Physiology High-Yield Topics – PULMONARY

Prepared by Sara Chakel (schakel@umich.edu)

1. Alveolar-arterial oxygen gradient and changes seen in lung disease

Alveolar gas equation: PAO2 = PIO2-(PACO2/R)

• PIO2 = inspired O2 = (barometric pressure – water vapor)(%O2 in air)
• PACO2 = CO2 in alveoli = PaCO2
• Works because no CO2 in atmosphere; therefore, all CO2 in alveoli must be in equilibrium with CO2 in blood
• R = respiratory exchange ratio for CO2 produced to O2 consumed; varies with metabolism (fats = 0.7, protein = 0.8, carbs = 1.0). We generally use 0.8.

A-a gradient = PAO2 – PaO2 = 10-15 mm Hg in normal person

• Increased A-a gradient signifies hypoxemia. Causes include:
• Shunting: Extreme V/Q mismatch; perfusion without ventilation
• High V/Q: More V/Q mismatch; ventilation without perfusion
• Diffusion block: Tissue fibrosis

Source: Dr. Bartlett case studies, 11/10/00

2. Mechanical differences between inspiration and expiration

Inspiration – Always an active process

• Diaphragm (most important): Pushes abdominal contents downward, lifts ribs upward and outward
• External intercostals, accessory muscles: Not used during normal quiet breathing; used during exercise

Expiration – Normally passive due to elasticity of lung-chest wall system

• Active during exercise or when airway resistance is increased because of disease (e.g., asthma)
• Abdominal muscles: Compress abdominal cavity and push diaphragm up
• Internal intercostals muscles: Pull ribs downward and inward

Source: BRS Physiology

3. Characteristic pulmonary function curves for common lung diseases (e.g., bronchitis, emphysema, asthma, interstitial lung disease)

Solid line: Normal flow-volume loop

Tall, skinny, dashed line: Restrictive disease

• By definition, ¯ TLC, ¯ FVC, and no obstruction
• Narrow PFT suggests restrictive disease (loss of volume)
• Ex. interstitial lung disease

Morse code line: Obstructive disease

• By definition, reduced FEV1/FVC
• Curve shows “coving”
• Ex. Asthma, emphysema, chronic bronchitis (only asthma is defined by PFT)
• COPD: Emphysema (anatomical dx) and chronic bronchitis (clinical dx)

Source: Dr. Arenburg notes (11/8/00) from Respiratory sequence

4. Gas diffusion across alveolocapillary membrane

Rates of diffusion for CO2 and O2 depends on partial pressure differences across membrane and area available for diffusion

• Capillary blood equilibrates with alveolar gas
• When partial pressures become equal, there is no more net diffusion
• Remember that alveolar air PO2 (100 mm Hg) is less than humidified tracheal air (150 mm Hg) and this is turn is less than dry inspired air (160 mm Hg). In the alveoli, this is because O2 has diffused across the membrane and equilibrated with capillary blood. In the trachea, the reduction in PO2 is due to the addition of H2O.

Perfusion-limited exchange (O2, N2O both under normal conditions)

• Gas equilibrates early along the length of the pulmonary capillary
• Increasing blood flow increases diffusion

Diffusion-limited exchange (O2 during strenuous exercise, fibrosis, or emphysema; CO)

• Gas does not equilibrate by the end of the pulmonary capillary
• Partial pressure gradient maintained between alveolar air and pulmonary capillary blood

Source: BRS Physiology

5. Responses to high altitude

1. Acute increase in ventilation
2. Chronic increase in ventilation
3. erythropoietin à hematocrit and hemoglobin (chronic hypoxia)
4. 2,3-DPG (binds to Hb so that Hb releases more O2)
5. Cellular changes ( mitochondria)
6. renal excretion of bicarbonate (e.g., use of acetazolamide) to compensate for respiratory alkalosis
7. Chronic hypoxic pulmonary vasocontriction results in right ventricular hypertrophy

Parameter	Response
Alveolar PO2	¯ (resulting from ¯ barometric pressure
Arterial PO2	¯ (hypoxemia)
Ventilation rate	(hyperventilation)
Arterial pH	(respiratory alkalosis)
Hemoglobin concentration	(polycythemia)
2,3-DPG concentration
Hemoglobin-O2 curve	Shift to right; ¯ affinity
Pulmonary vascular resistance

Source: First Aid 2001; BRS Physiology