Respiratory physiology Tom Archer, MD, MBA UCSD Anesthesia

The dance of pulmonary physiology— Blood and oxygen coming together. www.argentour.com/tangoi.html The dance of pulmonary physiology— Blood and oxygen coming together.

But sometimes the match between blood and oxygen isn’t perfect! http://www.bookmakersltd.com/art/edwards_art/3PrincessFrog.jpg

Outline (1) Failures of gas exchange In anesthesia– think mechanical first! Hypoxemia is easier to produce than hypercarbia—why? Measuring severity of poor oxygenation Two pulmonary players—the burly and weakling alveoli (V/Q mismatch) Shunt He3 MR imaging in V/Q mismatch Diffusion barrier

Outline (2) Dead Space (anatomical + alveolar = physiologic) Capnography and ETCO2 Airway flow problems and flow volume loops Large airway-- Intra and extra thoracic Small airway (Intrathoracic, e.g. asthma, COPD) Pulmonary hypertension Exactly how does it kill patients? Interventricular septum bowing Common hemodynamic management of all stenotic cardiopulmonary lesions.

Failures of gas exchange Shunt Low V/Q Alveolar dead space Diffusion barrier High V/Q

For gas exchange problems: Always think of mechanical problems first: Mainstem intubation Partially plugged (blood, mucus) or kinked ETT. Disconnect or other hypoventilation Low FIO2 Pneumothorax

For gas exchange problems: Hand ventilate and feel the bag! Examine the patient! Look for JVD. Do not Rx R mainstem intubation with albuterol! Do not Rx narrowed ETT lumen with furosemide! Consider FOB and / or suctioning ETT with NS. THINK OF MECHANICAL PROBLEMS FIRST!

In life / medicine / gas exchange problems: Beware of tunnel vision. Get used to asking yourself, “What am I not thinking of?” “Asthma” = tracheal stenosis / tumor? “Bronchospasm” = dried secretions in ETT? Hypotension despite distended peripheral veins = pneumothorax? “Coagulopathy” = chest tube in liver?

All That Wheezes Is Not Asthma: Diagnosing the Mimics www.mdchoice.com/emed/main.asp?template=0&pag...

Failures of gas exchange causing hypoxemia External compression of lung causing atelectasis. Obesity, ascites, surgical packs, pleural effusion Parenchymal disease (V/Q mismatch and shunt) Asthma, COPD, pulmonary edema, ARDS, pneumonia, Tumor, fibrosis, cirrhosis (Intra-cardiac shunts)

Measuring severity of oxygenation problem: A-a gradient (from alveolar gas equation). Calculates “PAO2” Needs FIO2, PB, PaCO2, PaO2 Shunt fraction equation Needs PAO2, CcO2, CvO2, CaO2 PaO2 / FIO2 (< 200 in ARDS) None of these give us etiology or physiology (shunt vs. V/Q mismatch).

Hypoxia occurs more easily than hypercarbia. Why?

Two pulmonary players: The burly alveolus (high V/Q).

Two pulmonary players: The weakling alveolus (low V/Q).

A fundamental question: In terms of arterial O2 and CO2 tensions, can the burly alveolus compensate for the weakling alveolus? No, for PaO2. Yes, for PaCO2. This basic fact explains a lot. Know it cold.

Shunt, or “weakling” (low V/Q) alveolus SaO2 = 75% Normal alveolus SaO2 = 96% “Burly” (high V/Q) alveolus SaO2 = 99% Equal admixture of “weakling” and “burly” alveolar blood has SaO2 = (75 + 99)/ 2 = 87%. http://www.biotech.um.edu.mt/home_pages/chris/Respiration/oxygen4.htm Modified by Archer TL 2007

Can the burly alveolus compensate for the weakling alveolus? The weakling alveolus (shunt or V/Q mismatch) The burly alveolus pO2 = 50 mm Hg pO2 = 130 mm Hg SaO2 = 80% SaO2 = 98% SaO2 = 75% SaO2 = 75% pO2 = 50 mm Hg pO2 = 40 mm Hg pO2 = 130 mm Hg pO2 = 40 mm Hg Can the burly alveolus compensate for the weakling alveolus? Not for oxygen! The burly alveolus can’t saturate hemoglobin more than 100%. SaO2 of equal admixture of burly and weakling alveolar blood = 89%

Low V/Q alveoli cause widened A-a gradient, just like shunt Weakling Normal Burly http://www.lib.mcg.edu/edu/eshuphysio/program/section4/4ch5/s4ch5_11.htm

