Shunt & Deadspace
By Donald R. Elton, MD, FCCP
Lexington Pulmonary and Critical Care

Introduction
Shunt and dead space are terms used to describe extreme conditions where either blood flow or ventilation does not meet the other in the lung as it should for gas exchange to take place. While in their pure sense, the terms refer to the extreme conditions, they can also be used to describe areas or effects where blood flow and ventilation are not properly matched though both may be present to varying extents. Some refer to shunt-effect or dead space-effect to designate the ventilation/perfusion mismatch states that are less extreme than absolute shunt or dead space.

Shunt:
that part of the cardiac output that returns to the left heart without the benefit of exposure to ventilated alveoli.

The oxygen content of mixed arterial blood (CaO2) is determined by the content of oxygen in the blood that reached ventilated alveoli (CcO2), the content of oxygen in blood that bypassed ventilated alveoli (CvO2), and the proportion of the two. Thus the formula:

QS/QT = (CcO2 - CaO2) / (CcO2 - CvO2)

Normal shunt fraction (QS/QT) is less than 0.05 (<5%).

Remember CxO2="1.39" x Hb x SxO2 + 0.003 x PxO2

CcO2 is the content of oxygen in pulmonary capillary blood and is estimated by plugging in 100% as the saturation (1.00 for the math) since the PcO2 (pulmonary capillary PO2) can be assumed to be high enough to assure 100% saturation. The PcO2 itself cannot be directly measured so we use PAO2 (from the alveolar air equation) in its place. This means that CcO2="1.39" x Hb + 0.003 x PAO2

Dead space:
that part of inspired air that is exhaled without the benefit of exposure to perfused alveoli.
The carbon dioxide content of mixed exhaled gas (PECO2) is determined by the carbon dioxide content of the gas that came in contact with perfused alveoli (PACO2), the content of the gas that did not come in contact with perfused alveoli, and the proportion of the two. It can be assumed that there is no carbon dioxide in inspired air and thus no carbon dioxide in that part of the inspired volume that does not come in contact with perfused alveoli. One can also assume that gas that does contact perfused alveoli will equilibrate to the carbon dioxide content in the perfusing blood PACO2="PcCO2" or arterial blood PcCO2="PaCO2" since arterial carbon dioxide content is not greatly influenced by shunting). Thus the formula:

VD/VT="(PaCO2" PECO2) / (PaCO2 PICO2)

if one assumes that PICO2="0" the formula is simplified to:

VD/VT="(PaCO2" PECO2) / PaCO2

Normal VD/VT is less than 0.33 (<33%).

Example Calculations

Available data:

Hb 10 gm% PaO2 75 SaO2 97% Pb 750 mm Hg PvO2 33 SvO2 65% PaCO2 45 mm Hg PECO2 15 mm Hg FIO2 40%

Calculate the shunt & dead space from the above data.

The dead space is the easiest using

VD/VT="(PaCO2" PECO2) / PaCO2

VD/VT="(45" 15) / 45

VD/VT="30/45"

The shunt equation is more complicated and takes more steps to complete. We start by calculating the contents to plug into the shunt equation:

QS/QT="(CcO2" CaO2) / (CcO2 CvO2)

arterial content:

CaO2="Hb" x SaO2 x 1.39 + 0.003 x PaO2

CaO2="10" x .97 x 1.39 + 0.003 x 75

CaO2="13.48" + 0.225="13.705" Vol %

mixed venous content:

CvO2="Hb" x SvO2 x 1.39 + 0.003 x PvO2

CvO2="10" x .65 x 1.39 + 0.003 x 33

CvO2="9.035" + 0.099="9.134" Vol %

Before we can calculate the CcO2, we must calculate the PAO2:

PIO2="FIO2" x (PB 47)

PIO2="0.4" x 713="285.2" mm Hg

PAO2="PIO2" PaCO2 x 1.25

PAO2="285.2" 45 x 1.25

PAO2="285.2" 56.25="228.95" mm Hg

pulmonary capillary content:

