Competencies
- PY6.3: Describe transport of gases
Introduction
Efficient transport of oxygen and carbon dioxide in blood is essential for cellular metabolism and acid-base homeostasis. Hemoglobin plays a central role in this process, while factors such as pH, carbon dioxide tension, temperature, and 2,3-diphosphoglycerate profoundly influence gas loading and unloading in the lungs and tissues.
- Gas transport refers to the carriage of oxygen and carbon dioxide by blood between the lungs and body tissues.
- This process is essential for cellular metabolism and represents a major physiological function of the circulatory system.
Oxygen Transport
- Oxygen transport from the lungs to tissues occurs in two forms: bound to hemoglobin and physically dissolved in plasma.
- Approximately 98 percent of oxygen is transported in combination with hemoglobin, whereas only about 2 percent is carried in dissolved form.
In Physically Dissolved Form
- The amount of oxygen dissolved in plasma is determined by Henry’s law.
- According to Henry’s law, the quantity of a gas dissolved in a liquid at a constant temperature is directly proportional to its partial pressure.
- In blood, oxygen solubility is approximately 0.003 milliliters per deciliter per millimeter of mercury.
- With a normal arterial oxygen partial pressure of about 95 millimeters of mercury, dissolved oxygen content is approximately 0.3 milliliters per deciliter of blood.
- Thus, 100 milliliters of arterial blood contains only about 0.3 milliliters of oxygen in the dissolved state.
- At a resting cardiac output of approximately 5 liters per minute, dissolved oxygen transport amounts to nearly 15 milliliters per minute.
- The resting oxygen consumption of an adult is approximately 250 milliliters per minute.
- Therefore, oxygen carried solely in dissolved form is insufficient to satisfy metabolic demands.
- Efficient oxygen delivery to tissues depends predominantly on hemoglobin-mediated transport.
Clinical Physiology
Hyperbaric O2 therapy improves tissue oxygenation:
- Hyperbaric oxygen therapy markedly increases the amount of oxygen dissolved in plasma by raising inspired oxygen pressure.
- Breathing 100 percent oxygen under hyperbaric conditions can provide sufficient dissolved oxygen to meet resting tissue requirements, even when hemoglobin-mediated oxygen transport is severely impaired.
In Combination with Hemoglobin
- More than 98 percent of oxygen in blood is transported in combination with hemoglobin, the oxygen-carrying protein within erythrocytes.
- Hemoglobin bound to oxygen is termed oxyhemoglobin, whereas hemoglobin not carrying oxygen is called deoxyhemoglobin or reduced hemoglobin.
Oxyhemoglobin Formation
- A hemoglobin molecule consists of four polypeptide chains collectively known as globin.
- Each globin chain contains a heme group with a central ferrous iron (Fe²⁺) atom.
- Each ferrous iron atom can bind one oxygen molecule; therefore, a single hemoglobin molecule can carry a maximum of four oxygen molecules.
- Oxygen binds only when iron remains in the ferrous state.
- Oxidation of ferrous iron to the ferric (Fe³⁺) state produces methemoglobin, which is incapable of binding oxygen.
- Methemoglobin may form following exposure to oxidizing agents such as nitrites, certain sulfonamides, and other drugs.
- Small quantities of methemoglobin are continuously produced under normal physiological conditions.
- Erythrocytes contain methemoglobin reductase, an enzyme that converts methemoglobin back to functional hemoglobin.
- Consequently, methemoglobin normally constitutes less than approximately 1 to 2 percent of total hemoglobin.
- Deficiency of methemoglobin reductase increases methemoglobin levels and reduces the oxygen-carrying capacity of blood.
- The combination of oxygen with hemoglobin is termed oxygenation, not oxidation, because iron remains in the ferrous state.
- Oxygen binding to hemoglobin is rapid, reversible, and highly regulated.
- Deoxygenated hemoglobin exists predominantly in the tense (T) state, in which oxygen affinity is relatively low.
