Pulmonary Circulation and Gas Exchange

These flashcards cover key concepts related to pulmonary circulation, gas exchange, and the physiological factors affecting ventilation and perfusion in the lungs.

What is Pulmonary Vascular Resistance (PVR) and its fundamental role in pulmonary circulation?

PVR is the resistance to blood flow within the pulmonary arterial system, measured between the right ventricle's outflow and the left atrium. It is analogous to systemic vascular resistance (SVR) but characterizes the low-pressure, high-compliance pulmonary circulation.

What formula is used to calculate Pulmonary Vascular Resistance (PVR)?

PVR is calculated using a modified Ohm's Law for fluid flow: PVR = (Mean Pulmonary Arterial Pressure [MPAP] - Left Atrial Pressure [LAP]) / Cardiac Output [CO] . LAP is often approximated by Pulmonary Capillary Wedge Pressure (PCWP) during catheterization.

What are the key physiological characteristics of the pulmonary circulation regarding pressure and resistance?

The pulmonary circulation is a low-pressure, low-resistance system. It can accommodate significant increases in cardiac output with only modest increases in pulmonary arterial pressure, largely due to recruitment and distension of its compliant vessels.

What are the two primary physiological mechanisms that decrease Pulmonary Vascular Resistance (PVR)?

The two primary mechanisms are recruitment (opening of previously closed capillaries) and distension (widening of already open capillaries). Both increase the total cross-sectional area for blood flow, thereby lowering overall resistance.

List significant factors that can increase Pulmonary Vascular Resistance (PVR).

Factors increasing PVR include: decreased alveolar oxygen ( PA O2 ) leading to hypoxia-induced vasoconstriction, hypercapnia/acidosis, increased sympathetic tone, histamine, serotonin, thromboxane, as well as extreme lung volumes (both very high and very low).

List significant factors that can decrease Pulmonary Vascular Resistance (PVR).

Factors decreasing PVR include: increased alveolar oxygen, alkaline pH, nitric oxide, prostacyclins, acetylcholine, and isoprenaline.

Why is it physiologically beneficial for PVR to be low and adaptable?

A low, adaptable PVR allows the right ventricle to pump blood through the lungs with minimal work, preventing right heart strain. Its adaptability ensures adequate pulmonary blood flow even with large variations in cardiac output, maintaining optimal gas exchange.

Define Recruitment in the context of pulmonary circulation.

Recruitment is the process where previously unperfused or closed pulmonary capillaries are opened and begin to carry blood flow in response to increased pulmonary arterial pressure or cardiac output. Physically, it increases the number of parallel vascular pathways.

How does Recruitment specifically reduce pulmonary vascular resistance?

By increasing the number of active capillaries, recruitment effectively increases the total cross-sectional area available for blood flow. This reduces overall resistance by providing more pathways for blood to flow through, thereby minimizing the pressure increase for a given increase in flow.

What are the main physiological triggers for Recruitment?

Recruitment is primarily triggered by increases in pulmonary arterial pressure or cardiac output. For instance, during exercise, the surge in cardiac output leads to recruitment of capillaries to maintain low resistance and prevent pulmonary hypertension.

Define Distension as it applies to pulmonary vessels.

Distension refers to the passive widening or stretching of already open pulmonary capillaries and arterioles. This occurs when there is an increase in intravascular pressure (e.g., from increased blood flow), leveraging the high compliance of pulmonary vessels.

How does Distension impact pulmonary vascular resistance?

Distension reduces PVR by increasing the radius of the blood vessels. According to Poiseuille's law (resistance is inversely proportional to the radius to the fourth power, R \propto 1/r^4), even a small increase in radius significantly decreases resistance.

What is the primary trigger for Distension in the pulmonary circulation?

Distension is primarily triggered by an increase in intravascular pressure within the pulmonary capillaries. As blood flow increases and pressure rises, the highly compliant vessel walls passively stretch and expand.

Distinguish between Distension and Vasodilation in the pulmonary vasculature.

Distension is a passive increase in vessel radius due to increased intraluminal pressure, leveraging vessel compliance. Vasodilation is an active, smooth muscle-mediated relaxation that increases vessel radius in response to neural, hormonal, or local stimuli (e.g., nitric oxide).

Define Functional Residual Capacity (FRC).

Functional Residual Capacity (FRC) is the volume of air remaining in the lungs after a normal, passive exhalation. It is the equilibrium point where the inward elastic recoil of the lung is balanced by the outward elastic recoil of the chest wall.

