Respiratory Physiology Module 2/3

Oxygen Transport

Oxygen Cascade and Partial Pressures


''What is the oxygen cascade?'' The oxygen cascade describes the journey of oxygen from the atmosphere to the mitochondria.
At room air, PO2 is about 159 mmHg.
Inspired air drops to 149 mmHg, alveolar to 100 mmHg,
pulmonary capillaries to 99 mmHg, and so on.
These steps occur due to physiological processes.

''How is inspired partial pressure of oxygen calculated?'' Inspired PO2 (PiO2) = (Barometric pressure - Water vapor pressure) x FiO2.
At sea level, barometric pressure is 760 mmHg,
water vapor pressure is 47 mmHg, and FiO2 is 0.21,
so PiO2 = (760 - 47) x 0.21 = 149.7 mmHg.

''What factors influence alveolar PO2?'' Alveolar PO2 (PAO2) depends on FiO2, barometric pressure,
and is also affected by alveolar PCO2 and the respiratory quotient.
The alveolar gas equation is: PAO2 = PiO2 - (PaCO2 / RQ).

''How does high altitude affect oxygenation?'' At the summit of Mount Everest, barometric pressure drops to about 250 mmHg.
PiO2 becomes (250-47) x 0.21 ≈ 42.6 mmHg.
In acclimatized individuals, arterial PO2 may be as low as 29.5 mmHg,
but oxygen content is maintained near normal (18.5 ml/dl)
due to increased hemoglobin (20.2 g/dl) and compensatory mechanisms.

''What is Dalton's law and its application in respiratory physiology?'' Dalton's law states that the total pressure of a gas mixture is the sum of the partial pressures of each gas.
In the lungs, even though the proportions of gases change,
the total pressure remains constant at 760 mmHg.
This principle explains how altering FiO2 affects the partial pressures of other gases.

Diffusion and Alveolar Gas Exchange


''How does oxygen diffuse from the alveolus into the blood?'' Oxygen diffuses down a partial pressure gradient.
Alveolar PO2 is about 104 mmHg, while capillary PO2 is 40 mmHg.
As red blood cells traverse the capillary,
oxygen equilibrates with alveolar PO2 by the end of the capillary.
The diffusion distance (alveolar-capillary membrane) is about 0.5-1 micrometer.

''What is the significance of red blood cell transit time in the pulmonary capillary?'' Total transit time through the pulmonary capillary is about 750 milliseconds.
Full oxygenation requires at least 250 milliseconds.
If transit time is shorter (e.g., high cardiac output)
or if diffusion distance is increased (e.g., edema),
oxygenation may be impaired.

''What is Fick's law of diffusion?'' Fick's law states that the rate of diffusion is proportional to:
(Diffusion constant x Surface area x Pressure gradient) / Thickness.
The diffusion constant depends on gas solubility and molecular weight.
This law applies to gas exchange in the lungs and tissues.

''What is the alveolar-arterial (A-a) gradient?'' The A-a gradient is the difference between alveolar PO2 (PAO2) and arterial PO2 (PaO2).
Normally it is 5-15 mmHg.
An increased gradient indicates impaired gas exchange due to V/Q mismatch, shunt, or diffusion limitation.

''How can shunt fraction be estimated at the bedside?'' Give the patient 100% oxygen for 10-15 minutes to eliminate diffusion and V/Q effects.
Then calculate the A-a gradient and divide by 20.
The result approximates the shunt fraction.
Normal shunt is <10%; 10-20% may respond to increased FiO2;
>20% requires other interventions.

Oxygen Content and Hemoglobin


''What is oxygen content and how is it calculated?'' Oxygen content (CaO2) is the total amount of oxygen in arterial blood,
including oxygen bound to hemoglobin and dissolved in plasma.
Formula: CaO2 = (1.34 x Hb x SaO2) + (0.003 x PaO2) ml/dl.
Normal CaO2 is about 20 ml/dl.

