Abril 2008

Fisiología Respiratoria
Lectura de capítulo

Espiración forzada
 nariz
boca
faringe

laringe

tráquea
pulmón

Bronquio derecho
Bronquio izquierdo

bronquiolo

diafragma alveolo
Mecánica de la Respiración

1. Los pulmones son estructuras elásticas

(spring-like) que son normalmente infladas
arriba de su estado de equilibrio.

2. The pulmones are situated with the chest

wall that is also an elastic structure.

3. At end-expiration, with no muscle activity,

the tendency for the lung to recoil inward is
exactly balanced by the tendency of the
chest wall to expand outward.

4. respiratorio muscles (inspiratory and

expiratory) can disturb this balance and
cause gas flow in and out of the lung.
 Chest wall

Lung
 Pleural pressure end-expiration
(Ppl) small lung recoil

~-4
expiration inspiration
Ppl
Ppl P=0
~-6
~-5

P =+1 P = -1

P=0
Large lung recoil
~-7
Ppl
end-inspiration
Lung compliance is a physical property of
the lung that tells how much pressure
change is required to produce a given
change is volume.

Lung Compliance = Volume/Pressure

Lung recoil is due to 2 physical factors:

1) Elastic connective tissue

2) Surface tension at air-water interface

Surface tension, a potentially very large

force, is minimized by the presence of
pulmonary surfactant, a phospholipid
molecule that acts like a detergent.
Eliminating the air-water interface, eliminates surface
tension and increases lung compliance.

Saline inflation
Lung
Volume

air inflation

Compliance = V/P = slope of above curve

 Airway flow resistance

Flow = P/R = (Pao – Palv)/Raw

Where: Pao = pressure at airway opening

Palv = pressure in alveoli
Raw = airway resistance

Radius of airways is
Major factor in airway resistance

R (radius)4 (Poiseuille’s Law)

forced expiration
Lab exercise: Forced expiratory vital capacity

“Effort-independent” expiration

Why are whales better than us?

Gas Exchange
VOLUMES

TIDAL VOLUME TOTAL VENTILATION FLOWS

~ 500 ml ~ 7,500 ml/min

DEAD SPACE ~150 ml FREQUENCY ~ 15/min

ALVEOLAR VENTILATION
ALVEOLAR ~ 5.250 ml/min
GAS ~ 3,000 ml
 ~1
PULMONARY BLOOD
FLOW ~ 5,000 ml/min

PULMONARY
CAPILLARY BLOOD
~70 ml
 INSPIRED GAS EXPIRED GAS

21% O2 (PO2 = 150 mmHg) ~ 16% O2 (PO2 = 115 mmHg)

~ 0 % CO2 ~ 4% CO2 (PCO2 = 28.5 mmHg)

PO2 = (%O2\100)(PB-PH2O)
= FO2 (760-47)

ALVEOLAR GAS (F = Fraction of total)

0.21 (760-47) = 150

~ 14% O2 (PO2 = 100mmHg)
~ 5.6% CO2 (PCO2 = 40 mmHg)

VENOUS BLOOD ARTERIAL BLOOD

PO2 = ~40 mmHg PO2 = ~ 95 mmHg

PCO2 = ~ 46 mmHg PCO2 = 40 mmHg
 O2 conc PO2
ml/liter mmHg
Air ~200 150
Water ~ 7 150

O2

O2
 CO2 expired – CO2 inspired = CO2 production by body (in steady-state)
O2 inspired – O2 expired = O2 consumption by body

CO2 production/min = 7500 ml/min x (0.04 - 0) = 300 ml/min

O2 consumption = 7500 ml/min x (0.21 –0.16) = 375 ml/min

respiratorio exchange ratio (R) =

CO2 prod = 300/375 = 0.80

O2 cons

300 ml/min CO2 375 ml O2/min

High CO2 low CO2

Low O2 high O2
 Because every breath includes a portion that is dead
space, total ventilation per minute (minute ventilation)
includes a portion that is dead space ventilation and a
portion that is alveolar ventilation. Only the alveolar
ventilation participates in gas exchange.

