Vita Servitium 2027 Physiology PDF - Transport of Oxygen and Carbon Dioxide

the O2 bound to Hgb and the dissolved PHYSIOLOGY O2. (Berne and Levy) Oxygen saturation TRANSPORT OF OXYGEN AND...

the O2 bound to Hgb and the dissolved PHYSIOLOGY O2. (Berne and Levy) Oxygen saturation TRANSPORT OF OXYGEN AND ○ Amount of O2 bound to Hgb relative to CARBON DIOXIDE IN BLOOD AND the maximal amount of O2 (100% O2 TISSUE FLUIDS capacity) that can bind Hgb. (Berne and Dr. Ma. Victoria O. Masculino Levy) Oxygen capacity OUTLINE ○ Maximal amount of O2 that can bind Hgb. (Berne and Levy) I. General Review V. Clinical Chloride shift II. Oxygen Conditions ○ The exchange of negative ions which Transport Associated with maintains the electrical balance between III. The Oxygen- Alterations in O2 blood plasma and red blood cells. Hemoglobin Transport Haldane effect Dissociation VI. Case Studies ○ Promotes carbon dioxide transport Curve VII. References Bohr effect IV. Carbon Dioxide VIII. Appendices and ○ Promotes oxygen transport Transport Terminologies Respiratory exchange ratio ○ The ratio of CO2 output to O2 uptake. Utilization coefficient ○ The percentage of the blood that gives I. GENERAL REVIEW up its O2 as it passes through the tissue Henry’s law capillaries. ○ The quantity of a gas that will dissolve in PRESSURE OF OXYGEN AND CARBON DIOXIDE a liquid (e.g. blood) is proportional to the IN THE LUNGS, BLOOD, AND TISSUES partial pressure of the gas and its solubility coefficient. The unit of concentration for a dissolved gas is mL PRESSURE GRADIENT ○ responsible for movement of gases of gas/100mL blood. ○ gases travel from high pressure gradient Dalton’s Law to lower pressure gradient ○ Partial pressure = total pressure x OXYGEN fractional coefficient ○ Oxygen diffuses from the alveoli into the Acetazolamide pulmonary capillary blood because PO2 ○ A carbonic anhydrase inhibitor that in the alveoli is greater than the PO2 in reduces CO2 transport from tissue the pulmonary capillary blood. ○ In the other tissues of the body, PO2 in Carbonic anhydrase the capillary blood is greater than the ○ An enzyme that catalyzes CO2 and water tissue PO2 causing the O2 to diffuse into reaction leading to the increase of the surrounding cells. reaction rate CARBON DIOXIDE Venous admixture ○ Metabolism of O2 in the tissue cells ○ Blood combined in the pulmonary veins causes a rise in the PCO2 of the tissues with the oxygenated blood from the causing the CO2 to diffuse into the surrounding tissue capillaries. alveolar capillaries In the lungs, PCO2 is higher in the Oxygen content pulmonary capillary blood ○ The O2 content in the blood is the sum of 1|11 PHYSIOLOGY: LESSON 15 | CPU-COM | VITA SERVITIUM  causing CO2 to diffuse to the alveoli. ○ When the blood reaches the lungs, the CO2 diffuses into the alveoli because the PCO2 in the pulmonary capillary blood is greater than that in the alveoli. Table 1. Partial Pressure of O2 and CO2 Gas Dry Humidified Alveolar Systemic Mixed Inspired Tracheal Air Arterial Venous Air Air Blood Blood PO2 160 150 100 100* 40 Addition of O2 has Blood has O2 has H2O diffused equilibrat diffused decreases from ed with from Figure 1. Transport of O2 in the Arterial Blood (Changes in PO2 in the PO2 alveolar alveolar arterial pulmonary capillary blood, systemic arterial blood, and systemic air into air (is blood into capillary blood, demonstrating the effect of “venous admixture.”) pulmona "arterializ tissues, ry ed") decreasin capillary g the PO2 blood, of venous About 98% of the blood that enters the left decreasi blood atrium from the lungs has just passed through ng the the alveolar capillaries and has become PO2 of alveolar oxygenated up to a PO2 of about 104 mmHg. air Another 2% of the blood has passed from the aorta through the bronchial circulation, which PCO2 0 0 40 40 46 CO2 has Blood has