Why is Pulmonary Vascular Resistance (PVR) normally lowest at Functional Residual Capacity (FRC)?

At FRC, the forces acting on pulmonary vessels are optimally balanced. Both alveolar capillaries (compressed by high lung volumes) and extra-alveolar vessels (compressed by low lung volumes) are at their least resisted state, leading to the lowest overall PVR.

How do high lung volumes (e.g., at Total Lung Capacity) affect pulmonary vascular resistance?

At high lung volumes, the alveoli are maximally inflated, which stretches and compresses the thin-walled alveolar capillaries. This compression increases the resistance of these vessels, leading to an overall increase in PVR.

How do low lung volumes (e.g., at Residual Volume) affect pulmonary vascular resistance?

At low lung volumes, the intrapleural pressure becomes less negative (or more positive), leading to the compression of the larger, extra-alveolar vessels (arteries and veins) within the lung parenchyma. This compression increases their resistance, thereby increasing overall PVR.

How does gravity affect the distribution of pulmonary blood flow (perfusion) in an upright lung?

Due to hydrostatic pressure effects, blood flow (perfusion) is greatest at the base (bottom) of the upright lung and progressively decreases towards the apex (top). This creates a perfusion gradient from base to apex.

What are West's Zones of the Lung?

West's Zones are a physiological model dividing the lung into three (or sometimes four) vertical regions based on the varying interplay of alveolar pressure ( PA ), pulmonary arterial pressure ( Pa ), and pulmonary venous pressure ( P_v ), which determine regional blood flow.

Describe the pressure relationships and blood flow characteristic of West's Zone 1 (Apex).

In Zone 1, alveolar pressure ( PA ) is highest and often exceeds both arterial ( Pa ) and venous ( Pv ) pressures. The relationship is typically PA > Pa > Pv . This results in little to no blood flow, as capillaries are compressed by alveolar pressure. Zone 1 is usually minimal or absent in healthy individuals but can be induced by hypovolemia or positive pressure ventilation.

Describe the pressure relationships and blood flow characteristic of West's Zone 2 (Middle).

In Zone 2, pulmonary arterial pressure ( Pa ) is greater than alveolar pressure ( PA ), which in turn is greater than pulmonary venous pressure ( Pv ), i.e., Pa > PA > Pv . Blood flow is determined by the difference between arterial and alveolar pressure (a 'waterfall' effect) and is intermittent, increasing with inspiration (deeper breaths).

Describe the pressure relationships and blood flow characteristic of West's Zone 3 (Base).

In Zone 3, both pulmonary arterial pressure ( Pa ) and pulmonary venous pressure ( Pv ) are greater than alveolar pressure ( PA ), i.e., Pa > Pv > PA . This results in continuous and maximal blood flow, driven by the complete arterial-venous pressure gradient.

What is the primary factor influencing the differences in blood flow across West's zones?

The primary factor is the effect of hydrostatic pressure on pulmonary arterial and venous pressures. As height increases above the heart, arterial and venous pressures decrease due to gravity, leading to the observed gradients.

What is West's Zone 4 and under what conditions might it appear?

West's Zone 4 is sometimes described as a region at the very base of the lung where interstitial pressure becomes higher than venous pressure, leading to compression of extra-alveolar vessels and reduced flow. It can occur in conditions causing interstitial edema (e.g., pulmonary edema).

State Fick's Principle as it applies to determining cardiac output.

Fick's Principle states that the total uptake or release of a substance (e.g., oxygen) by an organ equals the product of the blood flow to that organ and the arteriovenous concentration difference of the substance across the organ. For cardiac output, it applies to the body's total oxygen consumption relative to its transport by blood.

Write the formula for calculating Cardiac Output (CO) using Fick's Principle.

CO = \dot{V}O2 / (Ca O2 - C{\bar{v}} O2) where \dot{V}O2 is whole-body oxygen consumption, Ca O2 is arterial oxygen content, and C{\bar{v}} O2 is mixed venous oxygen content.

What does \dot{V}O_2 represent in the Fick's Principle cardiac output formula?

\dot{V}O_2 (pronounced 'V-dot-O2') represents the whole-body oxygen consumption rate, typically measured in mL O2/min via metabolic cart.

What does Ca O2 represent in the Fick's Principle cardiac output formula?