''What is the structure of hemoglobin relevant to oxygen binding?'' Hemoglobin is a tetramer with two alpha and two beta chains,
each containing a heme group with an iron atom.
Each iron can bind one oxygen molecule.
Hemoglobin exists in two conformational states:
tense (T) state with low oxygen affinity, and relaxed (R) state with high affinity.

''What is the Bohr effect?'' The Bohr effect describes how hemoglobin releases oxygen more readily in tissues with low pH and high CO2.
H+ and CO2 promote the formation of salt bridges that stabilize the tense (deoxygenated) state,
facilitating oxygen unloading.
Conversely, in the lungs, where CO2 is low, oxygen binding is favored.

Oxygen Dissociation Curve


''What is the oxygen dissociation curve?'' The oxygen dissociation curve plots hemoglobin saturation (y-axis) against PO2 (x-axis).
It is sigmoid-shaped due to cooperative binding.
At a PO2 of 100 mmHg, saturation is about 97-100%.
At tissue PO2 of 40 mmHg, saturation falls to about 75%.

''What is P50 and its significance?'' P50 is the PO2 at which hemoglobin is 50% saturated, normally about 27 mmHg.
It reflects hemoglobin's affinity for oxygen.
A right shift (increased P50) means decreased affinity, favoring oxygen unloading.
A left shift (decreased P50) means increased affinity, favoring oxygen loading.

''What causes a right shift of the oxygen dissociation curve?'' Right shift is caused by acidosis (low pH), hypercapnia (high CO2), increased temperature, and increased 2,3-DPG.
This enhances oxygen release to tissues.

''What causes a left shift of the oxygen dissociation curve?'' Left shift is caused by alkalosis (high pH), hypocapnia (low CO2), hypothermia, and decreased 2,3-DPG.
This increases oxygen affinity, which may impair tissue unloading.

Oxygen Delivery and Extraction


''What is oxygen delivery (DO2)?'' Oxygen delivery is the amount of oxygen transported to tissues per minute.
DO2 = Cardiac Output x Arterial Oxygen Content.
Normal DO2 is about 1000 ml/min (5 L/min x 20 ml/dl x 10).

''What is oxygen consumption (VO2)?'' Oxygen consumption is the amount of oxygen used by tissues per minute.
VO2 = Cardiac Output x (Arterial O2 content - Mixed Venous O2 content).
Normal VO2 is about 250 ml/min, giving an oxygen extraction ratio of 25%.

''What is critical oxygen delivery?'' Critical DO2 is the point below which oxygen consumption becomes supply-dependent.
Below this threshold, tissue hypoxia occurs, and lactate rises.
In sepsis, critical DO2 may be higher due to increased oxygen demand.

''How do changes in hemoglobin affect oxygen delivery?'' Hemoglobin is a key determinant of oxygen content.
Increasing hemoglobin (e.g., from 7.5 to 15 g/dl) doubles oxygen content,
thus improving delivery.
Conversely, anemia reduces oxygen delivery, but cardiac output may compensate.

Carbon Dioxide Transport

CO2 Transport Mechanisms


''How is carbon dioxide transported in the blood?'' CO2 is transported in three forms:
1. As bicarbonate (70-90%) – via carbonic anhydrase in RBCs.
2. As carbamino compounds (10-20%) – bound to hemoglobin.
3. Dissolved in plasma (5-10%).

''What is the chloride shift?'' When bicarbonate is formed inside RBCs, it is exchanged for chloride ions from plasma to maintain electroneutrality.
This is called the chloride shift or Hamburger phenomenon.

''What is the Haldane effect?'' The Haldane effect states that deoxygenated blood carries more CO2 than oxygenated blood.
Deoxyhemoglobin is more basic and binds H+ more readily,
shifting the bicarbonate reaction to the right and increasing CO2 carriage.

