Transcript Lecture 7

Ventilation
Intro: why do we
breathe?
Key Terms
• Ventilation: Movement of air into and out
of the lungs
• Gas exchange: Movement of gases across
membranes according to pressure
gradients
• Pressure gradients: Determined by the
partial pressure of the gas
• Gases: Oxygen necessary for cellular
respiration; Carbon dioxide is a volatile
acid
Breathing, ventilation and
respiration
• Used
synonymously
– Used to think
respiration occurred
in the lung
• Ventilation:
movement of air
• Respiration: cellular
utilization of O2
Ventilation
• Pulmonary minute
ventilation (VE.)
– The rate of expired
ventilation
– Usually expressed
in L/min
– VE = VT x f
– Expired ventilation
and inspired
essentially the
same, may differ in
transition from rest
to exercise
Environmental influences
• Temperature, pressure, water vapor all impact gas volumes
• Gas laws
– Boyle’s law: Pressure and volume inversely related; P1V1=P2V2
• So, as pressure goes up, volume goes down and vice versa
– Charles’ law: Temp and volume directly related; V1/T1 = V2/T2
• So, as temperature goes up, volume goes up and vice versa
– Dalton’s law: The total P of a gas is determined by the partial pressures
of all the constituent gases
– STPD
• Standard temperature, pressure, dry
• ST=0°C, P=760 mmHg, 0 mmHg H2O vapor pressure (PH2O)
– BTPS
• Body temperature, pressure, saturated
• Body temperature, P= ambient pressure, PH20=47 mmHg at 37°C
– ATPS
• Ambient temperature, pressure, saturated
• T=ambient, P=ambient, PH20=47 mmHg at 37°C
– Typically you collect at ATPS and convert to BTPS (ventilation) or STPD
(Vo2, Vco2); allows comparison across studies
Entry of O2 into the blood
Entry of O2 into the blood
• Determined Entirely by pressure gradients
• Partial pressure
– Pressure exerted by each gas in a composition
– Atmospheric pressure (PAtm): 760 mmHg
– Partial pressure of O2 (Po2): 159 mmHg (.2094 x
760)
– Rest is nitrogen, some argon and very little CO2
– When air reaches alveoli, Po2 falls, why?
• Think of gas laws
Entry of O2 into the blood
1) Water vapor
• Gas is fully humidified, so at normal body temp, water
vapor pressure is 47 mmHg
2) Co2 is also higher in the alveoli
• Thus, Po2 of alveoli about 100-105 mmHg
• 760 – 47 = 713 or the pressure of the air in the lung
– Dalton’s Law
• 713 x .2094 = 149 (inspired pressure of O2; PiO2)
• PAO2 = PiO2 – (PACO2/RER)
– Alveolar gas equation
• PAO2 = 149 – (40/.85) or 149-47 = 102
• RER = respiratory exchange ratio or Vco2/Vo2
– Usually about 0.85 at rest with mixed diet
Entry of O2 into the
blood
• Once O2 gets into alveoli it
diffuses into the blood
– Due to favorable oxygen gradient
(~100 to 40 mmHg)
– Most binds with Hb (~97%)
– Some dissolved in plasma (3%)
• Oxygen content of blood (CaO2)
CaO2=1.34*[Hb]*(%sat of Hb) + 0.003 * PaO2
CaO2 = 1.34 * (15mg/dl)*(.98) + 0.003* (100mmHg)
CaO2 = ~20 ml/dl
[Hb]= hemoglobin concentration
PaO2 = partial pressure of oxygen
Diffusion of gases: Lung
Pulmonary diffusion
• Diffusion of gases through tissues (gel)
• Major determinants
– Partial pressure difference (major)
– Solubility of the gas (minor)
• Gases of lower solubility typically have greater partial
pressure gradients
Rate of diffusion
• Determined by
– Area available
– Thickness
– Partial pressure
gradient (P1-P2)
– Diffusion
coefficient
• Determined by
solubility and
molecular weight
Rate of diffusion
• CO2 is slightly larger than O2 (MW; 44 vs
32 g/mol)
• CO2 has a much higher solubility
coefficient (0.57 vs 0.024)
• Thus, CO2 has a greater relative diffusion
coefficient (~20 x higher)
• Thus, O2 needs a larger pressure gradient
to “force” itself across biological
membranes
Arterial blood gas homeostasis
• Maintenance of blood
gases (PaO2 and
PaCO2) very
important
– Keep driving pressure
for CO2 and O2 high
– Driving pressure is the
difference between
arterial and venous
pressure (PaO2-PvO2)
– Note that gradients
increase with exercise
• Oxygen content
•
CaO2 = 1.34[Hb]*(%sat) + 0.003 * PaO2
• Cardiac output (Qc) = HR *
stroke volume
– Thus, total oxygen
transport capacity (or
delivery) is Qc*CaO2 or
Qo2
• Qo2 is a measure of how
much oxygen is circulated
around by the heart in one
minute
– So, if CaO2 = 20 ml/dl and
Qc equals 30 L/min
– Qo2 = 30 * 0.2 or
– Qo2 = 6L/min
Oxygen transport
Shifting of O2 dissociation curve
• Remember: we noted that
exercise increases the
pressure gradients
• How?: O2 dissociation
curve shifts
– Curve shows the relationship
between Po2, CaO2 and %
Hb saturation
• Right shifting increases O2
unloading
– Right shift called Bohr effect
• What shifts the curve?