- Binding of the first oxygen molecule induces a conformational change, converting hemoglobin into the relaxed (R) state.
- The relaxed state has a much higher affinity for oxygen, facilitating the binding of additional oxygen molecules.
- This phenomenon, known as cooperative binding, allows efficient oxygen loading in the lungs and unloading in peripheral tissues.
- At high oxygen partial pressures, such as in pulmonary capillaries, hemoglobin predominantly remains in the relaxed state and forms oxyhemoglobin.
- At lower oxygen partial pressures in tissue capillaries, hemoglobin shifts toward the tense state, promoting oxygen release to metabolically active cells.
O2-Carrying Capacity of Hb
- Oxygen-carrying capacity refers to the maximum amount of oxygen that can be bound by hemoglobin in blood.
- Each gram of hemoglobin can bind approximately 1.34 milliliters of oxygen when fully saturated.
- In a healthy adult with a hemoglobin concentration of 15 grams per deciliter, the oxygen-carrying capacity of blood is approximately 20 milliliters of oxygen per deciliter.
- Oxygen content denotes the actual amount of oxygen bound to hemoglobin in blood.
- In contrast, oxygen capacity represents the maximum quantity of oxygen that hemoglobin can potentially bind.
- Hemoglobin oxygen saturation expresses the proportion of available oxygen-binding sites occupied by oxygen.
- It is calculated as: Oxygen saturation = (Oxygen content ÷ Oxygen capacity) × 100.
- For example, if blood contains 15 milliliters of oxygen per deciliter and the oxygen capacity is 20 milliliters per deciliter, hemoglobin saturation is 75 percent.
- Under normal physiological conditions, arterial hemoglobin saturation is approximately 97 to 98 percent.
- Both arterial oxygen partial pressure and hemoglobin saturation are important indicators of the adequacy of oxygen transport.
\mathrm{S_{O_2} = {HbO_2\ content/HbO_2\ capacity} \times 100}
$$\mathrm{S_{O_2} = \frac{HbO_2\ content}{HbO_2\ capacity} \times 100}$$
Oxygen-Hemoglobin Dissociation Curve
- The oxygen-hemoglobin dissociation curve illustrates the relationship between blood oxygen partial pressure and hemoglobin oxygen saturation.
- The curve is characteristically sigmoid (S-shaped) over the physiological range of oxygen partial pressures.
- This sigmoid configuration results from cooperative binding of oxygen to hemoglobin.
- Binding of one oxygen molecule increases the affinity of hemoglobin for subsequent oxygen molecules.
- As oxygen partial pressure rises, hemoglobin saturation increases progressively, but the relationship is not linear.
- The shape of the curve enables efficient oxygen loading in the lungs and oxygen unloading in peripheral tissues.
- The curve consists of two major regions: the steep phase and the plateau phase.
Steep Phase
- The steep portion extends approximately between oxygen partial pressures of 10 and 60 millimeters of mercury.
- Within this range, small increases in oxygen partial pressure produce large increases in hemoglobin saturation.
- At an oxygen partial pressure of approximately 60 millimeters of mercury, hemoglobin is about 90 percent saturated.
- This region is physiologically important for oxygen delivery to tissues.
- During tissue metabolism, even a modest fall in capillary oxygen partial pressure results in substantial oxygen release from hemoglobin.
- Consequently, metabolically active tissues can extract large amounts of oxygen without marked reductions in blood oxygen tension.
Significance of Steep Phase
- The steep phase facilitates rapid unloading of oxygen in systemic capillaries where oxygen partial pressure is relatively low.
- Conditions associated with increased tissue metabolism promote oxygen release by shifting the dissociation curve to the right.
- Factors producing a rightward shift include increased hydrogen ion concentration, elevated carbon dioxide partial pressure, increased temperature, and increased concentrations of 2,3-diphosphoglycerate.
