*coloured blue parameters are already done**forced expiratory flow from 25-75% VC***mid-maximal expiratory flow: The third measure made by the spirogram is the average flow rate over the middle section of the vital capacity. This test has several names, including the MMEF (mid-maximal expiratory flow) and the FEF25-75 (forced expiratory flow from 25 to 75% of the vital capacity). It can be calculated from the spirogram by dividing the vital capacity into quarters, dropping a line from the first (25%) and third (75%) quartiles, and then connecting the lines and measuring the slope. Volume/time is a flow rate and thus the slope is a flow rate (the only real flow rate that can easily be obtained from the spirogram).
*VL corresponds to the lung volume at the instant we open the mouth valve and allow the He to beginequilibrating. If we wish to measure FRC, we open the valve just after the subject has completed a quietexpiration. If the subject has just completed a maximal expiration, then the computed VL is RV.
The constant, K, equals 863 mm Hg for conditions of BTPS and when Va and Vco2 are expressed in the same units (e.g., mL/min). BTPS means body temperature (310 K), ambient pressure (760 mm Hg), and gas saturated with water vapor. Using the rearranged form of the equation, alveolar Pco2 can be predicted if two variables are known: (1) the rate of CO2 production from aerobic metabolism of the tissues, and (2) alveolar ventilation, which excretes this CO2 in expired air. A critical point to be understood from the alveolar ventilation equation is that if CO2production is constant, then PaCO2 is determined by alveolar ventilation. For a constant level of CO2 production, there is a hyperbolic relationship between PaCO2 and Va. Increases in alveolar ventilation cause a decrease in PaCO2; conversely, decreases in alveolar ventilation cause an increase in PaCO2. Another way to think about the alveolar ventilation equation is to consider how the relationship between PaCO2 and Va would be altered by changes in CO2 production. For example, if CO2 production, or Vco2, doubles (e.g., during strenuous exercise), the hyperbolic relationship between PaCO2 and Va shifts to the right. Under these conditions, the only way to maintain PaCO2 at its normal value (approximately 40 mm Hg) is for alveolar ventilation to double also. The graph shows that if CO2 production increases from 200 mL/min to 400 mL/min, PaCO2 is maintained at 40 mm Hg if, simultaneously, Va increases from 5L/min to 10L/min.
* Doesn’t mean that ventilation and perfusion to the entire lung is normal ! E.g. in lobar pneumonia, V to the affected lobe is affected, and perfusion isnt….but since hypoxia causes vasoconstriction – eventually perfusion too is affected….so V/Q remains ‘normal’ though both V and Q are in fact abnormal
The effect of regional V/Q on blood gases is shown in the above table. Because overventilation relative to blood flow occurs in the apex, the PaO2 is high and the PaCO2 is low at the apex of the lungs. Oxygen tension (PO2) in the blood leaving pulmonary capillaries at the base of the lungs is low because the blood is not fully oxygenated as a result of underventilation relative to blood flow. Regional differences in V/Q tend to localize some diseases to the top or bottom parts of the lungs. For example, tuberculosis tends to be localized in the apex because of a more favorable environment (i.e., higher oxygen levels for Mycobacterium tuberculosis).
In continuation of the last table showing effects of V/Q in various lung zones on blood gases
*For example, in a person at rest, O2 consumption is about 250 mL O2/min. If O2 delivery to the tissues were based strictly on the dissolved component, then 15 mL O2/min would be delivered to the tissues (O2 delivery = Cardiac output × dissolved O2 concentration, or 5 L/min × 0.3 mL O2/100 mL = 15 mL O2/min). Clearly, this amount is insufficient to meet the demand of 250 mL O2/min. An additional mechanism for transporting large quantities of O2 in blood is needed-that mechanism is O2 bound to hemoglobin.