(CcO2): CcO2="Hb" x 1.39 + 0.003 x PAO2

CcO2="10" x 1.39 + 0.003 x 229

CcO2="13.9" + 0.687="14.59" Vol %

We can now fill in the final shunt equation:

QS/QT="(CcO2" CaO2) / (CcO2 CvO2)

QS/QT="(14.6" 13.7) / (14.6 9.1) QS/QT="0.9" / 5.5="0.16" %

Example Cases
Joe Crisco: A 64 year old male presents to the emergency room with chest pain, shortness of breath, and nausea. Initially he only had pain upon heavy exertion but over the last week he's had episodes at rest. Today he has had the pain continuously for the past hour. On physical examination he is acutely dyspneic and cyanotic. His lung exam reveals crackles up to the shoulders bilaterally and his neck veins are distended. A blood gas is drawn on 60% oxygen by mask and reveals a pH of 7.34, a PaCO2 of 33, and a PaO2 44.

1. What is wrong with this patient?

2. Why is he hypoxic?

3. What can be done therapeutically?

Cathy Crush: A 32 year old woman is in the hospital recovering from a fractured hip which she suffered in a motor vehicle accident. At 3 am one morning she develops sharp right sided chest pain and becomes acutely short of breath. She's never had these symptoms before. On physical examination she appears anxious and tachypneic. Her lung examination reveals a pleural friction rub heard over the right lateral chest. A chest x-ray is essentially normal and an electrocardiogram is significant for right atrial enlargement and tachycardia. A blood gas on a 40% oxygen mask shows a pH of 7.35, a PaCO2 of 33, and a PaO2 58.

1. What is wrong with this patient?

2. Why is she hypoxic?

3. What can be done therapeutically?

Winston Salem: This 49 year old man had his right lung removed because of lung cancer 6 months ago. He presents today for a routine follow-up visit and room air blood gasses are drawn revealing a pH of 7.42, a PaCO2 of 35, and a PaO2 88.

1. Why are this man's blood gasses normal?

Oxygen - Hemoglobin Affinity
By Donald R. Elton, MD, FCCP
Lexington Pulmonary and Critical Care

Introduction
It is commonly thought that shifts in the oxyhemoglobin dissociation curve are important factors in adaptation to hypoxic conditions. In actual fact, the subject is more complex than is generally recognized and benefits (or detriments) resulting from changes in hemoglobin's affinity for oxygen can only be demonstrated under extreme conditions. Structure = Function Human hemoglobin exhibits a sigmoid relationship between PO2 and hemoglobin saturation. This shape of curve offers benefits in that almost complete saturation can be obtained over a wide range of oxygen partial pressures at the lung while large quantities of oxygen can be delivered to peripheral tissues once the oxygen partial pressure falls to lower levels than those normally encountered at the alveoli. Several factors can cause shifts of the curve but the sigmoidal shape of the curve is ordinarily preserved except in cases of carbon monoxide poisoning. The sigmoidal shaped curve results from steric interactions between adjacent heme molecules as they bind successively with oxygen.

P50
It is common to use the concept of P50 to describe the affinity of a given hemoglobin for oxygen. The P50 is the PO2 at which the hemoglobin becomes 50% saturated with oxygen. As the P50 decreases, oxygen affinity increases and visa verse. Normal adult Hemoglobin A has a P50 of 26.5 mm Hg while Fetal Hemoglobin F has a P50 of 20 mm Hg and sickle cell anemia Hemoglobin S has a P50 of 34 mm Hg.

