Introduction
Ventilatory system is basically composed of two zones namely Lung respiratory and conducting zones.
Respiratory
zone – respiratory bronchioles, alveolar ducts & sacs Conducting
zone – bronchioles, bronchi, trachea
Alveoli is the structural and functional unit of the lungs. Alveoli have largest cross-sectional area
Bronchioles have smooth muscle &
cartilage
23 divisions of branches into ever smaller
conduits
Protective mechanisms in respiratory system
Mucous-secreting, ciliated cells line
conducting zone airways.
Large particles
stop at nose, smaller ones caught in cilia, finest particles (like asbestos)
make it into alveoli
Gaseous exchange in ventilatory system can be divided into four
functional components:
Ventilation – movement of air into lungs
(need pump to generate flow, pipes slow down flow – R)
Perfusion – movement and distribution of
blood through pulmonary circulation
Diffusion – movement of O2 and
CO2 across air-blood barrier or alveolar-capillary membrane
Control of breathing – process of
regulation of gas exchange to meet metabolic needs of moment
Respiratory quotient, RQ = CO2
produced = 200 ml/min. = 0.8 (average)
CO2consumed 250 ml/min.
Carb RQ = 1, fat RQ = 0.7, protein RQ = 0.8
A = alveolar
a = arterial blood
v = venous blood
Non-respiratory functions of respiratory
system:
(upper airway includes nose, paranasal
sinuses, naso- and oropharynx, larynx)
1)
route for water loss, heat elimination (warms, moistens air so alveoli
don’t dry out – oxygen and carbon dioxide can’t diffuse across a dry membrane)
2)
enhances venous return (respiratory pump)
3)
helps normalize pH by altering amount of CO2 (H+-producing)
exhaled
4)
enables speech, singing, other vocalization – larynx – vocal cords act
as ‘vibrator’
5)
defends against inhaled foreign matter (filters particulates or microbes
via mucous coat propelled towards larynx by ciliary action, cough reflex,
sneeze reflex, immunoglobulins – both locally produced and brought into lung
from other sites)
6)
removes, activates/deactivates various materials passing through
pulmonary circulation (i.e., turns prostaglandins off, angiotensin II on)
7)
nose – sense of smell
Respiratory mechanics
Lungs contain 300 million alveoli with – 0.3 mm in
diameter
total surface area of lungs is about 75 m2
(size of tennis court)
Collateral
ventilation – airflow between adjacent alveoli (via
pores of Kohn)
Pleurisy – inflammation of pleural sac (painful “friction rub”)
atmospheric pressure = 760 mmHg at sea
level, decreases as altitude increases
Intra-alveolar
pressure (intrapulmonary pressure) will equilibrate
with atmospheric pressure
Intrapleural
pressure (intrathoracic pressure) = 756 mmHg –
vacuum (called ‘-4’); closed cavity
Negative
intra-alveolar, intrapleural pressures provide driving force for
inhaling/exhaling
transmural pressure – pressure across
surface of lungs, = Palveolus
- Ppleural space
Two forces hold thoracic walls & lungs
in close apposition
thorax cannot be expanded its own without expanding the lungs
1) Intrapleural fluid’s cohesiveness (like
water between two slides)
2) Transmural pressure gradient (most
important)
intra-alveolar
pressure = 760 mmHg, pushes out against intrapleural p. of 756 mmHg
atmospheric
pressure = 760 mmHg, pushes in against intrapleural p.
Neither chest wall nor lungs are in their
resting position (both are actively pushing against space)
Pleural space has slightly negative
pressure because chest is pulling out, lungs are pulling in, and there’s no
extra fluid to fill expanded space
Pneumothorax – air enters pleural cavity, pressure equalizes with atmospheric
pressure, transmural pressure gradient is gone → lungs collapse, thoracic wall
springs out
Before inspiration – respiratory muscles are relaxed, no air is flowing,
intra-alveolar p. = atm. p.
Major inspiratory
muscles (diaphragm, external intercostals) contract → thoracic cavity enlarges
[Diaphragm is innervated by phrenic nerve; dome-shaped at rest,
contracts & pulls down. Responsible
for 75% of enlargement of thoracic cavity during inspiration. Contraction of external intercostals enlarges
cavity in lateral and AP dimensions (elevate ribs when contracting)]
As lungs expand, pressure decreases (to 759 mmHg) → air flows in
(alveolar pressure is negative during
inhalation, positive during exhalation)
Intrapleural
pressure drops to 754 mmHg (ensures that lungs will
be fully expanded)
Lung expansion is not caused by movement of air into lungs.
With deeper contractions, contract
diaphragm and external intercostals more forcefully & contract accessory inspiratory muscles (SCM,
scalenes, alae nasi, small muscles of neck/head) to raise sternum & first 2
ribs
At end of inspiration – inspiratory muscles relax, diaphragm is dome-shaped again, rib
cage falls because of gravity once external intercostals relax, chest walls
& stretched lungs recoil → volume decreases, pressure increases (to 761 mmHg) → air flows out
During quiet breathing, expiration is
passive (due to elastic recoil of lungs – no muscular/energy expenditure),
whereas inspiration is always active.
During heavy breathing – active expiration – contract abdominal muscles (increase
intra-abdominal pressure → pushes diaphragm up → increases intrathoracic
pressure), internal intercostal muscles (pull
ribs downward, inward) → lungs are emptied more forcefully.
During forceful expiration, intrapleural
pressure exceeds atmospheric pressure, but lungs don’t collapse because
intra-alveolar pressure increases, too (4 mmHg pressure gradient stays same)
Paralysis of intercostal muscles doesn’t
affect breathing much, but paralysis of diaphragm = can’t breathe. Phrenic nerve is C3-C5, so patients with
paralysis from neck down can still breathe.
Air flow
•
Flow,
V = ∆P/R
∆P = pressure gradient between atmosphere
and alveoli
R is
primarily determined by radius
Resistance of total airways circuit depends
on #, length, cross-sectional area of conducting airways. Each terminal
bronchiole has greater resistance to flow than trachea, but because of vast
cross-sectional area, their overall
contribution to total R is less than that of central airways (since
bronchioles are arranged in parallel).
In healthy patient, overall respiratory
system has extremely low R
Laminar vs. turbulent flow
Flow can be laminar (low flow rate) or
turbulent (fast flow rate)
In small airways, flow is usually laminar
For laminar
flow, R = 8ηl (Poiseuille’s Law) η = viscosity, l = length
πr4
Turbulent
flow has different properties – driving pressure is
proportional to square of flow (V2)
Turbulence is most likely to occur with high velocity, large diameter.
