Respiration• Includes:– Ventilation (breathing)– Gas exchange betweenblood and lungs andbetween blood and tissues– Oxygen utilization by tissuesto make ATP• Ventilation and gas exchange inlungs = external respiration• Oxygen utilization and gasexchange in tissues = internalrespiration
Respiratory Structures• Air travels down thenasal cavity Pharynx Larynx Trachea Right and leftprimary bronchi
Functions of Conducting Zone• Transports air to the lungs• Warms, humidifies, filters, and cleans theair– Mucus traps small particles, and cilia move itaway from the lungs.• Voice production in the larynx as airpasses over the vocal folds
Gas Exchange in Lungs• Occurs via diffusion• O2 concentration is higher in the lungsthan in the blood, so O2 diffuses into blood.• CO2 concentration in the blood is higherthan in the lungs, so CO2 diffuses out ofblood.
Alveoli• Air sacs in the lungswhere gas exchangeoccurs• 300 million of them– Provide large surfacearea (760 square feet)to increase diffusionrate
Alveolar Cells• Type I: 95−97% totalsurface area where gasexchange occurs• Type II: secretepulmonary surfactant andreabsorb sodium andwater, preventing fluidbuildup• Macrophages: removepathogens
Thoracic Cavity• Contains the heart,trachea, esophagus, andthymus within the centralmediastinum• The lungs fill the rest ofthe cavity.– .
Thoracic Cavity Cross Section– The parietal pleuralines the thoracicwall.– The visceral pleuracovers the lungs.– The parietal andvisceral pleura arenormally pushedtogether, with apotential spacebetween called theintrapleural space
II. Physical Aspects ofVentilation
Atmospheric Pressure• Can be measuredusing a barometer• At sea level, theatmosphericpressure is 760mmHg.
Lung Pressures• Atmospheric pressure:pressure of air outside the body• Intrapulmonary pressure:pressure in the lungs• Intrapleural pressure: pressurewithin the intrapleural space(between parietal and visceralpleura)• Transpulmonary pressue:Pressure difference betweenintrapulmonary and intraplueralpressures
Ventilation• Air moves from higher to lower pressure.– Pressure differences between the two ends ofthe conducting zone occur due to changinglung volumes.– Compliance, elasticity, and surface tensionare important physical properties of the lungs.
Pressure Differences When Breathing• Inhalation: Intrapulmonary pressure is lower thanatmospheric pressure.– Pressure below that of the atmosphere is calledsubatmospheric or negative pressure• Exhalation: Intrapulmonary pressure is greater thanatmospheric pressure.
Why Lungs stay inflated?• Intrapleural pressureis always lower thanintrapulmonary andatmosphericpressures in bothinhalation andexhalation– Keeps the lungsagainst the thoracicwall
Boyle’s Law• States that the pressure of a gasis inversely proportional to itsvolume– P = 1/V– An increase in lung volumeduring inspiration decreasesintrapulmonary pressure tosubatmospheric levels.• Air goes in.– A decrease in lung volumeduring exhalation increasesintrapulmonary pressureabove atmospheric levels.• Air goes out.
III. Mechanics of Breathing
Breathing• Also called pulmonary ventilation– Inspiration: breathe in– Expiration: breathe out• Accomplished by changing thoracic cavity/lung volume
Muscles Involved in Breathing• Diaphragm most important.– Contracts in inspiration– Relaxes in expiration• Inspiration: externalintercostals• Expiration: internalintercostals, abs
Mechanisms of Breathing• Inspiration: Volume of thoracic cavity (and lungs) increasesvertically when diaphragm contracts (flattens) andhorizontally when parasternal and external intercostals raisethe ribs.
Mechanisms of Breathing• Expiration: Volume of thoracic cavity (and lungs) decreasesvertically when diaphragm relaxes (dome) and horizontallywhen internal intercostals lower the ribs in forced expiration.
Normal vs. Forced Breathing
Lung Compliance• Is how easily lungs can expand whenstretched.• Defined as the change in lung volume perchange in transpulmonary pressure:ΔV/ΔP• Reduced by infiltration of connectivetissue proteins in pulmonary fibrosis
Elasticity• Lungs return to initial size after beingstretched.– Lungs have lots of elastin fibers.– Because the lungs are stuck to the thoracicwall, they are always under elastic tension.
Surface Tension• Resists distension• Exerted by fluidsecreted in thealveoli• Raises the pressureof the alveolar airas it acts tocollapse the
Law of Laplace• Pressure is directlyproportional tosurface tension andinverselyproportional toradius of alveolus.– Small alveoli wouldbe at greater risk ofcollapse withoutsurfactant.
