SS Passo, Ph.

D Respiratory Physiology Review Mechanics Spirometry Tidal Volume Dead Space Alveolar Ventilation Functional Residual Capacity Vital Capacity Obstructive vs. Restrictive Disease Compliance Surfactant Flow-Volume Loops Gas Exchange PO2 Oxyhemoglobin Dissociation Curve Bohr Effect PCO2 CO2 Content Ventilation /Perfusion Ratio Normal Distribution of Ventilation Distribution of Perfusion VA/Qc mismatch A-a Gradient for O2 Causes of Hypoxemia VA/Qc mismatch Right-to left shunt Non-pulmonary hypoxemia Control of Ventilation Peripheral Chemoreceptors Central Chemoreceptors Anemia, CO poisoning Altitude

Spirometry Tidal Volume = VT = Volume of air that enters the lungs per breath Frequency of breathing/minute = f = 12/min Minute Volume = V = VT x f = 500 x 12 = 6000 ml/min

Dead Space (VD): air in the respiratory tree that does not engage in gas exchange Anatomical Dead Space (anat VD): Volume of air in the conducting airways (ml. of air in the anat VD ideal weight in lbs (70kg=150lbs).) Composition: End of inspiration (fresh air; 0% CO2) End of expiration ( used air; same as in alveoli) Alveolar Ventilation (VA) = Volume of fresh air that enters the alveoli/breath VA = V T - V D (500 -150) = 350ml Alveolar Ventilation/minute = VA = Volume of fresh air entering alveoli/min VA = (VT VD)f (500-150)12 = 4200 ml/min Alveolar Dead Space (alv.VD) : refers to air in alveoli that is supposed to engage in gas exchange but cant because there is a problem with perfusion (embolus). Physiological Dead Space (physiolVD)= Total VD = anat VD + alv VD Physiol.VD = anatVD = normal 2

PhysiolVD > anatVD = implies the presence of alv.VD Functional Residual Capacity: The FRC is the volume of air left in the lungs at the end of a passive expiration . It represents the equilibrium position that is achieved when the respiratory muscles are relaxed and the inward elastic recoil of the lungs is exactly balanced by the outward elastic recoil of the thorax Thus, the elastic properties of the lungs will determine the FRC. In highly elastic lungs (fibrosis) the FRC is decreased and the patient appears sunken-chested. In lungs that have lost their elasticity (emphysema; old age) the FRC is increased. The patient appears barrel-chested; the diaphragm is flattened. The diagram below, while not easily duplicated on human subjects, can be used to determine the FRC. .

Vital Capacity: The Vital Capacity (VC) is the maximum volume of air that an individual can move in a single breath. The most useful assessment of the VC is to do it as quickly and forcefully as possible, i.e. a "timed" or Forced Vital Capacity (FVC). During a FVC maneuver, the volume of air exhaled in the first second is called the Forced Expiratory Volume 1sec (FEV1sec). .

FEV1sec = 80% FVC Normal people can only exhale 80% of their VC in one second because during a forced expiration, IPP becomes positive and airways become compressed. Compression of the airways limits expiratory flow rates. Maximum expiratory flow rates are "effort independent". Obstructive Lung Disease FVC - decreased FEV1sec- decreased FEV1sec / FVC - decreased FEF25-75% - decreased Lung Volumes FRC increased RV- increased TLC- increased or normal Compliance curves Restrictive Lung Disease FVC - decreased FEV1sec - decreased FEV1sec / FVC - increased FEF25-75% - increased Lung Volumes: FRC decreased RV -decreased TLC decreased

Surfactant: At tidal volumes above FRC, most of the work of inspiration is expended to overcome the surface tension that exists at the gas - liquid interface of each alveoli. This work would be greater, if not for the presence of surfactant. Surfactant (dipalmitoylphosphatidyl choline) is produced by alveolar type II cells, Surfactant reduces the surface tension and thus increases lung compliance. A. In the absence of surfactant, the surface tension of the film lining the inside of the alveolus is constant and high. Thus, a small alveolus generates a greater pressure than a large alveolus and empties more rapidly (prone to collapse). This leads to progressive atelectasis. Psmall > Plarge

B. In the presence of surfactant, lung compliance is increased and lung stability is promoted, i.e., surfactant prevents progressive atelectasis. It does this by reducing the surface tension more in small alveoli than in large alveoli. . Psmall = Plarge Lung washings from infants with Respiratory Distress Syndrome of the Newborn (RDS) have a high surface tension that shows little variation in S.T. with area. Premature birth and maternal diabetes are risk factors. A lecithin/sphingomyelin ratio (L/S) of 2.0 or greater indicates lung maturity and a minimal risk for RDS. A gestational age of 34 weeks divides those with increased incidence and mortality from those relatively free of the disorder.

