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Option D.6 Transport of respiratory gases Essential idea: Red blood cells are vital in the transport of respiratory gases D.6 Transport of respiratory gases Nature of science: Scientists have a role in informing the public—scientific research has led to a change in public perception of smoking. (5.1) Understandings: • Oxygen dissociation curves show the affinity of hemoglobin for oxygen • Carbon dioxide is carried in solution and bound to hemoglobin in the blood • Carbon dioxide is transformed in red blood cells into hydrogencarbonate ions • The Bohr shift explains the increased release of oxygen by hemoglobin in respiring tissues • Chemoreceptors are sensitive to change in blood pH • The rate of ventilation is controlled by the respiratory control centre in the medulla oblongata • During exercise the rate of ventilation changes in response to the amount of CO2 in the blood • Fetal hemoglobin is different from adult hemoglobin allowing the transfer of oxygen in the placenta onto the fetal hemoglobin D.6 Transport of respiratory gases Applications and Skills: • Application: Consequences of high altitude for gas exchange • Application: pH of blood is regulated to stay within the narrow range of 7.35 to 7.45 • Application: Causes and treatments of emphysema • Skill: Analysis of dissociation curves for hemoglobin and myoglobin • Skill: Identification of pneumocytes, capillary endothelium cells, and blood cells in light micrographs and electron micrographs of lung tissue Mammalian Ventilation System • Include ribs and intercostals (muscle between the ribs) as well as insert of alveoli Negative Pressure: air moves from high pressure to low pressure areas Alveoli: SEM D.S.6.2 Light micrograph of lung tissue: alveoli and bronchus Pneumocytes: Types 1 and 2 • Gas exchange occurs in alveoli • The alveolus is composed of a single layer of cells to facilitate oxygen and carbon dioxide diffusion • Alveoli are composed of specialized cells called pneumocytes • Type 1: very thin but has a large membrane surface area. Ideal for diffusion. If damaged, incapable of mitosis for replacement Pneumocytes: Types 1 and 2 • Type 2: cuboidal in shape (small membrane surface area) • Produce and secrete surfactant which reduces surface tension of moist inner surface of alveoli and prevents sides from sticking to each other • Capable of mitosis for replacement of both types of alveolar cells D.S.6.2 Electron micrograph: capillary with RBC and alveolar space • A = alveolar epithelium • B = basement membrane • C = endothelium • D = alveolar space RBC D D Control of Ventilation Partial Pressure • Atmospheric pressure: downward force exerted by air on the earth’s surface. • At sea level, this force is equivalent to the force of a column of mercury (Hg) = 760 mm Hg • Partial pressure of oxygen: since the atmosphere is 21% oxygen (by volume), the partial pressure of oxygen (abbreviated PO2) is 0.21 x 760 mm = 160mm Hg • This is the portion of atmospheric pressure contributed by oxygen (hence partial pressure) • The partial pressure of carbon dioxide at sea level is only 0.23 mm Hg Dissolved Gases • Dissolved gases are proportional to their partial pressure in the air and their solubility in water • Diffusion of gases: from a region of higher partial pressure to a region of low partial pressure • Blood arriving at the lungs has a lower PO2 and a higher PCO2 than the air in the alveoli • Diffusion of gases in tissues works the same way Respiratory Gases Oxygen Transport • At normal body temperature and air pressure, only 4.5 mL of oxygen can dissolve into a liter of blood. • During exercise, a person can consume almost 2 L of oxygen per minute leading to a need for 500 L of blood to be pumped per minute Unrealistic (average person has about 4.5-5.5 L of blood in whole body) • Most animals transport most of their oxygen bound to special proteins called respiratory pigments instead of dissolved in solution • Blood can carry 200 mL of oxygen per L in mammals Oxygen Transport • Respiratory pigment in vertebrates: hemoglobin (Hb) • Hemoglobin consists of 4 subunits, each with a cofactor called a heme group that has an iron atom at its center. Each hemoglobin can carry 4 molecules of O2 • Hemoglobin must bind oxygen reversibly, loading oxygen in the lungs and unloading it in other parts of the body Hemoglobin Peer Pressure among oxygen molecules • We see subunit cooperation (cooperativity)- binding of oxygen to one subunit induces the remaining subunits to change their shape slightly so that their affinity for oxygen increases • When one subunit unloads its oxygen, the other three follow quickly because of a conformation change that lowers their affinity for oxygen Hemoglobin binding to oxygen Oxygen dissociation curve • What follows are the oxygen dissociation curves for hemoglobin • In your text book you will see the normal dissociation curve at 37oC and the pH of 7.4 • You will also see the effect of lowering pH to 7.2 (increase in acidity resulting in the Bohr Effect) • You