Oxygen Pickup & Delivery
It is convenient to divide the function of hemoglobin into oxygen pickup and oxygen delivery. Oxygen is initially added to the circulation in the lungs in the form of dissolved gas and delivery to end tissue mitochondria is by the same mechanism. Movement of oxygen in the physically dissolved state is dependent upon movement across a short distance according to a partial pressure/concentration gradient. In the lungs, oxygen will move into blood if the oxygen partial pressure in the alveolus exceeds the partial pressure in the pre-alveolar capillary blood. Oxygen present in the dissolved state reversibly binds with available hemoglobin at a rate determined by the affinity of that hemoglobin for oxygen. Once the partial pressure in the capillary exceeds about 150 mm Hg, no more oxygen can be loaded onto hemoglobin and saturation is complete. In the tissues, as physically dissolved oxygen is removed from the circulation by mitochondria, the local PO2 falls. The oxygen removed in this manner is replaced by oxygen that dissociates from available hemoglobin until the hemoglobin has no more oxygen to give or until the oxygen delivery exceeds the consumption requirements of the mitochondrion. Oxygen can continue to move into functioning mitochondrion as long as there is at least a 1 mm Hg partial pressure gradient and mitochondrial function has been demonstrated at a local PO2 of 1 mm Hg.

Adaptation to Changes in Oxygen Affinity
There are several ways that tissues compensate for changes in hemoglobin's affinity for oxygen that prevent changes in oxygen delivery that might otherwise occur.

Oxygen Affinity at the Lung
If oxygen affinity is increased at the lung level, complete saturation will occur at lower ambient PIO2. This can result in the arterial content approaching nearly normal levels even at high altitude. A reduced oxygen affinity (rising P50) can result in reduced oxygen content and delivery potential at the lung level. Again, under most usual circumstances, these are negligible effects over the usual range of P50 values found with normal hemoglobins though there are animal and some abnormal human hemoglobins with P50 values ranging from as low as 10 to as high as 70 mm Hg. When these grossly abnormal human hemoglobins occur, they usually make up less than half of the total hemoglobin available. If oxygen affinity is decreased, then oxygen delivery can still be maintained either by an increased cardiac output or an increased hemoglobin concentration. Local factors such as pH and other chemical mediators can also influence the oxygen affinity back toward normal under some circumstances.

Oxygen Affinity at the Tissues
As hemoglobin's affinity for oxygen rises at the tissue level (P50 going down), oxygen extraction will fall if the PO2 and blood flow are held constant. In vivo, however, the PO2 falls and oxygen extraction and blood flow is constant. Only when the PO2 reaches very low levels will the local blood flow increase and severe anemia must frequently be present to actually demonstrate this effect when the P50 has been experimentally reduced.

Natural Models
There are several models that demonstrate effects of altered P50. Some are experimental models while others occur naturally in nature. In the human fetus, a reduced P50 aids in pickup of oxygen at the placenta owing to the increased oxygen affinity of fetal hemoglobin (which interestingly results from an alteration in fetal hemoglobin's sensitivity to levels of 2,3-DPG). So long as severe anemia or severely reduced blood flow to tissues is avoided, the effects of this reduced P50 at the tissue level is negligible. Llamas and humans who are chronically adapted to life at high altitudes have been shown to have reduced P50 levels which presumably offer benefits similar to those seen with fetal hemoglobin in the normal human fetus. The short-term effects of high altitude on two human subjects with a high oxygen affinity hemoglobin (inherited) were tested by Hebbel who found that in contrast to normal subjects, at 3,100 meters, the high affinity subjects had lesser increases in resting heart rate, minimal increases in erythropoietin, and no decrement in maximal oxygen consumption.

Experimental Models
In a study of the effects of increased oxygen affinity of hemoglobin in monkeys (caused by transfusions of blood lacking 2,3-DPG), Riggs found that mixed venous PO2's fell while cardiac output, A-V difference, and oxygen consumption remained constant. A study by Malmberg of rats exchange transfused with blood of differing oxygen affinity showed that rats with a normal P50 were more likely to survive experimental shock and anemia than those with a reduced P50. Summary Leftward shifts in the oxyhemoglobin dissociation curve (falling P50) would appear to have benefits in preserving oxygen delivery and extraction under circumstances of severe hypoxic stress such as might be found in cases of hypoperfusion, anemia, and ambient hypoxia. Under the vast majority of circumstances, however, these effects are minimal because of the human's large capacity for adaptive compensation by means of polycythemia, increased cardiac output, increased oxygen extraction, and regional changes in blood flow. It remains to be demonstrated whether there are any therapeutic benefits to be gained by attempting to artificially alter the P50 and attempts to do so would be complicated by the body's attempts to restore the P50 toward normal.