Surfactant• Secreted by type IIalveolar cells• Consists ofhydrophobic proteinand phospholipids• Reduces surfacetension between watermolecules• More concentrated insmaller alveoli• Prevents collapse
Surfactant• Production beginslate in fetal life, sopremature babiesmay be born with ahigh risk for alveolarcollapse calledrespiratory distresssyndrome (RDS).
Pulmonary Function Tests• Spirometry: Subject breathes into and outof a device that records volume andfrequency of air movement on aspirogram.• Measures lung volumes and capacities• Can diagnose restrictive and disruptivelung disorders
IV. Gas Exchange in theLungs
Dalton’s Law• The total pressure of a gasmixture is equal to the sum ofthe pressures of each gas in it.• Partial pressure: the pressureof an individual gas; can bemeasured by multiplying the %of that gas by the total pressure– O2 makes up 21% of theatmosphere, so partial pressureof O2 = 760 X 20% = 159 mmHg.
Total Pressure• Nitrogen makes up 78% of theatmosphere, O2 21%, and CO2 1%.Pdry = PN2+ PO2+ PCO2= 760 mmHg• When air gets to our lungs, it is humid, sothe calculation changes to:Pwet = PN2+ PO2+ PCO2+ PH2O= 760 mmHg
Partial Pressure• Addition of watervapor also takesaway from the totalatmosphericpressure whencalculating partialpressure O2.
Relationship Between Alveoliand Capillaries
Role of Gas Exchange• In the alveoli, thepercentage ofoxygen decreasesand CO2 increases,changing the partialpressure of each.
Partial Pressure in Blood• Alveoli and bloodcapillaries quicklyreach equilibriumfor O2 and CO2.– This helpsmaximize theamount of gasdissolved in fluid.– Henry’s Lawpredicts this.
Henry’s Law• The amount of gas that candissolve in liquid depends on:– Solubility of the gas in the liquid(constant)– Temperature of the fluid (moregas can dissolve in cold liquid);doesn’t change for blood– Partial pressure of the gases,the determining factor
Blood Gas Measurement• Uses an oxygenelectrode• Only measuresoxygen dissolved inthe blood plasma. Itwill not measureoxygen in red bloodcells.• It does provide agood measurementof lung function.If partial pressure oxygenin blood is more than 5mmHg below that oflungs, gas exchange isimpaired.
Partial Pressure Oxygen• Changes with altitude and location
Partial Pressure of Gas in Blood
VI. Hemoglobin and OxygenTransport
Oxygen Content of Blood• In 100 ml of bloodthere is a total of 20mlof O2•• Very little of O2 isdissolved (0.3 ml/100ml)• Most 02 in blood isbound to Hb insideRBCs asoxyhemoglobin• Hb greatly increases 02carrying capacity ofblood
Hemoglobin• Most of the oxygenin blood is bound tohemoglobin.– 4 polypeptideglobins and 4 iron-containing hemes– Each hemoglobincan carry 4molecules O2.– 248 millionhemoglobin/RBC
Forms of Hemoglobin• Oxyhemoglobin/reduced hemoglobin: Iron is in reduced form(Fe2+) and can bind with O2.• Carbaminohemoglobin: Hemoglobin bound to CO2; Normal• Methemoglobin: Oxidized iron (Fe3+) can’t bind to O2.– Abnormal; some drugs cause this.• Carboxyhemoglobin: Hemoglobin is bound with carbonmonoxide.• Bond with carbon monoxide is 210 times stronger thanbond with oxygen– So heme cant bind 0
% Oxyhemoglobin Saturation• % oxyhemoglobin to total hemoglobin• Measured to assess how well lungs haveoxygenated the blood• Normal is 97%• Measured with a pulse oximeter or blood–gas machine
Hemoglobin Concentration• Oxygen-carrying capacity of blood ismeasured by its hemoglobin concentration.– Anemia: below-normal hemoglobin levels,normal PO2 but total O2 low in blood– Polycythemia: above-normal hemoglobinlevels; may occur due to high altitudes• Erythropoietin made in the kidneysstimulates hemoglobin/RBC productionwhen O2 levels are low.