Minute ventilation = dead space ventilation + alveolar ventilation

Alveolar ventilation = (tidal vol – dead space vol) x freq

The functionally significant ventilation,
therefore, is the alveolar ventilation.

. . .
 WHAT DETERMINES ALVEOLAR GAS COMPOSITION?

Important relationship:

Lung CO2 excretion equals alveolar ventilation

times alveolar CO2 concentration.

In symbols:
. .
VCO2 = VA x FACO2

or
. .
PACO2  VCO2/ VA

. . .
In words, this says that alveolar gas composition is determined
by two variables: Metabolic rate and alveolar ventilation.
 . .

Alveolar PCO2  (Metabolic rate/Alveolar ventilation)

Alveolar PO2  inspired PO2 - (Metabolic rate/Alveolar ventilation)

Alveolar PO2  PIO2 - (Metabolic rate/Alveolar ventilation
 Diffusion of gases between alveolar gas and
pulmonary capillary blood

300 ml/min CO2 375 ml O2/min

High CO2 low CO2

Low O2 high O2
 In an Ideal lung

PO2 = 100

PO2 = 40 PO2 = 100

 Diffusion equilibrium in an ideal capillary

100 alveolar

normal
PO2,
mmHg

50
venous

exercise
0
0 0.25 0.50 0.75

Time in capillary (seconds

Why is gas exchange not ideal, even in a healthy person?
1) Diffusion equilibrium can be incomplete
2) The distribution of gas and blood in the lung may
not be uniform.

PO2 100
PCO2 40

normal

PO2 40 PO2 159

PCO2 46 PCO2 0

no airflow no blood flow

Some venous blood may bypass the lung without
exchanging with alveolar gas (this is called
SHUNT)

Shunt of blood past lung

Blood Gas Transport
 INSPIRED GAS EXPIRED GAS

ALVEOLAR GAS

PO2 = 100mmHg)
PCO2 = 40 mmHg)

Pulmonary blood flow = 7.5 liters/min

VENOUS BLOOD ARTERIAL BLOOD

PO2 = ~40 mmHg PO2 = ~ 95 mmHg

[O2] = 150 ml/liter [O2] = 200 ml/liter

PCO2 = ~ 46 mmHg PCO2 = 40 mmHg

[CO2] = 520 ml/liter [CO2] = 480 ml/liter
 O2 conc PO2
ml/liter mmHg
Air ~200 150
Water ~ 7 150

O2

O2
Oxygen is carried in two forms in the blood:

1) Dissolved oxygen, about 3 ml/liter in arterial blood

2) Oxygen bound to hemoglobin, about 197 ml/liter in

arterial blood.
Oxigeno binds to the iron atom in hemoglobin that is in the
ferrous (Fe2+) form. Each Hb molecule has 4 iron atoms
and they bind oxygen cooperatively; i.e., binding of the first
increases the affinity of the second, etc.
Oxyhemoglobin Dissociation Curve

Blood is equilibrated with gases of varying

PO2 values and the concentration of O2 or
the % saturation of the oxygen binding
sites on hemoglobin are determined.
Carbon dioxide transport in the blood

CO2 participates in several chemical reactions

after entering the blood and, like O2, depends
heavily on hemoglobin to facilitate transport.

CO2 CO2diss
CO2 + Hb-NH2 Hb-NH-COO- + H+

CO2 + H2O H2CO3 HCO3- + H+

carbonic anhydrase
CO2 reactions in the tissues
 Important points:
CO2 reactions in tissues
1. Only a small fraction of added CO2 is
carried as dissolved CO2 even
thought CO2 is 20-30 x more soluble
than O2

2. Most reactions occur within RBC

because of presence of hemoglobin
and carbonic anhydrase.

3. Conversion of CO2 to bicarbonate

(HCO3-) facilitated by hemoglobin
buffering of H+ and by export of HCO3-
to plasma in exchange for Cl-(the
Chloride Shift).