References
Hebbel RP, Eaton JW, Berger EM, Kronenberg RS, Zanjani ED, Moore LG: Hemoglobin oxygen affinity and adaptation to altitude: evidence for pre-adaptation to altitude in humans with left-shifted oxyhemoglobin dissociation curves. Trans Assoc Am Physicians, 91:212-28, 1978.
Klocke RA, Saltzman AR: Gas Transport, pp 173-94, in Textbook of Pulmonary Diseases, edited by Baum GL, Wolinsky E, Little Brown and Company, 1989.
Riggs, TE, Shafer, AW, Guenter, CA: Acute changes in oxyhemoglobin affinity: Effects on oxygen transport and utilization. J. Clin. Invest. 52:2660, 1973.
Malmberg PO, Hlastala MP, Woodson RD: Effect of increased blood-oxygen affinity on oxygen transport in hemorrhagic shock. J. Appl. Physiol. 47:889, 1979.

Pulmonary & Systemic Circulation
By Donald R. Elton, MD, FCCP
Lexington Pulmonary and Critical Care

Introduction
We will concern ourselves with two main types of blood vessels: systemic and pulmonary. After birth, systemic vessels (arteries and veins) supply peripheral tissues, including the lung and other organs, with oxygen and nutrients and remove carbon dioxide. The pulmonary vessels are responsible for carrying deoxygenated blood to alveoli in the lungs where gas exchange with the atmosphere takes place. Note that the systemic arteries and pulmonary veins both carry oxygenated blood while the systemic veins and pulmonary arteries carry deoxygenated blood. Pulmonary tissues themselves are supplied partially by the relatively deoxygenated pulmonary arteries and partially by the systemic bronchial arteries. All systemic arteries arise from the left ventricle and aorta while all pulmonary arteries arise from the right ventricle. All systemic veins drain into the vena cava and right atrium while all pulmonary veins drain into the left atrium.

Systemic Circulation
The systemic circulation is a high pressure system. Pressures within systemic arteries in some disease states can be as high as 300 mm Hg though normal pressures are below 150 mm Hg. The Aorta, the body's largest systemic artery, arises from the left ventricle and provides branches that supply the entire body. The important coronary arteries arise from the aorta just above the aortic valve at the left ventricular outflow tract. Systemic blood pressure (and really all blood pressures) are determined at a basic level by flow and resistance, namely the cardiac output and systemic vascular resistance. Cardiac output, in turn, is determined by heart rate and stroke volume (the volume pumped by the left ventricle in a single contraction). The body regulates the systemic blood pressure both by regulating the cardiac output and the systemic vascular resistance. Cardiac output can be increased or decreased by changing contractility (which results in alterations in stroke volume) or by changing the heart rate. There are several feed-back mechanisms involving primarily the kidneys and brain that regulate blood pressure. The kidneys play an important role as a certain amount of renal perfusion is required for their proper function and the brain is involved as it has high oxygen demands with little energy storage capability. Systemic arteries subdivide into smaller and smaller vessels until they become capillaries capable of allowing only one red blood cell to pass at a time. These capillaries are where gas exchange occurs between the oxygenated systemic blood and peripheral tissues. Capillaries, then empty into systemic veins that lead back toward the vena cava and right atrium. Unlike arteries, the systemic veins frequently have valves that assist in preventing back flow away from the heart. These are necessary as veins are the low pressure end of the systemic circulation and in animals like the human or giraffe, the vertical distance the venous blood has to travel to reach the right heart requires more pressure to overcome than will normally exist in the veins. Muscular activity and negative intrathoracic pressure both help push and pull systemic venous blood back toward the heart but they are not continuous forces so the valves prevent blood that was recently pushed or pulled toward the heart from sliding back into the distal legs and arms. Typical systemic venous pressures are in the range of 0 to 10 mm Hg. While there are some variations in arterial anatomy (i.e. finding one artery replacing two) arteries are fairly constant from one individual to another. Veins are much more variable with only the larger ones being constant across individuals. Humans can regenerate veins or generate collateral veins with little difficulty while this is frequently not possible with arteries. One reason why it is serious to damage or obstruct an artery is that there may well be necrosis of the tissue supplied by the artery before any repair or replacement of vasculature can take place. Arteries that supply a tissue without any collateral (backup) artery are called end arteries. Coronary arteries are frequently end arteries. Loss or obstruction of an end artery results in tissue necrosis. Obstruction of a vein results in alternative veins becoming engorged and can result in edema in the affected area but these changes normally do not result in tissue necrosis.