Volume of inflation of lung has important
effect on airway resistance
Pressure = (vol./compliance) +
flow * resistance P
= pressure required to breathe
Chronic obstructive pulmonary disease
(COPD)
Narrowing of lumina of lower airways. When airway R increases, larger ∆P must be
present to maintain same airflow.
Expiration is more difficult than inspiration – “wheeze” as air is
forced out through narrowed passages. In
normal patients, smaller airways collapse – further outflow stops only if lung
volume is very low (lungs can never be completely emptied)
Chronic bronchitis – triggered by frequent exposure to cigarette smoke, pollution,
other allergens. Airway lining thickens,
mucous production increases, ciliary mucous elevator is immobilized by
irritants. Increased mucous → bacterial
infections
Asthma –
obstruction due to 1) thickening of walls b/c of inflammation,
histamine-induced edema, 2) plugging of
airways by very thick mucous, 3) airway hyperresponsiveness – trigger-induced
spasms (allergens, irritants, infection).
Most common chronic childhood disease.
Emphysema –
collapse of smaller airways, breakdown of alveolar walls (irreversible). Can happen because of 1) excessive release of
trypsin from alveolar macrophages as defense against cigarette smoke irritants
(lungs normally protected by α1-antitrypsin, but can be
overwhelmed), 2) genetic inability to produce α1-antitrypsin
(asthma and emphysema start in small
airways – difficult to detect – ‘silent airways’)
Amount of inspired air that makes it to
alveoli depends on:
**Strength of pump (muscles)
**Airway resistance (frictional resistance,
80% total R)
**Elasticity/compliance
**Tissue resistance – frictional resistance
of lungs and chest wall (20% total R)
**Inertance – energy must be expended to
set system in motion
(Need to overcome stiff/elastic recoil,
frictional resistance, and inertance)
Pulmonary elasticity
1) elastic
recoil – returning to preinspiratory volume at end of inspiration
2) compliance
– measure of distensibility, magnitude of change in volume for given transmural
∆P Defined by slope of pressure-volume
curve for lungs – curve is steep in normal operating range (only at very
low/high volumes does curve flatten). Normal compliance is 200 cm/ml H2O. Different compliance for
expiration/inspiration b/c of surfactant – hysteresis. Static
compliance is measured without airflow; dynamic compliance is measured during airflow. (poor compliance =
stiff lung, restrictive disease = more work to breathe)
Pulmonary elastic behavior depends on:
1) CT in lungs has lots of elastic fibers (arranged in meshwork)
2) alveolar
surface tension
water
molecules want to be close together – resist expansion of surface area (the
greater the surface tension, the less compliant the lung). If alveoli were lined with water alone,
surface tension would be so great, airways would collapse.
pulmonary surfactant (lipid-protein
mixture) lowers surface tension
because water-surfactant attraction is not as strong as water-water → increases
pulmonary compliance, reduces lung’s tendency to recoil. Produced by type II pneumocytes
LaPlace’s Law à P = 2T/r P
= inward-directed collapsing pressure, T
= surface tension
Smaller airways are more likely to collapse
than large ones because of greater surface tension (smaller r), but surfactant
is more effective at lowering surface tension in smaller airways (less spread
out). Surfactant stabilizes small
alveoli.
**Evidence of these two factors of lung
elastic recoil is found in differing pressure-volume characteristics of
saline-filled vs. air-filled lungs (saline-filled are easier to stretch than
air-filled)
You can have separate pressure-volume
curves for chest wall, lungs – combine to get one for total respiratory
system. Two structures are in series,
interdependent – force required to inflate lung equals sum of pressure
difference across lung and across chest wall.
Interdependence of neighboring alveoli – surrounding alveoli resist collapse of
another alveolus.
Respiratory
Distress Syndrome (RDS) – not enough type II cells
to make surfactant
Work of Breathing
Normally only required on inspiration
Subdivided into compliance work (to expand lungs against lung/chest wall elastic
forces); tissue resistance work (to
overcome viscosity of lung/chest wall); airway
resistance work
Work
= P *
V
Measurements of Lung Volumes
3-5% of total energy expended by body goes to breathing (heavy exercise
– can increase 50-fold)
in obstructive lung disease, up to 30% of
body’s energy expenditure is for breathing – even at rest!
Quiet breathing – 2,200 ml (expiration) –
2,700 ml (inspiration) tidal volume =
500 ml
Tidal
volume (TV or
VT) – 500 ml at rest.
Amount entering/leaving lungs during one breath. As tidal volume increases, intrapleural and
intra-alveolar pressures decrease in direct proportion.
Inspiratory
reserve volume (IRV) – 3,000 ml. extra air you can breathe in, using
inspiratory muscles (beyond normal tidal volume)
Inspiratory
capacity (IC) – 3,500 ml. IC = TV
+ IRV
Expiratory
reserve volume (ERV) – 1,200 ml. extra air you can breathe out, using
expiratory muscles (beyond normal tidal volume)
Residual
volume (RV) – 1,400 ml. amount that can’t be expired from the lungs
(can measure with tracer like helium)
Functional
residual capacity (FRC) – 2,500 ml. Volume of lungs after normal passive
expiration. FRC = ERV + RV
Vital
capacity (VC) – 4,600 ml. Maximum volume change possible. VC = IRV + TV + ERV
Total
lung capacity (TLC) – 6,000 ml. TLC = VC + RV
Forced
vital capacity (FVC) – total volume expired from
maximum inspiration to maximum expiration; normal range is 80-120% normal tidal
volume.
Forced
expiratory volume in 1 second (FEV1) –
maximum volume that can be expired in one second. FEV1
= 80% VC (normal)
Maximum
mid-expiratory flow rate (MMEFR) – FEF25-75 – forced
expiratory flow over middle half of the FVC, gives us most information about
small airways (<2mm diameter)
Peak
expiratory flow rate (PEFR) – FEFmax –
highest expiratory flow achieved. Can
only be measured from flow/volume curve
Spirometry
Spirometer – air-filled drum floating in
water. Breathe into drum – records
volume changes on spirogram. Most lung
volume subdivisions can be measured directly from spirogram
trapped gas
within lung must be measured either by gas dilution method or by body plethysmography. Lung volumes can also be measured by x-ray – planimetry
Spirometry can measure TV, IRV, IC, ERV, VC (others measured indirectly,
calculated)
Forced
vital capacity (FVC) maneuver – take in deepest
breath possible, breathe out as much as possible. Data can be displayed as volume vs. time or
as flow vs. volume
if
airways resistance is normal, FEV1 >
70%
FVC
Obstructive
ventilatory defect – decreased air flow through
tubes, normal tidal volume. Can be from
1) upper airways disease; 2) peripheral airways disease (from asthma, cystic
fibrosis, chronic obstructive bronchitis, bronchiectasis); or 3) pulmonary
parenchymal disease (emphysema).