- A rightward shift decreases hemoglobin affinity for oxygen and enhances oxygen delivery to tissues.
Plateau Phase
- The plateau phase of the oxygen-hemoglobin dissociation curve begins at an oxygen partial pressure of approximately 60 millimeters of mercury and becomes nearly flat above 70 millimeters of mercury.
- In this region, large increases in oxygen partial pressure produce only small increases in hemoglobin saturation.
- Between oxygen partial pressures of 60 and 100 millimeters of mercury, hemoglobin remains highly saturated with oxygen.
- At an oxygen partial pressure of about 60 millimeters of mercury, hemoglobin saturation is approximately 90 percent.
Significance of Plateau Phase
- The plateau region provides an important physiological safety margin for oxygen transport.
- Moderate reductions in alveolar or arterial oxygen partial pressure, such as those occurring at high altitude or in mild pulmonary disease, cause only small decreases in hemoglobin saturation.
- Consequently, oxygen delivery to tissues is maintained despite moderate impairment of pulmonary function.
- The plateau phase also ensures that hemoglobin saturation remains relatively constant over a broad range of alveolar oxygen tensions.
- Therefore, fluctuations in alveolar oxygen partial pressure between approximately 60 and 100 millimeters of mercury have little effect on arterial oxygen content.
- In healthy individuals at sea level, breathing 100 percent oxygen or hyperventilating produces only minimal additional hemoglobin saturation because hemoglobin is already nearly fully saturated under normal conditions.
- However, in patients with hypoxemia or individuals exposed to high altitude, supplemental oxygen or hyperventilation can significantly improve hemoglobin saturation because a larger proportion of hemoglobin is initially in the deoxygenated state.
P50
- P50 is the oxygen partial pressure at which hemoglobin is 50 percent saturated with oxygen.
- It is an important indicator of the affinity of hemoglobin for oxygen.
- In healthy adults at sea level, the normal P50 is approximately 26 to 27 millimeters of mercury.
- Changes in P50 primarily affect the steep portion of the oxygen-hemoglobin dissociation curve.
- An increased P50 indicates reduced hemoglobin affinity for oxygen and is associated with a rightward shift of the curve.
- Conversely, a decreased P50 signifies increased oxygen affinity and a leftward shift of the curve.
Factors Affecting Hb-binding Affinity with Oxygen
- The affinity of hemoglobin for oxygen is influenced by several physiological factors, including temperature, carbon dioxide partial pressure, hydrogen ion concentration, and 2,3-diphosphoglycerate.
- Changes in these factors alter the position of the oxygen-hemoglobin dissociation curve and thereby regulate oxygen loading and unloading.
- A rightward shift of the curve decreases hemoglobin affinity for oxygen and increases oxygen release to tissues.
- Conversely, a leftward shift increases oxygen affinity and reduces oxygen unloading.
- The effects of carbon dioxide and hydrogen ions on hemoglobin affinity for oxygen are collectively termed the Bohr effect.
- The Bohr effect promotes oxygen delivery to metabolically active tissues.
- During exercise, tissues become warmer, produce more carbon dioxide, and generate additional hydrogen ions; these changes facilitate oxygen unloading.
Temperature
- An increase in body or tissue temperature shifts the oxygen-hemoglobin dissociation curve to the right.
- Elevated temperature reduces hemoglobin affinity for oxygen and promotes oxygen release.
- This response is particularly important in actively metabolizing tissues, such as exercising skeletal muscle, where local temperature rises.
- A decrease in temperature shifts the curve to the left, increasing hemoglobin affinity for oxygen and reducing tissue oxygen delivery.
pH
- Blood pH has a major influence on hemoglobin affinity for oxygen.
- A decrease in pH (acidosis) shifts the dissociation curve to the right and decreases oxygen affinity.
- An increase in pH (alkalosis) shifts the curve to the left, enhancing oxygen affinity.
