductase deficiency may be inherited or acquired (by ingestion of certain drugs and/or other chemicals).
Excessive oxidative stress may result in the formation of Heinz bodies (large rigid structures that distort the RBC membrane). Heinz bodies are formed when the SH groups of Hb become oxidized, and the globin precipitates. Horses that feed on red maple leaves, for example, sometimes develop an acute hemolytic anemia that is characterized by the formation of Heinz bodies and methemoglobin in erythrocytes. The oxidizing agent in red maple leaves has not been clearly elucidated.
Heinz body formation will generally occur within 24 hours of toxin exposure, and may occur with or without methemoglobinemia. Oxidative injury to erythrocytic membranes may also occur, with changes usually being irreversible, thus altering membrane deformability. The spleen generally functions to remove Heinz bodies from erythrocytes; consequently, if the spleen is removed, Heinz bodies persist in the circulation for longer periods of time. Compared to other domestic animals, the spleen of the cat is generally less capable of removing Heinz bodies from erythrocytes. Therefore, these inclusions may be seen in the blood of normal cats. Acetaminophen toxicity is a common cause of Heinz body anemia in cats. Because acetaminophen is normally detoxified in the liver via glucuronidation, and cats are less capable of glucuronidating xenobiotics, the circulating half-life of this drug increases, thus exacerbating the toxicity.
Onion ingestion is known to precipitate Heinz body formation in cattle, horses, dogs, and cats. The toxic agent is reported to be n-propyl disulfide, a compound which decreases erythrocytic glucose-6-phosphate dehydrogenase activity, thus decreasing NADPH generation and GSH production. Vitamin antioxidants available to the body include tocopherol (vitamin E), and ascorbate (vitamin C). Several problems associated with red cell glucose 6-phosphate dehydrogenase deficiency have reportedly improved following vitamin E administration. Uric acid is also reported to possess antioxidant activity, and may contribute to longevity in certain vertebrate species (Hediger MA, 2002; and Simoyi MF, et al, 2002).
SUMMARY
Chapter 30 discusses erythrocytic protection from oxygen (O2) toxicity. Erythrocytes, or red blood cells (RBCs), carry oxygen from the lungs to tissues and are involved in the transport of carbon dioxide from tissues to the lungs. The chapter explains the lifespan of RBCs in different animal species and the process of erythrocyte degradation and hematopoiesis. It also discusses the antigenic determinants on the surface of erythrocytes known as blood groups. The toxicity of oxygen is explained, including the production of reactive products such as superoxide anion, hydrogen peroxide, and hydroxyl radical. The chapter explores the effects of oxygen toxicity on proteins, DNA, and cell membranes. It also discusses cellular protection mechanisms against free radicals, including the enzymes superoxide dismutase, catalase, and glutathione peroxidase. Methemoglobin and Heinz body formation are also discussed, along with their causes and effects. The chapter concludes by mentioning vitamin antioxidants and uric acid as potential contributors to cellular protection against oxidative stress.
OUTLINE
I. Introduction to Erythrocytes
A. Function of erythrocytes in oxygen and carbon dioxide transport
B. Specialized characteristics of mature erythrocytes
C. Lifespan and replacement of erythrocytes
II. Erythrocyte Degradation and Hematopoiesis
A. Removal of aged erythrocytes by reticuloendothelial system
B. Constant need for hematopoiesis
C. Role of erythropoietin in red blood cell production
III. Blood Groups and Antigenic Determinants
A. Identification of blood groups on erythrocyte surface
B. Association of blood groups with specific carbohydrate elements
IV. Oxygen Toxicity
A. Toxic effects of breathing 100% oxygen
B. Production of reactive products from oxygen
C. Superoxide anion, hydrogen peroxide, and hydroxyl radical as reactive products
D. Sources of superoxide anion and hydrogen peroxide in erythrocytes
V. Consequences of Oxygen Toxicity
A. Hydroperoxidation of membrane lipids and its effects on membrane structure and function
B. Inhibition of enzymes and compromised metabolic processes
C. Oxidation of iron in hemoglobin and formation of methemoglobin
VI. Cellular Protection Against Free Radicals
A. Role of superoxide dismutase in lowering intracellular superoxide anion concentrations
B. Removal of hydrogen peroxide by catalase and glutathione peroxidase
C. Importance of glutathione as a free radical scavenger and protection against oxidizing agents
D. Methemoglobin reductase and conversion of methemoglobin back to functional form
VII. Heinz Body Formation and Oxidative Injury
A. Formation of Heinz bodies due to oxidation of hemoglobin SH groups
B. Factors contributing to Heinz body formation, including red maple leaves and onion ingestion
C. Role of the spleen in removing Heinz bodies from erythrocytes
VIII. Vitamin Antioxidants and Uric Acid
A. Role of tocopherol (vitamin E) and ascorbate (vitamin C) as antioxidants
B. Improvement of red cell glucose 6 P
QUESTIONS
Qcard 1:
Question: What is the primary function of erythrocytes?
