BIOM2012 Systems Physiology: Respiratory System L4 - Student Notes PDF

BIOM2012 - Systems Physiology: Respiratory System L4 Dr. Jacky Suen [email protected] Credit: A/Prof Stephen Anderson and Dr. Hardy Ernst Learning Objectives Pulmonar...

BIOM2012 - Systems Physiology: Respiratory System L4 Dr. Jacky Suen [email protected] Credit: A/Prof Stephen Anderson and Dr. Hardy Ernst Learning Objectives Pulmonary Ventilation and Respiratory mechanics Gas exchange Gas transport Blood pH regulation Control of Respiration Gas Transport: O2 and CO2 O2 and CO2 are transported between lungs and tissues via blood, BUT through different mechanisms Only 2% of O2 in the blood is dissolved; the remaining 98% is transported in combination with haemoglobin (Hb). The majority of CO2 is transported in the blood as bicarbonate. reduced Hb O2 transport  Dissolved O2 -> PO2 PO2 affects % haemoglobin saturation Plateau region: Large changes in PO2, small changes in % Hb saturation Why is this important? High attitude -> reduce O2 A decrease of 20 mmHg PO2 resulted in 5% drop of Hb saturation  Dissolved O2 -> PO2 PO2 affects % haemoglobin saturation Steep curve: Small changes in PO2, large changes in % Hb saturation During exercise, tissues can have even lower PO2 A decrease of 20 mmHg resulted in >50% drop in Hb saturation Internal Respiration (at tissues)  In theory, carbon dioxide is CO2 transport transported in the blood in five forms, although only the first three are important: Dissolved - 7% (plasma + Hb) Chemically bound to Hb (carbaminohaemoglobin) - 23% Bicarbonate ions (HCO3-) - 70% Carbonic acid (H2CO3) - not quantitatively important Carbonate (CO3-) - not quantitatively in erythrocytes most CO2 converted to HCO3 important  CO2 transport In theory, carbon dioxide is transported in the blood in five forms, although only the first three are important: Quick Quiz: Dissolved - 7% (plasma + Hb) Chemically bound to Hb What % of O2 dissolved in plasma and (carbaminohaemoglobin) - 23% what % binds to Hb? ions (HCO ) - 70% Bicarbonate 3- Carbonic acid (H2CO3) - not quantitatively important Carbonate (CO3-) - not quantitatively in erythrocytes most CO2 converted to HCO3 important Gas Transport  Internal Respiration (at tissues) In the tissues: O2 transported as oxyhemoglobin is released and O2 diffuses into the tissue for cellular respiration. Hb binds with hydrogen ions (H+) to form HHb. CO2 from tissue diffuses into the plasma and RBCs. In RBCs, the enzyme carbonic anhydrase rapidly converts CO2 and water into carbonic acid (H2CO3), which splits into bicarbonate (HCO3-) and hydrogen (H+). Bicarbonate (HCO3-) quickly diffuses from RBCs into plasma. To counterbalance the rapid outrush of negative bicarbonate ions from the RBCs, chloride ions (Cl-) move from the plasma into the RBCs to maintain electrical neutrality - “chloride shift”  External Respiration (at lungs) At the lungs the processes are reversed: Inhaled oxygen diffuses from the alveoli into the capillaries and erythrocytes, combining with HHb to form oxyhemoglobin (HbO2) and H+. Bicarbonate ions move into the RBCs and bind with H+ to form carbonic acid. Cl- diffuses out of the cell into plasma - reverse chloride shift Carbonic acid is split by carbonic anhydrase to release CO2 CO2 diffuses from the blood to alveoli for removal via expiration. Bohr effect During exercise Definition: The influence of CO2 and acid on the release of O2. CO2 and H+ can combine reversibly with Hb The result is a change in the molecular structure of Hb that reduces the affinity for O2. i.e. increase in [CO2] or decrease in pH à decrease in Hb’s O2 binding capacity à help offload more O2 Note: % Hb saturation refers only to the extent to which Hb is combined with O2, not any other gases. (Sherwood, Human Physiology, fifth edition) Haldane effect Increase in [O2] decrease Hb’s CO2 binding capacity Deoxyhaemoglobin (or reduced Hb) has greater affinity for H+ than haemoglobin Therefore, unloading O2 facilitates Hb pickup CO2-generated H+. This help maintains blood pH, as Hb mop up most of the H+ generated at the tissue level. (Sherwood, Human Physiology, fifth edition) Bohr effect and Haldane effect work in synchrony Bohr effect and Haldane effect work in synchrony Increased CO2 and H+ cause increased O2 release (Bohr effect) Increased O2 release from Hb in turn causes increased CO2 and H+ uptake by Hb (Haldane effect) As reduced Hb returns to the lungs to pick up O2, it brings CO2 and H+ with it. (Sherwood, Human Physiology, fifth edition)  Bohr effect – increase in CO2 lowers Hb-binding of O2 At tissue Lower O2 Higher CO2 Bohr Effect  Bohr effect – increase in CO2 lowers Hb-binding of O2 At tissue Lower O2 Higher CO2 Bohr Effect More deoxyhaemoglobin  Bohr effect – increase in CO2 lowers Hb-binding of O2 Haldane effect – deoxyhaemoglobin has higher binding of CO2 At tissue Lower O2 Higher CO2 LUNG Tissue (40 mmHg) (45 mmHg) More deoxyhaemoglobin  Bohr effect – increase in CO2 lowers Hb-binding of O2 