- When blood traverses systemic capillaries, carbon dioxide enters erythrocytes and generates hydrogen ions, lowering intracellular pH.
- The resulting acidic environment facilitates the release of oxygen from hemoglobin to tissues.
- Under physiological conditions, hydrogen ions bind to hemoglobin and stabilize its deoxygenated form, promoting oxygen unloading.
Carbon Dioxide
- Increased carbon dioxide partial pressure shifts the oxygen-hemoglobin dissociation curve to the right.
- Carbon dioxide contributes to this effect both indirectly, by increasing hydrogen ion concentration, and directly, through interaction with hemoglobin.
- Carbon dioxide combines with terminal amino groups of hemoglobin to form carbamino compounds.
- Formation of carbamino compounds alters hemoglobin conformation and reduces its affinity for oxygen.
- Consequently, tissues with high rates of metabolism and increased carbon dioxide production receive enhanced oxygen delivery.
- In metabolically active tissues, local hypercapnia, acidosis, and increased blood flow act together to optimize oxygen unloading.
2,3-DPG
- 2,3-Diphosphoglycerate (2,3-DPG), also known as 2,3-bisphosphoglycerate, is an intermediate produced during anaerobic glycolysis in erythrocytes.
- Because mature erythrocytes lack mitochondria, glycolysis is their primary source of energy.
- Erythrocytes contain much higher concentrations of 2,3-diphosphoglycerate than most other cells.
- This compound binds to deoxygenated hemoglobin in a central cavity formed between the two β-globin chains.
- Binding occurs in approximately a 1:1 ratio between 2,3-diphosphoglycerate and hemoglobin.
- Interaction of 2,3-diphosphoglycerate stabilizes the deoxygenated form of hemoglobin and reduces its affinity for oxygen.
- Consequently, the oxygen-hemoglobin dissociation curve shifts to the right, promoting oxygen release to tissues.
- Increased concentrations of 2,3-diphosphoglycerate enhance oxygen unloading, particularly in metabolically active tissues.
- Tissue hypoxia stimulates erythrocyte glycolysis, leading to increased production of 2,3-diphosphoglycerate.
- Erythrocyte 2,3-diphosphoglycerate levels increase in anemia, prolonged exercise, chronic hypoxemia, high-altitude exposure, and chronic pulmonary disease, thereby improving tissue oxygen delivery.
Factors that affect 2,3-DPG in Red Cells
- Several physiological and environmental factors influence 2,3-diphosphoglycerate concentrations in erythrocytes.
- Acidosis inhibits erythrocyte glycolysis and thereby reduces 2,3-diphosphoglycerate production.
- Fetal hemoglobin interacts weakly with 2,3-diphosphoglycerate because its γ-globin chains bind this compound less avidly than the β-globin chains of adult hemoglobin.
- Consequently, fetal hemoglobin exhibits a higher affinity for oxygen, facilitating oxygen transfer from maternal to fetal blood across the placenta.
- Fetal hemoglobin therefore shifts the oxygen-hemoglobin dissociation curve to the left.
- Growth hormone, thyroxine, and testosterone stimulate erythrocyte production of 2,3-diphosphoglycerate.
- Chronic hypoxia and exposure to high altitude increase 2,3-diphosphoglycerate synthesis, enhancing oxygen delivery to tissues.
- Prolonged storage of blood reduces erythrocyte 2,3-diphosphoglycerate levels, potentially impairing oxygen unloading after transfusion.
Myoglobin
- Myoglobin is an oxygen-binding pigment present in skeletal and cardiac muscle fibers.
- Structurally, myoglobin resembles hemoglobin but contains only a single heme group and therefore binds one oxygen molecule per molecule.
- Unlike hemoglobin, myoglobin exhibits a hyperbolic oxygen dissociation curve, reflecting its high affinity for oxygen and absence of cooperative binding.