For CO2, burly alveolus CAN compensate for the weakling alveolus. Normal alveolus Burly alveolus Admixture of burly and weakling alveolar blood Average alveolar PACO2 = 40 mm Hg. Hence, PaCO2 = 40 mm Hg http://focosi.altervista.org/alveolarventilation2.jpg Modified by Archer TL

Can the burly alveolus compensate for the weakling alveolus? pCO2 = 44 mm Hg pCO2 = 36 mm Hg pCO2 = 44 mm Hg pCO2 = 46 mm Hg pCO2 = 36 mm Hg pCO2 = 46 mm Hg Can the burly alveolus compensate for the weakling alveolus? Yes, for CO2! The burly alveolus, if it tries real hard, can blow off extra CO2. Pulmonary venous blood pCO2 and PaCO2 = 40 mm Hg

Shunt etiologies Normal Intracardiac Intrapulmonary Bronchial circulation Thebesian veins Intracardiac Tetralogy of Fallot, VSD, etc. Intrapulmonary Bronchial intubation Obesity Cirrhosis Osler-Weber-Rendu

Hypoxemia due to shunt Increased FIO2 helps at low shunt percentages by dissolving more O2 in oxygenated blood. At high shunt percentages, increased FIO2 does not help appreciably. HPV decreases perfusion of hypoxic alveoli.

http://advan.physiology.org/cgi/content/full/25/3/159

Normal shunt– bronchial circulation and Thebesian veins aorta Pulmonary veins http://www.lib.mcg.edu/edu/eshuphysio/program/section4/4ch5/s4ch5_10.htm Modified by Archer TL 2007

Intrapulmonary shunt in obesity: When FRC is below closing capacity, perfusion of non-ventilated alveoli is SHUNT.

V/Q mismatch Emphasized by John West in the 1970’s. Seen in most lung diseases. Prototypes are: asthma, COPD, ARDS. V/Q mismatch and shunt both cause hypoxemia despite possible hyperventilation (burly alveoli can’t compensate for weakling alveoli).

He3 MR showing ventilation defects in a normal subject and in increasingly severe asthmatics. Author Samee, S ; Altes T ; Powers P ; de Lange EE ; Knight-Scott J ; Rakes G Title Imaging the lungs in asthmatic patients by using hyperpolarized helium-3 magnetic resonance: assessment of response to methacholine and exercise challenge Journal Title Journal of Allergy & Clinical Immunology Volume 111   Issue 6   Date 2003   Pages: 1205-11

He3 MR scans – ventilation defects in asthmatics Baseline Methacholine Albuterol He3 MR scans – ventilation defects in asthmatics Modified by Archer TL 2007

Diffusion barrier (DB) to O2 and CO2 and DLCO Conceptually difficult Thickened alveolar capillary membrane. Exercise induced hypoxemia d/t dec transit time DLCO related to many factors: Membrane barrier thickness Perfused alveolar surface area (COPD, lung resection) Cardiac output Hemoglobin concentration DB not usually a significant clinical problem for us.

DLCO related to many factors: Membrane barrier thickness Perfused alveolar surface area (COPD, lung resection) Cardiac output Hemoglobin concentration http://www.lib.mcg.edu/edu/eshuphysio/program/section4/4ch3/s4ch3_25.htm

Diffusion in alveolar capillaries normally complete in 0.25 seconds. Thickened alveolar membrane may require more time for equilibration, which may not be available at higher cardiac outputs. Result: desaturation with exercise. http://www.lib.mcg.edu/edu/eshuphysio/program/section4/4ch3/s4ch3_27.htm

Dead space (DS) Volume of expired gas which has not participated in gas exchange. Physiological DS = Anatomical DS + Alveolar DS VT (minute vent) = VA (alv vent) + VD (DS vent). PaCO2 is inversely proportional to alveolar ventilation. Know these facts cold.

PaCO2 is inversely proportional to alveolar ventilation. http://focosi.altervista.org/alveolarventilation2.jpg Modified by Archer TL

The same minute ventilation can cause markedly different amounts of alveolar ventilation, depending on tidal volume. http://www.lib.mcg.edu/edu/eshuphysio/program/section4/4ch3/s4ch3_22.htm

Anatomic and alveolar dead space Anatomic dead space gas comes out BEFORE alveolar CO2. Alveolar dead space gas comes out at the same time as CO2 from perfused alveoli. Alveolar dead space gas DILUTES CO2 from perfused alveoli. This is why ETCO2 < PaCO2.