Volumes & Capacities Tidal volume x frequency of breaths = Total ventilation (L/min)
Factors affecting Vol & Capacities Inspiratory reserve volume (IRV) Current lung volume Lung compliance Muscle strength Comfort Flexibility of skeleton Posture Expiratory reserve volume (ERV) Same as above + strength of abdominal M
Why have RV? Airways would collapse Would take an unusually high pressure to inflate them during inspiration Modest RV minimizes airway collapse, thereby optimizing ventilation efficiency Would affect blood oxygenation Blood flow to the lungs and other parts of the body is continuous During collapse – Po2 will plummet
Normal Values FVC = 5.0 L FEV1 = 3.8 L FEF25-75 = 3.25 L/sec FEV1/FVC = 0.76 PEFR = 10 L/sec
FEV1 Volume of air that can expired in the 1st second of a forced maximal expiration Normally 80% of vital capacity, expressed as: FEV1/VC = 0.8 Obstructive lung disease (asthma) – FEV1 is reduced more than VC (FEV1/VC decreased) Restrictive lung disease (fibrosis) – both FEV1 & VC are reduced (FEV1/VC normal or increased – since their elastic recoil is more aggressive!)
Helium Dilution Method(for TLC & FRC)* [He]initial = 10% VS(initial) = 2 L [He]final = 5% (assume) Final Vol = VS + VL C1xV1 = C2xV2 [He]initial x VS= [He]final x (VS +VL)
Dead Space Volume that does not participate in gas exchange Anatomical & Physiological Anatomical DS Nose (and/or mouth), trachea, bronchi, and bronchioles Volume = 150 ml Hence out of VT only 350 ml reaches gas exchange areas First air expired – DS air To sample alveolar air - sample end-expiratory air
Anatomical DS: Fowler’s Method Assuming: Gray area: 30 sq. cm Pink area is 70 sq. cm Total volume expired = 500 ml DS would be:
Physiological DS: Bohr’s Method Based on: Measurement of Pco2 of mixed expired air (PeCO2) AND 3 assumptions: (1) All of CO2 in expired air comes from exchange of CO2 in functioning (V & Q) alveoli; (2) There is no CO2 in inspired air (3) Physiologic DS neither exchanges nor contributes any CO2 If Physiologic DS = 0 then, PeCO2 = alveolar Pco2 If Physiologic DS = x then, PeCO2 < alveolar Pco2 Diluted by physiologic DS
Physiological DS: Bohr’s Method Hence, by comparing PeCO2 with PaCO2, dilution factor can be measured This dilution factor reflects Physiologic DS Problem: alveolar air cannot be sampled directly Solution: arterial PaCO2 (PaCO2)reflects alveolar PaCO2 Fraction is dilution factor
Ventilation Rates Volume of air moved into & out of lungs per unit time Ventilation rate can be expressed in 2 ways: Minute ventilation Total rate of air movement into & out of lungs/minute VTx breathes/min = 500 x 12 = 6L/min Alveolar ventilation Total rate of air movement into & out of lungs/minute (corrected for DS) (VT – VD) x breathes/min (500 – 150) x 12 = 4200 ml/min
Example: Calculating Ventilation Rates A man who has the following data: Tidal volume = 550 mL Breathing rate = 14 breaths/min Pco2 (arterial blood) = 40 mm Hg Pco2 (expired air) = 30 mm Hg. What is his minute ventilation? What is his alveolar ventilation? What percentage of each tidal volume reaches functioning alveoli? What percentage of each tidal volume is dead space?
Alveolar Ventilation Equation Fundamental relationship of respiratory physiology Describes the inverse relationship b/w VA & alveolar Pco2 (PaCO2) or
Effect of Variations in Respiratory Rate and Depth of Alveolar Ventilation
Pulmonary Circulation Pulmonary artery (differences from systemic arteries) Thinner Larger in diameter Highly distensible Less no. of arterioles Overall VERY COMPLIANT (7 ml/mm Hg = entire systemic arterial tree!) Accommodate 2/3 of SV of right ventricle Pulmonary veins As distensible as systemic veins Bronchial vessels 1-2 % of total C.O. Oxygenated blood Supplies lung tissue Bronchial veins empty into the left atrium Bronchial (& coronary) vessels causing slight shunting of blood Physiological shunt (PO2 of arterial blood is 2 mm Hg < than pulmonary vein blood)
Pulmonary Circulation Pressures in pulmonary system Right ventricle Systolic 25 mm Hg Diastolic 0-1 mm Hg Pulmonary artery Systolic 25 mm Hg Diastolic 8 mm Hg Mean 15 mm Hg Pulmonary arteriolar P (mean) – 12 mm Hg Pulmonary capillary P (mean) – 10.5 mm Hg Pulmonary venous P (mean) – 9 mmHg
Pulmonary Circulation Left atrial P & pulmonary venous P Mean P in left atrium and major pulmonary veins – 2 mm Hg (recumbent) Pulmonary Wedge Pressure 5 mm Hg Role in estimating pulmonary capillary P & left atrial P Blood flow through the lungs and its distribution Blood flow through lungs = C.O. Poorly aerated areas – vasoconstriction Diversion of blood to better aerated areas Time spent by RBC in navigating pulmonary capillary – 0.75 sec (total amount 75 ml) During exercise – 200 ml with time shortened
Distribution of Pulmonary Blood Flow Pulmonary circ. is low pressure/low resistance Hence gravity affects it more This effect causes ‘uneven’ perfusion in lungs Blood flow increases from apex to base (upright posture) Recumbent posture: flow > in posterior than anterior Supine: flow equalizes In stress (excercise) All areas even out!
