Gas Exchange and Transport 2024 PDF

HUMAN PHYSIOLOGY BIO-5004A/ BIO5104 Gas exchange and transport Dr Tracey Swingler [email protected]  HUMAN PHYSIOLOGY BIO-5004A/ BIO5104 Lecture content Partial pressures of gases Alveolar gas exchange Transport of gases around the body Tissue gas exchange...

HUMAN PHYSIOLOGY BIO-5004A/ BIO5104 Gas exchange and transport Dr Tracey Swingler [email protected]  HUMAN PHYSIOLOGY BIO-5004A/ BIO5104 Lecture content Partial pressures of gases Alveolar gas exchange Transport of gases around the body Tissue gas exchange Factors that governs gas exchange  HUMAN PHYSIOLOGY BIO-5004A/ BIO5104 Learning outcomes Understand the concept of partial pressure Understand the factors that drive the movement of gases across the respiratory membrane Describe the transport of gases around the body and exchange at tissues Understand mechanisms that monitor Gas exchange and transport: Overview 1. Alveolar gas exchange Inhaled air: Blood picks up oxygen and unloads carbon dioxide 2. Gas transport Oxygenated bloods travels to the systemic tissues Blood loaded with CO2 transported to the lungs for exhalation 3. Systemic gas exchange The reverse process happens: Blood unloads the O2 and picks up the CO2 mospheric pressure Atmospheric air is a mixture of gases Daltons Law: Total atmospheric pressure is the sum of all the gases All the gases independently contribute to its total pressure PN2 + PO2 + PH2O + PCO2 597 + 150 + 3.7 + 0.3 = 760mmHg 78.6% Nitrogen (atmospheric pressure) 20.9% oxygen 0.04% carbon dioxide The separate contribution is the partial pressure Minor gases: argon, helium, methane, ozone (P) ie PO 2 Water vapour (0%-4%) Gas moves by two mechanisms BULK FLOW 1. BULK FLOW The movement of large volumes of fluid or gas due to a pressure gradient. DIFFUSI - Moving air into and out of the lungs ON (inhalation creates negative pressure in the thoracic cavity) - Circulating the blood round the body ( heart pumps blood creating pressure gradient) BULK FLOW 2. DIFFUSION Passive movement of molecules from an area of higher conc. or pressure. - Exchange of gases alveoli- blood- tissues - O2 alveoli - blood - tissues DIFFUSI - CO2 tissues - blood – alveoli ON Diffusion of each gas occurs independently due to a range of factor- pressure solubility etc Gas Exchange olar gas exchange: The respiratory membrane 2. 3. Henrys Law states: The amount of gas that dissolves in water is determined by its solubility in the water and its partial pressure in the air 1. 1. Water and Surfactant in the alveoli 2. Alveolar epithelial cells 3. Epithelial basement membrane 4. Interstitial space 5. Capillary basement membrane 6. Capillary endothelial cells 6. 4. 5. eolar/ Tissue gas exchange Atmospheric air Key points: Gases move down their own pressure gradient The gases behave independently, the diffusion of one gas doesn’t influence the other Alveoli O2 Respiratory membrane CO2 Capillaries Transported around the blood O2 Capillaries Internal CO2 Cells respirati eolar/ Tissue gas exchange Atmospheric: PO2 = 150mmHg 1. Freshly inspired air mixes with the PCO2 = 0.3mmHg residual air- O2 diluted CO2 enriched. 2. O2 moves into blood, down its PP Alveolar: gradient 1. 2 = 100mmHg PO PCO2 = 40mmHg 3. O2 arrives at tissues, where PPO2 low PO2 is low. O2 moves down PP gradient into tissues 5. External respiration PO2 = 40mmHg PO2 = 100mmHg 4. CO2 is a by-product of metabolism 2. PCO2 = 46mmHg PCO2 = 40mmHg and increased in tissues. CO2 moves down PP gradient into blood PO2 = 40mmHg PO2 = 100mmHg 5. Arrives at lungs where PCO2 is 3. PCO2 = 46mmHg 4. PCO2 = 40mmHg lower in lungs. CO2 moves down PP gradient into O2 consumption alveoli. depends on metabolic acti Internal PO2 = 40mmHg respirati Cells More exercise, decreased PO2 increased PC PCO2 = 46mmHg ors affecting alveolar gas exchange Loading of O2 and unloading of CO2 EFFICENCY depends on: 1. The time the RBC spends in near the alveoli 2. Time taken to load/ unload It takes about 0.25sec for gases to reach equilibrium It takes a RBC 0.75sec (at rest) to pass through alveolar