CO2 Dissociation Curve


''What is the CO2 dissociation curve?'' The CO2 dissociation curve plots total CO2 content against PCO2.
It is nearly linear in the physiological range.
At a given PCO2, deoxygenated blood has a higher CO2 content than oxygenated blood, illustrating the Haldane effect.

''What is the difference between arterial and venous CO2 content?'' Arterial CO2 content is about 480 ml/L, while venous is about 520 ml/L.
The difference reflects CO2 added from tissues.
Despite a small PCO2 difference (40 vs. 45 mmHg), the content difference is significant due to the Haldane effect.

Ventilation-Perfusion Ratio


Basic Concepts and Definitions


''What is ventilation-perfusion ratio (V/Q)?'' V/Q is the ratio of alveolar ventilation to pulmonary capillary blood flow per minute.
Normal alveolar ventilation is about 4.2 L/min, and cardiac output is 5 L/min,
giving a V/Q of 0.84.
In an ideal lung, V/Q = 1, but it varies regionally.

''How does V/Q vary in the upright lung?'' In the upright position, at the apex, V/Q is about 3.3 (high),
and at the base, V/Q is about 0.63 (low).
This is because ventilation increases from apex to base by about 0.5 cm H2O/cm height,
while perfusion increases by 1 cm H2O/cm height.

''What is the alveolar gas equation?'' PAO2 = PiO2 - (PaCO2 / RQ).
It shows that for every increase in PaCO2, PAO2 decreases, assuming constant RQ.

Types of V/Q Mismatch


''What is a shunt (V/Q=0)?'' Shunt occurs when blood perfuses alveoli that are not ventilated.
Examples: ARDS, pneumonia, pulmonary edema.
Hypoxemia due to shunt does not correct with 100% oxygen.

''What is dead space ventilation (V/Q=∞)?'' Dead space occurs when alveoli are ventilated but not perfused.
Example: pulmonary embolism.
This increases wasted ventilation and typically presents with low PaCO2 due to hyperventilation.

''What is low V/Q (V/Q < 1)?'' Low V/Q occurs when ventilation is reduced relative to perfusion, e.g., partial airway obstruction, COPD, asthma.
This leads to hypoxemia and an increased A-a gradient.

''What is high V/Q (V/Q > 1)?'' High V/Q occurs when perfusion is reduced relative to ventilation, e.g., hypotension, reduced cardiac output.
This increases dead space effect.

''What is the shunt equation?'' The shunt equation quantifies the fraction of cardiac output that is shunted:
Qs/Qt = (CcO2 - CaO2) / (CcO2 - CvO2),
where CcO2 is pulmonary capillary oxygen content.

Zones of the Lung (West Zones)


''What are the zones of the lung?'' The lung is divided into zones based on the relationship between alveolar pressure (PA), pulmonary arterial pressure (Pa), and pulmonary venous pressure (Pv).
Zone 1: PA > Pa > Pv – no blood flow (apical).
Zone 2: Pa > PA > Pv – flow intermittent (waterfall effect).
Zone 3: Pa > Pv > PA – continuous flow (basal).
Zone 4: Interstitial pressure > PA – reduced flow (lowest parts).

''What is the waterfall effect in Zone 2?'' In Zone 2, blood flow is determined by the difference between arterial pressure and alveolar pressure,
similar to a waterfall where flow depends on the height of the fall rather than downstream pressure.

''How does changing from upright to supine affect the zones?'' In the supine position, Zone 1 disappears as gravity now acts from anterior to posterior.
Zone 2 becomes the anterior part, and Zone 3 the posterior part.
Overall, V/Q matching improves.

Effects of Position, Gravity, and Anesthesia


''How does gravity affect ventilation and perfusion?'' Gravity causes a gradient in both ventilation and perfusion.
Perfusion increases more steeply from apex to base than ventilation,
resulting in a decreasing V/Q from top to bottom.