Ca O2 represents the arterial oxygen content, which is the total amount of oxygen carried per unit volume of arterial blood, including oxygen bound to hemoglobin and dissolved in plasma.

What does C{\bar{v}} O2 represent in the Fick's Principle cardiac output formula?

C{\bar{v}} O2 represents the mixed venous oxygen content, which is the total amount of oxygen carried per unit volume of blood sampled from the pulmonary artery (representing the average venous blood returning from all systemic tissues).

How is oxygen content of blood ( Cx O2 ) typically calculated?

Oxygen content is calculated by: Cx O2 = (Hemoglobin [Hb] \times 1.34 \times Oxygen Saturation [Sx O2]) + (0.003 \times Partial Pressure of Oxygen [Px O2]) . The '1.34' is the Hüfner constant (mL O2/g Hb), and '0.003' is the solubility coefficient of O2 in plasma.

What is the clinical significance of Fick's Principle?

Fick's Principle allows for the direct measurement of cardiac output, considered the gold standard for invasive cardiac output determination. It is crucial for understanding systemic oxygen delivery and consumption, and for diagnosing various cardiovascular conditions.

Define the Ventilation/Perfusion (V/Q) Ratio.

The V/Q ratio is a measure of the efficiency of gas exchange, representing the balance between alveolar ventilation (V, the amount of fresh air reaching the alveoli per minute) and pulmonary blood flow (Q, the blood reaching the pulmonary capillaries per minute).

What is the optimal global V/Q ratio in a healthy lung?

The optimal or ideal global V/Q ratio for a healthy lung is approximately 0.8. This signifies that for every 4 liters of alveolar ventilation, there are roughly 5 liters of pulmonary blood flow.

Why is the optimal global V/Q ratio not exactly 1.0?

The V/Q ratio is not 1.0 because, on a global scale, normal physiological shunt (e.g., bronchial circulation, Thebesian veins) means that total pulmonary perfusion (cardiac output) slightly exceeds total alveolar ventilation.

How does the V/Q ratio vary from the apex to the base of an upright lung?

Due to gravitational effects, both ventilation and perfusion increase from the apex to the base. However, perfusion increases more steeply than ventilation. This results in a relatively high V/Q ratio at the apex (often >1.0) and a relatively low V/Q ratio at the base (often <0.8).

What characterizes a high V/Q region in the lung?

A high V/Q region is one where ventilation significantly exceeds perfusion ( V >>> Q ). In the extreme, if perfusion is zero ( Q=0 ), it constitutes dead space where inspired air does not participate in gas exchange, essentially 'wasted ventilation'.

Provide physiological and pathological examples of high V/Q regions.

Physiologically, the apex of the upright lung has a relatively high V/Q ratio. Pathologically, a pulmonary embolism (blocking blood flow to a ventilated area) is a classic example of a high V/Q mismatch, leading to alveolar dead space.

What characterizes a low V/Q region in the lung?

A low V/Q region is one where perfusion significantly exceeds ventilation ( Q >>> V ). In the extreme, if ventilation is zero ( V=0 ), it constitutes a shunt, where blood flows through unventilated areas and does not get oxygenated, essentially 'wasted perfusion'.

Provide physiological and pathological examples of low V/Q regions.

Physiologically, the base of the upright lung has a relatively low V/Q ratio. Pathologically, conditions like asthma, bronchitis, pneumonia, pulmonary edema, or atelectasis (collapsed alveoli) cause low V/Q ratios due to impaired ventilation with relatively preserved perfusion.

What are the common consequences of V/Q mismatch on arterial blood gases?

Both high and low V/Q mismatches impair gas exchange. Low V/Q regions (shunts) are a primary cause of hypoxemia (low arterial P O2 ) because blood passes through unventilated areas. Severe V/Q mismatch can also lead to hypercapnia (high arterial P CO2 ).

What is Hypoxia-Induced Pulmonary Vasoconstriction (HPV)?

HPV is a unique physiological reflex where a decrease in alveolar partial pressure of oxygen ( PA O2 ) causes the associated pulmonary arterioles to constrict. This diverts blood flow away from poorly ventilated alveoli.

What is the primary physiological purpose of Hypoxia-Induced Pulmonary Vasoconstriction (HPV)?

The main purpose of HPV is to optimize local Ventilation/Perfusion (V/Q) matching. By constricting vessels in hypoxic (poorly ventilated) regions, blood is redirected to better-ventilated areas, thereby improving overall gas exchange efficiency and systemic arterial oxygenation.