Loading and Unloading• Loading: when hemoglobin binds to oxygen inthe lungs• Unloading: when oxyhemoglobin drops offoxygen in the tissuesdeoxyhemoglobin + O2 oxyhemoglobin• Direction of reaction depends on– PO2of the environment– affinity for O2.– High PO2favors loading.Loading in LungsUnloading in Tissues
Oxygen Unloading• Systemic arteries have a PO2of 100 mmHg.– This makes enough oxygen bind to get 97%oxyhemoglobin.– 20 ml O2/100 ml blood• Systemic veins have a PO2of 40 mmHg.– This makes enough oxygen bind to get 75%oxyhemoglobin.– 15.5 ml O2/100 ml blood– 22% oxygen is unloaded in tissues
PO2and % OxyhemoglobinS-shaped or Sigmoidal curveIn steep part of curve, smallchanges in P02 cause bigchanges in % saturation orunloading
Oxyhemoglobin Dissociation CurveConditionsthat shift thecurve to theright wouldcause lowaffinity andmoreunloading↑ CO2↑ [H+] Bohr effect↑ Temperature↑ 2,3-DPGFeverConditions thatshift the curveto the leftwould causemore affinityand lessunloading2,3-Diphosphoglyceric acid (2,3-DPG)concentration increase in RBCs increases inanemia and high altitude
Oxygen Dissociation Curve• Oxygen remaining in veins serves as anoxygen reserve.• Oxygen unloading during exercise is evengreater:– 22% at rest– 39% light exercise– 80% heavy exercise
Effect of pH and Temperature onOxygen Transport• pH and temperature changethe affinity of hemoglobin forO2.– This ensures that musclesget more O2 whenexercising.– Affinity decreases at lowerpH and increases athigher pH = Bohr effect.– More unloading occurs atlower pH.– Increased metabolism =more CO2 = lower pH
Factors That Affect O2 Transport
Fetal Hemoglobin• Adult hemoglobin (hemoglobin A) can bindto 2,3-DPG, but fetal hemoglobin(hemoglobin F) cannot.– Fetal hemoglobin therefore has a higheraffinity for O2 than the mother, so oxygen istransferred to the fetus.
Inherited Hemoglobin Defects• Sickle-cell anemia: found in 8−11% of African Americans– The affected person has hemoglobin S with a singleamino acid difference.– Deoxygenated hemoglobin S polymerizes into longfibers, creating a sickle-shaped RBC.– This hinders flexibility and the ability to pass throughsmall vessels.
Inherited Hemoglobin Defects
Inherited Hemoglobin Defects• Thalassemia: found mainly in people ofMediterranean heritage– Production of either alpha or beta chains isdefective.– Symptoms are similar to sickle-cell anemia.• Both inherited hemoglobin defects carryresistance to malaria.
Myoglobin• Red pigment found inskeletal and cardiacmuscles• Similar to hemoglobin, butwith 1 heme, so it can onlycarry 1 oxygen molecule– Higher affinity to oxygen;oxygen is only releasedwhen PO2 is very low– Stores oxygen and servesas go-between intransferring oxygen fromblood to mitochondria
VII. Carbon Dioxide Transport
Carbon Dioxide in the Blood• Carried in the blood in three forms:– Dissolved in plasma– As carbaminohemoglobin attached to anamino acid in hemoglobin– As bicarbonate ions
Chloride Shift16-76In tissues there are high C02 levels. This causes increased levels of CO2 in RBCscausing the following reaction to shift to the right.C02 + H2O ↔ H2C03 ↔ H++ HC03-This results in high H+& HC03-levels inRBCsH+is buffered by proteinsHC03-diffuses down concentration &charge gradient into plasma causingRBC to become more positively (+)chargedSo Cl-moves into RBC (chloride shift)to balance the chargeHCO3-acts as a major buffer in plasma
Reverse Chloride Shift• In lungs following reaction,C02 + H2O ↔ H2C03 ↔ H++ HC03-,moves to the left as C02 isbreathed out• Binding of 02 to Hbdecreases its affinity for H+– H+combines with HC03-&more C02 is formed• Cl-diffuses downconcentration & chargegradient out of RBC(reverse chloride shift)Fig 16.3916-77
VIII. Acid- Base Balance of theBlood
Acid-Base Balance in Blood• Blood pH is maintained within narrow pH rangeby lungs & kidneys (normal = 7.4)• Most important buffer in blood is bicarbonate– H20 + C02 ↔ H2C03 ↔ H++ HC03-– Excess H+is buffered by HC03-• Kidneys role is to excrete excess H+into urine16-78
Bicarbonate as a Buffer• Buffering cannotcontinue foreverbecause bicarbonatewill run out.– Kidneys help byreleasing H+in theurine.
