Wk 18 Lecture - Transport of Oxygen & Carbon Dioxide PDF

y tor pira es R io- r d Ca Transport of Oxygen & Carbon Dioxide  y tor pira es R io- r d Ca...

y tor pira es R io- r d Ca Transport of Oxygen & Carbon Dioxide  y tor pira es R io- r d Ca Learning Outcomes discuss how oxygen is transported in the blood explain the importance of the oxyhaemoglobin dissociation curve explain the function of foetal haemoglobin and myoglobin relate gas transport mechanisms to the amount of oxygen and carbon dioxide that is in arterial and venous blood and measured clinically as blood gases outline the chemical reaction between carbon dioxide and water and its importance in the body describe how carbon dioxide is transported in the blood explain how the basic rate of ventilation is determined describe the factors that influence the rate and depth of ventilation explain the differing terms used to describe lung volumes and capacities begin to understand the relationship of respiratory load, capacity and drive  y tor pira es R io- r d Ca Oxygen Transport  y tor pira es R io- r d Ca This picture represents a close up of an alveoli wrapped by the capillary network https://simplebiologyy.blogspot.com/2015/01/fa ctors-controlling-exchange-of-gases-in-alveolar- capillaries.html  y tor pira es R io- r d Ca Transport of Oxygen From alveolus to tissue cell there are 3 different events: 1. Diffusion of O2 from alveolus into pulmonary blood 2. Transport of blood through arteries to tissue capillaries 3. Diffusion of O2 from the capillaries to tissue cells  y tor pira es Ca r dio- R Oxygen Carriage Majority of oxygen is carried in the red blood cells on the iron/haem molecule portion of the haemoglobin 1.5% of the total oxygen carried in the blood is dissolved in the plasma Hb saturated with O2 = oxyhaemoglobin Hb without O2 = deoxyhaemoglobin  y tor pira es R o- Ca r di Structure of Haemoglobin (Hb Hae Hae m m Each Haemoglobin protein consists of 4 Haem molecules which each combine with 2 molecules of oxygen = Hb4O8 Each RBC carries Haem approximately 280 Haem million Hb proteins This picture represents a molecular structure of haemoglobin http://www.chemistry.wustl.edu/~edudev/LabTutorials/He moglobin/MetalComplexinBlood.html  y tor pira es R io- Ca r d Haemoglobin Oxygen is carried by haemoglobin because: – It can upload O2 when O2 is plentiful – Easily transports O2 without offloading it unnecessarily – Offloads it when needed and adjusts the amount of O2 offloaded to suit demand  y tor pira s r dio- Re Oxygen Saturation Ca How ‘fully’ combined a Hb protein is with oxygen is termed oxygen saturation SaO2 arterial O2 saturation measured on a blood- gas machine SpO2 peripheral O2 saturation measured with a pulse oximeter Normal value? Oxygen saturation (SaO2 or SpO2) 95-99%  y tor pira es R o- Ca r di Gaseous Pressure in Alveoli Gas & Blood Alveolar Air Venous Blood Arterial Blood O2 104 mmHg / 40 mmHg / 100 mmHg / 14 kPa 5.3 kPa 13.3kPa CO2 40 mmHg / 45 mmHg / 40 mmHg / 5.3 kPa 6kPa 5.3 kPa N2 569 mmHg / 569 mmHg / 569 mmHg / 78 kPa 78 kPa 78 kPa Therefore, a higher pressure of oxygen in arterial blood will lead to a higher saturation level when compared to venous blood Arterial blood saturation = approx. 98.5% Venous blood saturation = approx. 75%  y tor io- Respira Affinity r d Ca Affinity means binding ability: 1. As O2 binds to Hb affinity for O2 increases 2. As O2 is released, Hb affinity for O2 decreases the greater the affinity of Hb for oxygen the more likely the oxygen is to be picked up (helps in the lungs) The lower the affinity of Hb for oxygen the  y tor pira es R o- Ca r di Definition of Partial Pressure The partial pressure is the pressure that one gas would exert if it occupied the volume of the mixture at the same temperature. The total pressure of a gas mixture is the sum of the partial pressures of each individual gas in the mixture.  