RESPIRATION Function of respiration= gas exchange Inspiration: O2 inhaled in lungs Expiration: CO2 produced during oxidative process is exhaled Both gases are transported by the blood Both the cardiovascular and respiratory system are involved

The respiratory tract Best to breath through the nose (nasal turbinates) Pharynx Larynx (split for food) Trachea split into right and left main bronchi Lobar bronchi (3 right, 2 left) Alveoli balloons for gas exchange Alveolar sacs looks like grapes Diaphragm, intercostal muscles Pleural space between thoracic wall and the lung Surface of lung= visceral pleura Outside wall= partial pleura Left and right pleural space is separate

Pneumothorax Pleural space pressure = -5 cm H2O Pneumothorax= uncoupling of chest and lungs

Subdivisions of conducting airways/terminal respiratory units Conducting zone (cartilages, smooth muscles) Trachea Bronchi Bronchioles Terminal Respiratory zone Respiratory bronchioles Alveolar ducts Alveolar sacs

Function of conducting airways Defense against bacterial infection and foreign particles Epithelial lining of bronchi has half like projects called cilia Nicotine paralyzes them Epithelial glands secrete mucous Particles still to mucous and cilia sweep them to the pharynx Warm and moisten inhaled air Sound and speech Regulation of air flow: smooth muscles and contract and relax

Function of respiratory zone 300 million alveoli for gas exchange each alveoli has 1000 capillaries

Blood supply Pulmonary circulation: bring mixed venous blood to the lungs Bronchial circulation: supply oxygenated blood from systemic circulation to tracheobronchial tree No venous system goes with mixed venous blood

Alveolar cell types Epithelial Type I: little is known about the specific metabolic activities Type II: produce pulmonary surfactant Decrease surface tension of the alveoli Endothelial Walls of pulmonary capillaries Can be as thin as 0.1 micron Alveolar macrophages

Respiratory muscles Inspiratory Diaphragm (pulls down, abdomen goes up, lifts lower ribs) Innervated by phrenic nerves from cervical segments 3, 4, 5 Parasternal intercartilaginous (elevateribs) External intercostals (elevate ribs) Accessory (only used for exercise, active breathing) Sternocleido-mastoid (elevates sternum) Scalanus (anterior, middle, posterior) Expiratory relax inspiratory muscles Active breath Internal intercostals: depress ribs Abdominal muscles: push abdomen in and pushes diaphragm up Rectus abdominis, external oblique, transverse abdominis

Inspiration Diaphragm and intercostal muscles contract Thoracic cage expands Intrapleural pressure becomes SUBatomospheric Transpulmonary pressure increases Lungs expand Alveolar pressure becomes SUBatmospheric Air flow into alveoli

Expiration Diaphragm and external intercostal muscle stop contracting Chest wall moves inwards Intrapleural pressure goes back to preinspiratory value Transpulmonary pressure goes back towards preinspiratory value Lungs recoil Air in lungs is compressed Alveolar pressure is > atm Air flows out of lungs

Spirometrey Measure lungs Subject breats through a tube Air in upside down canister floating in water (spirometer) When subject breathes in canister goes down pen goes up

Terminology

Measurement of FRC Use helium dilution technique Helium in spirometer (measure volume & concentration) Breath out to FRC then open valve FRC= (C1xV1/C1) V1

Ventilation Minute ventilation: amount of air inspired or expired over one mine = Tidal volume x frequency Not all air inhaled into lungs reach the gas exchange area Anatomical dead space (air remains in the conducting airways) About 150 mL in adult (same as weight in pounds, estm) Alveolar ventilation= (tidal volume-dead space) x frequency

Alveolar dead space Pathological Due to decreased blood supply or no blood supply (blood clot) Physiological dead space= (alveolar + anatomical) dead space

Partial pressure = Total pressure x Fractional concentration in dry gas In dry gas = (Total pressure- 47mmHg) x Fractional concentration in dry gas In water vapor

Alveolar ventilation Hyperventilation: More O2 is supplied and more CO2 is removed than the metabolic rate required Ventilation exceed needs of the body Not in exercise

Alveolar hypoventilation Less O2 and more CO2 Due to: chronic obstructive lung disease, damage to respiratory muscles, chest cage is injured (lungs collapse), CNS is depressed