Capnographs– two types CO2 vs. time (commonest, what we have). CO2 vs. expired volume (more useful)

Single breath oxygen technique Anatomical dead space Single breath oxygen technique http://images.google.com/imgres?imgurl=http://www.lib.mcg.edu/edu/eshuphysio/program/section4/4ch3/4ch3img/page15b.jpg&imgrefurl=http://www.lib.mcg.edu/edu/eshuphysio/program/section4/4ch3/s4ch3_15.htm&h=379&w=271&sz=57&hl=en&start=33&tbnid=9bhXZpatrf-ajM:&tbnh=123&tbnw=88&prev=/images%3Fq%3Dalveolar%2Bventilation%2B%26start%3D20%26ndsp%3D20%26svnum%3D10%26hl%3Den%26lr%3D%26sa%3DN

http://images. google. com/imgres. imgurl=http://www. lib. mcg http://images.google.com/imgres?imgurl=http://www.lib.mcg.edu/edu/eshuphysio/program/section4/4ch3/4ch3img/page15b.jpg&imgrefurl=http://www.lib.mcg.edu/edu/eshuphysio/program/section4/4ch3/s4ch3_15.htm&h=379&w=271&sz=57&hl=en&start=33&tbnid=9bhXZpatrf-ajM:&tbnh=123&tbnw=88&prev=/images%3Fq%3Dalveolar%2Bventilation%2B%26start%3D20%26ndsp%3D20%26svnum%3D10%26hl%3Den%26lr%3D%26sa%3DN www.lib.mcg.edu/.../section4/4ch3/s4ch3_15.htm

Alveolar dead space gas (with no CO2) dilutes other alveolar gas. ETCO2 = 40 mm Hg With no alveolar dead space ETCO2 = 20 mm Hg With 50% alveolar dead space 20 40 40 20 Alveolar dead space gas (with no CO2) dilutes other alveolar gas. 40 40 40 46 46 46

Capnography Obvious: picks up changes in ventilation (such as disconnection). Not so obvious: picks up changes in pulmonary perfusion. Commonest cause of abrupt fall in ETCO2 is hypotension (+ fall in PA pressure) with acute increase in alveolar dead space. Also think air / clot embolus

Capnography Upsloping alveolar plateau as sign of V/Q mismatch and / or delayed expiration. http://www.caep.ca/CMS/images/cjem/v53-169-f1.png

Diagnosing airway flow problems with flow volume loops. Clinically used and useful? Not! On the test? Probably! Interesting? Maybe.

www.lib.mcg.edu/.../section4/4ch8/s4ch8_22.htm

Why are flow volume loops so confusing? Flow rate L/s Flow out of lung (+) Expiratory phase Peak inspiration at high lung volume (TLC) Start inspiration at low lung volume (RV). FVC Inspiratory phase Flow into lung (-)

Obstructive lesions of large airways www.nature.com/.../pt1/fig_tab/gimo73_F6.html Intrathoracic obstruction is most severe during expiration and is relieved during inspiration. Extrathoracic obstruction is increased during inspiration because of the effect of atmospheric pressure to compress the trachea below the site of obstruction.

Flow-volume loop mnemonic (Jensen) “Ex – In, In – Ex” Expiratory obstruction = Intrathoracic variable obstruction Inspiratory obstruction = Extrathoracic variable obstruction

“In-Ex” Variable Extrathoracic Obstruction Typically the expiratory part of the F/V-loop is normal: the obstruction is pushed outwards by the force of the expiration. During inspiration the obstruction is sucked into the trachea with partial obstruction and flattening of the inspiratory part of the flow-volume loop. This is seen in cases of vocal cord paralysis, extrathoracic goiter and laryngeal tumours.

“Ex-In” Variable Intrathoracic Obstruction This is the opposite situation of the extrathoracic obstruction. A tumour located near the intrathoracic part of the trachea is sucked outwards during inspiration with a normal morphology of the inspiratory part of F/V-loop. During expiration the tumour is pushed into the trachea with partial obstruction and flattening of the expiratory part of the F/V loop.

Extrathoracic Fixed stenotic lesions of trachea Intrathoracic Typical flattening of flow-volume loop in fixed airway obstruction Fixed Large Airway Obstruction This can be both intrathoracic as extrathoracic. The flow-volume loop is typically flattened during inspiration and expiration. Examples are tracheal stenosis caused by intubation and a circular tracheal tumour.

Obstructive lesions of small airways show up in mid-expiration as “bowing” of expiratory tracing Obstructive Lung Disease In patients with obstructive lung disease, the small airways are partially obstructed by a pathological condition. The most common forms are asthma and COPD. A patient with obstructive lung disease typically has a concave F/V loop.