y tor pira es R io- r d Ca Oxygen Dissociation Curve Shows the percentage of haemoglobin that is combined with oxygen at every oxygen pressure. The lower the partial pressure of oxygen (pO2) of the blood the lower the affinity of Hb for O2 and O2 is released to the tissues at a pH of 7.4 and at body temperature of 370C  y tor pira es R io- Ca r d The oxyhaemoglobin dissociation curve Percent of O2 unloaded by haemoglobin to Percent of oxygen saturation of tissues haemoglobin This picture represents the oxygen dissociation curve as an S shaped curve throughout the range of O2 partial pressures  y tor pira es Ca r dio- R Points to note Haemoglobin is fully saturated with oxygen when it leaves the lungs Normally haemoglobin is still 75% saturated after it has unloaded oxygen to the tissues There is a very large reserve to increase oxygen delivery if needed e.g. Exercise (saved O2)  y tor ira io- Resp Some values r d Ca PO2 KPa % (mm saturatio Hg) n of Hb 10 1.3 13.5 Percent of oxygen saturation of 20 2.7 35 30 4 57 O2 below 40 5.3 75 60mmhg 50 6.7 83.5 (8kPA) 60 8 89 is termed haemoglobin 70 9.3 92.7 80 10. 94.5 type 1 7 ‘respirat 90 12 96.5 ory 100 13. 98.5 3 failure’  y tor pira r d Mechanism that allows io- Res Ca increased offloading of oxygen totothe In exercise (and some tissues degree in infection/inflammation) when the tissues need more O2 the curve shifts to the right to offload more O2 triggered by: – Temperature increases – PCO2 increases – PH decreases – 2,3-diphosglyric acid (2,3-DPG) rises (RBC anaerobic respiration by product) (it enhances the ability of RBCs to release oxygen near tissues that need it most) This reduces the affinity of Hb for O2 hence for the same pO2 in the tissues, the oxyhaemoglobin  Oxyhaemoglobin dissociation curve shift to the RIGHT….. Percent of oxygen saturation of X This picture represents the right shift of the haemoglobin curve with X showing the extra oxygen unloaded for use by the tissues when this  y tor pira es Ca r dio- R RBC Concentration Polycythaemia - ↑ in RBCs – At altitude – used for athletic training – compensatory mechanism in respiratory disease Anaemia -↓HB(number) = ↓oxygen carrying capacity Haemoglobin saturation levels remain the same BUT overall oxygen carrying capacity of the blood is reduced leading to a decreased SaO2 (determined by an arterial  y tor pira es R Ca r dCarbon monoxide poisoning io- Hb has a much greater affinity for carbon monoxide than oxygen (x 300) Hb + CO = COHb (Carboxyhaemoglobin) COHb cannot then bind to oxygen Presence of COHb also shifts the HbO2 dissociation curve to the left for the remaining normal Hb so exacerbating the hypoxaemia – Death is from hypoxaemia  y tor pira es R io- d Ca r Other considerations with Haemoglobin Myoglobin Foetal haemoglobin  y tor pira es R o- Myoglobin di r Ca The muscles store of oxygen found in slow twitch (type I) skeletal and cardiac muscle Red pigment like Hb but only has one molecule of haem (so has ¼ the storage capacity of Hb) May have a role in supplying the mitochondria with oxygen in the initial phase of exercise before the body has adapted to the increasing need for oxygen from the blood Contributes to supplying oxygen to heart muscle during systole when the coronary arteries are occluded  y tor pira es R io- r d Ca Comparison of Mb and Hb dissociation curves This picture Haemoglobin 4 haems depicts that Haemoglob Myoglobin in has a higher affinity for 1 haem oxygen than Hb with the S curve steeper http://www.colorado.edu allowing the  y tor pira es R o- Ca r di Foetal Haemoglobin This picture depicts the difference between Foetal and maternal Hb Percent of oxygen saturation of with a steeper S shaped curve of the foetal Hb. The baby’s ability to gain oxygen from its mothers' blood in the placenta is haemoglobin facilitated as foetal Hb has a greater affinity for oxygen than the adult  y tor pira es R io- r d Ca Transport of carbon dioxide  y tor pira r dio- Res Carbon dioxide Ca transport Carbon dioxide is very soluble, and it is transported in three ways: 1. 