- The high oxygen affinity of myoglobin facilitates the uptake of oxygen from capillary blood and its storage within muscle cells.
- Myoglobin serves as an intracellular oxygen reserve, particularly during periods of increased metabolic demand or transient reduction in blood flow.
- Muscles subjected to regular endurance or sustained exercise contain increased amounts of myoglobin.
- Myoglobin also facilitates the diffusion of oxygen from the cell membrane to mitochondria, thereby supporting aerobic metabolism.
Effect of Carbon Monoxide (CO)
- Carbon monoxide competes with oxygen for the same binding sites on hemoglobin.
- The affinity of hemoglobin for carbon monoxide is approximately 200 to 250 times greater than its affinity for oxygen.
- Carbon monoxide binds with hemoglobin to form carboxyhemoglobin, thereby reducing the number of available oxygen-binding sites.
- Even low concentrations of carbon monoxide can markedly reduce the oxygen-carrying capacity of blood.
- Arterial oxygen partial pressure may remain normal during carbon monoxide poisoning because dissolved oxygen in plasma is unaffected.
- However, total blood oxygen content decreases substantially owing to reduced hemoglobin binding.
- Carbon monoxide also shifts the oxygen-hemoglobin dissociation curve to the left, impairing oxygen release to tissues.
- Consequently, severe tissue hypoxia may develop despite apparently normal arterial oxygen tension.
- In healthy individuals, carboxyhemoglobin usually constitutes approximately 1 to 2 percent of total hemoglobin.
- Chronic exposure to tobacco smoke or environmental pollution increases carboxyhemoglobin levels and compromises oxygen transport.
Clinical Physiology
CO poisoning produces hypoxia:
- Carbon monoxide poisoning produces a form of anemic hypoxia by markedly reducing the oxygen-carrying capacity of blood.
- Carbon monoxide binds strongly to hemoglobin, forming carboxyhemoglobin and preventing normal oxygen transport.
- Because carbon monoxide is colorless, odorless, and non-irritating, exposure may occur without the individual’s awareness.
- Arterial oxygen partial pressure often remains normal because dissolved oxygen in plasma is unaffected.
- Consequently, pulse oximetry and arterial oxygen tension may underestimate the severity of poisoning.
- Carboxyhemoglobin imparts a characteristic cherry-red discoloration to blood and skin, which may obscure clinical recognition of hypoxia.
- Carbon monoxide also shifts the oxygen-hemoglobin dissociation curve to the left, further impairing oxygen release to tissues.
- Immediate treatment includes administration of 100 percent oxygen to accelerate dissociation of carbon monoxide from hemoglobin.
- Hyperbaric oxygen therapy is indicated in severe poisoning because it hastens carbon monoxide elimination and improves tissue oxygenation.
Factors that Shift Oxy-Hb Dissociation Curve
Factors that Shift the Curve to the Right
- A rightward shift of the oxygen-hemoglobin dissociation curve decreases hemoglobin affinity for oxygen, increases P50, and enhances oxygen unloading to tissues.
- Factors producing a rightward shift include increased temperature, decreased pH, increased carbon dioxide partial pressure, increased 2,3-diphosphoglycerate, and chronic hypoxia.
Factors that Shift the Curve to the Left
- A leftward shift increases hemoglobin affinity for oxygen, decreases P50, and reduces oxygen release to tissues.
- Factors causing a leftward shift include decreased temperature, increased pH, decreased carbon dioxide partial pressure, reduced 2,3-diphosphoglycerate concentration, fetal hemoglobin, and carbon monoxide exposure.
Importance of Oxygen Saturation and Content
Oxygen Saturation
- Oxygen saturation represents the percentage of available hemoglobin oxygen-binding sites occupied by oxygen.
- Complete saturation occurs when all heme groups of hemoglobin are fully bound to oxygen.
- Oxygen saturation provides important information regarding the efficiency of pulmonary oxygen loading.