Effects of Co2 and pH on O2
transport
• The shape of the O2
dissociation curve is
altered by 4 variables
– pH
• < 7.4 = right shift
• >7.4 = left shift
– Temperature
• >38C = right shift
• <38C = left shift
– Co2
• >40 mmHg = right shift
• <40 mmHg = left shift
– 2,3 DPG
(diphosphoglycerate)
• Altitude increases this
Co2 transport
• Co2 must be transported
from tissues to blood
and lungs for removal
• Carried in 3 ways
– Bound to Hb (carbamino
compounds) (15-20%)
– Dissolved in plasma (510%)
– As bicarbonate (HCO3-),
~70%
Co2 transport
• More Co2
dissolves (than
O2) in plasma
due to greater
solubility
• Binding of Co2 to
Hb occurs at
different site than
O2
• Co2 combines
with H2O to form
bicarbonate
Co2 content
• Amount of Co2 carried
in the blood depends
upon Pco2
• Unlike oxygen, the Co2
curve is linear over a
much greater range
• Thus, as Co2 production
increases
– greater driving pressure
(from tissue to blood)
– As Co2 is extremely
soluble, this increases
Co2 transport (No upper
limit)
Effect of O2 on Co2 transport (and vice versa)
• When Co2 increases in
blood
– Shifts O2 curve to right
– Facilitates unloading
of O2 at the tissues
– Called Bohr effect
• When O2 falls
– Shifts Co2 curve up
and right
– Facilitates greater Co2
loading
– Called Haldane effect
• Thus, at the level of the
tissue, high CO2
facilitates unloading of
O2 which allows greater
amount of CO2 to be
carried in blood
• At the lung, high O2
forces CO2 from Hb
(and plasma) and it is
then exhaled
Arterial blood gases
• Note how
ventilation and
PaCo2 inversely
mirror each other
• Note also the effect
on pH
• Major function of
the ventilatory
system is to rid the
body of Co2 and
control pH
• VA = VCo2/PaCo2
Buffering of metabolic acids
• pH is a measure if the
acidity of the blood
• Several sources of
acid are during
exercise
– Lactic acid (HLa)
– Carbon dioxide
• These cause a fall in pH
– Bicarbonate is a very
effective buffer
• A buffer helps to prevent
a change in pH
pK: Dissociation constant. pH at
which acid (or base) is 50%
dissociated (50% acid and 50%
base)
Buffering of metabolic acids
• Lactic acid produced
– HLa → La- + H+
– H+ + HCO3- → H2CO3 → H2O + CO2 (exhaled)
• Co2 produced
– CO2 + H2O → H2CO3 → HCO3- + H+ (reverses at lung)
• pH
–
–
–
–
–
–
Negative logarithm of the hydrogen concentration
pH = pk for HCO3-+ log [base/acid)
pH = 6.1 + log [HCO3-/(pCO2 *0.03)] (Henderson-Hasselbalch eq.)
