1. Respiratory System: External Respiration
Ruben D. Zamora

2. Respiratory System Homeostasis Exchanges O2 with CO2 with environment
Regulates pH by adjusting rate of removal of acid forming CO2
Body systems maintain homeostasis
Homeostasis is essential for survival of cells
Cells
Requires O2 for cell respiration, a process which generates CO2 that must be removed.
CO2 generates carbonic acid which must be dealt with to maintain a narrow pH range.
Cells make
up body systems

4. The Physics of a Passive Process
Nonpolar gases diffuse across a permeable barrier like a cell membrane following a simple rule, Fick’s Law (Willmer et al. 2005). 𝐽 𝑛𝑒𝑡 =−𝐷 𝐴∆𝐶 ∆𝑥 D = coefficient of diffusion that varies w/ temp and m.w. A = surface area C = difference in concentration between two areas x = distance between the two areas

5. Modified Fick’s Law (Sherwood 1995):
𝑁𝑒𝑡 𝐷𝑖𝑓𝑓𝑢𝑠𝑖𝑜𝑛 𝑅𝑎𝑡𝑒= 𝑐𝑜𝑛𝑐𝑒𝑛𝑡𝑟𝑎𝑡𝑖𝑜𝑛 𝑔𝑟𝑎𝑑𝑖𝑒𝑛𝑡×𝑝𝑒𝑟𝑚𝑒𝑎𝑏𝑖𝑙𝑖𝑡𝑦×𝑠𝑢𝑟𝑓𝑎𝑐𝑒 𝑎𝑟𝑒𝑎 𝑑𝑖𝑠𝑡𝑎𝑛𝑐𝑒×𝑚𝑜𝑙𝑒𝑐𝑢𝑙𝑎𝑟 𝑤𝑖𝑒𝑔ℎ𝑡
Well, so what?
This equation shows that diffusion rates of gases like O2 or CO2 are:
Directly proportional to the difference in concentrations on either side of the membrane AND to the surface area across which diffusion takes place.
Inversely proportional to distance across which diffusion takes place. k

6. The exchange of gases CO2 and O2 at the lungs usually depends on the differences in the concentrations of these gases between the blood and the alveoli.
Pathological conditions can change this rate.

7. Some Pathologies Condition Description Effect on Diffusion Emphysema
Loss of alveolar walls causing larger but fewer chambers
 Respiratory surface area
 Diffusion rate
Pulmonary edema
Accumulation of interstitial fluid between alveoli and pulmonary capillaries from pulmonary inflammation or congestive heart failure
 Thickness of barrier between air and blood
Pulmonary fibrosis
Chronic exposure to irritants replaces delicate lung tissue w/ fibrous tissue
Pneumonia
Inflammatory fluid accumulation within or around alveoli

8. Gas Exchange Gases moves down partial pressure gradients.
Simple passive diffusion of O2 and CO2 down partial pressure gradients (PPG)
Pressure exerted by a particular gas in a mixture is proportional to the percentage of gas in the mixture
Atmospheric gas: 79% N2, 21% O2, and negligible amounts of CO2 (0.04%), H20 and other gases.

9. Individual pressure exerted independently by a particular gas is called partial pressure (Pgas).
At sea level, atmospheric pressure is 760 mm Hg.
PN2  0.79*760 mmHg  600 mm Hg
PO2  0.21*760 mmHg  160 mm Hg
PCO2  *760 mmHg  0.03 mm Hg =

10. Gases in liquids exert a partial pressure which depends on two factors:
Solubility of gas
Partial pressure of gas
The amount of O2 and CO2 dissolved in pulmonary capillary blood is directly proportional to the alveolar PO2 and PCO2.

11. There is a partial pressure gradient, or difference in partial pressures, between pulmonary blood and alveolar air.
PO2 in alveolar air > PO2 in pulmonary capillary blood
PCO2 in pulmonary capillary blood > PCO2 in alveolar air
Gas always diffuses down its partial pressure gradient from the area of higher to the area of lower partial pressure.

12. Oxygen enters and CO2 leaves the blood in the lungs passively down partial pressure gradients.

13. Why is the composition of alveolar air not the same as inspired atmospheric air?
Water vapor dilutes the partial pressure.
Inspired air is mixed with residual air (FRC)
PO2 = 100 mm Hg

14. Alveolar PO2 remains relatively stable. How?
Only small portion of alveolar air is exchanged with each breath (TV)
Quickly mixed w/ larger volume of retained air, with lower PO2
Small elevation in alveolar PO2 diminishes because O2 diffuses into blood
New O2 arriving, simply replaces O2 diffusing into blood
Pulmonary blood equilibrates w/ alveolar PO2
 O2 in blood available for tissues, varies only slightly during respiratory cycle.

15. Situation similar but reversed for CO2
CO2 produced by cellular respiration, added to blood in systemic capillaries.
At pulmonary capillaries, CO2 diffuses down PPG, blood to alveoli.
Ventilation removes alveolar CO2 and replenishes alveolar O2
Keeps PCO2 relatively low
PPGs between alveoli and blood are maintained which ensures O2 enters blood and CO2 leaves blood.

16. Systemic venous blood enters pulmonary capillaries from heart.
Pumped to lungs via pulmonary arteries
Relatively low in O2 (PO2 = 40 mm Hg)
Relatively high in CO2 (PCO2 = 46 mm Hg)
Diffusion of O2 and CO2 between pulmonary capillaries and alveoli occurs down their respective PPGs.
Both gases equilibrate.

