1. Respiratory System
Part II
Chapter 22

2. Gas Exchange (Blood, Lungs, Tissues)
As blood enters the lungs via pulmonary circuit, oxygen levels are low and carbon dioxide levels are high
In the alveoli oxygen is taken up and carbon dioxide is unloaded
Oxygen is delivered to body tissues and cells
Three factors influence the movement of these gases
(1). Partial pressure and gas solubilities
(2). Alveolar ventilation and pulmonary blood perfusion
(3). Structural aspects of respiratory membrane

3. Gas Laws and Properties of Gases
Gas exchange in the lungs and tissues takes place via simple diffusion
We measure gases in partial pressures
Dalton’s Law of Partial Pressure states that the total pressure exerted by a mixture of gases is the sum of the pressures exerted independently by each gas (it’s partial pressure) in the mixture.
N and O (21%) account for 99% of the gas in the atmosphere; 0.5% carbon dioxide
Total partial pressure of gases in atmosphere = 760 mmHg
PO2 = 159 mmHg (decreases at higher altitude = 110 mmHg)
Henry’s Law states that when a mixture of gases is in contact with a liquid, each gas will dissolve in the liquid in proportion to it’s partial pressure
The amount of gas that dissolves in a liquid is dependent upon the solubility of the gas and the temperature of the liquid.

4. Gas Solubility Solubility of gases depends on:
1. Solubility of a particular gas in a liquid
Carbon dioxide most soluble in air than O2
2. Temperature of the liquid/Pressure
As Temperature rises, gas solubility decreases
As Pressure increases, gas solubility increases
The composition of gases in the alveoli differs from that of the air (table 22.4)
Atm (mostly O2 and N2)
Alveoli – more CO2 and water vapor and less % of oxygen
Oxygen moves into the blood (lower in alveoli); mixture of new gases in the conducting tubes
P02 = 104; PCO2 = 40 mm Hg
The differences in PP of the gases allows for gas exchange via diffusion
Alveoli and gas pressure

5. Factors Influencing Movement of Gases
1. Partial Pressures and Gas Solubility's
Pressure difference across membranes allow movement
2. Ventilation-Perfusion Coupling
Ventilation (gas reaching the alveoli) must be almost at an equal rate to perfusion (blood flow in the capillaries)
3. Membrane Thickness
0.5 – 1.0 micron is optimal and efficient

6. Partial Pressure Gradients
Top: gradients promoting gas exchange in the lungs
Bottom: gas exchange at the tissue level
Gases measured in partial pressures
PO2
Movement is ‘down’ the concentration pressure gradient
Gas Exchange
Gas Exchange II

7. Ventilation-Perfusion Coupling in the Lungs
Definitions
Ventilation = gas that reaches the alveoli
Perfusion = blood flow in the pulmonary capillaries
Autoregulatory controls (affecting the alveoli)
1. If ventilation is poor (low PP of oxygen); terminal arteries contract shunting blood to areas where PP oxygen is high
2. If ventilation is high (high PP of oxygen); arterioles dilate which increases blood flow in the pulmonary capillaries
PP of carbon dioxide affect bronchiole diameter
1. Areas where PP CO2 is high, bronchioles dilate so that it can be eliminated
Results
1. This balances ventilation with perfusion
Poorly ventilated alveoli (low oxygen and high carbon dioxide), bronchioles dilate, and more air is brought in (more oxygen).

8. Ventilation and Perfusion Coupling

9. Oxygen Transport Oxygen-hemoglobin dissociation curve (22.20)
Most oxygen is transported via (1) hemoglobin and by (2) dissolved in plasma (1.5%)- low solubility in water
Hemoglobin is very important in that it transports around 98% of the oxygen to the tissues
HbO2 (oxyhemoglobin)  HHb + O2 (deoxyhemoglobin)
Oxygen gas is ‘loosely’ attached to hemoglobin
HHb + O2 ↔ HbO2 + H+ (oxyhemoglobin)
Loading and unloading of hemoglobin
Right: lungs; Left: tissues
Rate at which Hb binds or releases oxygen depends on temperature, blood pH, PCO2, BPG (organic chemical)
Influence of PO2 on hemoglobin saturation
Oxygen-hemoglobin dissociation curve (22.20)

10. Oxygen-hemoglobin Saturation Curve
Influence of PO2 on hemoglobin loading and unloading

11. Influence of PO2 on Hemoglobin Saturation
During resting conditions, PO2 = 100 mm Hg (98% saturation of Hb in arterial blood)
100 ml of systemic blood contains 20 ml of oxygen (20 vol %)
Blood flows into the systemic circuit (capillaries) - Hb saturation is 75%
5ml of oxygen is released / 100 ml of blood
Oxygen content is now 15% volume
Important points
1. At PO2 mm Hg, Hb almost fully saturated with oxygen. Increase in pressure causes very little increase in saturation.
Higher altitudes there is enough oxygen (sufficient Hb loading) when PP oxygen is lower

12. Influence of PO2 on Hemoglobin Saturation
Only around 25% of oxygen unloading occurs during one systemic circuit
High reserve of oxygen is left in the venous blood (venous reserve)
Applications for exercise (more oxygen will dissociate from hemoglobin during vigorous exercise and move into the tissues with out increasing respiratory rate or CO