Diffusion rate Alveoli capillary occur by passive diffusion Ficks Law: diffusion proportional to surface area (50-100 m2) Partial pressure gradient 1/thickness (~0.2mm) Surfactant, alveolar epithelium, epithelial membrane, interstitial space, capillary membrane, capillary endothelium, plasma, RBC ALSO gas must be soluble in the liquid amount of gas dissolved is proportional to its partial pressure (Henrys Law) CO2 is 20 X MORE soluble than o2 Difference in partial pressure is 10X SMALLER than for oxygen Time required to reach equilibrium for both gases is the same

Transit time Takes 0.75 seconds Reaches max at 0.3 If exercising: transit time is LESS 0.5 s but this is no problem IF pulmonary edema: fluid in interstitial space dash line No problem if not exercising BUT there is a problem during exercise

Pulmonary circulation and blood pressure RIGHT ventricle develops pressure of 25 mmHg (vs. 120mmHg) Pulmonary capillaries are THINNER and contain less smooth muscle Low vascular resistance (~10x) and high compliance to accept the whole cardiac output at all times Drop in pressure in pulmonary is 10x less than in systemic Don't need high pressure (short distance) DON'T want bleeding in alveoli

Accommodation of pulmonary blood vessels Can accommodate 2-3 increase in cardiac output without change in pressure Either by recruitment or distension DRUGS (serotonin, histamine, norepinephrine): contaction of smooth muscle= increase pulmonary resistance in larger arteries DRUGS (acetylcholine, isoproterenol): relax smooth muscle= decrease resistance Reflex vasoconstriction: where lungs are poorly oxygenated Nitric oxide (by endothelial cells) relax vascular smooth muscle= vasodilation

Effects of gravity on pulmonary blood flow Test performed by injecting radioactive xenon in peripheral vein More blood flow at the bottom of the lungs Slightly lower blood flow at bottom is due to extra-alveolar vessels being LESS expanded at low lung volumes

Effect of gravity on ventilation Alveoli at the top of the lungs are MORE OPEN at rest Think of a slinky Bottom can open more and thus the a larger change of volume GREATER ventilation at the bottom

Distribution of ventilation perfusion ration in the lungs Gravity has a greater effect on flood flow than ventilation TOP: more ventilation than blood flow Middle: perfect ratio Bottom: More blood flow than perfusion

Measuring pulmonary blood flow using Ficks principle Oxygen consumption per min= O2 taken up by the blood in the lungs in 1 min VO2(dot)= Q(dot) (concentration of O2 in arteries concentration of O2 in pulmonary artery)

O2 in plasma Directly proportional in partial pressure of gas O2 is very insoluble 0.3 mL of O2 in 100 Ml O2 consumption is about 300 ml/min Hemoglobin permets 6X more O2 4 subunits: heme (iron-oxygen bind) + globin (CO2 bind) Hb + O2 HbO2 O2 bound to hemoglobin= 19.5 Ml/100 mL plasma O2 bound to Hb does not contribute to the PO2 of the blood PO2 determines the amount of O2 that combines with Hb

The O2 dissociation curve Determines the amount of O2 carried by Hb Curve is flat at high values of PO2 and steep at low PO2 Load where O2 is available, unload where it is needed (tissues) Eg// PO2 drop from 4020= 75% to 35% 100 80 mmHg= decrease by 3% Anaemia= decreased Hb= less O2

Shape of hemoglobin shape determines affinity 1st heme +O2 increases the affinity for the second heme for O2 Called cooperative binding Myoglobin (skeletal) like Hb but only binds to 1 O2 HYPERBOLIC dissociation (only release at VERY low PO2)

The Bohr effect Hb O2 curve shift to the RIGHT when blood CO2 or temperature increases, or blood pH decreases Eg// exercise= for a given drop in PO2 an additional amount of O2 is released to working tissues desaturates faster Little effect on the total amount of O2 combined with Hb above 80 mmHg

Carbon monoxide poisoning CO has higher affinity for Hb (210x) Reduce O2 ALSO shirt O2 dissociation curve to the LEFT Oxygen is NOT released No increase ventilation because PaO2 remains normal

Transport of CO2 Physically dissolved (10%) Combined with Hb (11%) As bicarbonate (79%) Equation 1: CO2 + H2O with (CA) H2CO3 Equation 2: H2CO3 HCO3- + H+

The Haldane effect H + HbO2 HHb + O2 Hb release O2 and can bind to H+ Acts as a buffer Reduced Hb helps with blood loading of CO2 by pushing equation 1 and 2 to the right For a given PCO2, more CO2 is carried in deoxygenated blood than in oxygenated blood O2 saturation of blood SHIFTS CO2 dissociation by shifting it to the RIGHT THUS: mixed venous blood can carry more CO2 than arterial

