Stephen C. Wood, Ph.D.

Medical Physiology

Pulmonary Circulation and V/Q matching Learning Objectives

1. Describe the 4 functions of the pulmonary circulation. 2. Describe the normal anatomical shunts that add venous blood to arterialized blood leaving the left ventricle. 3. Contrast the systemic and pulmonary circulations with respect to normal pressures, resistance to blood flow, and vascular response to hypoxia. 4. Describe how pulmonary vascular resistance changes with alterations in pulmonary arterial pressure, lung volume, and alveolar hypoxia. 5. Describe the potential causes of pulmonary edema and pleural effusion. 6. Describe the cause of ventilation perfusion mismatch in normal lungs and the compensatory mechanisms to improve V/Q matching.

I. Pulmonary Circulation has 4 functions: blood filter, metabolic organ, blood reservoir, and gas exchange.
1. The lungs filter the blood and protect against clots (thrombi) and air or fat globules (emboli). 2. An important metabolic function of the lung is conversion of angiotensin I to angiotensin II by angiotensin converting enzyme (ACE) located in endothelial cells. 3. The pulmonary circulation is an important reservoir having about 500 ml of blood or 10% of total blood volume. This stabilizes left ventricle stroke volume when going from supine to standing. The pulmonary circulation is a high flow, low resistance, low pressure system. Arteries and veins are thin-walled and more compliant than systemic vessels. Vascular resistance is controlled mainly by local factors. When alveoli have low O2, the vessels serving those alveoli constrict. This response to low oxygen is opposite to that in the systemic circulation but is also beneficial by redirecting blood flow to areas of the lung that are better ventilated. 4. Gas exchange is the main business of the lungs. Efficient gas exchange across the air-blood barrier depends on a good matching
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of air flow (ventilation) and blood flow (perfusion). Gravity creates uneven matching of ventilation and perfusion. Both air flow and blood flow are higher at the base of the upright lung, but blood flow is more affected by gravity than air flow. The angiogram above shows the distended blood vessels at the base of the lungs.

II. Shunts
A shunt refers to blood that somehow bypasses the normal flow route. They can occur from arterial into venous blood (a left to right shunt) or from venous to arterial blood (a right to left shunt). Shunts can be both anatomical and physiological (e.g., blood that perfuses areas of the lung with low or no ventilation).

A. Normal Anatomical Shunts

Bronchial circulation supplies the connective tissue, septa, and large and small bronchi. Bronchial Normal NormalAnatomical Anatomical Shunts Shunts veins drain into the pulmonary veins producing a shunt. AO Bronchial arteries Coronary circulation supplies the heart muscle. Thebesian veins PA (venae cordis minimae) empty into the cardiac chambers which, on the left O2 side of the heart, creates a shunt. These normal shunts are about 1 to 2 PV Thebesian per cent of the total cardiac output and veins contribute equally with normal V/Q mismatch in accounting for the normal alveolar-arterial PO 2 difference of 5-20 mm Hg. The human fetus has additional normal shunts; i.e., the foramen ovale and the ductus arteriosis.

B. Abnormal
Congenital or pathological Abnormal Abnormal anatomical anatomical shunts shunts conditions, such as pulmonary arteriovenous fistulas produce AO PDA shunts in which venous blood is PFO PA added to arterial blood (right to left, or R L shunts). Intracardiac O defects may produce R L or L R shunts depending on the Pulmonary PV VSD pressures of the two connected AV fistula chambers. A right to left shunt is 4 examples harmful by adding deoxygenated blood to arterialized blood and lowering the oxygen of blood going to
2

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tissues. A left to right shunt is harmful by increasing pulmonary artery pressure. The direction of the shunt is determined by the pressure gradient.