70% is carried in solution in the blood as bicarbonate ions (HCO3- ) 2. 10% is dissolved as gas molecules directly in the blood 3. 20% as carbaminohemoglobins bound to Hb  y tor pira es R io- r d Ca CO2 Equation Carbon Carbonic Hydrogen dioxide acid and and bicarbonate water 70% is carried in solution in the blood as bicarbonate ions (HCO3- ) CO2 + H2O  H2CO3  H+ + HCO3- Carbon dioxide diffuses from the tissues into the blood plasma then into the RBCs to combine with water to form the weak acid – carbonic acid (H2CO3) catalyzed by the enzyme carbonic anhydrase in the RBCs This acid then partially and readily dissociates to H+ and bicarbonate ions The HCO3- ions largely diffuse back into the plasma to support buffering  y tor pira es R io- r d Ca The Haldane Effect The amount of CO2 transported is affected by the result of a left shift of the oxyhemoglobin dissociation curve : The Haldane effect The lower the PO2 (and Hb saturation with O2) the more CO2 can be carried by the Hb as deoxyhaemoglobin has a greater affinity for CO2 than oxyhaemoglobin O2 exchange at the lungs These pictures depict the transference of the CO2 molecules from the Hb across the capillary membrane to the alveoli for exhalation © 2011 Pearson Education, Inc.  CO2 exchange at the tissues These pictures depict the transference of the CO2 molecules from the Hb across the tissue membrane to the capillary for transport to the lungs © 2011 Pearson Education, Inc.  y tor Partial Pressures pira s io- Re of CO2 and O2 in the blood and r d Ca alveoli Oxygen Carbon dioxide mmHg/KPa mmHg/KPa Pulmonary arteriolar blood = systemic veins 40/ 5.3 45/6 Alveolar air 104/13.9 40/5.3 Pulmonary venule blood = systemic arteries 100/13.3 40/5.3 Atmospheric air 160/21.3 0.3/0.04 1kPa ~ 7.5mmHg 1mmHg ~ 0.13kPa Therefore the normal levels of systemic arterial (and venous blood gases) are: Arterial blood gases Venous blood gases pH 7.35 - 7.45 pH 7.34 – 7.37 PaCO2 4.6-6.0 kPa PvCO2 5.8 - 6.1 kPa (35-45 mm Hg) (44 – 46 mmHg) PaO2 11-14 kPa PvO2 5.0 – 5.5 kPa (80-100 mm Hg) (38 – 42 mmHg) HCO3- 22-26 mmol/L HCO3- 24-30 mmol/L SaO2 95-98% SvO2 ~ 75%  y tor pira es R io- r d Ca Control of Ventilation  y tor pira es R Ca r dio- Control of ventilation Respiratory centres Chemoreceptors – Peripherally and centrally Baroreceptors in the aortic arch Stretch receptors – Prevent over inflation (detect blood pressure) Reaction to irritants/noxious fumes in respiratory tract – Irritants e.g. particles/ toxic fumes /fluids – Cough, sneeze and laryngospasm – Bronchoconstriction Voluntary control – partial Anticipation of exercise  Control of respiratory rate and depth Respiratory control Rate and depth of centres inspiration and expiration is set by rhythmic firing of neurones in the respiratory centre in the brain stem. These centres receive input from sensory neurons to alter the  y tor pira es R io- Ca r d Chemoreceptors CO2 + H2O ↔ H2CO3 ↔ H+ + HCO3 - The basic respiratory rate and rhythm is influenced by concentrations of hydrogen ions (H+) carbon dioxide (CO2) and oxygen (O2) in the blood detected by central and peripheral  y tor pira es R io- r d Ca Chemoreceptors Central receptors – medullary receptors sensitive to H+ (from CO2) in the cerebrospinal fluid (no buffering systems in CSF) – rising levels of H+ from rising CO2 increases rate and depth of respiration Peripheral receptors – In the Aortic and Carotid bodies sensitive to – ↓ PO2 < 8-9 kPa – ↑ PCO2 but less so than central receptors – ↑ H+ can be from carbon dioxide or of metabolic origin  Diagrammatic Brain overview of chemoreceptors Medullary receptors External carotid artery Internal carotid artery Carotid body Common carotid artery Cranial nerve X (vagus nerve) Aortic bodies in aortic arch Aorta Heart © 2004 Pearson Education, Inc  y tor pira es Baroreceptors R io- r d Ca Carotid and aortic baroreceptor stimulation – Affects blood pressure and respiratory centres When blood pressure falls ventilation increases (baroreceptor