CO2 has supplies mainly the deep tissues of the lungs and been equilibrat diffused is not exposed to lung air. added ed with from from alveolar tissues Shunt flow - blood that is shunted past the gas pulmona air into exchange areas. Upon leaving the lungs, the PO2 ry venous of the shunt blood is approximately that of capillary blood, blood increasin normal systemic venous blood—about 40 mm into g the Hg. alveolar PCO2 of When this blood combines in the pulmonary air venous blood veins with the oxygenated blood from the alveolar capillaries, venous admixture of blood *Actually, slightly < 100 mmHg because of "physiologic shuts" causes the PO2 of the blood entering the left heart and pumped into the aorta to fall to about 95 mmHg. 2|11 PHYSIOLOGY: LESSON 15 | CPU-COM | VITA SERVITIUM  ○ Therefore, during exercise, even with a shortened time of exposure in the capillaries, the blood can still become almost fully oxygenated because the blood normally stays in the lung capillaries about three times as long as needed to cause full oxygenation. Figure 3. Diffusion of O2 from the Peripheral Tissue Capillary to the Tissue Cells. (PO2 in interstitial fluid = 40 mm Hg; in tissue cells, PCO2 = Figure 2. Uptake of O2 by the Pulmonary Capillary Blood 23 mm Hg.) (The curve in this figure was constructed from data in Milhorn HT Jr. Pulley PE Jr: A theoretical study of pulmonary capillary gas exchange When the arterial blood reaches the peripheral and venous admixture. Biophys J 8:337, 1968.) tissues, its PO2 in the capillaries is still 95 mm Hg. The interstitial fluid that surrounds the tissue During strenuous exercise, a person’s body may cells averages only 40 mm Hg. require as much as 20 times the normal amount of oxygen and the time that the blood remains in Thus, there is a large initial pressure difference the pulmonary capillary may be reduced to less that causes O2 to diffuse rapidly from the than one-half normal due to the increased capillary blood into the tissues—so rapidly that the capillary PO2 falls almost to equal the 40 mm cardiac output. Hg pressure in the interstitium. Because of the great safety factor for diffusion of O2 through the pulmonary membrane, the Therefore, the PO2 of the blood leaving the tissue blood still becomes almost saturated with O2 by capillaries and entering the systemic veins is the time it leaves the pulmonary capillaries due also about 40 mm Hg. to the following: ○ The diffusing capacity for oxygen increases almost threefold during II. OXYGEN TRANSPORT exercise. ○ This results mainly from the increased surface area of capillaries participating ADULT HEMOGLOBIN in the diffusion and from a more nearly ideal ventilation-perfusion ratio in the Globular protein of 4 subunits. upper part of the lungs. Each subunit contains a heme moiety which is ○ Under non-exercising conditions, the an iron-containing porphyrin. blood becomes almost saturated with The iron is in ferrous state (Fe2+) and binds with oxygen by the time it has passed O2. through one-third of the pulmonary Each subunit has a polypeptide chain: capillary and little additional O2 normally ○ 2 alpha chains enters the blood during the latter ○ 2 beta chains two-thirds of its transit. 3|11 PHYSIOLOGY: LESSON 15 | CPU-COM | VITA SERVITIUM  Oxygen molecules combine loosely and reversibly with the heme portion of hemoglobin When PO2 is high, as in the pulmonary capillaries, O2 binds with the hemoglobin. When PO2 is low, as in the tissue capillaries, O2 is released from the hemoglobin B. OXYGEN TRANSPORT Oxygen is transported in these forms: ○ Dissolved in solution ○ Bound to hemoglobin (predominant form) Figure 5. Leftward Shift (increased affinity) and Rightward Shift (decreased affinity) of the Oxygen-hemoglobin dissociation curve. A. FACTORS THAT AFFECT THE III. THE OXYGEN-HEMOGLOBIN OXYGEN-HEMOGLOBIN DISSOCIATION