Distribution of Pulmonary Blood Flow Hydrostatic Pressure (HP) difference in lungs Difference between highest & lowest point in lung – 30 cm apart This causes a pressure gradient of 23 mmHg 15 mmHg above heart level 8 mmHg below heart level Another way to look at it: Every 1 cm that an artery has to ‘ascend’ the lung A change in HP of 0.74 mmHg (1 cm H2O) occurs So an ‘ascend’ of 10 cm above heart level Induces HP change of 7.4 mmHg HP at heart level = 14 mmHg So, 14 <minus> 7.4 = 6.6 mmHg (arterial P in upper areas)
Distribution of Pulmonary Blood Flow Gravity affects arteries & veins alike throughout lung fields This also affects ventilation (V/Q ratios) Meaning, perfusion affects ventilation Conversely, alveolar pressure also influences perfusion Meaning, ventilation affects perfusion
Distribution of Pulmonary Blood Flow PA = pulmonary alveolar pressure Pa = pulmonary arterial pressure PV = pulmonary venous pressure
Lung Zones Zone 1 No blood flow during any part of cardiac cycle PA > Pa > PV Occurs in abnormalities such as: Positive pressure ventilation (Palv >>>) Hemorrhage (Ppc <<<) Zone 2 Pa > PA > PV Going down into zone 2 Hydrostatic P increases increasing Pa Zone 3 Pa > PV > PA
Normally, Zone 2 present in 10 cm above heart level to upper lung areas Zone 3 present in 10 cm above heart level to lower lung areas During exercise – entire lung may become – Zone 3! In vivo During respiratory cycle: PA b/c –ve during inspiration (promoting dilation of capillaries) During expiration it becomes +ve (constricting capillaries) During cardiac cycle P in arterioles & capillaries is >>> during systole Thus promoting dilation of pulmonary capillaries And is lowest during diastole Thus promoting dilation of pulmonary capillaries Thus blood flow through an alveolar vessel would be greatest when inspiration coincides with systole!!
Ventilation-Perfusion Ratio (V/Q) Defined as ratio of ventilation to blood flow Can be defined for: Single alveolus (VA / capillary flow) Group of alveoli Entire lung (Total VA / C.O.) Normal lung Overall V/Q = 0.8 Total VA = 4 L/min, CO = 5 L/min This value is averaged – differs in various zones
Ventilation-Perfusion Ratio (V/Q) V/Q only describes the nature of relationship b/w V & Q So a normal V/Q only means the relation is normal*
Integrating Lung Zones & V/Q Concept V & Q are both gravity-dependent; both increase down the lung Q shows about a 5-fold difference b/w the top & bottom of lung V shows about a 2-fold difference This causes gravity-dependent regional variations in the V/Q Ranging from 0.6 (base) - 3 or higher (apex) Q is proportionately greater than V at the base, and V is proportionately greater than Q at the apex
V/Q Affects Gas Exchange Three scenarios Va/Q = 0 Alveolar air equilibrates with venous blood Va/Q = infinity Alveolar air equilibrates with inspired air Va/Q = normal
Ventilation-Perfusion Ratio (V/Q) Physiological Shunt (V/Q= less than normal) Some blood may not get oxygenated due to poorly ventilated alveoli – shunted blood This, along with bronchial & coronary blood – Physiological Shunt Measurement: analyzing the concentration of O2 in both mixed venous blood and arterial blood, along with simultaneous measurement of cardiac output. Greater the physiologic shunt - greater the amount of blood that fails to be oxygenated!