Pulmonary hypertension— What causes it? Exactly how does it kill patients?

What is the flow-limiting resistance in the entire circulation? Normally it is NOT the pulmonary circulation or any of the heart valves. Normally it is the systemic resistance arterioles (<0.4 mm in diameter)

Pulmonary vascular resistance in normal lung Normally, increased CO causes decreased Pulmonary Vascular Resistance via recruitment and distention of pulmonary capillaries. Normally, PA pressure stays the same despite increased CO.

Passive Influences on PVR: Capillary Recruitment and Distension http://www.lib.mcg.edu/edu/eshuphysio/program/section4/4ch4/s4ch4_19.htm

Normal circulation at rest. Pulmonary vasculature Tricuspid Aortic Mitral Pulmonic Normal circulation at rest. Cardiac output is limited by SVR. Heart gives body tissues what they “ask for”. Resistance arterioles

Pulmonary vascular resistance falls Tricuspid Aortic Mitral Pulmonic Normal circulation during exercise / arteriolar dilation: SVR falls, CO increases. Pulmonary resistance falls. Resistance arterioles– decreased SVR

http://www.pathguy.com/lectures/hipbp.gif

Pulmonary hypertension Acute pulmonary thromboembolism

Pulmonary hypertension Chronic pulmonary thromboembolism

Pulmonary hypertension develops when pulmonary arteries develop abnormal resistance When pulmonary vessels become high resistance (fibrosis, muscular hypertrophy) they can NOT dilate or recruit and PA pressure rises with increased CO.

Minimal LV compression Minimal RV distention High pulmonary resistance at rest Slight bowing of IV septum into LV cavity. Resistance arterioles

LV cavity compressed (diastole) RV distention and failure LV cavity compressed (diastole) Fixed or increased pulmonary resistance and / or increased CO RV distention and failure Intraventricular septal bulging poor LV filling fall in CO / BP death. Resistance arterioles—decreased SVR

Marcus JT

Dong SJ. Smith ER. Tyberg JV Dong SJ. Smith ER. Tyberg JV. Changes in the radius of curvature of the ventricular septum at end diastole during pulmonary arterial and aortic constrictions in the dog. [Journal Article] Circulation. 86(4):1280-90, 1992 Oct.

How does pulmonary hypertension kill patients? By causing the interventricular septum to bow into the LV cavity, diminishing its capacity. Cardiac output falls, BP falls, patient dies.

How do we keep PH from killing patients? Keep Pulmonary Vascular Resistance down. Keep Systemic Vascular Resistance up. Prevent increases in CO. This same logic applies to any stenotic cardiac lesion, such as AS!

Aortic stenosis at rest Pulmonary capillaries LV dilation / hypertrophy Tricuspid Aortic stenosis Mitral Pulmonic Aortic stenosis at rest Cardiac output not sufficient to cause critically high LV intracavitary pressure / LV failure. Resistance arterioles

Pulmonary capillaries (edema) LV failure / ischemia Tricuspid Aortic Stenosis Pulmonic Mitral Aortic stenosis with increased cardiac output / arteriolar vasodilation: Decreased SVR Fall in systemic BP and / or increase in LV intracavitary pressure ischemia or LV failure. Resistance arterioles– decreased SVR

Hemodynamic management of all stenotic cardio-pulmonary lesions: Keep systemic vascular resistance up and CO down. Avoid anemia, vasodilating anesthetic techniques. In PH, keep PVR as low as possible (avoid hypoxia, acidosis, hypothermia, consider pulmonary vasodilators)

Outline (1) Failures of gas exchange– 5 generic types. In anesthesia– think mechanical first! Hypoxemia is easier to produce than hypercarbia—why? Measuring severity of poor oxygenation Two pulmonary players—the burly and weakling alveoli (V/Q mismatch) Shunt He3 MR imaging in V/Q mismatch Diffusion barrier

Outline (2) Dead Space (anatomical + alveolar = physiologic) Capnography and ETCO2 Airway flow problems and flow volume loops Large airway-- Intra and extra thoracic Small airway (Intrathoracic, e.g. asthma, COPD) Pulmonary hypertension Exactly how does it kill patients? Interventricular septum bowing Common hemodynamic management of all stenotic cardiopulmonary lesions.

Outstanding resources for pulmonary physiology Medical College of Georgia: http://www.lib.mcg.edu/edu/eshuphysio/program/section4/4outline.htm Capnography.com

The End