Answer: Erythrocytes carry oxygen from the lungs to tissues and transport carbon dioxide from tissues to the lungs.
Qcard 2:
Question: What is the main component of erythrocytes that contributes to their red color and gas-carrying capacity?
Answer: Hemoglobin (Hb) constitutes about one-third of the weight of erythrocytes and contributes to their red color and gas-carrying capacity.
Qcard 3:
Question: How are aging erythrocytes removed from circulation?
Answer: Aging erythrocytes are removed from circulation by cells of the reticuloendothelial (RE) system, predominantly macrophages in the spleen.
Qcard 4:
Question: What is the primary stimulatory factor for red blood cell production?
Answer: Erythropoietin (EPO), a protein hormone produced largely by vascular endothelial cells of the kidney, is the primary stimulatory factor for red blood cell production.
Qcard 5:
Question: What are the reactive products derived from oxygen that contribute to its toxicity?
Answer: The reactive products derived from oxygen that contribute to its toxicity are the superoxide anion (O2 –.), hydrogen peroxide (H2O2), and the hydroxyl radical (OH).
Qcard 6:
Question: What are the consequences of hydroperoxidation of membrane lipids in erythrocytes?
Answer: Hydroperoxidation of membrane lipids increases the hydrophilic nature of the lipid, which changes membrane structure and inhibits some enzymes, compromising normal function and leading to anemia.
Qcard 7:
Question: What are the four cellular mechanisms that protect against the harmful effects of oxidants?
Answer: The four cellular mechanisms that protect against the harmful effects of oxidants are superoxide dismutase (SOD), catalase, glutathione peroxidase, and glutathione reductase.
Qcard 8:
Question: What is the inactive form of hemoglobin in which the iron has been oxidized?
Answer: Methemoglobin (metHb Fe+++) is the inactive form of hemoglobin in which the iron has been oxidized from the ferrous (Fe++) to ferric (Fe+++) state.
Qcard 9:
Question: What are Heinz bodies and how are they formed?
Answer: Heinz bodies are structures that are formed from the breakdown of hemoglobin in red blood cells. They occur due to oxidative damage from toxins, medications, or as a result of underlying G6PD deficiency or thalassemia12. Heinz bodies look like small dark spots inside red blood cells. They form when hemoglobin molecules in the red blood cells break down due to oxidative damage1. Hemoglobin is a red blood cell protein that binds to and carries oxygen to cells throughout the body
Erythrocyte Structure and Function
Oxygen Toxicity
Cellular Protection Against Free Radicals
Hemoglobin (Hb)
Lifespan of RBCs
Blood Groups
Reactive products derived from O2
Superoxide anion (O2 –.)
Hydrogen peroxide (H2O2)
Hydroxyl radical (OH.)
Effects of oxygen toxicity on tissues
Prevention of oxygen toxicity in premature infants
Mechanisms to reduce harmful effects of oxidants
Superoxide dismutase (SOD)
Catalase
Glutathione peroxidase
Glutathione reductase
Methemoglobin and methemoglobin reductase
Formation of Heinz bodies and oxidative injury to erythrocytic membranes
Factors affecting cellular protection against free radicals
Vitamin antioxidants (E and C)
Uric acid
Note: The mind map is not exhaustive and may not include all sub-branches or details.
Read and understand the introduction to Chapter 30.
Focus on the role of erythrocytes in oxygen and carbon dioxide transport.
Study the structure of mature erythrocytes, including the composition of hemoglobin and its contribution to the cell's function.
Take notes on the lifespan of erythrocytes in different animal species and the process of their removal from circulation.
Review the concept of hematopoiesis and its importance in maintaining a balance between erythrocyte degradation and production.
Understand the role of erythropoietin (EPO) in stimulating red blood cell production.
Focus on the source of EPO production and its regulation.
Take note of any factors that can influence erythropoiesis.
Study the concept of blood groups and their significance in erythrocytes.
Understand the antigenic determinants present on the surface of erythrocytes and their association with specific carbohydrate elements.
Take note of any exceptions or variations in blood group identification.
Learn about the toxicity of oxygen and its potential damage to various organs.
Focus on the production of reactive products, including the superoxide anion, hydrogen peroxide, and the hydroxyl radical.
Understand the sources of these reactive products and their effects on proteins, DNA, and cell membrane lipids.
Take note of the consequences of hydroperoxidation of membrane lipids and its impact on cellular function.
Study the four cellular mechanisms involved in reducing the harmful effects of oxidants.
Focus on the role of superoxide dismutase (SOD) in lowering intracellular superoxide anion concentrations.
Understand the actions of catalase and glutathione peroxidase in removing hydrogen peroxide.
Learn about the importance of glutathione and its role as a free radical scavenger.
Take note of the role of methemoglobin reductase in converting methemoglobin back to its functional form.
Note: Throughout the study plan, make sure to review and reinforce the key