How does the pulmonary vascular response to hypoxia differ from the systemic vascular response?

This is a critical distinction: pulmonary arterioles constrict in response to hypoxia (HPV), whereas systemic arterioles typically dilate in response to hypoxia to increase blood flow to oxygen-deprived tissues.

What is the effect of localized HPV?

Localized HPV is beneficial as it prevents wasteful perfusion of unventilated or poorly ventilated lung segments (e.g., in atelectasis or pneumonia), ensuring that blood passes primarily through areas where it can be effectively oxygenated.

What is the effect of generalized HPV (e.g., at high altitude or in severe lung disease)?

If hypoxia is widespread (generalized), such as at high altitude or in severe diffuse lung disease (e.g., ARDS), generalized HPV can lead to a significant increase in overall PVR, resulting in pulmonary hypertension, which can strain the right ventricle.

Name some factors that can inhibit or attenuate Hypoxia-Induced Pulmonary Vasoconstriction (HPV).

Factors that can inhibit HPV include: certain vasodilators (e.g., inhaled nitric oxide), calcium channel blockers, high cardiac output (overriding local constriction), acidemia (can both inhibit or prolong HPV depending on severity), and some volatile anesthetics.

Define Physiological Shunt (Normal Shunt).

A physiological shunt refers to the fraction of cardiac output that passes from the right side to the left side of the circulation without participating in gas exchange in the pulmonary capillaries. This unoxygenated blood mixes with oxygenated blood, leading to a slight reduction in arterial P O_2 .

Identify the primary anatomical sources of normal physiological shunt from the bronchial circulation.

A major source is the bronchial circulation. The bronchial arteries supply oxygenated blood to the conducting airways, but a portion of this deoxygenated venous blood drains directly into the pulmonary veins, mixing with oxygenated blood returning to the left atrium.

Identify the primary anatomical sources of normal physiological shunt within the heart.

The Thebesian veins (venae cordis minimae) are small cardiac veins that drain a small amount of deoxygenated blood directly from the myocardial wall into the left atrium and left ventricle, contributing to the physiological shunt.

Why does a physiological shunt lead to hypoxemia, and how does it respond to supplemental oxygen?

Shunted blood bypasses the alveoli entirely, so it remains deoxygenated regardless of the oxygen concentration in the alveoli. Therefore, hypoxemia caused by a significant shunt is often refractory to supplemental oxygen because the shunted blood never sees the increased oxygen partial pressure.

How does a pathological shunt differ from normal physiological shunt?

A pathological shunt (e.g., due to atelectasis, severe pulmonary edema, ARDS, or congenital heart defects like ventricular septal defects) involves a much larger volume of shunted blood, leading to clinically significant and often severe hypoxemia that is resistant to oxygen therapy.

What is Dead Space Ventilation?

Dead space ventilation is the portion of each inspired breath that does not participate in gas exchange. This 'wasted' ventilation means air reaches certain parts of the respiratory system but does not exchange oxygen or carbon dioxide with the blood.

Define Anatomical Dead Space.

Anatomical dead space is the volume of the conducting airways (nose, pharynx, larynx, trachea, bronchi, and bronchioles) where no gas exchange occurs. Air in these passages is inhaled but does not reach the alveoli.

What is the approximate volume of anatomical dead space in a healthy adult?

The anatomical dead space is approximately 150 \text{ mL} , or roughly 2 \text{ mL per kilogram of ideal body weight} .

How can anatomical dead space be measured?

Anatomical dead space can be measured using Fowler's method (a single-breath nitrogen washout technique). This method tracks the concentration of nitrogen in exhaled breath after a single breath of 100% oxygen.

Define Alveolar Dead Space.

Alveolar dead space refers to the volume of alveoli that are ventilated with air but are not perfused with blood. These alveoli receive fresh air, but there is no blood flowing past them to pick up oxygen or release carbon dioxide.

What are common causes of increased Alveolar Dead Space?

Causes of increased alveolar dead space include: pulmonary embolism (blocking blood flow to ventilated alveoli), very low cardiac output (insufficient perfusion), very high alveolar pressure (e.g., PEEP in Zone 1 conditions), and very low pulmonary arterial pressure.

Define Physiological Dead Space.