IF hyperventilating: too much O2, increase PO2 because flat relationship DON'T increase amount of oxygen in blood IF hyperventilating: too much CO2, decrease PCO2 decrease CO2 content in blood

Respiratory failure of Gas exchanging capabilities: pulmonary edema Neural control of ventilation Neuromuscular breathing apparatus

Hypoxia (Hypoxemia) Deficient blood oxygenation (low PaO2, low % Hb) Cause Inhalation of low PO2 (high altitude) Hypoventilation Ventilation/perfusion imbalance Shunts of blood across the lungs Venous blood bypass gas exchange region (foremen valley) O2 diffusion impairment

Voluntary vs. Automatic breathing CNS integrates all information: Cerebral hemisphere: voluntary Brainstem (pons and medulla): involuntary Breaking point between voluntary and automatic (PCO2=50mmHg, PO2=70 mmHg: don't memorize)

Basic elements in the respiratory control system Sensors: gather info about lung volume, and O2 and CO2 content Controllers: information is integrated Effector: neural impulse sent to respiratory muscles

Medulla Contains pacemaker 2 groups Ventral respiratory group that generates the basic rhythm Dorsal respiratory group that receives several sensory inputs They are connected Generate the basic respiratory RHYTHMICITY

Upper pons Also called rostral pons Turn of inspiration Smaller tidal volume, increased breathing frequency Cutting pneumotaxic centers cause breathing to become deep and slow Same effect as cutting the vagus nerves which bring afferent information Removing upper pons and the vagus nerves causes APNEUSES (tonic inspiratory activity

Lower pons Also called apneustic center Promote inspiration Chemoreceptors Measure PO2, PCO2, pH Information carried to respiratory neurons Activity increase if PaO2 LESS than 60 mmHg, or PaCO2 GREATER than 40 mmHg Decrease if PaO2 GREATER than 100 mmHg or PaCO2 LESS than 40

Central chemoreceptors Located on ventral surface of the medulla Detect pH of CSF Give rise to the main drive to breath under normal conditions Bathes in ECF: if CO2 increases diffuse blood brain barrier (NOT HCO3 or H+) decrease of pH stimulate chemoreceptor VERY sensitive

Peripheral chemoreceptor Detect changes in PO2 but also stimulated by increased PCO2 and decreased pH Located in carotid bodies and aortic bodies Made of blood vessels, structural supporting tissue, and umerous nerve endings of glossopharyngeal (carotid, IX nerve) and vagus nerve (in aortic, X nerve) Afferent project to dorsal group of respiratory nerons in the medulla Only sensitive when PO2 is below 60 mmHg Sensitive at any PCO2 level

Mechanical receptors Pulmonary stretch receptors Irritant receptors Juxta-capillary or J receptors (c-fibers) All afferent travel in vagus nerve If it is cut slow, deep breathing

Pulmonary stretch receptors Located in smooth muscle of trachea down to terminal bronchioles Innervated by myelinated fibers: dishcnage Dischange in response to distension of the lung Activity sustained as long as lung is distended Activitiy increases as lung volume increases

Hering Breuer Inflation Reflex Decrease in frequency due to prolongation of expiratory time Increase in lung volume inhibit beginning of the next inspiratory effort Reflex is weak in adults, noticeable in infants and animals First feedback loop ever studies in physiology

Irritant receptors Located between airway epithelial cells in the trachea down to respiratory bronchioles Stimulated by noxious gases, smoke, histamine, cold air, dust Innervated by myelinated fibers Stimulation bronchoconstruction and hyperpnea (increase in breathing depth) Allergic asthmatic attack: bronchoconstriction triggered by histamine

Juxta-capillary receptors Located in alveolar walls close to capillaries Innervated by NON-myelinated fibers with short lasting burst of activity Stimulated by increase in pulmonary interstitial fluid Effects: rapid, shallow respiration can cause apnea May play role in dyspnea (difficulty in breathing) Associated with left heart failure, lung edema, congestion

Elastic properties of the lungs and chest wall To evaluate: measure change in recoil pressure for a given change in lung volume Recoil pressure: difference between inside and outside Lung volume measured by spirometer Pressure measured using manometer