capillary/ 0.3sec during vigorous exercise Several variables affect the efficiency of gas exchange: 1. Pressure gradients of the gases 2. Solubility of the gases 3. Membrane thickness Alveoli cross section. (TEM): 1. Pressure gradients of the gases Alveloar Carbon Magnitude of partial pressure gradient dioxide (HENRYS LAW) 40mmHg The greater the pressure different the more Alveolar rapid the Oxygen gas exchange 100mm Hg PO2 in the alveolar is 100mmHg 100mm PO2 in the blood is 40mmHg Hg Oxygen therefore diffuses into the blood and reaches about 100mm Hg 40mm Hg PCO2 in the blood arriving at the alveolus is 46mmHg 46mmH g At high altitude: Partial Pressure of all atmospheric gases are lower, the gradient of oxygen is smaller, therefore takes more time to diffuse into the blood 2. Solubility of the gases CO2 O2 Since gas exchange happens between the air and the liquid, the movement of individual gases depend on their individual solubility in water Gases differ in their ability to dissolve in water Carbon dioxide is about 20 times more soluble than oxygen Even though the pressure gradient of oxygen is much greater than carbon dioxide Across the respiratory membrane, equal amounts of the two gases are exchanged because CO2 is CO2 is more 20 more soluble and diffuses more rapidly Nitrogen despite being plentiful in the times more atmosphere and the alveoli does not diffuse into the blood as it has low solubility soluble in water 3. Thickness of the respiratory membrane The thinner the membrane the faster the gas diffuses The respiratory membrane is 0.5mm thick (less than the diameter of single RBC 8mM) Diseases such a pneumonia, heart failure- - pressure builds up in the lungs and causes membranes to become thickened The gases have further to travel to O2 can’t load onto the haemoglobin as quickly Under these conditions blood leaving he lungs has an unusual low PO2 and high PCO2 4. Membrane area The amount of gas exchange is directly proportion to the contact surface between the blood and the alveoli air In good health the lungs have an area 70M2 of respiratory membrane available for gas exchange. Diseases that reduce gas exchange efficiency produce low blood oxygen levels Several diseases reduce the surface area of gas exchange Emphysema and lung cancer 5. Ventilation-perfusion coupling Ventilation Perfusion V/ Q=1 Amount of gas that particpiates in gas exchange in the lungs needs to be matched to the rate of perfusion Needs to be as matched as possible =1 5. Ventilation-perfusion coupling Ventilation Amount of gas that patriciate in gas exchange in the lungs Needs to be as matched as possible =1 Perfusion V/ Q=1 If alveoli blocked (i.e. mucus)- ventilation decreased ⁻ CO2 in alveoli increases ⁻ O2 levels go down ⁻ Low O2 levels tell the blood vessel to constrict  Therefore, drop in ventilation = drop in perfusion- ma Blockage in alveoli If capillary blocked- perfusion has dropped O2 decreases O2 increases ⁻ Gases can’t exchange CO2 increases CO2 decreases ⁻ Decreased CO2 tells the bronchioles to constrict O2 CO2  Therefore, drop in perfusion = drop in ventilation - ma Blockage in blood vessel NB. Pulmonary arteries are opposite to systemic arteries, which dilate in response to Key points so far: Atmospheric pressure- mixture, off all gases contributing their individual pressures 760mmHg Gases move into the lung via bulk flow, but diffuse down their individual pressure gradient Gases exchange across the respiratory membrane (6 layers ALVEOLI water layer blood endothelial cell B A number of factors affect the efficiency of gas exchange in the lungs: Pressure Solubility Thickness of the resp. membrane Membrane area Matched ventilation-perfusion Gas Transport: 1. Oxygen 2. Carbon dioxide Oxygen transport as transport: Oxygen Plasma 55% A RBC contains approx. 250 million WBC/ platelets 4% haemoglobin molecules: Abbreviated Hb RBC 41% Made up of 4 subunits, each containing an iron ion (Fe2+) O Each haem group bind 1 O2 molecule 2 Increases the total blood oxygen capacity seventy-fold compared to dissolved oxygen in blood. 