Respiratory Physiology I

Front 1

Ventilation Perfusion Ratio (V/Q)

Back 1

• Ratio of alveolar ventilation (rate at which gas enters/leaves lungs) (VA) to pulmonary blood flow
• The ratio is important for ideal gas exchanged
• The normal value is about 0.8 (0.8 – alveolar ventilation (L/min) is 80% of the value for pulmonary blood flow (L/min))
o If V/Q is normal, than PaO2 will be normal (100 mmHg) and PCO2 will be normal (40 mmHg)
- V/Q is average for the whole lung, different in the 3 zones,
- regional variations in ventilation not as great as regional variations in blood flow -- V/Q is highest in zone 1, lowest in zone 3

Front 2

Oxygen Cascade

Back 2

• From the atmosphere to alveolar air and from alveolar air to the cell (mitochondria)
o Partial pressure of oxygen is higher in the atmosphere and lower in the tissue because the tissue utilizes the oxygen
o The lowest pressure is in the mitochondria of exercising muscles (~0.5 mmHg)
• Pressure of oxygen is 150 mmHg

Front 3

Systems Coordinate Their Output (must be synchronized)

Back 3

• Example of desynchronization: transplanted heart is deinnervated so there is no synchronization between the heart and the metabolic demand (those with transplanted heart cannot exercise with the same intensity)

Front 4

Body O2 stores: A major limitation

Back 4

• Most oxygen is bound to Hb
• 1.34 mL/1g of fully saturated Hb
o If [Hb] = 15g/100ml, and blood volume is 5 L:
o 1.34 ml/g x 15 g/100ml x 5 L = 1.005 L (total amount of oxygen bound to Hb)
• # of saturated Hb x concentration of Hb x Blood volume = Total O2 bound to Hb
• The actual volume is lower than 1.005 L since part of the blood is venous and not all of the Hb is fully saturated
• There is also a negligible amount of oxygen dissolved in the plasma that is very important
• Negligible amount of oxygen bound to myoglobin (in the muscle)

Front 5

Importance of oxygen dissolved in plasma

Back 5

o This creates the partial pressure of oxygen which is crucial for diffusion
o Dissolved in plasma at 37 degrees C
o 0.023ml/1ml plasma/1 atm
o 0.023 ml x 100/760 = 0.003 mlO2/ml plasma
o X 2500 ml plasma = 7.5 ml (total amount of oxygen dissolved in the plasma)

Front 6

oxygen cascade

Back 6

O2 moves from the atmosphere to the alveoli, and from the alveoli into the arterial blood, and from the arterial blood into the mitochondria of the tissues.
PO2 is high in the atmosphere and low in the tissues
PO2 is lowest in the mitochondria of exercising muscle cells.
The O2/CO2 output of the heart, lungs, and muscles needs to be perfectly synchronized.
-people with heart transplants can't perform intense exercise, because their hearts aren't coordinated with their other systems

Front 7

Oxygen Storage

Back 7

1. Hb bound: most of the body's oxygen is found bound to Hb. A total of 4 O2 molecules can bind to every Hb molecule.
1 g of Hb can bind a maximum of 1.34 ml O2
The maximum amount of oxygen the Hb can store is about 1,000 ml, or 1 L, although the actual amount at any given time in the body will be less than this, due to deoxygenated venous blood and incompletely saturated Hb.
1 L can provide for approximately 6 minutes of survival.
2. Dissolved in the plasma: in addition to the bound oxygen, there is also a small amount of oxygen (approximately 7.5 ml) dissolved in the plasma. This dissolved oxygen creates the partial pressure of O2 that regulates the rate of O2 diffusion into the blood. Hb-bound oxygen does not contribute to the partial pressure of oxygen in the body
3. Bound to myoglobin.
4. Stored in the lungs About 400 mL of O2 are stored in the lungs, even after expiration. This stored oxygen is called the functional residual capacity of the lungs.

In total, there is about 1.5 L of O2 stored in the body.