Oxygen Content
- Oxygen content refers to the total amount of oxygen present in a unit volume of blood.
- It includes oxygen bound to hemoglobin and the small quantity dissolved in plasma.
- Because dissolved oxygen contributes minimally, blood oxygen content depends primarily on hemoglobin concentration and its oxygen-binding capacity.
- Therefore, oxygen saturation and oxygen content are related but not identical physiological variables.
Clinical Physiology
Oxygen content is important in anemic patients:
- In anemia, arterial oxygen partial pressure and hemoglobin saturation may remain within normal limits despite inadequate tissue oxygen delivery.
- Reduced hemoglobin concentration markedly lowers blood oxygen content, producing tissue hypoxia.
- Therefore, assessment of oxygen content is more clinically relevant than oxygen saturation alone when evaluating oxygenation in anemic patients.
Oxygen Extraction
- Oxygen extraction refers to the quantity of oxygen removed by tissues from the blood during capillary transit.
- It serves as an indicator of tissue oxygen utilization and metabolic activity.
- The oxygen extraction ratio is calculated by dividing the amount of oxygen consumed by tissues by the amount of oxygen delivered.
- Tissues with high metabolic demands extract a greater proportion of delivered oxygen.
- For example, the myocardium has a resting oxygen extraction ratio of approximately 70–80 percent, reflecting its continuous metabolic activity.
Applied Physiology
Measurement of Oxygen Saturation of Hb
Pulse Oximetry
- Pulse oximetry is a noninvasive technique used to estimate arterial hemoglobin oxygen saturation continuously.
- It is widely employed for monitoring hospitalized patients, particularly those in intensive care settings.
- A pulse oximeter probe is commonly placed on the fingertip, toe, or ear lobe, where pulsatile arterial blood is easily detected.
- The device emits red and infrared light through the vascular bed and analyzes differences in light absorption.
- Oxyhemoglobin and deoxyhemoglobin absorb light differently, allowing estimation of arterial oxygen saturation.
- The pulsatile component of light absorption represents arterial blood, whereas nonpulsatile absorption reflects venous blood and surrounding tissues.
- Pulse oximetry provides rapid assessment of oxygenation but does not measure arterial oxygen partial pressure or blood oxygen content directly.
Pulmonary Damage by Free Radicals
- Although oxygen is essential for cellular metabolism, excessive or abnormal oxygen metabolism can damage tissues.
- During mitochondrial ATP production, oxygen is normally reduced completely to water by accepting four electrons.
- Leakage of electrons from the mitochondrial electron transport chain may result in incomplete reduction of oxygen.
- Incomplete reduction generates free radicals, highly reactive molecules capable of damaging cellular components.
- The lungs are particularly vulnerable to oxidative injury because they are continuously exposed to high oxygen concentrations.
- Oxidative injury to pulmonary capillaries increases vascular permeability and may contribute to pulmonary edema.
Reactive Oxygen Species and Antioxidants
- A free radical is an atom or molecule containing one or more unpaired electrons.
- Important reactive oxygen species include the superoxide radical, hydroxyl radical, hydrogen peroxide, and peroxynitrite.
- Collectively, these molecules are termed reactive oxygen species.
- Excessive reactive oxygen species damage lipids, proteins, nucleic acids, and cell membranes, contributing to tissue degeneration.
- The body possesses several antioxidant defense mechanisms that limit oxidative injury.
- Major antioxidant enzymes include superoxide dismutase, catalase, and glutathione peroxidase.
- Oxidative stress develops when reactive oxygen species generation exceeds antioxidant capacity.
- Reactive oxygen species are also generated during inflammation, especially during the respiratory burst of activated neutrophils.
- Reperfusion of previously ischemic tissues may further increase reactive oxygen species production, leading to reperfusion injury and additional tissue damage.
Clinical Physiology
Reperfusion-induced injury produces further damage:
- Reperfusion injury occurs when blood flow is restored to previously ischemic tissues, resulting in excessive generation of reactive oxygen species.