''What happens to V/Q in the lateral decubitus position under anesthesia?'' In the awake lateral position, the dependent lung has better ventilation-perfusion matching.
Under anesthesia, the dependent lung may be compressed by abdominal contents and mediastinum,
while the non-dependent lung is better ventilated, leading to V/Q mismatch.

''How does prone positioning improve oxygenation in ARDS?'' In ARDS, dorsal lung regions are collapsed but well-perfused in supine position.
Prone positioning recruits dorsal alveoli, improving ventilation to these well-perfused areas,
thus reducing V/Q mismatch and improving oxygenation.

''What is hypoxic pulmonary vasoconstriction (HPV)?'' HPV is a protective mechanism that constricts pulmonary arteries in hypoxic lung regions,
diverting blood to better-ventilated areas.
Anesthetic agents may inhibit HPV, worsening V/Q mismatch.

Clinical Implications


''Why does hypoxemia due to shunt not correct with oxygen?'' Shunted blood bypasses ventilated alveoli entirely, so increasing FiO2 does not affect it.
The admixture of shunted venous blood lowers arterial PO2 regardless of alveolar PO2.

''What happens to PaCO2 in V/Q mismatch?'' In pure shunt, PaCO2 may be normal or low due to compensatory hyperventilation.
In dead space, PaCO2 may rise if total ventilation is inadequate, but typically patients hyperventilate, causing low PaCO2.

''How does anesthesia affect lung volumes and V/Q?'' Anesthesia reduces FRC, promotes atelectasis, and impairs HPV.
It also alters ventilatory responses to CO2.
These changes increase V/Q mismatch and risk of hypoxemia.

''What is the effect of PEEP on V/Q?'' PEEP recruits collapsed alveoli, improving ventilation to dependent regions.
However, excessive PEEP can overdistend non-dependent alveoli, increasing dead space.
Optimal PEEP balances recruitment and overdistension.

''In COVID-19 patients, what V/Q abnormalities are seen?'' COVID-19 pneumonia often involves thrombotic microangiopathy, leading to perfusion defects and increased dead space.
Shunt areas also exist due to alveolar filling.
Prone positioning is beneficial to improve dorsal ventilation.


Interactive Questions and Answers


''Question 1: If a patient's saturation is 92%, which intervention increases oxygen delivery most?'' Options:
  1. Increase stroke volume by 10%
  2. Increase heart rate by 5%
  3. Increase hemoglobin by 12%
  4. Increase saturation by 5%
  5. Increase PaO2 by 30 mmHg
.
The best answer is C (increase hemoglobin by 12%).
Hemoglobin is the major determinant of oxygen content; small changes in saturation or PaO2 have minimal effect due to the flat part of the ODC.

''Question 2: In the normal upright position, which statements are correct?''
  1. Ventilation decreases from apex to base
  2. Ventilation increases from apex to base
  3. Perfusion increases from apex to base
  4. Perfusion decreases from apex to base
  5. A and C are correct
  6. B and D are correct

Answer: E (A and C are correct). Ventilation is higher at apex and decreases; perfusion is lower at apex and increases.

''Question 3: When changing from upright to supine, what happens to lung zones?''
  1. Zone 1 changes to Zone 2, Zone 2 changes to Zone 3
  2. Zone 2 changes to Zone 1, Zone 3 changes to Zone 2
  3. Zone 3 disappears
.
Answer: A. In supine position, gravity acts from anterior to posterior, so Zone 1 disappears and zones shift.

''Question 4: Zero shunt (V/Q=0) is seen in which condition?''
  1. Pneumonia
  2. Chronic bronchitis
  3. Pulmonary edema
  4. Hypotension

Answer: C (pulmonary edema). In pulmonary edema, alveoli are filled with fluid, so ventilation is zero while perfusion continues.

''Question 5: ARDS benefits most from which position?''
  1. Lateral
  2. Supine with PEEP
  3. Prone

Answer: C (Prone) Answer: C (Prone). Prone position recruits dorsal alveoli, improving ventilation to well-perfused areas.