pH = 6.1 + log [24 /1.2)
pH = 6.1 + 1.3
pH = 7.4
Control of pH
• Co2 and pH (actually
the H+) stimulate
ventilation
– Chemoreceptors
• Carotid sinus
• Centrally (medulla)
– Sensitive to changes
in Pco2 and H+
• Stimulate breathing to
expel CO2 and partially
compensate for the
metabolic acidosis
Ventilation
• Gross Anatomy
–
–
–
–
Pharynx
Trachea
Bronchus
Alveolus
Ventilation
• Ventilation
– Moves air into and out
of lung
• Two separate areas of
lung
– Conducting zone
– Respiratory zone
– Conducting zone
• Network of tubes whose
function is movement of
air
– Trachea and Bronchi
– Respiratory zone
• Large, thin area where
gas exchange occurs
– Respiratory
bronchioles and
alveolar ducts
Ventilatory mechanics
• Diaphragm
– Main muscle of
ventilation
– Only skeletal muscle
necessary for life
• Accessory muscles
– Intercostals
• External
– Inspiration
• Internal
– Expiration
– Sternocleidomastoid,
Scalenes
• Inspiration
– Abdominal muscles
• Expiration
Ventilatory volumes
• Note how much
ventilation can
increase
– Due to large
increases in tidal
volume and
frequency
– Increases in tidal
volume (VT) largely
due to accessory
muscles
– Increases in
frequency (f) due to
diaphragm
Dead space and alveolar ventilation
• Ventilation (VE) is the total
amount of air moved in
and out of the lungs
– VE = VDS + VA
– Dead space (VDS)
• Anatomic dead space
– Conducting zone
• Physiologic dead space
– Diseased areas
• Dead space/tidal volume ratio
– At rest ratio of VD/VT ~2540%
– With exercise VD/VT falls,
why?
– Alveolar ventilation
• Ventilation of the gas
exchange units
Static lung volumes
• Volumes and capacities
– Volume: single measure
• Residual volume (RV)
– The amount of air in the lung after a maximal expiration
• Expiratory reserve volume (ERV)
– The amount by which you can increase expiration after a normal exhalation
• Inspiratory reserve volume (IRV)
– The amount by which you can increase inspiration after a normal inspiration
• Tidal volume (VT)
– The volume of a normal breath
• Total lung capacity (TLC)
– RV, ERV, VT and IRV
• Vital capacity
– ERV, VT and IRV
• Functional residual capacity
– RV, ERV
• Where humans breath from
• Inspiratory capacity
– VT, IRV
Composition of Alveolar gases
100% oxygen
Air breathing;
no water or
CO2
Movement of gas: diffusion
Diffusion
• Oxygen
– Breathed into lungs
– Diffuses across blood gas
barrier
– Binds with hemoglobin
(97%)
– Dissolved in plasma (3%)
– Circulated to tissues
– Diffuses into tissues
– Binds with myoglobin
• Keeps oxygen pressure
homogeneous within
tissues
– Utilized in
mitochondria
Mb
Transit time
• Capillary blood volume
(Vc)
– The blood that is in the
capillaries at one instant in
time
• Transit time
•
•
•
•
– the ratio of VC/blood flow
VC =~70 ml
Qc = 100 ml/s
TT = 0.7 sec
More than adequate for
equilibration of blood
gases
• Note that CO2
equillibrates MUCH
faster than O2; why?
Control of ventilation
• Respiratory
control center
– Brainstem
• Medulla
• Pons
• Feed forward
– Central command
• Feedback
– Peripheral and
central
chemoreceptors
Central and peripheral control
• Feed forward
– Sometimes called “central command”
– Co-activation of cardiovascular, ventilatory
and musculoskeletal systems
• Central chemoreceptors
– Sensitive to changes in pH
– Caused by Co2 as H+ cannot cross Blood
brain barrier
• CO2 + H2O
H2CO3
HCO3- + H+
• Peripheral chemoreceptors
– Carotid sinus
– Muscle metaboreceptors
• Both sensitive to changes in pH, PCO2 and PO2
(particularly at high atltitude)
• Peripheral mechanoreceptors
– Sensitive to limb movement
Feed forward 1
1
Peripheral3
Peripheral3
Central
2
3&4
Peripheral
chemoreceptors and
mechanoreceptors