- These free radicals aggravate cellular damage, increase inflammation, and may worsen organ dysfunction.
- Reperfusion injury contributes to the progression of severe shock, myocardial infarction, stroke, and ischemic tissue damage following trauma or surgery.
Carbon Dioxide Transport
- Carbon dioxide is produced primarily during aerobic metabolism and is transported from tissues to the lungs for elimination.
- In blood, carbon dioxide is transported in three major forms.
- Approximately 7 percent is carried physically dissolved in plasma.
- About 70 percent is transported as bicarbonate ions, whereas nearly 23 percent is carried as carbamino compounds.
- Carbamino compounds are formed when carbon dioxide combines with hemoglobin and plasma proteins.
In Dissolved Form in Plasma
- The quantity of carbon dioxide dissolved in plasma is directly proportional to its partial pressure, in accordance with Henry’s law.
- Carbon dioxide is highly soluble in plasma, with a solubility approximately 20 times greater than that of oxygen.
- Consequently, a significant amount of carbon dioxide remains physically dissolved in blood and contributes to the arterial carbon dioxide partial pressure.
- Plasma contains very little carbonic anhydrase; therefore, conversion of carbon dioxide to carbonic acid within plasma is relatively slow.
- A small proportion of dissolved carbon dioxide combines with plasma proteins to form carbamino compounds.
As Bicarbonate Ions4: Chloride Shift
- Within erythrocytes, carbon dioxide is converted to bicarbonate ions and hydrogen ions by the action of carbonic anhydrase.
- The resulting increase in intracellular bicarbonate concentration promotes its diffusion from erythrocytes into plasma.
- To maintain electrical neutrality, chloride ions move from plasma into erythrocytes in exchange for bicarbonate ions.
- This exchange occurs through the chloride-bicarbonate exchanger, also known as anion exchanger 1.
- The movement of chloride into erythrocytes in exchange for bicarbonate is termed the chloride shift.
- Chloride accumulation within erythrocytes slightly increases their osmotic content and volume.
- Hydrogen ions generated during carbonic acid dissociation remain largely within erythrocytes because the cell membrane is relatively impermeable to hydrogen ions.
- Most of these hydrogen ions are buffered by hemoglobin, thereby limiting changes in intracellular pH.
- Binding of hydrogen ions to hemoglobin reduces its affinity for oxygen and shifts the oxygen-hemoglobin dissociation curve to the right.
- This response facilitates oxygen unloading to peripheral tissues and enhances carbon dioxide transport.
- In pulmonary capillaries, the process reverses: oxygenation of hemoglobin promotes release of hydrogen ions and facilitates carbon dioxide elimination.
- Although most carbon dioxide transport reactions occur within erythrocytes, the majority of carbon dioxide is ultimately carried in plasma as bicarbonate ions.
Clinical Physiology
Hematocrit of venous blood is more:
- During systemic capillary transit, the chloride shift increases intracellular chloride concentration in erythrocytes.
- Chloride entry draws water into erythrocytes by osmosis, causing a slight increase in red cell volume.
- Consequently, the hematocrit of venous blood is typically about 2–3 percent higher than that of arterial blood.
As Carbamino Compound
- Approximately 20 to 25 percent of carbon dioxide in blood is transported as carbamino compounds.
- Carbon dioxide reacts reversibly with free amino groups of hemoglobin to form carbaminohemoglobin.
- This reaction occurs predominantly within erythrocytes and does not involve the heme iron.
- Deoxygenated hemoglobin binds carbon dioxide more readily than oxygenated hemoglobin, thereby enhancing carbon dioxide transport from tissues to the lungs.
CO2 Dissociation Curve
- The carbon dioxide dissociation curve depicts the relationship between blood carbon dioxide content and carbon dioxide partial pressure.