17. Pulmonary venous blood returns back to heart to be pumped out to body tissues as systemic arterial blood.

18. Blood returning to lungs still has O2.
PO2 of systemic venous blood = 40 mm Hg
Can be used when O2 demands 
Blood leaving lungs still contains CO2.
PCO2 of systemic arterial blood = 40 mm Hg
Plays important role in acid-base balance.
Important in driving respiration.

19. During exercise PPGs increase.
More O2 extracted from blood at tissues.
When blood returns to the lung
During rest, PPG from alveoli to blood = 60 mm Hg (100  40)
With exercise, PPG from alveoli to blood may equal to 70 mm Hg (100  30)
 More O2 diffuses from alveoli into blood.
The additional transfer replaces the increased amount of O2 consumed.

20. Similarly, the amount of CO2 diffusing to the alveoli from blood matches the CO2 picked up at the tissues.

21. Factors other than the partial pressure gradient influence the rate of gas exchange.

22. Gas exchange across systemic capillaries also occurs down partial pressure gradients.
Only place gas exchange occurs, pulmonary and systemic capillaries.
 Arterial blood reaching systemic capillaries is the same blood that left the lungs.
Through oxidative metabolism, cells constantly consume O2 and produce CO2.
Average cellular PO2 = 40 mm Hg
Average cellular PCO2 = 46 mm Hg

23. The gases move by diffusion down their PPGs toward approximate equilibrium.*
The systemic venous blood is returned to the heart, then pumped to lungs to complete the cycle.
*Partial pressures of systemic blood gases never completely equilibrate.

24. Gas Transport Table 10-5. Method of gas transport in the blood Gas
Method of Transport
Percent Carried in This Form O2
Physically dissolved
1.5
Bound to hemoglobin
98.5
CO2 10 30
As bicarbonate (HCO3-) 60

25. Most O2 in the blood is transported bound to hemoglobin.
Only about 15 mL O2/min can be dissolve in normal pulmonary flow.
Yet, even under resting conditions, cells consume more than 16x that amount (250 mL/min).
There must be a additional mechanism for carrying O2 in the blood.
The mechanism is the iron-bearing molecule hemoglobin (Hb)

26. Hb forms a loose, easily reversible combination with O2.
Hb + O ⇆ Hb O 2
Important questions about the role of Hb in O2 transport:
What determines whether O2 and Hb are combined or dissociated?
Why does Hb combine w/ O2 in the lungs and release at the tissues?
How can a variable amount of O2 be released at the tissue level, depending on the level of tissue activity?
How can we talk about O2 transfer between blood and surrounding tissues in terms of O2 PPGs when 98.5% of the O2 is bound to Hb, which does not contribute to the PO2 of blood at all?
reduced hemoglobin
oxyhemoglobin

27. The PO2 is the primary factor determining the percent hemoglobin saturation.
The percent hemoglobin (%Hb) saturation measures the extent to which the Hb present is combined with O2.
Can vary from 0% to 100%
Most important factor determining %Hb saturation, PO2 of the blood.
And this is related to blood O2 concentration.
Law of mass action describes for a reversible reaction, that if one of the substances involved in a reversible reaction is increased, the reaction is driven toward the opposite side.
The converse is true if we decrease that substance.

28. Applying this law to our reversible reaction for O2 and Hb:
An increase in PO2 as in the pulmonary capillaries would increase HbO2 formation.
An decrease in PO2 as in the systemic capillaries drives the reaction to the left, causing more O2 to dissociate from Hb.
Thus, because of differences in PO2 at the lungs and tissues, O2 is “loaded” and “unloaded,” respectively.
Hb + O ⇆ Hb O 2

29. The relationship between blood PO2 and %HB saturation is nonlinear.
Upper end flattens off between blood PO2 of 60 and 100 mm Hg.
But, between 0 and 60 mm Hg, there is a marked change in %HB saturation.
There is a physiological significance to both upper and lower parts of the curve.

30. What is the significance of the plateau portion of the O2-Hb curve?
Observation: PO2 decreases by 40% from 100 to 60 mm Hg, but %Hb saturation only decreases by just under 8% percentage points. This, even though dissolved O2 has also decreased by 40%.
Significance: Provides a good margin of safety in O2 carrying capacity of the blood.
When individuals have pulmonary diseases that reduced ventilation or gas exchange.
Circulatory disorders that reduce blood flow to lungs.
At higher altitudes.

31. What is the significance of the steep portion of the O2-Hb curve?
Observation: At resting, PO2 drops from 100 to 40 mm Hg, and %Hb saturation is still at 75%. Further drop in PO2 during exercise, from 40 to 20 mm Hg, results in a rapid decrease to about 30% Hb saturation.
Significance: In this PO2 range, a small drop between 40 and 20 mm Hg in systemic capillaries, makes a large amount of O2 immediately available to more actively metabolizing tissues.
During strenuous exercise, even more oxygen would be made available to muscles due to circulatory and respiratory adjustments that increase flow rate of oxygenated blood through the active tissues.

32. By acting as a storage depot, hemoglobin promotes the net transfer of O2 from the alveoli to the blood.
Blood PO2 depends entirely on dissolved O2, not on O2 bound to HB.
Hb plays a crucial role

33. Increased CO2, acidity, temperature, and 2,3-diphosphoglycerate shift the O2-Hb dissociation curve to the right.

34. Oxygen-binding sites on hemoglobin have a much higher affinity for carbon monoxide that for O2.

35. The majority of CO2 is transported in the blood as bicarbonate.

36. Various respiratory states are characterized by abnormal blood gas levels.

37. Why is the composition of alveolar air not the same as inspired atmospheric air?
Water vapor dilutes the partial pressure.
Inspired air is mixed with residual air (FRC)
PO2 = 100 mmHg