98.5 % of oxygen is bound to haemoglobin in the RBC Oxygen has a low water solubility, 1.5% is dissolved in the blood plasma Binds reversibly and cooperatively xygen: Cooperative binding T-R state is triggered by the binding of one oxygen Causes a slight change in shape of the subunit HHb HbO2 that is carrying the oxygen deoxyhaemoglobin oxyhaemoglobin Cooperative binding- facilitates the uptake of the second At low PO2, O O22 saturation of Haemoglobin is slow, then rapid increase in O2 loading as PO2 rises Cooperative binding results in a sigmoid shape in the oxygen-dissociation curve T (tense) state - deoxy Haem  R (relaxed) state - oxy haem Factors affecting the binding- pH and CO2 levels, temperature, metabolic products The binding of O2 in haemoglobin is cooperative and allows haemoglobin to bind oxygen more Dynamic process ensures that efficient oxygen efficiently when oxygen levels are high- ie in the release / delivery where its most needed in the lungs body The oxygen-haemoglobin dissociation curve Graphical representation of the relationship between the partial pressure of oxygen (pO2) and the percentage saturation of haemoglobin At higher PP haemoglobin has higher affinity for oxygen, At lower PP the oxygen has lower affinity for haemoglobin In the lungs pO2 is high = 100mmHg In tissues pO2 is lower = 40mmHg During exercise pO2 = 25mmHg Exercise Partial pressure of oxygen (p02, mmHg) The oxygen-haemoglobin dissociation curve At 100mmHg (at the alveoli) = 97.5% saturated (Almost all O2 sites are filled) At 40mmHg (tissue) = 75% saturated When exposed to lower O2 partial pressure about (22% O2 dissociates) At 25mmHg (exercise) = 45% saturated Very low surrounding O2 levels Exercise (50% O2 dissociates) Therefore, the more O2 your cells needs, the Partial pressure of oxygen (p02, mmHg) more O2 is released. The shape of the curve is important!!!!3. Hb forms different kinds of bonds with the O2 depending on the partial pressure of O2 in its surroundings 1. Has a sigmoidal form because of the 2. cooperative binding of haemoglobin 2. Steep part: Represents the range of PP of oxygen where the Haemoglobin changes rapidly from unsaturated (deoxy) to saturated (oxy). Important for delivering oxygen to the tissues, where even a small drop in oxygen pressure causes a large release of oxygen from haemoglobin 3. Flat part- the range of partial pressures of oxygen where haemoglobin remains mostly Partial pressure of oxygen (P02, mmHg) saturated. This part is important for picking up oxygen in the lungs, where even a large increase in oxygen pressure causes only a small increase in oxygen binding to haemoglobin The dissociation curve can shift left or right. RIGHT SHIFT: Haemoglobin lower affinity 92% for O2 gives up its O2 more readily Increased CO2, decreased pH (Carbonic acid), 75% increased temp, metabolic products In tissues, haem now is only 50% saturated, compared to 75% 50% LEFT SHIFT: Haemoglobin higher affinity for O2 releases less O2 Decreased CO2, increased pH, decreased temp, foetal Hb In tissues, haem is 92% saturated, compared to 75% During exercise, O2 is used up faster, more CO2 produced. The local environment ( the Hb lets go of more O2 Factors that affect the dissociation curve pH TEMPERATURE Haemoglobin doesn’t unload the same amount of O2 to all of its tissues, some need more, some less, depending on their activity. During exercise, cells need more O2. Therefore the Hg lets go of more O2 1. pH – Active tissues produce more CO2. Raises H+. H+ weaken the bond between the Hb and O2. (BOHR effect) CO2 Metabolic compound 2,3-BPG 2. TEMP- Active tissues, temp rises, shift to the right, promoting O2 unloading 3. CO2- Higher PCO2, shift to the right, promote oxygen release (BOHR effect) 4. BPG- metabolic product - Bisphosphoglycerate. Promotes O2 unloading Carbon dioxide transport on dioxide: Transport and exchange, from tissues Cell Blood Blood  Alveolus Carbon dioxide transported in blood three ways: 1. Bicarbonate buffer system 75% 2. Bound to Hb 20% 3. Dissolved in plasma 5% 1. Bicarbonate