- Within the physiological range of carbon dioxide partial pressure, approximately 40 to 46 millimeters of mercury, the curve is nearly linear.
- This relationship differs from the sigmoid shape of the oxygen-hemoglobin dissociation curve.
- Because of its relatively steep and linear configuration, large amounts of carbon dioxide can be loaded or unloaded with only small changes in carbon dioxide partial pressure.
- Blood has a substantially greater capacity to carry carbon dioxide than oxygen because carbon dioxide is highly soluble and is transported in multiple forms.
Haldane Effect
- The Haldane effect describes the influence of oxygenation on carbon dioxide transport.
- Oxygenation of hemoglobin decreases its ability to bind carbon dioxide and hydrogen ions.
- Consequently, in the pulmonary capillaries, oxygen uptake promotes the release of carbon dioxide from blood into the alveoli.
- Conversely, in systemic tissues, release of oxygen from hemoglobin increases the capacity of blood to carry carbon dioxide.
- Thus, at any given carbon dioxide partial pressure, blood with a lower oxygen saturation contains more carbon dioxide than oxygenated blood.
- The Haldane effect enhances carbon dioxide loading in peripheral tissues and facilitates efficient carbon dioxide elimination in the lungs.
Bohr Effect
- The Bohr effect refers to the reduction in hemoglobin affinity for oxygen caused by increased carbon dioxide concentration and decreased pH.
- In metabolically active tissues, carbon dioxide enters the blood and generates hydrogen ions, lowering blood pH.
- The resulting acidosis shifts the oxygen-hemoglobin dissociation curve to the right.
- Increased tissue temperature further contributes to this rightward shift.
- A rightward shift increases P50 and promotes the release of oxygen from hemoglobin to tissues.
- Deoxygenated hemoglobin also binds hydrogen ions more readily, facilitating buffering within erythrocytes.
- Therefore, the Bohr effect enhances tissue oxygen delivery while simultaneously promoting carbon dioxide uptake by blood.
Important Questions
- 1. Long essay questions commonly asked in examinations include:
- Describe the mechanisms involved in the transport of oxygen from the lungs to the tissues.
- Describe the mechanisms involved in the transport of carbon dioxide from the tissues to the lungs.
- Oxygen-hemoglobin dissociation curve, carbon dioxide dissociation curve, chloride shift, P50, Haldane effect, and Bohr effect are frequently asked as short-answer questions.
- In viva voce examinations, the following direct questions may be asked:
- State Henry’s law.
- In what forms is oxygen transported in blood?
- How is oxyhemoglobin formed?
- What is the oxygen-carrying capacity of hemoglobin?
- What are the different phases of the oxygen-hemoglobin dissociation curve?
- What is the physiological significance of the plateau phase of the oxygen-hemoglobin dissociation curve?
- What factors affect the affinity of hemoglobin for oxygen?
- How does temperature affect the oxygen-hemoglobin dissociation curve?
- How does pH affect the oxygen-hemoglobin dissociation curve?
- How does carbon dioxide affect the oxygen-hemoglobin dissociation curve?
- How does 2,3-diphosphoglycerate affect the oxygen-hemoglobin dissociation curve?
- What factors influence erythrocyte 2,3-diphosphoglycerate concentration?
- What is the role of myoglobin in oxygen transport?
- How does carbon monoxide affect oxygen transport?
- How does carbon monoxide poisoning produce hypoxia?
- What factors shift the oxygen-hemoglobin dissociation curve to the right?
- What factors shift the oxygen-hemoglobin dissociation curve to the left?
- Define oxygen saturation.
- What is oxygen extraction?
- Why is oxygen content clinically important in patients with anemia?
- How is hemoglobin oxygen saturation measured?
- In what forms is carbon dioxide transported in blood?
- Why is the hematocrit of venous blood higher than that of arterial blood?
- What is chloride shift?
- What is Hamburger shift?
- What is the Haldane effect?
- What is the Bohr effect?
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