DISSOCIATION CURVE CURVE Shift to the Decrease in pH* right Increased CO2 concentration Increase in blood temperature Increase in DPG (2,3- diphosphoglycerate) Increased uptake of oxygen in lungs Shift to the Increase in pH* left Decrease in temperature Decrease in DPG (2,3- diphosphoglycerate) Decrease in CO2 concentration Figure 4: Oxygen-hemoglobin Dissociation Curve. Increased oxygen release to tissue A plot of PO2 versus % saturation of hemoglobin. *pH: from normal value of 7.4 to 7.2 The curve demonstrates a progressive increase in the percentage of hemoglobin bound with O2 as blood PO2 increases, which is called the percent saturation of hemoglobin. The sigmoid shape of the curve is the result of the change in affinity of hemoglobin as each successive O2 molecule binds to the heme site. 4|11 PHYSIOLOGY: LESSON 15 | CPU-COM | VITA SERVITIUM  BPG mechanism can be crucial for adapting to hypoxia, particularly in cases of poor tissue blood flow. C. THE BOHR EFFECT A shift in the oxygen-hemoglobin dissociation curve in response to changes in blood CO2 and H+ has significant effects in enhancing oxygenation of the blood in the lungs and in enhancing release of O2 from the blood to the tissues. IN THE TISSUES As the blood passes through the tissues, CO2 diffuses from the tissue cells into the blood. Diffusion increases the blood PCO2, which in turn Figure 6. Left Shift of the Oxygen-hemoglobin Dissociation Curve and raises the blood H2CO3 (carbonic acid) and the Right Shift of the Oxygen-hemoglobin Dissociation Curve. hydrogen ion concentration. Shifting the O2-hemoglobin dissociation curve to the right and downward, forcing O2 away from the hemoglobin Delivering increased amounts of O2 to the tissues. IN THE LUNGS Arriving at the lungs, the CO2 diffuses from the blood into the alveoli. Diffusion reduces the blood PCO2 and decreases the hydrogen ion concentration, shifting the O2-hemoglobin dissociation curve to the left and upward. The quantity of O2 that binds with the hemoglobin at any given alveolar PO2 becomes considerably increased. Allowing greater O2 transport to the tissues. Figure 7. Fetal hemoglobin has a higher affinity to Oxygen than the Adult Hemoglobin. IV. CARBON DIOXIDE TRANSPORT B. EFFECT OF BPG TO CAUSE RIGHTWARD SHIFT A. DIFFUSION OF CO₂ FROM THE PERIPHERAL OF THE OXYGEN-HEMOGLOBIN DISSOCIATION TISSUE CELLS INTO THE CAPILLARIES AND FROM CURVE THE PULMONARY CAPILLARIES INTO THE Normal BPG in blood shifts the O2-hemoglobin ALVEOLI dissociation curve slightly to the right. When O₂ is used by the cells all of it becomes In prolonged hypoxic conditions, BPG quantity CO₂ and this transformation leads to increased significantly increases, shifting the curve even PCO₂. farther right. CO₂ diffuses from cells into capillaries and then ○ This shift results in O2 release to tissues is carried by blood to the lungs. at pressures up to 10 mm Hg higher than ○ CO₂ can diffuse about 20 times as without increased BPG. rapidly as O₂. 5|11 PHYSIOLOGY: LESSON 15 | CPU-COM | VITA SERVITIUM  This occurs within a short distance (about one-third) into the capillaries. ○ Rapid equilibration of PCO2 between pulmonary capillary blood and alveolar air. Figure 8. Uptake of Carbon dioxide by the blood in the capillaries. B. EFFECT OF TISSUE METABOLISM AND (PCO2 in tissue cells= 46 mm Hg, and in interstitial fluid = 45 mm Hg) BLOOD FLOW TO TISSUE PCO2 The CO2 pressures are approximately the following: ○ Intracellular PCO2 = 46 mm Hg ○ Interstitial PCO2 = 45 mm Hg ○ Pressure differential = only 1mmHg Arterial Blood PCO2 (entering tissue) = 40 mm Hg. Venous Blood PCO2 (leaving the tissue) = 45 mm Hg. Tissue Capillary Blood Equilibrium: Tissue capillary blood reaches equilibrium with the interstitial PCO2 of 45 mm Hg. Blood Entering Pulmonary Capillaries (Arterial End) PCO2 = 45 mm Hg. Alveolar Air PCO2 = 40 mm Hg. Figure 10. Effect of blood flow and metabolic rate on peripheral tissue ○ Pressure Difference: There is a 5 mm Hg PCO2. pressure difference that drives CO2 diffusion from the pulmonary capillaries Decreased Blood Flow (Point A to Point B): into the alveoli. ○ Blood flow reduced to one quarter of normal. ○ Peripheral tissue PCO2 increases from 45 mm Hg to 60 mm Hg. Increased Blood Flow (Point A to Point C): ○ Blood flow increased to six times normal. ○ Interstitial PCO2 decreases from 45 mm Hg to 41 mm Hg, approaching the arterial blood PCO2 (40 mm Hg). 