buffer system 75% CO2 + H2O  H2CO3 (carbonic acid) H2CO3 (Unstable)  H+ + bicarbonate ions (HCO3-) HCO3- transported out of the RBC, exchanged for a Cl- Allows for the allows for the continued uptake of carbon dioxide into the blood down its Chloride shift: concentration gradient 1. Maintains acid base balance H+: bind to Hb to limit pH shift 2. Ensure electrical neutrality 3. Enhances CO2 transport 2. CO2 binds Hb (carbamino compounds) 20% 4. Facilitates Oxygen unloading hemoreceptors Breathing is regulated by pCO2, pO2 and H+ concentration Central chemoreceptors and Peripheral chemoreceptors Monitor the composition of blood and CSF Normally arterial blood is: P02= 100mmHg, PCO2 40mmHg The rate and depth of breathing is adjusted to Hypoxia- Too little O2 maintain these values Hypercapnia- Too much CO2 Hypocapnia- Too little CO2 The most potent chemical stimulus for breathing is: Central chemoreceptors Peripheral chemoreceptors 1.pH- most significant (H+) Under the control of negative 2.CO2 feedback 3.O - least significant  Blood pH O2 + H2O H2CO3 HCO3- + H+ The central chemoreceptors in the medulla oblongata mediate about 75% of the change in respiration induced by pH shifts Respiratory acidosis: Blood become acidic as lungs can’t H+ don’t cross the blood brain barrier very easily. remove enough CO2 (COPD, Asthma) But CO2 does + H2 O H2CO3 HCO3- + H+ Once in the brain CO2 reacts with H2O to produce carbonic acid which dissociates into HCO3 and H + Respiratory alkalosis: CSF contains very little protein so can’t Blood become alkaline caused by buffer the H+ , remains free and stimulates hyperventilation the chemoreceptors 2 + H2 O H2CO3 HCO3- + H + Peripheral chemoreceptors mediate about 25% of the respiratory response to pH changes Key points:  Oxygen transported on Hb, binding is competitive  Oxy-haemoglobin dissociation curve: relationship between the partial pressure of oxygen and the percentage saturation of haemoglobin  Shifted left or right, CO2, pH, temp, metabolic products, foetal Hb  Carbon dioxide transported three ways in the blood: 1) Bicarbonate buffer system, 2) bound to Hb, 3) Dissolved in plasma  Chemoreceptors in the brain are most important for monitoring H+ in the body  Respiratory centres send signals to muscles involved in breathing to adjust rate and depth of breathing  HUMAN PHYSIOLOGY BIO-5004A/ BIO5104 Learning outcomes Understand the concept of partial pressure Understand the factors that drive the movement of gases across the respiratory membrane Describe the transport of gases around the body and exchange at tissues Understand mechanisms that monitor ANY QUESTIONS? What causes a right shift? Haemoglobin doesn’t unload the same amount of O2 to all of its tissues, Some need more, some less, depending on their activity. During exercise, cells need more O2. 75% Therefore, the Hb lets go of more O2 At P02 40mmHg Hb, is 75% saturated 50% During a right shift, Haemoglobin is now 50% saturated-given up more oxygen 1. Increased CO2: The Bohr Shift describes the movement of the oxygen dissociation curve to the right of normal. This occurs due to increased levels of carbon dioxide, such as when a person increases their exercise level, 2. Decreased pH: An increased concentration of carbonic acid to be formed. 3. Temperature increase: Active tissues- temp In conditions where haemoglobin gives up rises, shift to the right, promoting O2 its O2 more readily: Shifts to the right unloading 4. Metabolic product BPG: What causes a left shift? higher pH 90% lower carbon dioxide lower temperature lower BPG 75% Foetal Hb 50% Fetal Haemoglobin- Higher O2 affinity: ie. more O2 bound at lower PO2. Two alpha and two gamma subunits Fetal Hb has a higher affinity for O2 at all partial pressures More reluctant to let go of the O2 Foetal haemoglobin is able to bind oxygen Usually associated with decreased with greater affinity than the adult form, metabolic activity and tissue demand giving the developing foetus better access to for oxygen. oxygen from the mother’s bloodstream. Hb-Higher affinity for oxygen.