III. Pulmonary Pressures and Volumes

The pressures in the various parts of the pulmonary circulation and systemic circulation are shown in the figure to the right. The mean driving pressure in the pulmonary system is about 10 mm Hg, (mean PA = 15 minus mean LA = 5) compared with a driving pressure of about 91 mm Hg in the systemic circulation (93 2). Since the flows are equal, the vascular resistance of pulmonary circulation is about 9 times less than that of the systemic circulation. A. Left Atrial Pressure is Measured via a Pulmonary Artery Catheter Pulmonary artery balloon catheters (Swan-Ganz) can be used to measure pulmonary artery and left atrial pressures. When the balloon is inflated blood flow stops. Since there is no flow, there is no pressure difference between the tip of the catheter and the left atrium. Therefore the pressure measured at the tip of the catheter equals left atrial pressure. Elevated left atrial pressure can be due to mitral stenosis and can cause pulmonary edema.

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B. Pulmonary Blood Volumes

The pulmonary circulation has less smooth muscle and is much more compliant than the systemic circulation. Consequently, the total volume changes readily with changes in intrathoracic pressures; e.g., Valsalva and Mller maneuvers. Normal total volume is about 500 ml. Capillary volume is also variable but normally about 70 100 ml. This range is similar to the normal range of resting stroke volume.

IV. Control of Pulmonary Vascular Resistance

As noted above, the pulmonary vascular resistance (PVR) is about 9 times less than the systemic vascular resistance.1 PVR is controlled by 3 main factors; lung volume, cardiac output, and local chemical control (O 2, CO2, and pH). Because the job of the lung is to match air flow and blood flow, vascular smooth muscle in pulmonary arteries behaves opposite to vascular smooth muscle in systemic arteries in response to these 3 chemical factors. Also, the pulmonary vascular smooth muscle is responding to O2 and CO2 levels in alveolar gas and not in the blood in the pulmonary arteries (remember, this is mixed venous blood).

Vascular resistance = pressure difference/flow Pulmonary vascular resistance = 10 mm Hg/6 L/min 1.7 mm Hg/L/min Systemic vascular resistance = 91 mm Hg/6 L/min 15.2 mm Hg/L/min

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A. Lung volume affects PVR

Lung volume is an important passive factor in determining pulmonary vascular resistance (PVR). PVR is minimum at FRC. PVR is high at low and high lung volumes as shown to the right. At low lung volumes extra-alveolar vessels are compressed from the positive intrapleural pressure (forced expiration is necessary to get to residual volume). At high lung volumes, the pleural pressure is more negative, expanding the extraalveolar vessels and the capillaries are stretched and compressed by enlarging alveoli so resistance is increased.

B. Cardiac Output affects PVR

Increasing pulmonary artery pressure; e.g., during exercise, results in a decrease of PVR. The decrease in PVR shown above is not occurring in a single vessel but across the vascular bed and happens because of an increase the total x-sectional area and in the number of parallel resistances. The mechanisms of the observed fall in PVR with increasing pressure are recruitment and distension of pulmonary vessels by increased pressure. The effect of the fall in PVR with increasing arterial pressure allows a large increase in pulmonary blood flow with modest increases in pulmonary artery pressure.

C. Lung Hypoxia Increases PVR

Low PO2 in the alveoli acts directly on pulmonary vascular smooth muscle to cause vasoconstriction and increase PVR. It is not the PO 2 of blood that causes vasoconstriction (remember the alveoli are perfused with venous blood). The vasoconstriction is enhanced by high alveolar
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PCO2. This phenomenon is beneficial at the regional level, but now when hypoxia is global because pulmonary hypertension is the result. This effect of hypoxia is opposite to what is seen in the systemic circulation where low oxygen produces vasodilatation. Hypoxic pulmonary vasoconstriction (HPV) is initiated by inhibition of O2-sensitive, voltagegated (Kv) channels in pulmonary arterial smooth muscle cells (PASMCs). Kv inhibition depolarizes membrane potential (E M), thereby activating Ca+ + influx via voltage-gated Ca++ channels. HPV is weak in extrapulmonary, conduit pulmonary arteries (PA) and strong in precapillary resistance arteries. Hypoxia also causes release of endothelin-1 from the vascular endothelium causing contraction of smooth muscle. In the systemic circulation, hypoxia causes endothelium to release nitric oxide (NO) which, in turn, increases cGMP synthesis. cGMP activates protein kinase G which inhibits Ca++ influx and decreased calcium-calmodulin stimulation of myosin light chain kinase producing decreased muscle tension and vasodilation. (drugs that inhibit breakdown of cGMP; e.g., Viagra, potentiate this effect of NO. For more on vascular smooth muscle see: http://www.cvphysiology.com/Blood %20Pressure/BP026.htm http://circres.ahajournals.org/cgi/content/full/circresaha;88/12/1228