10-fold Increase in Tissue Metabolic Rate: ○ Elevates interstitial fluid PCO2 significantly at all blood flow rates. Decrease in Tissue Metabolic Rate (One-quarter normal): ○ Interstitial fluid PCO2 decreases to around 41 mm Hg, closely approaching arterial blood PCO2 (40 mm Hg). Figure 9. Diffusion of carbon dioxide from the pulmonary blood into C. CARBON DIOXIDE TRANSPORT FORMS the alveolus. Dissolved CO₂, small amount – 7% ○ Account for the smallest percentage PCO2 in Pulmonary Capillary Blood Decreases (7%). ○ It rapidly approaches the alveolar PCO2 ○ Upon reaching the lungs, it diffuses into of 40 mm Hg. the alveolar air and is exhaled. 6|11 PHYSIOLOGY: LESSON 15 | CPU-COM | VITA SERVITIUM  Carbamino hemoglobin (HB-CO₂) – 23% F. CARBON DIOXIDE DISSOCIATION CURVE ○ A higher percentage (23%) of CO₂ combines with carbamino compounds. Bicarbonate ions (HCO3 - ) – 70% ○ The greatest percentage of which CO₂ is transported. D. CHLORIDE SHIFT Exchange of negative ions (HCO3- and Cl-) maintains electrical balance between blood plasma and red blood cells (RBCs). Dissolved CO2 in blood reacts with water to create carbonic acid (H2CO3). Inside RBCs, the enzyme carbonic anhydrase Figure 12. Carbon dioxide Dissociation Curve. catalyzes CO2 and water reaction, increasing the reaction rate 5000-fold. Normal Blood PCO₂ Range: Carbonic acid in RBCs breaks down into ○ Arterial blood: 40 mm Hg hydrogen (H+) and bicarbonate ions (HCO3−). ○ Venous blood: 45 mm Hg H+ mostly binds to hemoglobin in RBCs as it Normal Total CO2 Concentration in Blood: acts as a strong acid-base buffer. ○ Approximately 50 volumes percent Many HCO3− diffuse from RBCs into the Exchange of CO2 during Normal Transport: plasma, and chloride ions move into RBCs, Only about 4 volumes percent of the total CO2 is Resulting in higher chloride content in venous exchanged during the typical journey from RBCs compared to arterial RBCs, known as the tissues to lungs. chloride shift. CO2 Concentration Changes: Bicarbonate-Chloride Carrier Protein shuttles ○ Increases to around 52 volumes percent the ions in opposite directions at rapid velocities while passing through tissues. Administering a carbonic anhydrase inhibitor like ○ Decreases to about 48 volumes percent acetazolamide reduces CO2 transport from as it moves through the lungs. tissues. Result: Tissue PCO2 may increase to 80 mm Hg G. THE HALDANE EFFECT from the normal 45 mm Hg, highlighting the The binding of O₂ with Hb tends to displace CO₂ importance of carbonic anhydrase in CO2 from the blood, enhancing O₂ transport. transport. Combination of O₂ with Hb in the lungs causes the Hb to become a stronger acid, displacing CO₂ from the blood into the alveoli in 2 ways: ○ More highly acidic Hb has less tendency to combine with CO₂ to form carbaminohemoglobin, thus displacing much of CO₂ that is present in carbamino form from the blood. ○ Increased acidity of Hb causes release of H+, which binds with HCO3- to form H2CO3, dissociating into H₂O and CO₂ and the latter is released from the blood to the alveoli. In the tissue capillaries: causes increased pick-up of CO₂ because of O₂ removal from the hemoglobin. In the lungs: causes increased release of CO₂ because of O₂ pick-up in the hemoglobin. Figure 11. Chloride Shift. 