Front 8

Changes in O2 Pressure During Respiration

Back 8

1. Atmospheric air enters the trachea. When this happens, the partial pressure of oxygen immediately drops from 160 to 150 mmHg, due to the addition of water vapor from the trachea into the inhaled air.
2. Air moves down the trachea, into the alveoli. In the alveoli, PO2 drops dramatically, to approximately 100 mmHg. This pressure drop is due to
i. The addition of CO2 from the deoxygenated blood into the alveoli
ii. The loss of O2 from the alveoli, into the blood
More O2 is removed from the alveoli than CO2 is added. In addition, more CO2 is produced by the body than O2 is consumed.
The ratio between the O2 lost and the CO2 gained is called the respiratory exchange ratio (RER).
The RER is approximately 0.85, and varies, depending on the metabolites the body uses as fuel (since different metabolites require different amounts of O2).
Because about 20% more oxygen is used than CO2 is produced, the partial pressure of oxygen falls in the alveoli.
3. O2 diffuses out of the alveoli and into the capillaries. PO2 drops even further as O2 enters the blood, due to the right to left shunt that allows a small amount of venous blood to enter directly into the left side of the heart, bypassing the pulmonary system. This blood comes from the Thebesian veins, which drain the heart, and dilutes the oxygen concentration in the blood, causing a drop in PO2 in the blood.
4. As the blood carries O2 to the tissues, PO2 drops even further, and O2 is consumed.
PO2 is at its lowest in the mitochondria.

Front 9

Dalton's Law

Back 9

The sum of the partial pressures of all the gases in a closed system equals the total pressure of the system.
- The partial pressure of a gas is determined only by the concentration of that gas. It is unaffected by the concentrations of any other gases that may be present in the

Front 10

alveolar arterial PO2 difference

Back 10

The difference between the alveolar and arterial partial pressures is called the alveolar arterial PO2 difference, and is used as a marker of respiratory efficiency.
In a healthy individual, the alveolar-arterial difference is about 10 mmHg. In sick patients, it is much higher.
The higher the alveolar-arterial PO2 difference, the less efficiently the respiratory system is working.
To calculate the alveolar arterial-PO2 difference:
1. Measure PO2 in the arterial blood (a)
2. Alveolar PO2 (A) can be calculated:
i. PAO2 = PO2(inspired) - PaCO2/R
R = VCO2/VO2, which is approximately equal to 0.8
An alveolar-arterial difference greater than 20 mmHg (when breathing room air at sea level) is indicative of severe respiratory impairment.

A shortcut for calculating PAO2:
PAO2=PCO2 + PO2
-values between 120--130 are ok. Values less than this indicate a difference larger than 20 mmHg, i.e. respiratory impairment.

Front 11

Hypoxia

Back 11

Hypoxia refers to a decreased PO2 in the arterial blood.
PO2 in the blood should be approximately equal to 109 - (.45 x patient's age)
-a lower PO2 is considered hypoxic

Physiological mechanisms of hypoxia:
1. High altitude, which means that less O2 will be inspired
2. Limitation of O2 diffusion (for example, because of diseased alveoli). This is rare, because the diffusion of gas in the lungs is very efficient, and rarely gets poor enough to cause hypoxia.
3. V/Q mismatching--the V/Q ratio (ventilation to perfusion ratio) should be about 1. A low V/Q (i.e. a lot of blood flow and not enough O2) ratio will lead to hypoxygenated blood.
4. Hypoventilation--not enough breathing
5. Right to left shunt, which sends deoxygenated blood to the left side of the heart, bypassing the lungs
Factors that will aggravate, but not cause, hypoxia:
1. Low CO2
2. Low mixed venous PaO2
3. anemia --> decreased hemoglobin

Of the five aforementioned mechanisms of hypoxia, the most clinically important ones are low V/Q ratio, hypoventilation, and right to left shunt.

Front 12

Regulation of Respiration

Back 12

The medulla and the pons control breathing. They are stimulated by:
1. Chemical stimuli acting on chemoreceptors for O2 and CO2. Chemoreceptors increase the rate of inspiration in response to hypoxia. They can be peripheral or central:
i. Peripheral chemoreceptors--the carotid and aortic bodies, located in the bifurcation of the carotid and arch of the aorta are sensory organs that detect PCO2 in the blood. The large volume of blood that flows past these sensory organs ensures that the PCO2 that they sense is not significantly affected by the arterial-alveolar PCO2 difference.
1. Chemoreceptors in the aortic body (only!) also increase the rate of ventilation in response to low pH.
ii. Central chemorecptors--central chemoreceptors in the brainstem increase the rate of respiration in response to low pH in the CSF (which results from a high PCO2).
2. Lung inflation that signals mechanoreceptors
3. Various receptors in the lungs that respond to stress and irritants