Physiological dead space is the sum of both anatomical dead space and alveolar dead space. In a healthy individual, alveolar dead space is negligible, so physiological dead space is approximately equal to anatomical dead space.

How is Physiological Dead Space (VD/VT) calculated or estimated?

Physiological dead space as a fraction of tidal volume (VD/VT) is calculated using the Bohr Equation: VD/VT = (Pa CO2 - PE CO2) / Pa CO2 , where Pa CO2 is arterial P CO2 and PE CO2 is mixed expired P CO2 .

What are the clinical consequences of a significant increase in physiological dead space?

Increased physiological dead space means a larger portion of each breath is 'wasted' and ineffective for gas exchange. This leads to inefficient CO2 removal (hypercapnia), an increased work of breathing (as more total ventilation is required to achieve effective alveolar ventilation), and potentially hypoxemia.

What is the Alveolar-arterial (A-a) Oxygen Gradient?

The A-a gradient is the difference between the partial pressure of oxygen in the alveoli ( PA O2 ) and the partial pressure of oxygen in the arterial blood ( Pa O2 ). It quantifies the efficiency of oxygen transfer from the alveoli into the arterial blood ( A-a \text{ gradient} = PA O2 - Pa O2 ).

What is the formula for calculating Alveolar P O2 ( PA O_2 )?

The alveolar gas equation is: PA O2 = FI O2 \times (P{atm} - P{H2 O}) - (Pa CO2 / R) . Where: FI O2 is fraction of inspired O2, P{atm} is atmospheric pressure, P{H2 O} is water vapor pressure, Pa CO2 is arterial P CO_2 , and R is the respiratory quotient (typically 0.8).

What is the approximate normal A-a gradient in a young, healthy adult at sea level?

The normal A-a gradient in a young, healthy adult breathing room air at sea level is typically 5-15 \text{ mmHg} . This small gradient accounts for normal physiological shunt and mild V/Q mismatch.

How does age affect the normal A-a gradient?

The normal A-a gradient tends to increase with age. A rough estimation is \text{A-a gradient} \approx (\text{Age in years} / 4) + 4 \text{ mmHg} , primarily reflecting age-related changes in V/Q matching.

When is hypoxemia present with a normal A-a gradient? Identify key causes.

Hypoxemia with a normal A-a gradient suggests a problem with the delivery of oxygen to the alveoli, not with gas exchange efficiency across the alveolar-capillary membrane. Key causes are: hypoventilation (e.g., opioid overdose, CNS depression) or low inspired oxygen fraction ( FI O2 ) (e.g., high altitude).

Why does hypoventilation cause hypoxemia with a normal A-a gradient?

Hypoventilation leads to a proportional decrease in both alveolar P O2 ( PA O2 ) and arterial P O2 ( Pa O2 ) due to increased alveolar P CO_2 . Since both decrease proportionally, their difference (the A-a gradient) remains normal.

When is hypoxemia present with an increased A-a gradient? Identify key categories of causes.

Hypoxemia with an increased A-a gradient indicates impaired oxygen transfer across the alveolar-capillary membrane. The primary categories of causes are: V/Q mismatch, physiological shunt, and diffusion limitation.

Give examples of specific conditions that cause an increased A-a gradient due to V/Q mismatch.

Conditions causing V/Q mismatch include: Chronic Obstructive Pulmonary Disease (COPD), asthma, pulmonary embolism, and interstitial lung diseases. These conditions lead to regions of the lung where the balance between ventilation and perfusion is disrupted.

Give examples of specific conditions that cause an increased A-a gradient due to a significant physiological shunt.

Conditions causing significant physiological shunt include: Atelectasis (lung collapse), pneumonia, Acute Respiratory Distress Syndrome (ARDS), severe pulmonary edema, and congenital heart defects (e.g., right-to-left shunts).

Give examples of specific conditions that cause an increased A-a gradient due to diffusion limitation.

Conditions causing diffusion limitation (impairment of oxygen movement across the alveolar-capillary membrane) include: pulmonary fibrosis, severe emphysema (destruction of alveolar walls), and sometimes severe pulmonary edema, especially during exercise.

How is the A-a gradient clinically useful in differentiating causes of hypoxemia?

The A-a gradient helps differentiate between hypoxemia caused by problems outside the lungs (e.g., hypoventilation, which has a normal A-a gradient) and hypoxemia caused by problems within the lungs (e.g., V/Q mismatch, shunt, diffusion limitation, which have an increased A-a gradient).