7|11 PHYSIOLOGY: LESSON 15 | CPU-COM | VITA SERVITIUM  CARBON MONOXIDE SOURCES V. CLINICAL CONDITIONS ASSOCIATED WITH Car in the garage (Ventilation of place) ALTERATIONS IN O2 TRANSPORT Vehicles in the streets Use of coal in power plants A. CARBON MONOXIDE POISONING Appliances at home CO combines with hemoglobin at the same point Wooden stove of the hemoglobin molecule as does O₂, thus displacing O₂ and decreasing the O₂-carrying CARBON MONOXIDE EXPOSURE capacity of the blood. CO is called the “silent killer” because if early CO binds to hemoglobin with about 250 times as signs are ignored, a person may lose much tenacity as of O₂. consciousness and be unable to escape to safety. Under certain conditions, lethal concentrations of CO have occurred within 10 minutes in the confines of a closed garage with a car engine running inside or when a portable generator is used in or near a house. The health effects of breathing in CO depend on: ○ The concentration of CO in the air. ○ The duration of exposure. ○ The health status of the exposed person. ○ People with heart diseases are more likely to be affected by CO even in low concentrations. First signs of exposure: ○ Mild headache Figure 13. Carbon monoxide-hemoglobin dissociation curve. Note the ○ Breathlessness with moderate exercise extremely low carbon monoxide pressures at which carbon monoxide combines with hemoglobin. Continued exposure can lead to flu-like symptoms: ○ More severe headaches ○ Dizziness ○ Tiredness ○ Nausea that may progress to confusion ○ Irritability ○ Impaired judgment, memory, and coordination Figure 14. Effect of carbon monoxide on the hemoglobin-O₂ dissociation curve. 8|11 PHYSIOLOGY: LESSON 15 | CPU-COM | VITA SERVITIUM  acid (vitamin B9)] Blood transfusion (If hemoglobin is below 10g/dL with blood loss) VI. CASE STUDIES CASE 1 Francisca, a freshman at CPU Med School has Figure 15. Cherry-red skin color produced by CO poisoning. symptoms of light-headedness, easy fatigability, and a Usually occurs when lethal doses have been inhaled light complexion which she attributed to her being a Chinese mestiza. She prefers fast foods and skips meals. Treatment of Carbon Monoxide Poisoning Pure O₂ BP: 90/60, CR: 120, RR: 18, Temp: 37 C ○ At high alveolar pressure displaces CO PPE: pale skin, pale conjunctiva rapidly from its combination with Hb. Administration of 5% CO₂ Diagnosis: Anemia ○ Strongly stimulates the respiratory center in the brain, increasing the alveolar CASE 2 ventilation reducing the alveolar CO D. ANEMIA Peter was trapped at the CPU compound because of MECHANISM heavy downpour and slept overnight inside the car with ○ Low hemoglobin, decreasing the O₂ the car air conditioning unit on. In the morning, the carrying capacity of the blood. security guards found him disoriented. SYMPTOMS (may vary depending on the cause At the ER: BP: 90/60, CR: 98, RR: 18 and the Body of anemia but may include:) Temperature is 37ᵒC. ○ Fatigue ○ Weakness PPE: Disoriented, Cherry Red Skin ○ Pale skin (pallor) Diagnosis: Carbon Monoxide Poisoning ○ Fast/irregular heartbeat ○ Shortness of breath CASE 3 ○ Chest pain ○ Dizziness ○ Cognitive problems Tito Jimmy, a 40-year-old male, was treated in the ○ Cold hands and feet emergency department after 48 hours for severe lacerations and possible abdominal injuries sustained in ○ Headache an automobile accident. He was admitted to the DIAGNOSIS hospital for observation and further evaluation. On ○ History and physical Examination admission, a complete blood count (CBC) was ordered. ○ Complete Blood Count (CBC) ○ Peripheral Blood Smear (PBS) Diagnostic test results: TREATMENT (Depends on the underlying cause) RBC: 2.9x106 = low ○ Generally: Hgb: 10 g/dL = low (NV: 13.5-18 g/dL) Hct: 36.8 % = low Lifestyle and dietary (40-54%) modifications WBC: 12x10^9/L = high (3.6-11) Vitamin supplementations [ferrous sulfate (FeSO4) and folic 9|11 PHYSIOLOGY: LESSON 15 | CPU-COM | VITA SERVITIUM PLT: 500x10^9/L = high Tissue Hypoxia (150-450) MCV: 90 fL = normo, normo Tissue hypoxia will trigger an increase in 2,3-BPG MCH: 27 pg that shifts the O2 dissociation curve to the right MCHC: 32 g/dL (decreased O2 affinity of hemoglobin) and results in increased delivery of oxygen to tissue. PBS: ○ Thus with persistent anemia, the body Normal RBC morphology, although some develops physiologic adaptations to polychromatophilia was noted. increase the oxygen-carrying capacity of a reduced amount of hemoglobin, which improves oxygen delivery to tissue. ○ Reduced delivery of oxygen to tissues caused by reduced hemoglobin concentration elicits an increase in erythropoietin secretion by the kidneys. Erythropoietin stimulates the RBC precursors in the bone marrow, which leads to the release of more RBCs into the circulation. ○ It should be noted that with rapid blood loss, the hemoglobin and hematocrit may be initially unchanged because there is balanced loss of plasma and cells. However, as the drop in blood volume is compensated for by movement of fluid from the extravascular to the intravascular compartment or by administration of resuscitation fluid, there will be a dilution of RBCs and anemia. Diagnosis: Anemia Anemia Oxygen-Hgb Dissociation Curve Greek word “anaimia” = means “without blood” “Not a disease but a manifestation of underlying disease or deficiency” Operationally: a reduction in the hemoglobin content of blood that can be caused by a decrease in RBCs, hemoglobin, and hematocrit below the reference interval. Functionally: a decrease in the oxygen-carrying capacity of the blood, resulting in tissue hypoxia. Acute Anemia is due to blood loss or hemolysis. If blood loss is mild, enhanced O2 delivery is achieved through changes in the O2–hemoglobin dissociation curve mediated by a decreased pH or increased CO2 (Bohr effect). 10|11 PHYSIOLOGY: LESSON 15 | CPU-COM | VITA SERVITIUM  CASE 4 R Macromolecule Reactions Utilization Kika was tired from her graveyard shift and decided to sleep in her car overnight. She was then found in the 1.00 Person uses 1 molecule of morning, disoriented and dizzy, with cherry red skin. She carbohydrates for body CO2 is formed in felt dizziness, weakness, and nausea. metabolism every 1 O2 molecule Diagnosis: Carbon Monoxide Poisoning consumed VII. REFERENCES 0.7 Person uses fats for O2 reacts to H+ metabolism ions to form H2O OmVi trans Respiratory Guyton and Hall Textbook of Medical Physiology quotient in 14th ed., Chapter 41, pp. 521-530 chemical Dr. Masculino’s Powerpoint Presentation reaction in Group reports tissues = 0.7-1.00 VIII. APPENDICES AND TERMINOLOGIES 0.825 Person who consumes average amounts of O₂ Content - O₂ content in blood is the sum of carbohydrates, fats, the O2 bound to Hgb and the dissolved O₂ and proteins (Berne and Levy). O₂ Capacity - maximal amount of O₂ that can bind Hgb (Berne and Levy). O₂ Saturation - amount of O₂ bound to Hgb relative to the maximal amount of O₂ (100% O₂ capacity) that can bind Hgb (Berne and Levy). Chloride Shift - exchange of negative ions which maintains the electrical balance between blood plasma and red blood cells. Bohr Effect - shift in the O₂-Hgb dissociation curve in response to change in blood CO₂ and H+ enhancing oxygenation of the blood in the lungs and release of O₂ from the blood to the tissue. Haldane Effect - binding of O₂ with Hgb promoting release of CO₂. Respiratory Exchange Ratio - ratio of expired CO₂ to O₂ uptake (Berne and Levy). Under normal conditions, is 0.8 (80 CO₂ to 100 O₂). Utilization coefficient - percentage of the blood that gives up its O₂ as it passes through the tissue capillaries (Guyton). 𝑅 𝑜𝑓 𝐶𝑂2 𝑜𝑢𝑡𝑝𝑢𝑡 𝑅= 𝑅 𝑜𝑓 𝑜𝑥𝑦𝑔𝑒𝑛 𝑢𝑝𝑡𝑎𝑘𝑒 11|11 PHYSIOLOGY: LESSON 15 | CPU-COM | VITA SERVITIUM