Flow-Volume loops found in obstructive and restrictive diseases are shown below. In obstructive disease, the flow-volume loop begins and ends at abnormally high lung volumes and the expiratory flow rate is lower than normal ( often exhibiting a scooped - out appearance ). In restrictive disease, the flow - volume loop begins and ends at unusually small lung volumes. When expiratory flow rates are compared at specific lung volumes, the rates in restrictive disease are somewhat greater than normal.

Gas Exchange Partial Pressure of Alveolar Gas: The partial pressure of alveolar gas depends on the ratio of alveolar ventilation (VA) to pulmonary capillary blood flow (QC). Ideal VA/QC = 0.8

Consequences of a change in VA/Qc : Low VA/Qc (<0.8)= decreased PAO2; increased PACO2 High VA/Qc (>0.8)= increased PAO2; decreased PACO2 O2 Transport Dissolved O2 PO2 reflects the concentration of O2 physically dissolved in the blood.. At a PO2 is 100 mmHg: 0.3 ml O2 is dissolved in 100 ml of blood (0.3 vol%). Maximum hyperventilation raises the PO2 to 130-135 mmHg (0.4 vol%).

Oxyhemoglobin: HbO2 % Saturation The PO2 in blood determines the percent of sites on Hb occupied by O2. When the PO2 is 100 mmHg, the Hb is 97.5% saturated. When the PO2 is 40 mmHg , the Hb is 75%. Same for anemia or polycythemia)

HbO2 Content: Each gram of Hb can combine with 1.34 ml. of O2. If the [Hb] is 15 gm/100ml, then the maximal amount of O2 per 100 ml. in combination with Hb: HbO2 content = (1.34 x Hb conc.)% satn HbO2 (1.34 x 15 )1.00 = 20 ml O2/100 ml blood = 20 vol%

When the PO2 is 100 mmHg, the Hb is 97.5% satd , carrying 19.5 out of a possible 20.0 ml of O2 in every 100 ml of blood (19.5 vol%). At a PO2 of 40 mmHg, the HbO2 content is 15 vol% (75% satd). Hyperventilation can significantly increase the PaO2 , but will have little effect on HbO2 content. Total O2 Content (vol%) = ml O2 dissolved + ml HbO2 PaO2 = 100 mmHg = PaO2 = 130 mmHg = 0.3 0.4 + + 19.5 19.5 = 19.8 vol% = 19.9 vol%

Thus, hyperventilation of healthy units does not add significant amounts of O2 to the blood leaving those units and cannot compensate for the low O2 of blood leaving units with a low VA/Qc Pulmonary disease always leads to hypoxemia Bohr Effect An increase in the PaCO2 , H+, or temperature of blood shifts HbO2 dissociation curve to the right, indicating a decrease in the affinity of O2 for Hb. Thus, the a-v O2 difference increases. A shift in the position of the oxyhemoglobin curve to the left indicates an increase in the affinity of O2 for Hb 2,3 DPG: An increase in 2,3, DPG shifts curve to right. Major stimulus is hypoxemia. 2,3 DPG decreases in outdated blood. Fetal Hb does not bind 2,3, DPG and is shifted to the left

Diffusing Capacity of the Lung for O2 The Diffusing Capacity indicates how many ml.O2 /min diffuse across the lungs Decreased in fibrosis, edema. Increased in exercise

CO2 Transport CO2 Gas Equation: PaCO2 = .86 VCO2 VA The equation predicts that doubling VA will halve the PaCO2

Hyperventilation of healthy lung units can compensate for the high CO2 in blood coming from diseased regions of the lung. Thus, in pulmonary disease the PCO2 can be high, low or normal (depending on degree of hyperventilation and/or severity of disease) CO2 , produced by cellular metabolism, diffuses into the blood where it is carried in 3 different forms:

1) Dissolved CO2 - responsible for the PCO2 2) Carbamino compounds - CO2 reacts with the free amino groups on Hb 3) Reduced Hb better buffer than oxyHb more free NH2 groups exposed 4) HCO3 -- Both in RBC and plasma. Most of the CO2 produced by metabolism is carried in the plasma in the form of HCO3

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Ventilation - Perfusion Ratio Regional variation in the distribution of Ventilation.

The above diagram refers to a normal individual in the erect position: Because of the weight of the lung (gravity), the IPP is less negative at the base than at the apex. As a consequence, alveoli at the base of the lung are relatively more compressed at FRC, but expand better on inspiration than those at the apex Alveoli at base are more compliant than those at the apex. Upon inspiration, more air goes to the base of the lungs than to the apex. Regional variation in pulmonary blood flow.

The above diagram refers to a normal individual in the erect position. Because the right ventricle develops a low pressure, blood flow to the apex of the lung is compromised. Most of the blood ejected by the right ventricle goes to the base.