Haldane effect – Hb free of O2 has higher binding of CO2 At tissue: Lower PO2 à Hb unloads O2 à more deoxy-Hb High PCO2 à higher CO2 bound to Hb à reduced Hb binding of O2 (Bohr effect) à Hb unloads even more O2 à even more deoxy-Hb Deoxy-Hb has higher binding of CO2 (Haldane effect) à able to carry more CO2 toward the Lungs At lungs: High PO2 à increased binding of O2 à more oxyhaemoglobin Low PCO2 à blood unload CO2 into lungs à lower PCO2 à increased Hb binding of O2 (Bohr effect) As Hb get oxygenated, their binding of CO2 drops à offload more CO2 into lungs (Haldane effect) % Hb saturation ≠ Amount of O2 transported Normal blood 15 g Hb/100 ml blood O2 carrying capacity = 20 ml O2 / 100 ml blood (15 x 1.34 ml O2 / 100ml blood) O2 content of arterial blood = 20 ml O2 / 100 ml blood (Hb saturation with O2 = 100 % at a PO2 = 100mmHg) O2 content of venous blood = 15 ml O2 / 100 ml blood (Hb saturation with O2 = 75 % at a PO2 = 40mmHg) % Hb saturation ≠ Amount of O2 transported Anemic blood 7.5 g Hb/100 ml blood O2 carrying capacity = 10 ml O2 / 100 ml blood (7.5 x 1.34 ml O2 / 100ml blood) O2 content of arterial blood = 10 ml O2 / 100 ml blood (Hb saturation with O2 = 100 % at a PO2 = 100mmHg) O2 content of venous blood = 7.5 ml O2 / 100 ml blood (Hb saturation with O2 = 75 % at a PO2 = 40mmHg) Quick Quiz An anaemic patient is presented at ED, due to massive blood loss. Would giving this patient an oxygen mask help? Quick Quiz An anaemic patient is presented at ED, due to massive blood loss. Would giving this patient an oxygen mask help? Sudden decompression of an aircraft cabin at 9000m altitude ??? ??? ??? ??? PO2 in air @ 9000m = 47 mm Hg Sudden decompression of an aircraft cabin at 9000m altitude Oxygen is less than 30% of that at sea level. Drastically reduced Hb saturation with O2. O2 deprivation of the brain results in unconsciousness. Death from hypoxia PO2 in air @ 9000m = 47 mm Hg PO2 in alveoli @ 9000m = 18 mm Hg | Medical Physiology | Effect of Breathing Pure Oxygen on Alveolar PO2 at Different Altitudes Summary: Do you know the partial pressure of O2 and CO2 at various part of respiratory system? And factors that regulate these numbers? Are you clear of the relationship between PO2, haemoglobin saturation and oxygen-carrying capacity? Do you know the difference between O2 and CO2 gas transport? Haemoglobin saturation with O2 decreases as A. PO2 increases B. [H+] decreases C. PCO2 increases D. PCO2 decreases E. body temperature decreases What is the most important factor determining how much oxygen binds to haemoglobin? A. systemic blood pressure B. pH of the blood C. PCO2 of the blood D. PO2 of the blood E. diastolic blood pressure If alveolar PO2 is 130 mmHg, what will be the blood PO2 leaving the lungs? What impact will that have on % Hb saturation? A. 130 mmHg, significantly higher B. 130 mmHg, around the same C. 100 mmHg, significantly higher D. 100 mmHg, around the same E. 100 mmHg, lower T/F – oxygen transport is mostly through plasma T/F – haemoglobin is not involved in carbon dioxide transport T/F – partial pressure of oxygen is linearly proportional to haemoglobin saturation T/F – amount of oxygen dissolved in plasma has very little impact on oxygen transport Function Location Influencing factors Ventilation Airways Airway resistance Lung compliance Alveolar surface tension Gas exchange Respiratory membrane Gas characteristics Pressure gradient Diffusion Coefficient Membrane characteristics V/Q matching Gas Transport Blood PO2, PCO2 Haemoglobin level and saturation Respiratory rate Learning Objectives Pulmonary Ventilation and Respiratory mechanics Gas exchange Gas transport This module does not cover cellular respiration Blood pH regulation Control of Respiration Learning Objectives Pulmonary Ventilation and Respiratory mechanics Gas exchange Gas transport Blood pH regulation Control of Respiration Internal Respiration (at tissues)  Blood pH buffering The normal physiological pH of blood is between 7.35 to 7.45. The CO2/HCO3- buffering reaction is the most important physiological system that regulates pH. Production of CO2 leads to an increase in H+ (more acid) Removal of CO2 leads to a decrease in H+ (more basic)  Acidosis - Alkalosis Production of CO2 leads to an increase in H+ (more acid) Removal of CO2 leads to a decrease in H+ (more basic) Pathophysiology Respiratory acidosis is a decrease in pH due to an increase pCO2, from decrease alveolar ventilation, decrease diffusion capacity or ventilation-perfusion mismatch. Respiratory alkalosis is an increase in pH due to a decrease in pCO2, from increased alveolar ventilation or hyperventilation. Note there are also metabolic causes of acid-base imbalance. Kidney compensation usually occurs. Davenport diagram Arterial Blood Gas Report Arterial blood gas report Pred Range Observed Temp 37 FiO2 0.21 Bar Pressure 760 pH 7.35 - 7.45 7.28 PaCO2 35 – 45 mm Hg 55 mm Hg PaO2 95 -100 mm Hg 78 mm Hg Bicarb 22 – 27 mM (mmol/L) 24 mM PA-aO2 < 10 mm Hg 3 mm Hg