D. Autonomic Control is not Important

Although sympathetic and parasympathetic nerves are present in the lungs, the autonomic nervous system exerts little or no control over pulmonary circulation in humans. However, pulmonary vascular resistance is altered by vasoactive drugs; e.g., beta 2 agonists used to treat asthma cause vasodilation as well as their intended effect of bronchodilation.

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V. Fluid Exchange in Pulmonary Capillaries

The Starling forces for systemic capillaries also determine fluid balance in the pulmonary circulation. Two additional forces are important in lungs: alveolar pressure and surface tension. Pulmonary edema (excess fluid in the interstitial space or alveoli) can result from increased hydrostatic pressure, capillary permeability, or increased surface tension or from decreased colloid osmotic pressure.

A. Pulmonary Edema has multiple Causes

The Starling equation gives all of the factors that determine fluid flux from pulmonary capillaries:

Where Kf is the filtration coefficient, or ease with which solvent moves across the membrane and is the reflection coefficient, or resistance to solute moves across the membrane (ranges from 0 or no resistance to 1 or complete resistance). 1) Increased hydrostatic pressure. Mitral stenosis and congestive heart failure result in increased left atrial and pulmonary hydrostatic pressure. The high capacity of the lymphatic system to remove excess filtered fluid (lymphatic reserve) means that edema does not start to form until left atrial pressure is elevated to above 20 mm Hg. This type of edema is called cardiogenic edema.

Jv = Kf [( Pc Pi) - (p - i)]
2) Increased permeability. Damage to capillary and alveolar endothelium allows
Rate of edema Formation, ml/min
10 Why doesnt Edema form?

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0 5 10 15 20 25 30 35 40

LAP, mm Hg

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plasma proteins to leak into the interstitial space and alveoli. Water then moves into the interstitial space and alveoli by osmosis. Inflammation and heroin overdose are two examples of factors causing this type of edema. This type of edema is called noncardiogenic edema.

Jv = Kf [(Pc Pi) -

(p - i)]

3) High surface tension. If surfactant is reduced, which happens when edema fluid enters alveoli, surface tension will increase leading to fluid movement into the interstitial space and alveoli. Acute respiratory distress syndrome (ARDS) is associated with both an increase capillary permeability and decreased surfactant. Both factors result in pulmonary edema. 4) Decreased plasma protein. Decreased colloid osmotic pressure can also result in pulmonary (as well as systemic; e.g., ascites) edema. (Examples; starvation, liver disease, hemodilution from intravenous solutions).

Jv = Kf [(Pc Pi) - ( p - i)]

5) Impaired lymphatic drainage or increased central venous pressure. In the lungs, fluid out of capillaries exceeds fluid in producing a steady flow of lymph. If the lymphatics are blocked or lymph drainage back to central veins is impeded by high central venous pressure, edema will result (examples; cancer, heart failure). 6) High altitude pulmonary edema. Global hypoxia, due for example to COPD or high altitude leads to pulmonary hypertension. In COPD patients, this often leads to right heart failure (Cor Pulmonale). A small percentage of normal subjects at high altitude develop pulmonary edema (HAPE) but the mechanism is not clear. Lung fluid collected from HAPE patients has elevated protein levels indicating a non-cardiogenic cause (inflammatory response). ?
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Jv = Kf [(Pc Pi) - ( p - i)]

7) Drowning. Freshwater and saltwater drowning fill the lungs with water (unless the victim has a laryngospasm). Freshwater is rapidly taken up by pulmonary blood. The resulting hemodilution ruptures red cells and the released potassium leads to death by ventricular fibrillation and asphyxiation. Salt water is hypertonic and leads to water loss from blood into lungs. Death is by asphyxiation.