4. Most CO2 carried finally as plasma

HCO3- even though the reactions
occur primarily within the RBCs.
 Note: Loss of O2 from hemoglobin cause CO2 curve
to shift upward and to the left, increasing the
amount of CO2 carried at any PCO2. This is known
as the HALDANE EFFECT. Compare to Bohr Effect.

CO2 DISSOCIATION CURVE

CO2 transport and PCO2 value has acid-base consequences

CO2 + H2O H2CO3 HCO3- + H+

High PCO2 results in

respiratorio
ACIDOSIS

Low PCO2 result in

respiratorio ALKALOSIS
Control of Breathing
 CONTROL Respiratorio

The centro respiratorio in the brainstem has an

intrinsic rhythm generator that drives breathing.

The output of this center is modulated by inputs

from peripheral and central chemoreceptors,
from mechanoreceptors in the pulmones, and
from higher centers in the brain, including
conscious control from the cerebral cortex.

The outcome is that the system holds the

regulated variables within a narrow range, it
minimizes the energetic cost of breathing, and it
adapts to special circumstances like speaking,
swimming, eating, etc.
 EVIDENCE FOR CONTROL

1. respiratorio variables (blood PO2, PCO2, and pH)

are held (regulated) within narrow limits under
most circumstances.

2. Breathing is stimulated when variables are

artificially manipulated.

3. Specialized receptors and a feedback control

system participate in regulating these variables
Peripheral
Chemoreceptors
CO2 Response Curve
 Increased breathing during exercise cannot be explained
by an increase in alveolar or arterial PCO2

80
Alveolar Ventilation in liters/min

60

Exercise
40 breathing

exercise
20 CO2 breathing

rest
0
0 20 40 60 80 100
Alveolar or Arterial PCO 2 in mmHg
 Exercise data obtained in Bio 80 Lab

160
Step Test
Alveolar Ventilation (liters/min)

140
Bicycle
120

100

80
Remember:
60
PACO2  VCO2/VA
40

20

0
0 1 2 3 4 5
CO2 Production (liters/min)
 35

30
Alveolar PCO2 (calculated)

25

20

15

10

0
0 10 20 30 40 50 60
Oxygen Consumption Rate in ml (Kg.min)
Respiratory Exchange Ratio (VCO2/VO2) 1.2

1.0

0.8

0.6

0.4

0.2

0.0
0 1 2 3 4 5

Oxygen consumption rate in liter (min)-1

 Key mechanisms: 1) hyperventilation
2) increased red blood cells
3) unloading on steep part of O2DC

Oxygen at High Altitude

Inspired Alveolar Arterial Venous Mitochondria
gas gas blood blood
sea level
150
PO2 in mmHg

100

50 15,000 feet

0
0 1 2 3 4
 sea level sea level
venous arterial

altitude
altitude arterial
venous
What about at very high altitude, such as Mt. Everest?
 Oxygen at High Altitude
Inspired Alveolar Arterial Venous Mitochondria
gas gas blood blood
sea level
150
PO2 in mHg

100 Morococha

Mt. Everest
50 o
o o
o

0
0 1 2 3 4
 Curve shifted at high
altitude due to low Sea High
PCO2 and high pH level altitude
25

High 20
altitude Sea level

15

10

0
 EXERCISE ON MT. EVEREST
250

200
Ventilation (liters/min)

Sea level

150 "summit"

100

50

0
0 1 2 3 4 5

Oxygen Consumption (liters/min)

 EXERCISE ON MT. EVEREST
180

160
"summit"
140
Ventilation (liters/min)

120
Sea level
100
Our subject
80

60

40

20

0
0 1 2 3 4 5

Oxygen Consumption (liters/min)

 EXERCISE ON MT. EVEREST
80
respiratorio Frequency (breaths/min)

"summit"
70

60
sea level

50

40

30

20

10
0 1 2 3 4 5

Oxygen Consumption (liters/min)