Ventilation and Acid-Base BalanceThe normal pH of blood is between 7.35 and 7.45. A major bufferwhich regulates this pH is HCO3-. This bicarbonate ion traps H+if thepH gets too low or releases H+if the pH is too high, thus buffering thesystem.If there is a decrease in [H+] (or pH increase), thenH2CO3 H➔ ++ HCO3-If there is an increase in [H+] (a pH decrease), thenHCO3-+ H+➔ H2CO3the bicarbonate ion thus functions as a major buffer in blood
• 2 major classes of acids in body:– A volatile acid can be converted to a gas• E.g. C02 in bicarbonate buffer system can be breathed out– H20 + C02 ↔ H2C03 ↔ H++ HC03-– All other acids are nonvolatile & cannot leave blood• E.g. lactic acid, fatty acids, ketone bodiesAcid-Base Balance in Blood continued16-80
Blood pH: Acidosis• Acidosis: when blood pH falls below 7.35– Respiratory acidosis: hypoventilation– Metabolic acidosis: excessive production ofacids, loss of bicarbonate (diarrhea)
Blood pH: Alkalosis• Alkalosis: when blood pH rises above 7.45– Respiratory alkalosis: hyperventilation– Metabolic alkalosis: inadequate production ofacids or overproduction of bicarbonates, lossof digestive acids from vomiting
Ventilation and Acid-Base Balance• Ventilation controls the respiratorycomponent of acid-base balance.– Hypoventilation: Ventilation is insufficient to“blow off” CO2. PCO2 is high, carbonic acid ishigh, and respiratory acidosis occurs.– Hyperventilation: Rate of ventilation is fasterthan CO2 production. Less carbonic acidforms, PCO2 is low, and respiratory alkalosisoccurs.
Ventilation and Acid-Base Balance• Ventilation can compensate for themetabolic component.– A person with metabolic acidosis willhyperventilate.– A person with metabolic alkalosis willhypoventilate.
V. Regulation of Breathing
Brain Stem Respiratory Centers• Automatic breathing isgenerated by a rhythmicitycenter in medulla oblongata– Consists of inspiratoryneurons that driveinspiration & expiratoryneurons that inhibitinspiratory neurons• Their activity varies ina reciprocal way &may be due topacemaker neuronsInsert fig. 16.2516-48
Brain Stem Respiratory Centers• Inspiratory neuronsstimulate spinal motorneurons that innervaterespiratory muscles• Expiration is passive &occurs when inspiratoriesare inhibitedInsert fig. 16.2516-48
Brain Stem Respiratory Centers• Activities of medullaryrhythmicity center isinfluenced by centers inpons– Apneustic centerpromotes inspiration bystimulating inspiratoriesin medulla– Pneumotaxic centerantagonizes apneusticcenter, inhibitinginspirationInsert fig. 16.2516-48
Chemoreceptors• Automatic control of breathingis influenced by feedback fromchemoreceptors, whichmonitor pH of fluids in thebrain and pH, PCO2 and PO2 ofthe blood.– Central chemoreceptors inmedulla– Peripheral chemoreceptorsin carotid and aorta arteries
Chemoreceptors• Aortic body sends feedback tomedulla along vagus nerve.• Carotid body sends feedbackto medulla alongglossopharyngeal nerve.
Regulation of Ventilation
Effects of pH and PCO2onVentilation• When ventilation is inadequate, CO2 levelsrise and pH falls.carbon dioxide + water = carbonic acid• In hyperventilation, CO2 levels fall and pHrises.• Oxygen levels do not change as rapidlybecause of oxygen reserves inhemoglobin, so O2 levels are not a goodindex for control of breathing.
Effects of PCO2on Ventilation• Ventilation is controlled to maintainconstant levels of CO2 in the blood.Oxygen levels naturally follow.
Chemoreceptors in the Medulla• When increased CO2 inthe fluids of the braindecrease pH, this issensed bychemoreceptors in themedulla, and ventilationis increased.– Takes longer, butresponsible for70−80% of increasedventilation
Peripheral Chemoreceptors• Aortic and carotidbodies respond torise in H+due toincreased CO2levels.• Respond muchquicker
Effect of Blood PO2on Ventilation• Indirectly affects ventilation by affectingchemoreceptor sensitivity to PCO2– Low blood O2 makes the carotid bodies moresensitive to CO2.
Pulmonary Receptors andVentilation• Unmyelinated C fibers: affected bycapsaicin; produce rapid shallow breathingwhen a person breathes in pepper spray• Receptors that stimulate coughing:– Irritant receptors: in wall of larynx; respond tosmoke, particulates, etc.– Rapidly adapting receptors: in lungs; respondto excess fluid
Pulmonary Receptors andVentilation• Hering-Breuer reflex: stimulated bypulmonary stretch receptors• Inhibits respiratory centers as inhalationproceeds• Makes sure you do not inhale too deeply
IX. Effect of Exercise and HighAltitude on RespiratoryFunction
Ventilation During Exercise• Exercise produces deeper, faster breathing to matchoxygen utilization and CO2 production.– Called hyperpnea• Neurogenic and humoral mechanisms control this.
Acclimation to High Altitude• Adjustments must be made to compensate for loweratmospheric PO2.– Changes in ventilation– Hemoglobin affinity for oxygen– Total hemoglobin concentration