B. Pleural Effusion
Pleural effusion is edema of the pleural space. At FRC, pleural fluid has a negative pressure (about 4 mm Hg) due to tendency of lungs to collapse and chest wall to spring out. The pleural space, normally collapsed due to negative pressure, is between the visceral and parietal pleura. Pleural fluid balance is determined by both fluid balance in both the visceral and parietal surface capillaries. X-ray shows blunting of the costophrenic angle (where ribs (costo) meet diaphragm (phrenic). The base of the lung is always more susceptible to edema because of the higher hydrostatic pressures.

VI. Matching of Ventilation and Perfusion in the Lung

Mean pulmonary arterial pressure is about 14 mmHg. This is equivalent to a column of blood with a maximum height of 18 cm above the right ventricle2. The top of the lung is about 18 cm above the right ventricle. Therefore the top of the lung has very low intravascular pressures. The bottom of the lung has additional hydrostatic pressure due to gravity.
2

How do you convert mm of mercury (Hg) into cm of blood? Mercury is 13.5 more dense than blood but a mm is 1/10 as long as a cm, so you multiply mm Hg x 1.35 to get cm H 2O.

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A. Effect of Gravity
Gravity creates higher blood flow and higher air flow at the base of the lungs, but the effect is unequal. Air flow is higher at the base because the alveoli are smaller and more compliant. Blood flow is higher at the base because the pressure is highest. Most of the gas exchange occurs where most of the air and blood are located; i.e., at the base of the lung.

B. Extreme V/Q Mismatch and Compensation

The effects of gravity cause the matching of V and Q to vary widely in normal lungs. In pathology, the mismatch of V and Q gets even worse and is the leading cause of arterial hypoxemia in lung disease. More on this topic in the lecture on mechanisms of hypoxemia.

SUMMARY
1. The normal volume of the pulmonary circulation is about 500 ml (10% of total blood volume) with about 75 ml in the capillaries. 2. Normal anatomical shunts are the bronchial venous blood draining into the pulmonary vein and Thebesian coronary veins draining into the left atrium and ventricle. 3. "Starling" forces coupled with membrane properties (filtration and reflection coefficients) act on pulmonary capillaries to determine the net fluid movement into or out of the capillaries. 4. The potential causes of pulmonary edema and pleural effusion are increases in capillary hydrostatic pressure, increases in interstitial colloid osmotic pressure, decreased plasma colloid osmotic pressure, increased vascular permeability, and increased surface tension (loss of surfactant). Edema due to hydrostatic pressure is called cardiogenic edema. Edema due to osmotic pressure and membrane properties is called noncardiogenic pulmonary edema.
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5. Pulmonary vascular resistance is the ratio of driving pressure to flow and is about 9 times less than systemic vascular resistance. 6. Pulmonary and systemic vascular resistance responds in the opposite way to low oxygen. Pulmonary arterioles vasoconstrict and systemic arterioles vasodilate. In both cases, the response is adaptive to maximize blood flow to well ventilated areas of the lung and to increase blood flow to metabolically active tissues. 7. Pulmonary vascular resistance decreases with increasing flow and pressure due to recruitment and distension of pulmonary resistance vessels. 8. Lung volume is an important determinant of pulmonary vascular resistance. This is due to resistance of both extra and intra alveolar vessels. At high lung volumes, PVR is increased and this is important to remember for patients on a ventilator. High PVR causes increased after load for the right ventricle and could lead to right heart failure. 9. Gravity results in higher flow of both air and blood at the base of the lung. This means that most of the gas exchange occurs at the base of the lung where V/Q ratios and oxygen levels are lower.