will find more dissociation curves in the review guide and your IB textbook Oxygen Dissociation Curves: graphs the affinity of hemoglobin for oxygen Oxygen Dissociation Curves • Show the relationship between the % saturation of hemoglobin (or myoglobin) and the partial pressure of oxygen • Normal conditions: a) When pO2 is high, hemoglobin binds with large amounts of oxygen and is almost fully saturated b) When pO2 is low, hemoglobin is only partially saturated and oxygen is released from hemoglobin c) Therefore, in pulmonary capillaries, a lot of oxygen binds with Hb, but in tissue capillaries where the pO2 is lower, Hb does not hold as much oxygen and the oxygen is released for diffusion into tissue cells Oxygen Dissociation Curve d) Note that a pO2 of 40 mm Hg, the average pO2 of tissue cells at rest, only 25% of the available oxygen splits from Hb and is used. (Big reserve of oxygen) e) Several other factors influence the affinity of Hb for oxygen, the strength of the Hb-O2 binding. Keep in mind that metabolically active cells need oxygen and produce acids, carbon dioxide, and heat Effect of Acidity • In an acid environment, hemoglobin’s affinity for oxygen is lower and oxygen splits more readily from hemoglobin • This is referred to as the Bohr effect • When H+ ions bind to certain amino acids in Hb, they alter its structure and decrease its oxygen-carrying capacity • This makes more oxygen available for tissue cells Acidosis • When the body’s pH is lower than 7.35 • Respiratory Acidosis is when you cannot get rid of CO2 • Asthma, injury to chest, obesity, overuse of drugs or alcohol, muscle weakness in chest, nervous system problems • Metabolic Acidosis is issues with the kidneys • Diabetic, hyperchloremic (loss of sodium bicarbonate), lactic (too much lactic acid) Change in pH Partial Pressure of Carbon Dioxide: Better discussion in review guide and in Campbell • Carbon dioxide is carried dissolved in plasma (7%), as bicarbonate ions (70%), and as carbaminohemoglobin (20-25%) • Carbon dioxide in blood is temporarily converted to carbonic acid. This conversion is catalyzed by an enzyme in red blood cells called carbonic anhydrase. This carbonic acid dissociates into H+ ions and bicarbonate ions • Most of the carbon dioxide (70%) is transported in blood as bicarbonate ions. As H ions increase, pH decreases. Many of the H+ combine with Hb or other plasma protein buffers • As bicarbonate ions accumulate inside the RBC, some of them diffuse into the plasma, down their concentration gradient (facilitative diffusion) Chloride Shift • In exchange, chloride ions (Cl-) diffuse from plasma into the RBCs. This exchange of negative ions maintains the ionic balance between plasma and RBCs and is known as the chloride shift • The net effect of these reactions is that carbon dioxide is carried from tissue cells as bicarbonate ions in plasma • Low pH can also result from lactic acid, a by-product of anaerobic metabolism within muscles Summary of gas transport showing the Bohr effect and Chloride Shift Blood and carbon dioxide transport Temperature • As temperature increases, so does the amount of oxygen released from hemoglobin • Temperature rises as the result of activity and infection Oxygen dissociation curve fetal hemoglobin Fetal Hemoglobin • Fetal hemoglobin differs from adult hemoglobin in structure and in affinity for oxygen • So when pO2 is low, fetal hemoglobin can carry up to 30% more oxygen • As maternal blood enters the placenta, oxygen is readily transferred to fetal blood • This is good because oxygen saturation in maternal blood in the placenta is low Fetal Hemoglobin D.A.6.1 Acute Mountain Sickness (High altitude sickness) • As a person ascends in altitude, the atmospheric pO2 decreases, the alveolar pO2 decreases correspondingly, and less oxygen diffuses into the blood • For example, at sea level, pO2 is 160 mm Hg • At 10,000 feet, it decreases to 110 mmHg • At 20,000 ft to 73 mm Hg and at 50,000 ft to 18 mm Hg Symptoms of Altitude Sickness • Shortness of breath • Headache • Fatigue • Insomnia • Nausea • Dizziness • Over a period of time, the person becomes acclimatized Acclimatization • Red blood cell production is stimulated by the hormone, erythropoietin from kidney • Ventilation rate increases • Muscles produce more myoglobin and develop a dense capillary network • People living permanently at high altitude have greater lung surface area and larger lung capacity and larger tidal volume than those living at sea level • Might even have variant hemoglobin • Only restrict amount of oxygen • Do not stimulate pressure experienced at high altitude • No benefits seen in studies • According to Alex Viada, a successful hybrid-training coach and founder of Complete Human Performance, such high-altitude devices "simulate altitude in the same way sticking your head in a toilet simulates swimming." Ouch. • While some users proclaim they can breathe better after using an altitude mask, I bet if I jammed a pillow down someone's throat and asked him to run a mile, he'd be able to breath much