activity decreases parasympathetic activity) When blood pressure increases Brain stem Higher brain centres (cerebral cortex—voluntary control over breathing) Other receptors (e.g., pain) + and emotional stimuli acting – through the hypothalamus + – Respiratory centers (medulla and pons) Peripheral + chemoreceptors O2 , CO2 , H+ + – Stretch receptors in lungs Central Chemoreceptors – CO2 , H+ + Irritant receptors Receptors in muscles and joints © 2001 Benjamin Cummings  As your O2 declines so does ventilation Normal minute ventilation is between 5 and 8 Liters of air per minute As your CO2 increases so does your ventilation Wk.18 CResp Lecture  The resultant lung volumes and capacities - some definitions Tidal volume (TV) 500mls in the the amount of air that moves in or out of the adult lungs with each respiratory cycle. Respiratory Rate per minute (RR) 12-15 in the adult Minute volume (MV) = TV x RR 6,000mls/(6 the amount of gas inhaled or exhaled from a litres) person's lungs in one minute. Anatomical dead space 150mls volume of air that remains in the conducting zone Alveolar ventilation 4500mls/4.5l the amount of fresh /new air that reaches the Therefore, if anatomical dead space is constant what is the effect of alveoli per minute= RR x (TV – anatomical dead shallow breathing or slow, deep breathing? space) i.e. 12 Inhalation x (500-150) effectively increasing the anatomic dead space. Exhalation decreases the amount of anatomic dead space. Spirometry – measuring lung volumes using a Vitalograph (more detail in week 20) FEV1 Forced expiratory volume the amount of air FVC you can force from your lungs in the FEV1 first second Volume (L) Normally: FEV1/FVC > 80% FVC Forced vital capacity the total volume 1 of air that can be Time (s) exhaled during a maximal forced expiration effort Spirometry measurements Lung Lung volumes capacitie s IRV IC VC TLC VT ERV RV FRC Wk.18 CResp Lecture  y tor pira es R o- Ca r di Volumes and capacities VT tidal volume (usually called TV clinically) IRV inspiratory reserve volume (The extra volume of air that can be inspired with maximal effort after reaching the end of a normal) ERV expiratory reserve volume (The maximal amount of air that can be expired beyond the normal) RV residual volume– the one that needs specialist equipment to measure (The volume of air remaining in the lungs after maximum forceful expiration) IC inspiratory capacity (the sum of IRV and TV) VC vital capacity – often measured maximally and called FVC – forced vital capacity TLC total lung capacity (the sum of IRV+TV+FRC+RV) FRC functional residual capacity (very important capacity with lots of physiotherapy treatments aiming to increase FRC) (is the volume of air present in the lungs at the end of normal passive expiration.)  Respiratory Drive (Control of ventilation) Pump Respiratory Load on the capacity muscle pump pump Failure to ventilate the lungs adequately The may be due to defects in respiratory Fatiguing control or the respiratory muscles or to Process an increase in the work that the muscles have to perform. Ventilatory Moxham, 1990 failure  y tor pira r dio- Res Bibliography Ca Fox, S. I. (2009). Human physiology. (11th ed.). Boston: McGraw Hill Higher Education. Marieb, E. N. & Hoehn, K (2010). Human anatomy and physiology. (8th ed.). Pearson Benjamin Cummings. San Francisco: London. Martini, F. H. (2006). Fundamentals of anatomy and physiology. (7th ed.). San Francisco: Pearson Benjamin Cummings. Moxham, J. (1990). Respiratory muscle fatigue: mechanisms, evaluation and therapy. British Journal of Anaesthesia, 65, 43-53. Stanfield, C. L. & Germann, W. J. (2008). Principles of human physiology. (3rd ed.). San Francisco: Pearson Benjamin Cummings. Thibodeau, G. A. & Patton, K. T. (2007). Anatomy and physiology. (6th ed.). St Louis, Missouri: Mosby Elsevier. Widmaier, E. P., Raff, H. & Strang. K.Y. (2006). Vander’s human physiology: The mechanisms of body function. (10th ed.). Boston: McGraw Hill.