Restrictive
ventilatory defect – normal flow, normal R, but small
vital capacity, FVC, FEV1 are reduced (in ratio to each other). Can be chest wall, pleural, space-occupying
intra-thoracic lesion, extra-thoracic conditions (obesity, pregnancy, ascites),
or interstitial lung disease. Reduction
in lung volumes below 80% of predicted values.
Examples of lung volumes being smaller than
predicted (restrictive defect):
Fibrosing
(scarring) – increased elastic recoil
Diseases
of chest wall (kyphoscoliosis) – increased elastic recoil
Diseases
of the pleural space (pleural effusion) – compress lung
Tests of gas exchange function of lungs
Arterial
blood gas determination (ABGs) – measurement of
dissolved tensions of CO2 and O2 as well as pH of sample
of arterial blood
Pulse
oximetry – photometric measurement of saturation of
hemoglobin with O2.
(non-invasive)
DLCO – diffusing capacity of lung for carbon monoxide, usually done by ‘single breath’ method (DLCOsb). DLCO is affected by factors other
than characteristics of gas exchange membrane; membrane thickness and increased
surface area reduce DLCO.
Ventilation (V – ventilation, Q – perfusion)
Volume of air breathed in and out in one
minute
Respiratory
(minute) ventilation, V• = TV
(ml/breath) * f, respiratory rate (breaths/min)
At rest:
6,000 ml = 500
* 12 (6 L air breathed
in and out per min.)
With exercise, can increase 25-fold, to 150
L/min.
TV is more important than respiratory rate
when minute ventilation increases
Dead
space (VD) – volume of air-filled space
incapable of gas exchange with blood
=Anatomical
dead space – 150ml. volume of conducting airways (350ml
used for gas exchange)
(equal to individual’s lean body weight in
pounds)
Alveolar
ventilation, VA• = (TV
– VD, dead space) * f, respiratory rate
At rest:
4,200 ml = (500-150) * 12
Alveolar ventilation is about 5 L per
minute = cardiac output (excellent transfer of gases)
Normal respiratory rate is 12-15 breaths/minute
**if you breathe deeply & slowly,
respiratory ventilation can stay same but alveolar ventilation increases
**if you breathe shallowly & rapidly,
respiratory ventilation can stay same but alveolar ventilation decreases (even
to zero)
Each tidal breath does not completely
fill/empty an alveolus – reservoir of
gas ‘stored’ within alveoli that’s only gradually replenished. Volume = 3,000
ml – prevents fluctuation in alveolar gas tensions with each tidal breath.
(alveolar ventilation is more important
measurement than respiratory ventilation, since that’s where gas exchange is
done)
alveolar
gas equation:
PAO2 = FiO2 (PB – PH20) - (PACO2/R)
solving for conditions at sea level & R
= 0.8: PAO2 =
0.21(760-47) – (40/0.8)
PAO2 = 100
obstructive
lung disease – easy to fill lungs, hard to empty
TLC
is normal
FRC,
RV are increased
VC,
FEV1, FEV1/VC% are decreased
restrictive
lung disease – lungs are less compliant than normal
TLC,
IC, VC are decreased
RV
is normal
FEV1/VC%
is normal or even increased
Increasing
tidal volume is most efficient way to increase
alveolar ventilation (increase respiratory rate and alveolar ventilation
increases somewhat, but dead space is also increased)
Not all alveoli are equally ventilated with
air, perfused with blood → alveolar dead
space
(minimal in healthy patients, but can be
lethal) ventilated, but don’t
participate in gas transfer
physiologic
dead space – sum of anatomical & alveolar dead
space
Lower
regions of lung are better ventilated than upper zones.
Gravity
is largely responsible. pleural pressure
is more negative at top of thoracic cavity – greater distending pressure for
alveoli at top of lungs (top alveoli are larger in size). alveoli on bottom vs. top operate on different
parts of a pressure-volume curve
lower
regions of lung are better perfused than upper zones.
gravity
is primary determinant. hydrostatic
pressure gradient from top to bottom b/c lowest point in lung is 30 cm below
highest point à pressure gradient of 30 cm water = 23
mmHg (15 mmHg above heart, 8 mmHg below heart)
Perfusion conditions in lung divided
into three zones (a=pulm.art, A=intra-alveolar, v-pulm.vein)
Zone
1: Pa < PA collapse of vessel
before it crosses alveolus; no forward flow; doesn’t exist in normal lungs –
might occur if person has hemorrhaged (BP, intravascular volume are low)
Zone
2: Pa > PA > Pv flow driven by difference between
arterial/alveolar pressure; primary area of distension, recruitment of vessels
during exercise
Zone
3: Pa > PA, Pv > PA continuous forward flow
through distended vessels.
Matching of ventilation to perfusion
there is not perfect matching of
ventilation to perfusion in most alveoli.
non-uniform distribution of both results in alveolar units with varying
ratios of ventilation to perfusion (V/Q)
alveoli
at apex are overall poorly ventilated, perfused,
but relatively better ventilated than perfused = high V/Q ratio
if no perfusion but good ventilation,
alveolar gas tensions will be same as in trachea (PAO2 =
150, PACO2 = 0).
No effect on downstream gas tensions – part of dead space. But if there is some degree of perfusion à PAO2
will be high, PACO2 will be low
alveoli
at base are well ventilated, perfused, but better
perfused than ventilated = low V/Q ratio
if no ventilation, but some perfusion,
alveolar gas tensions in unit will be same as those in mixed venous blood (no
fresh air being added). PAO2
will be low, PACO2 will be high (blood exiting capillary
will be low in O2, high in CO2)
units with low V/Q ratios have greater effect on overall gas exchange since
they receive greater proportion of total pulmonary blood flow.
A high
V/Q unit can’t compensate for impact of low V/Q unit because it’s at flat
part of S-shaped oxygen-hemoglobin dissociation curve – raises PO2,
which results in more dissolved O2, but not much more HbO2
Any rise
in PCO2 in arterial blood stimulates respiratory centers to increase alveolar ventilation à removal of CO2 through alveolar units with better V/Q
ratios. Overventilation of these units
can’t raise PaO2 since they are operating on flat upper
portion of oxygen-Hb saturation curve
Measurement of V/Q mismatch
alveolar-arterial
gradient – P(A-a)DO2 or A-a gradient –
refers to pressure difference for O2 between alveolar conditions and
arterial blood. Measurement of
inefficiency of oxygen transfer.