Systemic Arterial Pressure Monitoring
Systemic arterial pressure measurement is done either with a manual or automatic blood pressure cuff (sphygmomanometer) or with an indwelling arterial catheter attached to a strain gauge pressure transducer via a fluid filled catheter. It is normally desirable to use the cuff method so long as pseudo-hypertension does not occur from hardening of arterial walls and so long as the blood pressure is not so low as to make the cuff readings unreliable (the cut-off varies from patient to patient but an arterial catheter would normally be used if the blood pressure is below 70 mm Hg). Arterial catheters are saved for life threatening conditions because they are frequently associated with complications such as bleeding (you can exsanguinate a patient in very short order if tubing disconnects inadvertently) and occlusion of the artery which can result in loss of the hand, fingers, or other distal structures. Clots can form on an arterial catheter which can embolize (break free) and the clots can travel downstream occluding distal arteries resulting in tissue necrosis. A less frequently recognized complication of arterial blood pressure monitoring that is particularly important when they are used in pediatric or neonatal patients but still valid in adults is the pressure that can be exposed to the circulation when flushing the catheter. Most monitoring systems use an IV bag pressurized to 300 mm Hg that is then regulated via a down-regulating device to allow a few ml's per hour of heparin-containing fluid to pass through the catheter to keep the catheter from clotting off. When blood is drawn through the catheter, there is a button or switch that will briefly allow the 300 mm Hg pressure to be applied directly to the catheter, bypassing the regulator. This can cause a rapid rise in arterial pressure depending on the diameter of the catheter in use and can dislodge clots from the catheter pushing them both downstream (their normal direction of travel) and upstream which could result in emboli being sent far from the artery where the catheter sits. This could even cause a stroke or blindness if clots were washed toward the head during a catheter flush. To improve the safety of arterial catheter usage, they should only be placed when absolutely necessary, they should not be used for routine blood draws (other than perhaps blood gasses), they should only be used in an intensive care unit setting where they can be closely watched, they should only be placed in vessels that have collaterals (i.e. not in femoral or brachial arteries), and they should be removed as soon as possible or as soon as any sign of a complication presents.

Systemic Arterial Oxygen Monitoring
In the absence of unusual shunts, arterial blood from any systemic artery will have the same oxygen content as blood from any other systemic artery.

Systemic Venous Pressure Monitoring
Venous pressure monitoring is only done in the large or central veins. This is to avoid local variations in limbs and to avoid the effect that valves have on the pressures. Normally this means a catheter must be placed into the vena cava or right atrium of the heart. Typical access sites would include the internal or external jugular veins or the subclavian veins or femoral veins. Because venous pressures are lower, they can be measured with a column or with a transducer like that used for arterial pressure monitoring. Columns are simpler and cheaper but are seldom used today because of the availability of transducers which are more accurate when used properly and offer continuous rather than intermittent monitoring. The central venous pressure (CVP) can be estimated by physical exam (see diagram above) by measuring the vertical distance between the top of the internal jugular venous pulsation in the neck and the sternal angle and adding 5 to the value to give you the CVP in units of cm H2O.

