Allied Science Physiology 09-10. Respiratory System. Lecture 4. Allied Science Physiology. Respiratory System. Lecture 4. 1 • Transported in 2 modes: a) 1.5% dissolved in plasma – At rest we consume 250 mlO2/min – CO = 5 l/min – O2 breathed per min: 1 liter – In arterial blood: 200ml O2 / 1 l of blood – 3 ml of O2 / 1l blood dissolves b) 98.5% bound to haemoglobin (Hb) – Hemoglobin located in red blood cells – 4 globins (structural; CO2 binding site) – 4 heme groups per haemoglobin (each with an iron atom) – Oxygen binds reversibly to heme group (iron) in Hb – Thus each hemoglobin can bind 4 O2 molecules – Amount of O2 bound to Hb is a function of the PO2 Allied Science Physiology. Respiratory System. Lecture 4. oxyhemoglobin deoxyhemoglobin Hb.O2 Hb + O2 Figure 17.6 Allied Science Physiology. Respiratory System. Lecture 4. 2 • Binding of oxygen to hemoglobin follows Law of Mass Action – More oxygen more binds to hemoglobin – Non-linear relationship • Positive cooperativity • Saturation of hemoglobin is a measure of how much oxygen bound to hemoglobin – 100% saturation all 4 binding sites on hemoglobin have oxygen bound to them • 98.5 % saturated in arterial blood (arterial PO2=100mmHg) • 75% saturated in mixed venous blood (venous PO2 = 40mmHg) • Summarised by: Hemoglobin-Oxygen dissociation curve Allied Science Physiology. Respiratory System. Lecture 4. Figure 17.7 Allied Science Physiology. Respiratory System. Lecture 4. 3 Figure 17.8 Allied Science Physiology. Respiratory System. Lecture 4. • Rightward shift (unloading, decreased affinity): – Tissue level – H+ ( pH, Bohr effect) – PCO2 – Temperature – 2,3 DPG • Leftward shift (loading, increased affinity): – Lung level – H+ ( pH, Bohr effect) – PCO2 – Temperature Figure 17.9 Allied Science Physiology. Respiratory System. Lecture 4. 4 • Increase in metabolic activity increases temperature • Increase in temperature decrease Hb affinity for O2 • Decrease affinity increases oxygen unloading in tissue Opposite effect at lung level Figure 17.10a Allied Science Physiology. Respiratory System. Lecture 4. • When oxygen binds to hemoglobin, hydrogen ions are released • Hb + O2 Hb.O2 + H+ • Active tissue produces H+ This increases oxygen unloading in tissue (equation to the left) Opposite effect at lung level Figure 17.10b Allied Science Physiology. Respiratory System. Lecture 4. 5 • CO2 reacts with Hb to form carbaminohemoglobin Hb + CO2 HbCO2 PCO2 PCO2 • Increased metabolic activity increases CO2 reaction to the right change in Hb conformation and decreases Hb affinity for O2 • Increases oxygen unloading in active tissue Opposite effect at lung level Figure 17.9 Allied Science Physiology. Respiratory System. Lecture 4. • 2,3-DPG = 2,3-diphosphoglycerate • Produced in red blood cells under conditions of low oxygen such as anemia and high altitude 2,3-DPG • High HbO2: inhibit DPG synthesis; Low HbO2: stim. DPG synthesis • In tissue: 2,3-DPG decreases affinity of hemoglobin for O2 enhancing O2 unloading At lung level: decreases affinity of Hb for O2 (negative side) Figure 17.9 Allied Science Physiology. Respiratory System. Lecture 4. 6 • Hemoglobin has greater affinity for carbon monoxide (CO) than for oxygen (24 times!) • Prevents oxygen from binding to hemoglobin • Toxic, can be fatal Allied Science Physiology. Respiratory System. Lecture 4. • 3 modes of transport: – 5 – 6% transported dissolved in plasma – 5-8% transported bound to hemoglobin – 86-90% transported dissolved in the plasma as bicarbonate ions Carbonic Anhydrase CO2 + H2O ----------------- H2CO3 H+ + HCO3Law of Mass Action: An increase in CO2 causes an increase in bicarbonate and hydrogen ions (note that bicarbonate is transported out of the erythrocyte into the plasma) Allied Science Physiology. Respiratory System. Lecture 4. 7 Figure 17.11 Allied Science Physiology. Respiratory System. Lecture 4. Oxygen decreases affinity of hemoglobin for carbon dioxide Figure 17.12 Allied Science Physiology. Respiratory System. Lecture 4. 8 Remember: -Haldane effect: O2 decreases affinity of Hb for CO2 -Bohr effect: Hb + O2 Hb.O2 + H+ -Carbomino effect: Hb + CO2 HbCO2 Figure 17.13 Allied Science Physiology. Respiratory System. Lecture 4. 9