**measurement of A-a exists even in normal patients,
contributed to by 1) ventilation-perfusion mismatch in normal lung, 2) small
amount of shunt caused by bronchial, Thebesian circulations.
**A-a gradient can be calculated using
alveolar gas equation to calculate expected ideal PAO2, measure
actual PaO2.
**Normal A-a gradient varies with age –
rough estimate is 25% of person’s age in years
**If A-a
gradient is higher than normal, due to:
increased
V/Q mismatch
increased
shunt fraction
markedly
abnormal diffusion of oxygen – rare clinically b/c of free diffusion of O2,
CO2
Venous
admixture – proportion of blood flowing through
true right-to-left shunts or hypoventilated lungs (units with low V/Q ratios) –
measure of wasted perfusion. Calculated from variation of shunt equation:
Qva = CiO2 - CaO2
QT CiO2 - CvO2
Physiologic
dead space – proportion of ventilation to both anatomic
dead space and hypoperfused lung (high V/Q ratios) – measure of wasted ventilation.
Calculated from equation:
VD
=
PaCO2 - PECO2
VT PaCO2
Normal VD/VT ratio
during resting breathing is 0.2 – 0.35
Gas Exchange
CO2
and O2 are exchanged via simple diffusion – no active
transporters – passively move down partial pressure gradients.
When bulk movement of air ceases at
terminal bronchioles, oxygen moves towards alveolus by diffusion, carbon
dioxide diffuses away from alveolus.
ideal gas law: PV=nRT n
= # moles of gas, R = gas constant, T = absolute temperature
Boyle’s
Law: as
volume of gas increases, pressure decreases
Normal atmospheric air = 79% N2,
21% O2, a little CO2, pollutants, etc.
Total atmospheric air pressure = 760 mmHg,
of which 79% is from N2, 21% from O2, etc.
Partial pressure of oxygen, PO2 is normally 160 mmHg (or
torr)
PN2
is normally 600 mmHg PCO2 is normally 0.03 mmHg
Alveolar PO2 > pulmonary
capillary PO2, so more oxygen goes into blood (diffuses until equal).
Alveolar PO2 < atmospheric PO2
because 1) air is warmed to 37°C & saturated with water once it enters;
water vapor adds 47 mmHg partial pressure, essentially ‘diluting’ partial
pressure of other gases, 2) air inspired is mixed with lots of old, “dead” air
(FRC). Only 1/7 of total alveolar air is replaced with each breath (<15%
alveolar air is “fresh”).
Average alveolar PO2 is 100 mmHg,
remains nearly constant throughout cycle (as does blood PO2, as does
oxygen in blood available to tissues)
Average alveolar PCO2 is 40 mmHg,
also fairly constant
Average arterial PO2 is 100 mmHg,
PCO2 is 40 mmHg
Blood entering pulmonary capillaries is
systemic venous blood (via pulmonary arteries),
systemic
venous blood PO2 = 40 mmHg, PCO2 = 46 mmHg
O2 expelled from lungs = O2 extracted, used by tissues
During exercise, venous blood PO2
can drop to 30 → increases ∆P at alveoli → more O2 diffuses from
alveoli into blood.
Other factors influencing rate of gas
transfer
Partial pressure gradients are the main
factor determining rate of gas transfer, but there are others.
Surface
area
during
exercise, pulmonary bp increases b/c of increased cardiac output → forces open many of previously closed pulmonary
capillaries → increases surface area for gas exchange
emphysema
– SA reduced because many alveolar walls are lost – fewer, larger chambers (same when part of lung is collapsed or when
part of lung is surgically removed)
Wall
thickness
pulmonary
edema – increased interstitial fluid between alveoli and pulmonary capillaries,
caused by pulmonary inflammation or
left-sided congestive heart failure
pulmonary
fibrosis – replacement of delicate lung tissue with thick fibrous tissue in
response to certain irritants
pneumonia
– inflammatory fluid accumulation in/around alveoli. (viral/bacterial/aspirating food)
increasing tidal volume increases surface
area by stretching alveolar walls, and makes walls thinner.
Clinical measurement of diffusion
characteristics of alveolar-capillary membrane done by test called ‘diffusing capacity for carbon monoxide
(DLCO).’
Alveolar-capillary membrane has vast
surface area (70 m2) with very short distance (0.5 microns) for
diffusion. Layers of separation between air and blood:
1)
fluid layer lining alveolus,
containing surfactant
2)
alveolar epithelium – mostly
type I cells
3)
epithelial basement membrane
4)
interstitial space between two
basement membranes
5)
capillary basement membrane –
may be fused with epithelial BM (in which case interstitial space is a
potential space)
6)
capillary endothelial cell membrane
Diffusion
coefficient
Rate of gas transfer is proportional to
diffusion coefficient, D (related to solubility
& MW)
D is proportional to (solubility)/(sq. root
MW)
D for CO2 is 20x D for O2 because CO2 is far more
soluble in body. Faster diffusion rate
is offset by CO2’s smaller ∆P (6 mmHg) than O2 (60 mmHg),
so CO2 & O2
diffusion more or less equilibrates.
In diseased lung, O2 transfer is more seriously impaired than
CO2 transfer because of the difference in diffusion coefficient.
Pulmonary caps and systemic caps are only
two places in circulation where gas exchange occurs.
Arterial systemic capillary blood: PO2 = 100 mmHg, PCO2 = 40 mmHg
Venous systemic capillary blood: PO2 = 40 mmHg, PCO2 = 46 mmHg (same as tissue conditions)
The more actively the cell is metabolizing,
the more cellular PCO2 rises, PO2 drops – more O2
diffuses from blood into cells, more CO2 diffuses from cells into
blood.
Net diffusion of oxygen is from alveoli
into blood, then from blood into tissues (CO2 – opposite)
GAS
TRANSPORT
Oxygen is present in blood in two forms
total O2 content in arterial
blood is 20 ml O2/100 ml
blood
Physically dissolved in plasma – only 1.5%,
because oxygen is not very soluble in body fluids
0.003 ml O2/100ml blood can be dissolved
for each mmHg of pressure, so normal dissolved
O2 content of blood is 0.3 ml O2/100 ml. Tissue O2 consumption is 250
ml/min at rest, so need extra way to transport O2.
PO2 is related to oxygen
dissolved, not oxygen bound to Hb
Chemically bound to hemoglobin (Hb) – 98.5% 19.7
ml O2/100 ml blood
Hb + à HbO2 (reversible)
Reduced
hemoglobin oxyhemoglobin
Hb binds reversibly with 1.34 ml O2 per gram of Hb. Normal Hb content = 15 grams
PO2 determines Hb saturation
Each Hb molecule has 4 Fe, is capable of binding
to 4 O. “fully saturated” if 4 O are
bound.