Ventilation-Perfusion Ratio (V/Q) Physiological Dead Space (V/Q= greater than normal) Ventilation ‘wasted’ Ventilation is also wasted in anatomical DS Together : Physiological DS Measurement: appropriate blood and expiratory gas measurements into the following: When the physiologic dead space is great - much of the work of ventilation is wasted
Abnormalities of V/Q ratio Abnormal V/Q - Upper and Lower in Normal Lung Normal person – upright position Lung upper regions: Va/Q higher (Physio. DS) Lung lower regions: Va/Q lower (Physio. Shunt) In both cases – lung’s effectiveness for gas exchange decreases In exercise – situation improves!
Abnormalities of V/Q ratio Abnormal V/Q in COPD various degrees of bronchial obstruction occurs Emphysema occurs resulting in 2 scenarios: Small bronchioles obstructed – alveoli unventilated – V/Q=0 Other areas – wall destruction causes loss of blood vessels – ventilation wasted – V/Q = infinity
Alveolar-Arterial Difference (AaDO2) Relationship b/w PAO2 and PaO2 Even in normal people – there is a slight difference b/w the two Difference is called AaDO2 This slight difference is caused bu mixing of venous blood (thebesian + broncial veins) into oxygenated blood Increased AaDO2 is indicative of impaired gas exchange
Pulmonary Edema Any factor – causing pulmonary interstitial fluid pressure to rise from : -ve to +ve Left-sided heart failure or mitral valve disease Damage to the pulmonary blood capillary membranes caused by infections (pneumonia) or noxious material Pulmonary Edema Safety Factor Pulmonary Capillary Pressure must rise - 7 mm Hg to > 28 mm Hg to cause pulmonary edema This provides an acute safety factor against pulmonary edema of 21 mm Hg
Forms of Gases in Solution In alveolar air: There is one form of gas (expressed as a partial pressure) In solutions (blood): Gases are carried in additional forms: Gas may be dissolved It may be bound to proteins It may be chemically modified. Hence total gas concentration in solution= dissolved gas + bound gas + chemically modified gas Partial pressure of gas in a solution is exerted only by dissolved form!!
Gas Transfer & Transport Two types of gas movements in lungs Bulk flow (trachea to alveoli) Diffusion (alveoli to blood) Henry law states At equilibrium, amount of gas dissolved in a liquid (at a given temperature) is directly proportional to parital P & solubility of a gas Fick law states Volume of gas diffusing per minute across a membrane is directly proportional to: membrane surface area diffusion coefficient of the gas partial pressure difference of the gas And is inversely proportional to membrane thickness
Capillary blood flow & gas uptake Perfusion-limited vs Diffusion-limited gases* Difference b/w N2O, O2 and CO
O2 Transport in Blood O2 is carried in 2 forms in blood: Dissolved Bound to Hb Dissolved form Free in solution Approx. 2% of total O2 content of blood The only form of O2 that produces a partial pressure At normal PaO2 = 100 mm Hg, Concentration of dissolved O2 = 0.3 mL O2/100 mL Insufficient to meet tissue demands*
Bound with Hb Remaining 98% of the total O2 content of blood is reversibly bound to Hb Hemoglobin Globular protein consisting of four subunits Each subunit can bind one molecule of O2 - total of four molecules of O2 per molecule of Hb For the subunits to bind O2, iron in the heme moieties must be in the ferrous state (i.e., Fe2+)
O2-binding Capacity, O2Content&O2Saturation O2-binding capacity – max. amount of O2 that can be bound to Hb per volume of blood 1 g Hb = 1.34 mL O2 Normal conc. of Hb = 15 g/100 mL O2-binding capacity of Hb= 20.1 mL O2/100 mL blood O2content - actual amount of O2 per volume of blood
Problem An arterial blood gas reveals: PaO2 = 60 mmHg O2 saturation (SaO2) = 90% Patient's Hb = 14 g/dl What is the total (Hgb-bound +dissolved) O2 content?