REFERENCES/READINGS
Rhodes and Tanner

STUDY QUESTIONS
1) Patients with postural hypotension may experience dizziness when they stand up suddenly. The transient decrease in cardiac output when someone stands up is actually greater in the right ventricle than the left ventricle. This is due primarily to: A. stimulation of the carotid baroreceptors. B. activation of the renin-angiotensin system. C. reservoir function of the pulmonary vasculature D. the low compliance of pulmonary vasculature E. increased intrathoracic pressure 2) The pulmonary circulation is one source of the normal anatomical shunt that contributes to the normal alveolar-arterial PO2 difference. The arterial systems of the lungs are best described as: A. bronchial artery carrying oxygenated blood; pulmonary artery carrying deoxygenated blood. B. Thebesian arteries carrying oxygenated blood; pulmonary artery carrying deoxygenated blood.
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C. pulmonary artery carrying oxygenated blood; bronchial carrying deoxygenated blood. D. brachial artery carrying oxygenated blood; pulmonary artery carrying oxygenated blood. 3) Which of the following best characterizes the pulmonary circulation? Flow Pressure Resistance Compliance (A) Low High Low High (B) High Low High Low (C) Low Low Low High (D) High Low High High (E) High Low Low High

4) Regional differences in ventilation perfusion ratios affect gas tensions in the pulmonary blood. Which of the following best describes the gas tensions in the blood leaving the alveolar capillaries of a healthy standing individual? O2 tension (PO2) CO2 tension (PCO2) (A) Lowest at base Highest at apex (B) Highest at base Lowest at base (C) Highest at apex Lowest at apex (D) Highest at apex Lowest at base (E) Lowest at base Lowest at base 5) A 26-year-old patient has a cardiac output of 5 L/min and mean pulmonary arterial and left atrial pressures of 20 and 5 mm Hg, respectively. What is her pulmonary vascular resistance? (A) 4 mm Hg/L per minute (B) 3 mm Hg/L per minute (C) 0.33 mm Hg/L per minute (D) 0.25 mm Hg/L per minute 6) High altitude residence and other causes of chronic alveolar hypoxia (e.g., emphysema, hypoventilation, and kyphoscoliosis) sometimes result in right heart failure (cor pulmonale). A likely mechanism of right heart failure is: A. B. C. D. E. pulmonary hypertension as a result of hypoxia. metabolic alkalosis leading to decreased contractility of heart prolonged inhibition of angiotensis converting enzyme (ACE) increased preload on the right ventricle failure of medullary cardiac center
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7) Which of the following graphs best illustrates the rate of edema formation (y axis) as a function of left atrial pressure (x axis):
1 2

0 3

25 4

25

25

25

A. B. C. D.

1 2 3 4

8) Pulmonary vascular resistance is decreased (A) At low lung volumes (B) By breathing low oxygen (C) At high lung volumes (D) With increased pulmonary arterial pressure 9) A patient with emphysema and heart failure is taken to the emergency room after complaining of shortness of breath. The following values are obtained from pulmonary catheterization: cardiac output = 3L/min; mean pulmonary artery pressure = 40 mmHg; left atrial pressure = 30 mmHg; mean aortic pressure = 62 mmHg; mean right atrial pressure = 2 mmHg. The pulmonary vascular resistance in this patient is calculated to be approximately: A. B. C. D. 3.3 mmHg/L/min 20 mmHg/L/min 1.6 mmHg/L/min 16.3 mmHg/L/min

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10) Patients on ventilators with incorrect settings may develop right heart failure (Cor Pulmonale) due to elevated pulmonary vascular resistance. A possible cause of this iatrogenic (=screw up) pulmonary hypertension is: A. B. C. D. alveolar hypocapnia. ventilation at high lung volumes. high viscosity due to polycythemia. systemic hypertension.

Click on or go to the link below for answers to questions http://rossmedphysiology.com/answerstostudyquestion.pdf

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