PO2 of blood is most important
factor determining %Hb saturation (related to [O2 dissolved])
Law
of mass action
if blood PO2 is increased (i.e.,
in pulmonary caps), reaction shifts to right, get more HbO2.
if blood PO2 is decreased (i.e.,
in systemic caps), HbO2 dissociated, releases its oxygen.
O2-Hb dissociation curve is
S-shaped, not linear.
at PO2
= 100 mmHg, Hb. is 97.5% saturated
even at PO2
= 60 mmHg, Hb. is 90% saturated
from 60-760 mmHg PO2, Hb.
saturation only changes 10% - provides margin of safety in O2-carrying
capacity of blood. Even if PO2
falls to 60 mmHg (high altitudes, stuck in a vault, pathological conditions),
body can maintain high %Hb saturation.
Mixed venous blood carries substantial amount of O2 – reserve
which can be unloaded under extreme conditions (exercise).
at
PO2 = 40 mmHg, Hb. is 75% saturated (resting systemic capillaries,
venous blood)
Hb
saturation decreases as cell metabolism increases
from
PO2 = 0-60 mmHg, a small drop leads to a steep drop in %Hb
saturation.
during
strenuous exercise, up to 85% of Hb. gives up its oxygen
pulse oximeter can non-invasively measure
Hb saturation
Utilization
coefficient - % of Hb that gives up its oxygen as
it passes through tissue capillaries.
Normal value = 25%, can
increase up to 85% during exercise.
Hemoglobin as a storage unit
**Hb. acts as “storage depot” for oxygen –
removing oxygen from solution as soon as it enters blood from alveoli. (when oxygen is bound to Hb., it doesn’t
count towards PO2). Once Hb
is saturated as much as it can be for that PO2, then O2
coming into blood increases PO2 until it equilibrates with alveoli.
**Hb. also helps get oxygen into tissues
PO2 of systemic blood (95 torr) is
higher than tissue PO2 (40 torr), so O2 diffuses
across. PO2 drops → Hb has to
release oxygen → PO2 increases.
Diffusion continues until Hb can’t unload more oxygen, PvO2
= 40 torr until it reaches pulmonary capillary beds.
tissue PO2 is affected by rate
of blood flow past tissues & rate of tissue metabolism.
Hb plays role in total quantity of oxygen
blood can pick up in lungs or drop off in tissues.
If Hb levels are reduced by 50% (i.e., with
anemia), O2-carrying capacity of blood drops by 50%.
Other factors affecting Hb-O2
affinity
PO2 is most important factor
affecting Hb-O2, but there are others…
↑ PCO2 – shifts O2-Hb curve to right (less HbO2 at a
given PO2)
↓ pH (increased acidity) – shifts O2-Hb curve to right CO2 à H2CO3
exercising
muscles make more carbonic acid, lactic acid → forces HbO2 to unload
more O2 at these tissues
Bohr
effect – CO2 & H+ can
combine reversibly with Hb at site other than O2 binding site –
reduces O2 affinity.
Important in enhancing oxygenation of blood in lungs, releasing oxygen
at tissues.
↑
temperature – shifts O2-Hb curve to
right (exercising muscles generate heat, demand more O2)
**Above three factors are only in systemic
capillaries. Hb has higher affinity for
oxygen in pulmonary capillaries than in systemic capillaries.
Inside RBCs, 2,3-bisphosphoglycerate (BPG) binds reversibly to Hb and reduces O2 affinity. 2,3-BPG is produced during RBC
metabolism. Production gradually
increases if Hb is chronically undersaturated (when HbO2 is low –
high altitudes, anemia, some circulatory/respiratory diseases)
Since 2,3-BPG is present throughout
circulation, it not only increases HbO2’s ability to unload oxygen
at the tissues, but it decreases its ability to load O2 from alveoli. (shifts curve to right)
Carbon monoxide poisoning
Hb’s affinity for binding to CO is 240x
that for oxygen. HbCO =
carboxyhemoglobin
Even small amounts of CO make cells O2-starved.
Carbon dioxide
CO2 is transported in the blood
in 3 ways
total CO2 content in arterial
blood is 59 ml O2/100 ml
blood
1)
physically dissolved – depends
on PCO2, normal PvCO2 = 45 torr; normal PaCO2
= 40 torr. 5% of CO2 in arterial blood is dissolved (10% in venous
blood).
2)
bound to Hb à HbCO2 = carbaminohemoglobin, 5% of CO2 in arterial blood (30% in venous blood), CO2
binds to terminal amine groups of blood proteins – to globin part of Hb, not heme part.
Hb has greater affinity for CO2 than HbO2 (HbO2
becomes Hb at tissues, picks up CO2)
3)
transported as bicarbonate (HCO3-)
– 90% in arterial blood (60% in
venous blood)
taking place rapidly, in RBCs, with carbonic anhydrase catalyzing first
reaction:
CO2
+ H20 à H2CO3 à
H+ + HCO3-
HCO3- is more soluble
in blood than CO2.
RBC has HCO3—Cl-
carrier that passively facilitates diffusion of these ions (in opposite
directions). Membrane is relatively
impermeable to H+, so HCO3- diffuses alone.
HCO3- diffuses out
into plasma, Cl- diffuses into RBC = chloride shift
Most H+ that’s left behind binds
to Hb (reduced Hb has greater affinity for H+ than HbO2)
– Hb helps keep acid-base balance between arterial & venous blood.
Haldane
effect – removing O2 from Hb increases
its ability to pick up CO2, H+
Bohr effect & Haldane effect feed into
one another
↑ CO2, ↑ H+ à ↑ O2 release
↑ O2 release à ↑ CO2, ↑ H+
CO2
dissociation curve – depicts relationship between PCO2
and total content of CO2 in blood.
curve is much steeper than that for
oxygen. 4% volume of CO2 is
exchanged during normal transport of CO2 from tissues to lungs.
Respiratory
exchange ratio (R) – ratio of CO2 output
to O2 uptake.