O2 content = (14gm/dl x 1.34) x 90/100 + 0.3ml/dl O2 content = 17.18 ml/dl (normal = 20 ml/dl) The patient is treated with 30% supplemental O2, and a repeat arterial blood gas reveals: PaO2 of 95 mmHg O2 saturation of 97% What is the total O2 content now? 18.49
O2 Transport in Blood Quaternary structure of Hb determines its O2 affinity: T (tense) configuration: Hb in deoxygenated blood R (relaxed) configuration: Hb in oxygenated blood R statehas 500-fold more affinity for O2 than T state Positive cooperativity
O2 Transport in Blood Hb –O2 Dissociation Curve Studies the relation between PO2 and hemoglobin % saturation or O2 content of blood (O2 volume %) At arterial PO2 = 95 mmHg (resting conditions) Hb % saturation = 97% O2 volume % = 19.4 ml (~ 20 ml) At venous PO2 = 40 mmHg (resting conditions) Hb % saturation = 75 % O2 volume % = 14.4 ml P50 – partial pressure of O2 at which ½ Hb is saturated Basis of shape of the curve being sigmoid Positive cooperativity
Hb –O2 Dissociation Curve Maximum amount of O2 that can combine with Hb Normal conc. of Hb in blood = 15 gms/dl 1 gm Hb can bind = 1.34 ml O2 15 gm Hb can bind = 19.4 ml O2 (~20 volume %) In other words every 100 ml (dl) delivers ~ 20 ml of O2 Amount of O2 released from Hb to tissues Arterial blood status PO2: 95 mmHg Hb% saturation: 97% O2: 19.4 volume % Venous blood status PO2: 40 mmHg Hb% saturation: 75% O2: 14.4 volume %
Hb – Tissue Oxygen Buffer ‘Based on tissue need’ Under basal conditions Tissue O2 requirements = 5 ml/dl Change in Po2 = 55 mmHg O2 release = 5 ml/dl Under heavy exercise Extra 15-25 mmHg change in Po2 achieves – large release of O2 to tissues Reason: Po2 < 40 mmHg lies on STEEP part of curve – LESS change in Po2 results in MORE O2 release
Hb – Tissue Oxygen Buffer ‘Buffering action at fluctuating Alveolar Po2’ Alveolar Po2 fluctuates: At high altitudes: alveolar Po2 DECREASES In deep sea: alveolar Po2 INCREASES If alveolar Po2 falls to 60 mmHg – Blood Hb% - 89% (only 8% less than max. saturation) Hb%= 89 (5 ml O2 taken away – resting Po2 in venous blood 35 mmHg) If alveolar Po2 rises to 500 mmHg – Blood Hb% - 100% (only 3% above max. saturation) Hb%= 100 (5 ml O2 taken away – resting Po2 in venous blood is only slightly higher)
Shift of Hb – O2 Dissociation Curve Temperature Increase – right shift Decrease – left shift High temperature decreases Hb affinity for O2 Excercising muscle! Skin in cold temperature! 2,3-DPG @ rest – right shift in systemic circulation (beneficial) May cause difficulty in O2 pickup in lungs (if conc. Increases) Exercise Right shift
Shift of Hb – O2 Dissociation Curve Acid (Bohr pH effect) Metabolically active tissues – H+ production – displaces O2 from incoming Hb – Right shift Lungs – increased Po2 – displaces H+ - left shift CO2 (Bohr CO2 effect) Hypercapnia in tissues – right shift CO poisoning, HB-F Left shift
CO Poisoning Hb binding site for O2 and CO is the same! Binding capability of CO with Hb is 250 folds more than O2 Alveolar pressure of 0.4 mmHg (1/250 of normal Po2) CO competes equally with O2 for hemoglobin causes 1/2 Hb to bind with CO instead of with O2 Alveolar pressure of 0.6 mmHg – Lethal Clinical scenario Patient comes in with nervous signs No obvious signs of hypoxemia (no cyanosis, bright red blood,) Po2 is normal – body does not detect hypoxia! Treatment Pure O2 with 5% CO2