Front 13

3 groups of neurons in the brainstem that control involuntary breathing

Back 13

The pons modulates the information coming from the medulla, and prevents persistent inspiration.
1. Medullary respiratory center--located in the reticular formation, the medullary respiratory center contains two centers:
i. The inspiratory center, (dorsal) which controls the frequency of inspiration: gets input from peripheral chemoreceptors via glossopharyngeal (CNIX) and vagus (CNX) nerves and mechanoreceptors in lungs via vagus nerve, sends output to diaphragm via phrenic nerve
ii. The expiratory center, (ventral) which controls expiration. Because expiration is normally a passive process, these neurons are quiescent during normal breathing and only become active during forced expiration (i.e exercise).
2. Apneustic center--located in the lower pons. When stimulated → excites neurons in medulla → prolonged action potentials in phrenic nerve → it produces apneustic breathing, characterized by prolonged, gasping inspiration and brief expiration.
3. Pneumotaxic center--located in the upper pons, the pneumotaxic center turns off inspiration, and is quiescent during normal breathing. When active, it functions to limit the amount of air in the lungs and regulate the respiratory rate. (limits bursts of action potentials in phrenic nerve)

Front 14

Stimuli for inspiration:

Back 14

1. Hypoxia
2. High CO2 partial pressure
3. Low pH
4. High temperature
5. Pain

Front 15

ventilatory responses to carbon dioxide and oxygen

Back 15

decrease in arterial PO2 --> detected by peripheral chemoreceptors --> increase in ventilation
- rate of ventilation increases hyperbolically at PO2 lower than 40 mm Hg (optimal)
- arterial O2 saturation and ventilation have similar relationship but linear
The response of ventilation to PCO2 is the opposite of its response to PO2. An increased rate of respiration (hyperventilation) will cause PCO2 to go down. Therefore, as PCO2 goes down, ventilation goes down, and as it goes up, ventilation goes up.
Morphine suppresses the respiratory center in the medulla, thereby slowing the rate of ventilation and creating a right shift of the curve.

Front 16

hypoxic response element (HIF)

Back 16

- in every cell, sense hypoxia, have different effects in different cells
- in kidney: activate erythropeitin --> RBC production
- vascular muscle cells --> angiogenesis

Front 17

Innervation of the Respiratory System

Back 17

All the intercostal muscles are innervated by the corresponding spinal cord segment.
The diaphragm is innervated by C3-5. “C 3,4,5 keeps the diaphragm alive”
Spinal cord damage at the low cervical levels will lead to paralysis of the intercostal muscles. Spinal cord damage at the high cervical level will lead to paralysis of the diaphragm, impairing the ability of the patient to breath independently.

Front 18

what happens to the diaphragm when you breath?

Back 18

at rest the diaphragm is curved, when you breath in it flattens (i.e lowers) allowing more space for your lungs to fill up

Front 19

what happens to your ribs when you breath?

Back 19

upon inhalation the intercostal muscles contract, causing the ribs to go from diagonal to horizontal, making more space for air to fill the lungs
- normal expiration is passive, during forced expiration the abdominal muscles contract pushing the diaphragm upwards

Front 20

Pressure

Back 20

When not inflated with air, healthy lungs tend to collapse, due to the elastic recoil, which acts to return the lungs to their resting state.
The larger the volume of the lungs, the larger the elastic recoil. (Imagine a balloon. The larger you blow it up, the more strongly the walls of the balloon will have to stretch.)
The pressure in the intrapleural space is negative. The intrapleural pressure can be measured by inserting a device that measures pressure, called a manometer into the pleural space (ouch!) or by inserting a tube into the esophagus (less ouch) to measure the pressure in it. Because the esophagus is non-elastic and adjacent to the pleural space, the intrapleural pressure is directly related to the esophageal pressure.

Front 21

Compliance

Back 21

Compliance = change in vol/change in pressure. Compliance is a measurement of how easily a structure can be deformed. The more elastic a structure is, the more pressure will be needed to deform it.
-units of compliance are usually L/cm
-the compliance of the lungs can be measured by inserting a manometer into the esophagus and asking the patient to take and hold a breath, so that the lungs stay at a constant volume.

Front 22

Pathologies that change lung compliance

Back 22

Lungs that are fibrotic (scarred) will be able to hold less volume and are less compliant (so more pressure will be needed to inflate them).
Emphysema will damage the elastic fibers of the lungs, causing loss of elasticity. This will increase the lung compliance, and the lungs will be easier to inflate. Loss of elastic recoil means the lungs will inflate easily, but will have trouble deflating, and will remain inflated. Thus, overinflated lungs is a classic symptom of emphysema.
compliance = change in volume/change in pressure