R
= VCO2
VO2
Under normal resting conditions, 4ml CO2:
5 ml O2 à 0.8
(80%)
Pulmonary Blood Flow
Physiologic anatomy of pulmonary
circulation
high flow (5L/min), low pressure (15 mmHg),
low resistance (1-2 mmHg/L/min) circuit
pulmonary
artery extends only 5 cm above RV before
dividing. Vessels are thin-walled, distensible
– can accommodate most of stroke volume of RV.
pulmonary
capillaries form a dense network in alveolar walls
– air spaces are nearly completely surrounded by flowing blood. (large surface area for gas exchange, short
air-blood barrier)
small
pulmonary veins collect oxygenated blood from
capillaries, run between lobules, form four large pulmonary veins
Pressures in pulmonary circulation
Pulmonary
artery
systolic
pressure averages 25 mmHg, diastolic pressure averages 8 mmHg,mean pulmonary
arterial pressure is 15 mmHg
distribution of blood in lung is not
complex – only need enough pressure to lift blood to top of lung
work required of RV is much less than LV à RV is less muscular than LV
pulmonary capillary pressure is estimated
using flow-directed pulmonary artery (Swan-Ganz)
catheter to measure back pressure from LA.
Normal “pulmonary capillary wedge pressure” (PCWP) = 5 mmHg. [helps determine LA filling pressure (would
be elevated with stenotic mitral valve, left-sided congestive heart failure)]
pulmonary
capillaries are surrounded by gas – subjected to
pressure shifts occurring within alveolar spaces during ventilation. Swings in alveolar pressure may affect flow
pressure in caps.
if
alveolar pressure is higher than pressure in capillary, it will collapse
pressure
difference between inside, outside of vessel = transmural pressure
larger pulmonary arteries, veins (“extra-alveolar”) are subjected to much lower pressures than alveolar (smaller)
vessels – pulled open as lung expands on inspiration
pulmonary
vascular resistance (PVR) = input pressure – output pressure
blood
flow
PVR is about one-tenth that of systemic circulation (1.7 mmHg/L/min). Resistance doesn’t need to be so high since
there is no demand to regulate blood flow to various vascular beds/organs.
Lungs have mechanisms to keep pressures low. With exercise, Q through lungs increases
several fold, but pressure doesn’t rise because PVR decreases (via recruitment and distension of airways)
as lung inflates, alveolar, extra-alveolar
vessels are stretched.
Blood volume of lungs
normal blood volume of lungs is 450 ml
(70ml in capillaries)
pulmonary vessels act as reservoir, accommodate up to twice as
much blood volume.
volume of blood
in lungs varies with intrathoracic p. – high intrathoracic pressure expels
blood from lungs; LV
failure causes pooling of blood in lungs à rise in pulmonary p.
Factors affecting vascular resistance
Passive
changes in vascular resistance
pulmonary
arterial pressure (PAP) increase à PVR decreases
LA
pressure increases à PVR decreases
blood
volume increases à PVR decreases
transpulmonary
pressure increases à PVR increases
Active
changes in vascular resistance – vessels are
reactive because of smooth muscle in walls
Vasoconstriction:
alveolar hypoxia – most
potent stimulus causing vasoconstriction (adaptive mechanism to match best
ventilation with best perfusion) PVR
increases
acidemia – PVR increases
humoral
substances – histamine, prostaglandin F2a
Vasodilation:
humoral
substances – ACh, prostaglandin E1, nitric oxide, bradykinin
**ANS stimulation has no effect on human
PVR
Additional
functions of pulmonary circulation
blood
volume storage – change from standing to lying posture
filtration
– stray blood clots
metabolic –
biologic activation (angiotensin I to II by ACE), inactivation (bradykinin,
serotonin, PGE1, PGE2, PGF2α)
CONTROL
OF RESPIRATION
“Pacemaker” activity for respiration is in
respiratory control centers of brain. Neural control of respiration includes:
1)
factors responsible for alternating inspiration/expiration rhythm
(match body needs)
2)
factors that regulate magnitude (rate, depth) of
ventilation
3)
factors that modify respiratory activity to serve other
purposes
both voluntary
(i.e., with speech) & involuntary
(i.e., sneeze/cough) control.
The medullary
respiratory center is the primary respiratory control center; provides
output to respiratory muscles. Two other
centers, in pons, apneustic center,
pneumotaxic center – influence output from primary center.
Cell bodies for neuronal fibers of phrenic,
intercostals nerves are in spinal cord.
Impulses from medullary center
terminate there à stimulate nerves for inspiratory muscles. When neurons are not firing, inspiratory
muscles relax and expiration occurs.
Medullary
respiratory center
*Dorsal respiratory group (DRG) – nucleus
tractus solitarius; mostly inspiratory
neurons, terminate on motor neurons that supply inspiratory muscles (initial
processing station for feedback from peripheral sensors)
*Ventral respiratory group (VRG) – nucleus
retroambiguus; both inspiratory
& expiratory neurons – both remain inactive during quiet breathing. Called into play by DRG as ‘overdrive’
mechanism. Especially important in
active expiration. Only during active
expiration do impulses travel to expiratory muscles.
Generation of respiratory rhythm comes from
rostral ventromedial medulla, near
upper (head) end of VRG. Drives rate at
which inspiratory neurons fire. Rhythm
starts with latent period of several seconds, followed by APs, which crescendo
over a few seconds – leading to ‘ramp’ pattern of inspiratory muscle activity.
Pontine centers exert ‘fine tuning’
influences on medullary center à ensure
normal, smooth breathing, influence timing of switching between inspiration
& expiration. Pneumotaxic center (upper
pons) sends impulses to DRG to ‘turn
off’ inspiratory neurons. Apneustic
center (lower pons) prevents inspiratory neurons from being turned off. Of the two, the pneumotaxic center
dominates. Without pneumotaxic ‘brakes,’
apneusis = prolonged inspiratory
gasps with very brief interrupting expirations.
(can occur with severe brain damage)
Cortex – involved in voluntary control of
respiration
Hypothalamus, limbic system – can alter
pattern of breathing, i.e., affective states like fear, rage.
Respiratory effects of brainstem transections (see page 4 of notes for
diagram)
*rostral
to pons (top) – little effect on
spontaneous respiratory rhythm
*mid-pontine–
eliminates neurons associated with pontine respiratory group, removing tonic
excitation, resulting in slowed
frequency, increased tidal volume. Vagus
is also transected here – input from lung stretch receptors is lost, resulting
in apneusis
*pontomedullary
transection – irregular breathing
pattern of gasping (loss of vagal afferents has no effect)
*transection
of spinal cord – eliminates all descending drive, results in apnea
Sensors
Central
chemoreceptors
near ventral surface of medulla in vicinity
of exit of 9th and 10th CNs
distinct from respiratory center neurons
bathed in brain ECF, respond to changes in
[H+] (composition of ECF determined by CSF, local blood flow, and
local metabolism)
CSF contains less protein than blood =
poorer buffering capacity. à change in PCO2 will change pH of CSF more than it
changes pH of blood.