Systemic Venous Oxygen Monitoring
Systemic venous oxygen contents reflect the oxygenation of the tissues they drain. For this reason, if the practitioner needs to know the venous oxygen content, the blood must be drawn from an area where all of the systemic venous blood in the body has mixed. The only suitable location to find such blood is in the pulmonary artery. While mixing actually starts at the level of the vena cava, studies have shown that mixing is not complete until the pulmonary artery. Some Swan-Ganz pulmonary artery catheters have a built-in oximeter that can continuously monitor the oxygen saturation in the pulmonary artery.

Pulmonary Circulation
The pulmonary circulation is a low pressure system. Normal pressures are less than 30 mm Hg though in certain disease states the pulmonary artery pressure can be 70 mm Hg or more and may approach the systemic arterial pressure. There is very little blood flow through the pulmonary circulation before birth but after the first breath, the pulmonary vascular resistance falls rapidly allowing blood that previously passed through the patent ductus arteriosis and foramen ovale to pass through the lungs to pick up oxygen and lose carbon dioxide. Pressures are lower in the pulmonary circulation because the pulmonary vascular resistance is lower. In the absence of shunts, pulmonary and systemic blood flow are equal. The lower pressures are the reason why the right ventricle has a thinner wall than the muscular left ventricle which must deal with higher systemic blood pressures. The pulmonary vascular resistance is really never too low but it can be made too high by a variety of disease states.

Pulmonary Hypertension
Elevations in pulmonary vascular pressures result primarily from increases in vascular volume, increases in pulmonary vascular resistance, or from blockage or destruction of pulmonary vessels. Pulmonary vascular resistance can be increased by hypoxemia or acidemia or by some drug effects. The increase caused by hypoxemia or acidemia has a useful function as these are the conditions that exist when a part of the lung is underventilated. If you underventilate a part of the lung but do not change the pulmonary blood flow to that area then the blood going to the underventilated segment of lung will not be brought up to arterial oxygen levels and will be added to the oxygenated blood from the well ventilated segments as a shunt. By clamping down on vessels to underventilated areas, the lung prevents shunts from developing. Because the pulmonary circulation can handle large increases in cardiac output with minimal pressure elevations, shutting down blood flow to a segment or even lung usually does not result in significant pulmonary hypertension. However, if you globally reduce oxygenation or have acidosis, then all pulmonary vessels will clamp down resulting in an increase in the pulmonary vascular resistance and resultant pulmonary hypertension. This is an example of how a normal adaptive mechanism can cause pathology in some disease states. Obstruction of pulmonary vessels can occur as a result of pulmonary embolic disease or from destructive lung diseases such as emphysema or cystic fibrosis. Usually, 30-50% of the pulmonary circulation must be lost before significant pulmonary hypertension occurs. Pulmonary vascular pressure monitoring This will be covered during the lectures on the Swan-Ganz catheter.

Congenital Heart Disease
There are numerous congenital heart defects that result in alterations in normal anatomy and physiology of the pulmonary and systemic circulatory systems. Some defects result from abnormal shunts or openings between the two circulatory systems such as in atrial or ventricular septal defects or persistence of fetal circulation and other defects result in abnormal connections of normal vessels such as transposition of the great vessels or anomalous pulmonary venous return. Some of these defects cause right to left shunting (reduced pulmonary blood flow) and these defects result in severe hypoxia. Other defects cause left to right shunting (increased pulmonary blood flow) and these result in milder hypoxia resulting from pulmonary edema. It is important to have an idea of what sorts of defects can occur as many of these defects are barely symptomatic and can escape detection until adulthood and may be noted incidentally when a Swan-Ganz catheter is inserted for management of an unrelated condition but they can cause unexpected pressures and oxygen contents to be measured.

Tags: physiology, pah