better once I took it away, too. • http://www.bodybuilding.com/content/do-elevation-maskswork.html • Chemosensors are sensitive to changes in pH • The rate of ventilation is controlled by respiratory center in the medulla oblongata Exercise • Leads to increased metabolic activity and therefore an increase in carbon dioxide output which lowers blood pH • This change in pH is detected by chemosensors in the carotid arteries and aorta that send impulses to the breathing center of the brain= (pons and medulla oblongata) • Nerve impulses are then sent to the diaphragm and the intercostal muscles to increase contraction or relaxation rates D.S.6.1 Myoglobin vs Hemoglobin • Oxygen dissociation curve for myoglobin is NOT S shaped as is hemoglobin • Myoglobin has a different protein structure than hemoglobin Myoglobin • Consists of 1 heme group attached to a globin • Used to store oxygen in muscle • Myoglobin has higher affinity for oxygen than hemoglobin • At moderate pO2, hemoglobin releases oxygen and myoglobin binds it • Myoglobin does not release oxygen to tissue until the pO2 is very low in tissues • Delays the shift to anaerobic cell respiration Myoglobin Emphysema • Emphysema is the replacement of alveolar tissue by thick, inelastic connective tissue • Also one of the diseases collectively called chronic obstructive pulmonary disease or COPD • Main causes are smoking tobacco, marijuana smoke, and air pollution including fumes from manufacturing plants and coal dust • The constant irritation from the pollutant slowly destroys the alveoli which are replaced by thick, inelastic connective tissue • Vilia lining airways which expel mucus are damaged and cease to function, so mucus builds up in lungs causing infections Emphysema: chronic, slowly progressive disease Emphysema D.A.6.3 Emphysema • Turns healthy alveoli into large, irregularly shaped structures with gaping holes • Inflamed and damaged cells and white blood cells release trypsin (protease) which digests elastic fibers in lungs. Eventually causes complete breakdown of alveolus walls • This reduces surface area for gas exchange so less oxygen reaches the bloodstream • Lungs lose elasticity, making it increasingly difficult to exhale • Mucus accumulation causes coughing and wheezing Alveolar space increased Decreased surface area Normal Emphysema Symptoms and treatment of emphysema • Shortness of breath, initially in response to strenuous activity • Over time, inability to get sufficient gas exchange becomes constant • There is no cure for emphysema once it is severe enough to be diagnosed but progression can be slowed with the cessation of smoking or wearing of protective mask when working around dust or chemical fumes • Some medications can help to relieve the symptoms (dilate the bronchi) • Supplemental oxygen from a container can be administered through small tubes into the nostrils • Training in breathing techniques to reduce breathlessness • Surgery to remove damaged lung tissue and less commonly, lung transplants Bronchogenic Carcinoma (Lung Cancer) • Common lung cancer starts in the walls of the bronchi • The constant irritation by inhaled smoke and pollutants cause the mucus producing cells of the bronchial epithelium to enlarge • They respond by secreting excessive mucus • The basal cells also respond to the stress by undergoing cell division so fast that they push into the area occupied by the mucus and other epithelial cells • Cancerous growth takes over areas of healthy tissue that once provided a combination of bronchioles and alveoli. Can result in internal bleeding in the lungs Healthy lung vs cancerous lung Causes of Cancer • Smoking- tobacco smoke contains mutagens/carcinogens that cause tumors to develop. Nearly 90% of lung cancers caused by smoking • Passive or 2nd hand smoking- smoking bans should reduce this • Air pollution- sources include diesel exhaust fumes, nitrogen oxides from vehicles and smoke from wood and coal fires. • Radon gas- leaks out of rocks, especially granite. • Asbestos and silica- dust from these cause cancer if deposited in lungs Consequences of Lung Cancer • Difficulties with breathing • Persistent coughing (so-called “dry” cough) • Coughing up blood • General fatigue • Chest pain • Loss of appetite • Weight loss (unexplained) Treatment • Best treatment is achieved when the disease is diagnosed early in its progression • Lung cancer has a very high mortality rate • Surgery may be used to remove the tumor along with the diseased part of the lung • Radiation therapy uses high-energy X-rays to kill cancer cells or keep them from growing. It can be used before surgery to shrink the tumor. It can be used after surgery to kill any cancer cells left in the lungs. It can be used on metastases Treatment • Chemotherapy means the use of special drugs to destroy cells throughout the body • Targeted therapies directly address the mutations that are causing the cancer cells to grow uncontrollably • Cause less side effects by “targeting” the cancer cells and reducing the damage to the healthy cells Lung Cancer