Peripheral
chemoreceptors
Carotid bodies (most important), aortic
bodies
Respond primarily to decreases in PO2 – less so to decreases in pH, increases
in PACO2.
When PaO2 falls below
100 torr, rapid response; below 60 torr
– dramatic response
Glomus
cells in receptor release catecholamines that
stimulate glossopharyngeal nerves
Pulmonary
stretch receptors
Airway smooth muscle
Discharge in response to distension of the
lung; activity sustained with lung inflation
Impulse travels in vagus
Hering-Breuer reflex – when VT
> 1 L (during exercise, etc.), pulmonary stretch receptors in small muscle
of airways are activated à APs
travel through afferent nerve fibers to medullary center, inhibit inspiratory
neurons. (negative feedback to keep
lungs from being over-inflated)
Irritant
receptors
Between airway epithelial cells
Stimulated by noxious gases, cold air,
particulates
Impulses travel in vagus, leading to
bronchoconstriction, hypernea
“J”
receptors
Juxta-capillary receptors in
alveolar-capillary membrane
Impulses travel in vagus à rapid, shallow breathing
Stimulated in interstitial lung disease or
pulmonary edema
Other receptors
*Nose and upper airway receptors – respond
to mechanical, chemical stimuli (like irritant receptors in lower airways)
*Joint, muscle receptors – impulses from
moving limbs may be part of stimulus to increase minute ventilation
*Gamma system – muscle spindles in
intercostals, diaphragm that sense elongation of these muscles, strengthen
contraction
*Arterial baroreceptors – increased
systemic BP can cause reflex hypoventilation, apnea. (decreased BP à hyperventilation)
[H+] in brain ECF is primary
regulator of ventilatory magnitude
Arterial blood gases are held very constant
in normal range by varying magnitude of ventilation to match body’s needs for
oxygen uptake/carbon dioxide removal.
Signals sent to medullary respiratory center à sends signals to adjust rate/depth of ventilation.
Decreased arterial oxygen, increased carbon
dioxide does stimulate ventilation, but [H+] is more important.
Response to CO2, PaCO2 is most important factor
in control of ventilation under normal conditions. PaCO2 is maintained within 3 torr when awake
Ventilatory response to PaCO2
is reduced by sleep, increasing age, genetic factors, athletic training.
Central
chemoreceptors are main players; peripheral
chemoreceptors play minor role
Response to O2 – minor role in
control of normal ventilation, except at high altitudes
becomes
important in chronic hypoxemia
Response to pH – difficult to separate from
response to PCO2
Decreased PO2
Monitored by peripheral chemoreceptors –
carotid/aortic bodies. Not sensitive to
modest changes in PO2.
Arterial PO2 must be < 60 mmHg (40% reduction) for
chemoreceptors to send afferent impulses to medullary inspiratory neurons. (happens with severe pulmonary disease, reduced atmospheric pressure). Until you get to 60 mmHg, you’re still in
plateau range of Hb-O2 dissociation curve (safe). If it weren’t for peripheral chemoreceptors,
the low PO2 would depress respiratory centers à stop breathing.
Chemoreceptors respond to PO2, not oxygen content.
Anemia, CO poisoning – PO2
is normal, but total O2 is too low.
Increased PCO2
PCO2 is most important input
regulating magnitude of ventilation under resting
conditions. Changes in alveolar
ventilation have immediate, pronounced effect on arterial PCO2
(unlike PO2). Even slight
alterations from normal PCO2 induce significant reflex. Increased PCO2 à increased ventilation. Carotid/aortic bodies are only weakly
responsive to changes in PCO2.
Central chemoreceptors in
medulla are sensitive to changes in CO2-induced
[H+] (not sensitive to CO2 itself).
BBB is permeable to CO2, so
increased arterial PCO2 à
increased brain ECF PCO2 à
increased [H+] à
stimulates central chemoreceptors à
increases ventilation by stimulating respiratory centers.
H+
can’t permeate BBB – reason central chemoreceptors
don’t respond to [H+] in plasma.
If you hold your breath > 1 minute, CO2 builds up, [H+]
in brain ECF builds up, increased PCO2-H+ stimulant to
respiration overrides voluntary input to respiratory centers, and breathing resumes.
Very
high CO2 levels directly depress entire brain, including respiratory centers (like low O2 does). If you increase PCO2 up to 70-80
mmHg, ventilation increases to blow it off.
Above 80 mmHg, respiratory
neurons are depressed à respiratory acidosis. (Reason why, in closed environments like
space shuttle/submarine, you need something to remove CO2, pump in O2.)
With some kinds of COPD– prolonged hypoventilation à elevated PCO2 and reduced PO2. Usually synergistic – sum of stimulatory
inputs is greater than individual. But
in some severe cases, patient loses
sensitivity to high PCO2.
Prolonged high [H+] in brain ECF allows time for HCO3-
to cross BBB and buffer/neutralize H+. Brain ECF [H+] seems normal, and
body is unaware of high PCO2.
Level of ventilation is unusually low, considering high PCO2. In this case, hypoxic O2 drive to
increase ventilation becomes primary respiratory stimulus.
[H+] in arterial blood
Aortic/carotid
body chemoreceptors are highly responsive to changes in [H+]. Any change in PCO2
leads to change in [H+] (in both arterial blood & brain
ECF). Increased [H+] in
arterial blood stimulates ventilation, though central chemoreceptors are more
important stimulant. Arterial [H+] can change without
increased PCO2 – i.e, during diabetes mellitus because of
increased keto acids in the blood. The
peripheral chemoreceptors’ sensitivity to changes in [H+] serves to
regulate the acid-base balance.
Exercise increases ventilation – why?
Alveolar ventilation can increase up to 20-fold
with exercise. Yet,
PO2
stays the same, or even increases a little,
PCO2
stays the same, or even decreases a little
During mild/moderate
exercise, [H+] doesn’t increase because CO2 is held
constant. With heavy exercise, though, [H+] increases because of lactic
acid buildup (from anaerobic metabolism).
Ventilation increases within a few seconds
of exercise – not long enough for changes in arterial blood gases to stimulate
it. Mechanism for its increase is poorly
understood. Possible reasons are:
1) reflexes
from body movements – joint/muscle receptors excited during muscle
contraction stimulate respiratory centers (reason even passive movement
increases ventilation);
2) increased
body temperature – energy generated during muscle contraction is converted
to heat (same reason increased ventilation accompanies fever);
3) epinephrine
release from adrenal medulla increases during exercise;
4) impulses
from cerebral cortex, especially at onset, to respiratory center &
muscles
Ventilation can be influenced by other
factors, beyond O2/CO2
*Protective
reflexes – sneezing, coughing, govern respiratory activity
temporarily.