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VA/Qc in the Erect Position (Normal) More air and more blood go to the base of the lungs than to the apex. However, more blood than air goes to the base. Low VA/QC at the base (low PaO2). Alveoli at the apex receive too much air for the amount of blood perfusing them High VA/QC at the apex (high PaO2). A - a Gradient for O2 Indicates the presence of a VA/Qc mismatch; the greater the mismatch, the larger the A -a gradient. If gas from an alveolus with a high PO2 mixes with gas from an alveolus with a low PO2, the PO2 in the resultant gas mixture is the arithmetic mean. If blood with a high PO2 mixes with blood with a low PO2, the PO2 in the resultant blood mixture is less than the arithmetic mean. This latter effect is a direct consequence of the shape of the HbO2 dissociation curve. A - a gradient for O2 Normal pulmonary function (5-10 mmHg): results from the VA/Qc mismatch between apex and base when the thorax is erect. Essentially disappears in the supine position. In the normal range in the hypoxemia associated with anemia and hypoxemia of non-pulmonary origin (coma, myasthenia gravis) Pulmonary disease: > 5-10 mmHg.

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Causes of Hypoxemia VA/Qc mismatch: Some regions of the lung have VA/Qc < 0.8 but not 0.

Amenable to O2 therapy. A a gradient increased CO2 can be high, low or normal. CO2 retention occurs as severity of disease worsens Right-to-left shunt : Some regions of the lung have VA/QC = 0

Not amenable to O2 therapy A a gradient increased CO2 can be high, low or normal. CO2 retention occurs as severity of disease worsens Non-pulmonary hypoxemia: Entire lung VA/Qc < 0.8 (coma, myasthenia gravis, obesity) Amenable to O2 therapy A a gradient in the normal range CO2 always high

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VA/Qc > 0.8

VA/Qc = infinity

VA/Qc = infinity represents alv. VD

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Regulation of Respiration Mechanoreceptors Slowly-Adapting Stretch Receptors: Located in small airways and connected to respiratory centers by afferent fibers in both vagus nerves. Increased afferent vagal activity generated by lung stretch inhibits further inspiration. Bilateral section of both vagus nerves results in a slow, deep pattern of breathing (Hering-Breuer Reflex). J receptors: Free nerve endings in the lung parenchyma that cause a rapid, shallow pattern of breathing when interstitial fluid accumulates (pneumonia, congestive heart failure). Peripheral Chemoreceptors Carotid Body: afferents to CNS in glossopharyngeal nerve (IX) Aortic Body: afferents to CNS in vagus nerve (X) The carotid body is the most important peripheral chemoreceptor in man. It receives the most blood per gram of tissue in the body and can meet all of its requirements for O2 by utilizing the O2 dissolved in blood. Thus, the carotid body will be stimulated whenever the PaO2 falls to a low enough value. Stimuli Primary stimuli: Decrease in PaO2 Decrease in pH Decrease in blood flow Secondary stimulus : Rise in PaCO2;. Sensitivity Oxygen: Carotid body does not begin to fire significantly until the PaO2 falls to 50 - 60 mmHg. Carbon Dioxide: Only about 10-20% of the total ventilatory response to inhaled CO2 is the result of carotid body stimulation.. Hydrogen Ion: A decrease in the pH of blood perfusing the carotid body will lead to an extremely deep and rapid pattern of breathing. Kaussmauls breathing in individuals with a diabetic keto-acidosis Blood Flow: A severe fall in blood flow (anaphylactic or hypovolemic shock) can compromise O2 delivery to the carotid body. Adaptation; Do not adapt

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Central Chemoreceptors Located on the ventrolateral surface of the medulla in contact with CSF. Stimulus:The hydration of CO2 and subsequent dissociation of H2CO3 in the CSF generates H+ . CSF H+ is the stimulus to central chemoreceptor. Sensitivity: Extremely sensitive. These receptors are responsible for the moment - to - moment control of breathing. Adaptation: The system does adapt; usually within 12-24 hours. Mechanism of adaptation may be the pumping of HC03 into or out of the CSF. Abnormal Situations: Chronic hypoventilation: Though the PaO2 is decreased and the PaCO2 is increased, only the peripheral chemoreceptors are driving respiration. Anemia: Total O2 content is decreased, but the PaO2 is normal. Therefore, there is no peripheral chemoreceptor response to this kind of hypoxia. CO is life - threatening because of the leftward shift in the HbO2 dissociation curve.

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High altitude The fall in ambient PO2 caused by the decrease in TBP leads to a decrease in PaO2. The hypoxia-induced ventilatory response is due to peripheral chemoreceptor activation and leads to a decreased PaCO2 (respiratory alkalosis) . Other acclimatory responses include an increase in 2,3, DPG and an erythropoetin-stimulated increase in the hematocrit. Associated with the alveolar hypoxia at high altitude is pulmonary vasoconstriction (pulmonary hypertension and right ventricular hypertrophy). The same holds for the alveolar hypoxia associated with pulmonary disease (cor pulmonale). The central chemoreceptors adapt to the respiratory alkalosis so that there is an additional increase in ventilation 12-24 hours after arriving at a high altitude.

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