13. Dissociation Curve and the Bohr Shift

14. Other Factors Influencing Hemoglobin Saturation
Temperature, blood pH, PCO2 and BPG(2,3-bisphosphate) affect saturation at a given PO2 in blood
Cells metabolize glucose using oxygen and produce CO2 and H+ (lowers pH) levels in the capillary blood
Occurs during cell respiration. More oxygen is needed by the cell to continue respiration
All factors modify hemoglobin structure-affects it’s affinity for oxygen
Increase in all of the factors listed above will decrease Hb affinity for oxygen (curve to shift right)
Declining pH and increasing PCO2 weakens the Hb bond which is called the Bohr Effect.
Allows for oxygen to be unloaded when really needed
Decrease in factors causes higher affinity and curve shifts left
Increasing pH causes higher Hb affinity for oxygen

15. Carbon Monoxide and Hb Affinity
Any inadequate delivery of oxygen to the tissues is called hypoxia.
Hb saturation falls below 70%
1. Anemic
2. Ischemic – congestive heart failure blocks blood flow
3. Histotoxic – cells cannot use oxygen due to poisons (CN)
4. Hypoxemic – reduced air flow to lungs; CO poisoning
Carbon monoxide poisoning
200 times Hb affinity for CO compared to oxygen
Takes oxygen’s place
Cyanosis, headache and respiratory distress

16. Making Sense of CO2 Transport
Transported by following means
(1). Blood plasma (7%)
(2). Chemically bonded to hemoglobin (carbaminohemoblobin) (23%)
CO2 + Hb ↔ HbCO2
(3). HCO3- (70%)
Bicarbonate ion in plasma
CO2 + H2O ↔ H2CO3 ↔ H+ + HCO3-
Carbonic anhydrase in RBCs
Carbonic acid converted to H+ and binds to Hb increasing the RELEASE OF OXYGEN!
Hb loading increases O2 unloading!
HCO- is released into the plasma and onto the lungs
Cl- moves into the cell to account for the loss of the negative ion (chloride shift)

17. Gas Transport

18. Haldane Effect
Lower PO2 and lower Hb saturation - the more CO2 can be transported
As CO2 enters systemic bloodstream, causes more oxygen to dissociate from Hb (Bohr effect) 22.22A
Allows for more CO2 to combine with Hb
HbO  O2 + Hb
Opposite in pulmonary circulation
Hb saturated with oxygen, the H+ released combines with HCO  unloads carbon dioxide
O2 + HHb  HbO2 + H+
H+ + HCO  H2CO  CO2 + H2O unloaded in lungs 22.22b

19. Buffering pH Changes Carbonic Acid – Bicarbonate Buffer System
CO2 + H2O ↔ H2CO3 ↔ H+ + HCO3-
Points
Resists shifts in pH
If concentration of H+ rises (pH falls) will be tied up by bicarbonate to form carbonic acid (weak acid- changes pH very little)
Maintains pH of around 7.3

20. Neural Pathways Medullary groups (control respiration)
1. DRG (dorsally near root of CN IX)
Integrate peripheral sensory input; modify rhythms of VGR
Takes input from peripheral stretch and chemoreceptors and sends to the VGR
VRG
Rhythm generators ‘drive’ respiration
VRG neurons fire which activate respiratory motor neurons which cause inspiratory muscles to contract (inspiration)
Expiratory neurons fire inhibiting the VRG and expiration occurs
Neural Pathways

21. Neural Pathways Pons PGR (pontine respiratory group)
Sends impulses to the VRG of the medulla
Helps to modify the rhythm of the VRG (during sleep, voice, exercise)

22. Neural and Chemical Influences on Medullary Respiratory Centers
Irritant Receptors
Mucus, dust constrict bronchioles (-)
Inflation Reflex (stretch)
Baroreceptors: lungs over-inflate sends signals to medulla which causes decrease in inspiration (-)
Chemical Factors
PCO2 ; PO2; pH

23. Chemical Factors
Chemoreceptors monitor gas levels and H+ levels in the blood
1. Effects of PCO2 (central chemoreceptors)
As carbon dioxide rises, pH falls in the cerebrospinal fluid --- increase in respiration (hypercapnia)
2. Effects of PO2 (peripheral chemoreceptors)
Levels must drop below 60 mm Hg before it causes increased ventilation
Will stimulate ventilation even if carbon dioxide levels are normal
3. Effects of pH
Falling pH levels is monitored by the peripheral chemoreceptors
Causes increased breathing
Central chemoreceptors are not involved due to the lack of H+ diffusing from the blood to the cerebrospinal fluid

24. Location of Chemoreceptors

25. Adjustments Exercise High Altitude
Breathing becomes hyperpnia but not hyperventilation
Gas levels maintained (actually oxygen may increase slightly)
Higher Exercise induced ventilation caused by
Psychic stimuli, proprioceptors relay stimuli to respiratory centers
High Altitude
As oxygen levels drop above 8000 ft. carbon dioxide sensors become more sensitive
Low oxygen levels means increased ventilation
After 2 or 3 days you acclimatize or respiratory volume stabilizes at a level 2-3 L/min higher than at sea level
Hb saturation is only 67% at 19,000 feet; but Hb unloads only 25% of oxygen so tissue oxygen needs are met
If all out effort takes place then fatigue sets in. Kidneys will produce EPO and more erythrocytes