*Pain
reflexly stimulates respiratory center.
*Emotional
expressions – laughing, crying, sighing, groaning.
*Respiratory system reflexly inhibited
during swallowing.
*Cerebral
cortex allows for voluntary control of breathing – sends impulses directly to motor neurons in spinal cord
that supply respiratory muscles. (You
can voluntarily hyper- or hypoventilate to a certain point.)
Local controls on smooth muscle of
airways, arterioles
**If
alveolus has too much blood compared to air
O2 level in alveolus and
surrounding tissues falls below normal (blood is extracting more O2
from alveolus). Decreased [O2] →
vasoconstriction → reduced blood flow
**If
alveolus has too much air compared to blood
Increased
[O2] → vasodilation → increased blood flow
(opposite of effect in systemic
circulation, where decreased [O2] leads to vasodilation)
As a result of CO2 & O2
local controls, little air/blood is wasted → most efficient exchange possible
ANS can modestly adjust airway size
Bronchomotor tone is provided by smooth
muscle in airway walls.
Parasympathetic
cholinergic neurons on muscarinic receptors (quiet, relaxed situation) promotes bronchoconstriction (via smooth muscle
contraction)
ACh,
methacholine, humoral substances (histamine), decrease in PACO2
Sympathetic
adrenergic neurons on bronchiolar beta receptors cause bronchodilation to ensure maximum
airflow with minimum resistance (more oxygen available).
Circulating
catecholamines – epinephrine, isoproterenol
β2
adrenergic receptors (albuterol – β2 agonist)
Work capacity
Best single predictor of a person’s work
capacity is maximum volume of O2 the person can use per minute to
oxidize nutrients for energy production, = maximal
oxygen consumption, max VO2.
Have person exercise until exhausted – measure volume of air, O2,
CO2 content. VO2
depends on respiratory system, circulatory system, muscles.
Respiratory states with abnormal blood
gas levels/abnormal breathing patterns
Asphyxia – oxygen starvation of tissues (lack of O2 in air,
respiratory impairment, or inability of tissues to utilize oxygen)
Cyanosis – blueness of skin from insufficiently oxygenated blood in arteries
Eupnea – normal breathing
Hypernea – increased pulmonary ventilation to meet increased metabolic needs
(exercise)
Hyperventilation – increased pulmonary ventilation in excess of metabolic needs à
PCO2
↓, get respiratory alkalosis (anxiety, fever, aspirin poisoning) voluntary or
involuntary
Hypocapnia – below normal CO2 level in arterial blood, caused by
hyperventilation
Hypoventilation – underventilation in relation to metabolic requirements à
PCO2
↑, get respiratory acidosis
Hypercapnia – excess CO2 in arterial blood, caused by
hypoventilation
Hypoxia– insufficient O2 at cellular level, inadequate tissue
oxygen delivery; determined by cardiac output, oxygen content of arterial
blood, tissue oxygen uptake.
Anemic hypoxia: reduced O2-carrying capacity of
blood (decreased RBCs, Hb in RBCs, or CO poisoning) PO2
is normal, but O2 content is too low
Circulatory
hypoxia: (stagnant hypoxia) too little
oxygenated blood delivered to tissues, can be restricted to one area (local
vascular spasm/blockage) or generalized (congestive heart failure, circulatory
shock) arterial PO2, O2 content normal, but not enough
blood reaches cells.
Histotoxic
hypoxia: inability of cells to utilize oxygen available to them (cyanide
poisoning)
Hypoxic hypoxia: caused by 1) respiratory malfunction involving inadequate gas exchange (normal
alveolar PO2, but reduced arterial blood PO2) or 2)
exposure to high altitude/suffocating environment
(alveolar & arterial PO2 are reduced).
Hypoxemia – reduction in tension of oxygen dissolved in blood (reduced PaO2). If severe enough, leads to Hb desaturation à reduced CaO2
Respiratory
arrest – permanent cessation of breathing
Suffocation – O2 deprivation as result of inability to breathe
oxygenated air.
Hyperoxia – above normal PO2; impossible if breathing normal
atmospheric air at sea level. Breathing
supplemental oxygen can increase alveolar and arterial PO2 – total O2
content isn’t changed much since Hb was already 97.5% saturated. If PO2 is too high à oxygen toxicity (brain &
retinal damage)
Biot’s breathing – a series of breaths of
equal depth irregularly alternating with period of apnea (seen most often in meningitis)
Apneustic breathing – prolonged inspiratory
gasps (seen in head trauma, neurologic disorders)
Cheyne-Stokes – gradual increase in depth,
sometimes rate, to a maximum, followed by gradual decrease, resulting in
apnea. Cycles are 30 seconds to 1 minute in length. (seen in severe hypoxemia, at high altitudes
while asleep, in severe heart disease
or brain damage)
Apnea – transient cessation of breathing; during
sleep, ventilation decreases & central chemoreceptors are less sensitive to
arterial PCO2 (especially during REM sleep). Sleep apnea – may stop breathing for a few
seconds or up to 1-2 minutes 500 times per night!
Obstructive –
cessation of ventilation due to intermittent obstruction of the pharynx by the
tongue during sleep. Central controller
output is increased.
Central
– intermittent cessation of central controller output à cessation of ventilation
Sudden infant death syndrome (SIDS) – 2-4
month old babies, often with poorly developed carotid bodies. Sleeping on stomach, exposure to nicotine
increases chances.
Dyspnea – difficult/labored breathing; people
have subjective sensation that they are not getting enough air, feel shortness
of breath even though their PCO2, PO2 may be normal. Can be from anxiety; increased work of
breathing due to restrictive/obstructive factors
Conditions at high & low altitudes
Mountain
climbing – At 10,000 feet, PO2 falls
into steep part of O2-Hb dissociation curve – Hb saturation rapidly
declines as you go above 10,000 feet (not in plateau range anymore). At 18,000 feet, atmospheric pressure = 380
mmHg, PO2 = 45 mmHg. Acute mountain sickness – hypoxic
hypoxia, hypocapnia-induced alkalosis (CO2 blown off more rapidly
than produced).
Deep
sea diving – atmospheric pressure doubles at 30
feet below sea level! More N2
dissolves in tissues à nitrogen narcosis (“rapture of the
deep”). At 150 feet under – euphoric,
drowsy. At 350-400 feet under – lose
consciousness (oxygen toxicity).
If you ascend too quickly – decompression sickness (“the
bends”). N2 forms bubbles as
it quickly converts from solution into gas.