Pressures Lung: alveoli- pleural Pleural pressure= pressure in esophagus Measure using a flexible balloon Wall: pleural- body surface Transrespiratory: alveoli- body surface

Compliance of lungs Ease with which structure can be distended C= change in volume/ change in pressure Measured by determining static pressure-volume relationship which lung is decreased from TLC Decreases with lung volume Fibrosis: fibrotic tissue on alveoli stiff lungs LOWER compliance Emphysema: destruction of alveolar walls difficult to deflate HIGHER compliance Actually C= change in V/{(Palv-Ppl)1-(Palv-Ppl)2} Elastance= 1/compliance

Compliance of chest wall Elderly have stiffer chest wall Cw= change in volume/change in pleural pressure 60% vital capacity= equilibrium size of chest Large volume want to collapse: + pressure Small volume want to expand: - pressure

Volume pressure relationship of chest wall and lung TOTAL pressure= chest wall pressure + lung pressure FRC: when pressure=0 Whole system is in equilibrium

Dynamics of a breath Asthma: hyper contractility of smooth muscles (inflammatory) Respiratory system= pup with elastic and flow-resistive properties At rest: FRC and Ppl is NEGATIVE During inspiration: MORE negative Ppl= expansion of lungs Flow= (Palv-Patm)/R

One breath As lung pulled out Ppl becomes more subatomic As volume increase: gas in lungs is decompressed Palv becomes NEGATIVE Negative pressure gradient= air flow TO lungs Lung filled with air= pressure gradient and air flow gradually decrease STOPS when Palv=Patm

Rate of change in pleural pressure depends on contraction of diaphragm and airway resistance Dashed line= amount of pleural pressure necessary to overcome airway and tissue resistance

Airway resistance Raw= (Palv-Pao)/Flow Large diameter= large flow= smaller resistance Resistance is related to airway caliber Important determinant of lung function Asthma= high resistance

Dynamic compression of airways Descending portion of flow-volume curve is INDEPENDENT of effort b/c compression of airways by intrathoracic pressure

Forced expiration Pressure drop along the airways as flow begins There is a point at which there is a positive pressure tending to CLOSE the airways

Diseases Pulmonary fibrosis (restrictive disease): max flow rate and max volume exhaled are reduced at given volume= greater flow Emphysema (obstructive diseases): low flow rate, scooped out appearance at given volume= smaller flow

Surface tension Molecules in surface of film tend to arrange themselves in the configuration involving the lowest energy Water more attracted to themselves than air If surface is curved tension can produce pressure LaPlaces Law: P=4T/r Small bubble= greater pressure Small bubbles will collapse

Pulmonary surfactant Reduce surface tension in alveoli Decrease surface tension MORE in smaller alveoli In smaller ones: they are stacked up in layers Babies in vitro do not have surfactant

Minute ventilation during exercise Both tidal volume and breathing frequency increase proportionally At some point tidal volume plateaus Because lung compliance decreases at high lung volumes Increasing tidal volume takes too much energy Spend the rest of energy increasing frequency Decrease time of expiration MORE than inspiration Usually it takes longer for expiration Greater peak expiratory flow rate than peak inspiratory flow rate

Ventilation does NOT limit exercise Resting values of minute ventilation can increase 35 x Cardiac output can only increase 5-6x Ventilation/perfusion ratio is about 1 at rest Exercise= increase in ratio Similar values for a less fit individual Alveolar surface area is 50m2 Average blood volume is 5L only 4% is in the lungs

Minute ventilation and metabolic rate during exercise Minute ventilation increases linearly with metabolic rate UP TO ABOUT 50% to 65% of max metabolic rate Then ventilation rate is GREATER than the change in VO2 Ventilator inflection point (not understood- not lactic acid) Hyperventilating THUS: you are not limited by ventilation

Controls of ventilation in exercise Central chemoreceptors: pH increases in medullary ECF This DECREASES ventilatory response THUS: this is only important at rest Peripheral chemoreceptors PaO2 is constant PaCO2 decreases pH decreases (lactic acid) and PaO2 fluctuates subtly Possible that the fluctuations increase the sensitivity of peripheral chemoreceptors to CO2 and H+ Peripheral mechanoreceptors Muscle spindles, golgi tendons, skeletal joint receptors Does produce an increase in ventilation BUT very SMALL

Onset and recovery from exercise Ventilation starts increasing BEFORE exercise starts Control is thought to be neural Similar control is thought to operate at the end of exercise Humoral control is believed to be responsible for the ventilator response during the exercise event