Download The Respiratory System

The Respiratory System
Part III
Dr. Adelina Vlad
Pulmonary Circulatory System
CO2
O2
O2
CO2
LA
RV
ATP
CO2
O2
Normal anatomic right-to-left-shunt: after
passing through capillaries, about half of the
bronchial blood anastomoses with oxygenated
blood in the pulmonary venules
Characteristics of Pulmonary
Circulation
•
-
Low pressure system
it needs to pump blood only to the top of the lung
important for avoiding the flooding of lung with edema fluid
•
-
Low resistance system, less than 1/10 that of systemic circulation due to:
shorter and wider vessels (
)
higher number of less muscular arterioles with a low resting tone
• High compliance vessels
- due to the thin walls and the paucity of smooth muscle
- can accept large amounts of blood
- can dilate in response to modest increases in PA pressure
- the pulse pressure is low
Pressures in the Pulmonary System
Pressure pulse contours
Pressures in the pulmonary system D,
diastolic; M, mean; S, systolic
Pulmonary Capillaries
•
•
•
•
•
Pulmonary blood volume = 450 mL (220-900 mL)
Capillary blood volume = 75 ml at rest, up to 200 ml during exercise
There are 280 billion highly anasomosing capillary segments = nearly
1000/ alveolus, creating a gas exchange surface of 100 square meters
Blood passes through the pulmonary capillaries in about 0.8 s at rest and
can shorten to 0.3 s when the cardiac output increases
Alveolar capillaries are collapsible:
If capillary pressure falls below alveolar pressure, the capillaries close
off, diverting blood to other pulmonary capillary beds with higher
pressures.
Influence of Gravity on Regional
Perfusion
•
At rest and in orthostatic position, hydrostatic pressure gradient is about
15 mm Hg at the apex, resulting in a 25 – 15 = + 10 mm Hg systolic Pa and
an 8 – 15 = – 7 mm Hg diastolic Pa
 the capillary beds located at more than 10 cm above the midlevel of
the heart are closed during RV diastole (zone 2)
Ppc<PAlv because the diastolic value (8 mm Hg) cannot overcome the
hydrostatic pressure gradient
•
In the lower regions of the lung, capillaries remain continuously open
(zone 3) because Ppc remains greater than zero (= PAlv) during both
systole and diastole  Blood is directed toward the base of the lung.
•
Zone 1 occurs only under abnormal conditions: very high PAlv or
exceedingly low systolic Ppc
Influence of Gravity on Regional Perfusion
•
In an upright subject, perfusion is
greatest near the base of the lung
and falls towards the apex
Influence of Gravity on Regional
Ventilation
•
Because of the action of gravity, for an upright subject PIP is lower at the
apex (- 7.5 cm H2O) compared to the base of the lung (- 2.5 cm H2O)
 alveoli at the top of the lung are more distended compared to the
alveoli at the base
 the alveoli at the base are more compliant = during inspiration, the
same DPIP produces a grater DVL near the base than near the apex
 for an upright subject, regional ventilation is greater at the base than
at the apex of the lungs
Matching Ventilation and Perfusion
•
The local ventilation-perfusion ratio (VA/Q) determines the local alveolar
concentration of O2 and CO2
•
In the lungs of an upright subject VA/Q varies with height:
– Is lowest near the base where Q exceeds VA (VA/Q < 1)
– Gradually increases to 1 (VA/Q = 1) at the level of the 3rd rib, where Q
= VA
– Further increases toward the apex, where Q falls more than V A (VA/Q
> 1)
•
When alveoli are ventilated but not perfused = alveolar dead space
ventilation, VA/Q ∞; although the alveoli are ventilated, they are not
engaged in gas exchange
•
Compensatory changes correct the mismatch:
blood flow is redirected toward the normal parts of the lung that
become hyperperfused  VA/Q decreases in these areas
alveolar dead space ventilation lowers local alveolar PCO2 and triggers
compensatory bronchiolar constriction  airflow diverts toward
normally perfused areas
starved pneumocytes II in the hipoperfused alveoli produce less
surfactant, resulting a local decrease in compliance with a further
decrease of local ventilation

the compensation tends to correct VA/Q in both hypoperfused and
normal areas, improving gas exchange
A natural cause is pulmonary embolism; as lungs are filtering small
emboli, they deal will small regions of dead space ventilation on a
recurring basis
•
When alveoli are perfused but not ventilated (shunt, VA/Q tends to zero)
- airflow is redirected to normal parts of the lung,
- the decrease in local alveolar O2 triggers a compensatory hypoxic
pulmonary vasoconstriction  blood is redirected towards normally
ventilated areas
 The normal areas are better ventilated and perfused, whereas the shunt
zone looses the blood flow  the compensation tends to correct VA/Q in
both hypoventilated and normal areas, improving the alveolar gas
exchange
Natural causes generating a functional shunt: atelectasis (collapse of the
alveoli), foreign bodies or tumors inside the airway
Local Control of Arterioles and
Bronchioles by O2 and CO2
Gas
composition
Bronchioles
Pulmonary
arterioles
Systemic
arterioles
↑ PCO2
Dilate
Constrict
Dilate
↓ PCO2
Constrict
Dilate
Constrict
↑ PO2
Constrict
Dilate
Constrict
↓ PO2
Dilate
Constrict
Dilate
Strong effects are marked in bold
Local Control
Compensates
Ventilation Perfusion
Mismatches
Mechanisms for Keeping the Alveoli
Dry
•
The pulmonary capillaries and the pulmonary lymphatic system
- maintain a slight negative pressure in the interstitial spaces
- are able to carry away the excess interstitial fluid
(20 ml/ hour)
Capillary Exchange of Fluid in the Lungs
•
Pulmonary edema safety factor
-
The protection mechanisms are overwhelmed when the capillary
hydrostatic pressure (7) rises up to the plasma osmotic pressure (28)
edema
-
In acute conditions the safety factor is 21 mmHg (7  28 mm Hg)
-
In chronic conditions, due to lymph vessels expansion, the safety factor
rises to 30 - 35 mm Hg
Examples: acute conditions  left-sided heart failure
chronic conditions  mitral stenosis
Diffusion of Respiratory Gases
Partial Pressures of Respiratory Gases
N2
O2
CO 2
H 2O
TOTAL
Atmospheric air
(mm Hg)
597.0 (78.62%)
159.0 (20.84%)
0.3
( 0.04%)
3.7
(0.50%)
Humidified air
(mm Hg)
563.4 (74.09%)
149.3 (19.67%)
0.3
(0.04%)
47.0
(6.20%)
Alveolar air
(mm Hg)
569.0
(74.9%)
104.0
(13.6%)
40.0
(5.3%)
47.0
(6.2%)
Expiratory air
(mm Hg)
566.0
(74.5%)
120.0
(15.7%)
27.0
(3.6%)
47.0
(6.2%)
760.0
760.0
760.0
760.0
(100%)
(100%)
(100%)
(100%)
• The pressure of a mixture of gases is equal to the sum of the pressures of all
of the constituent gases alone:
PressureTotal = Pressure1 + Pressure2 ... Pressuren
• Each gas contributes to the total pressure of a mixture of gases in direct
proportion to its concentration:
Partial pressure = Total pressure x Gas concentration
Slow replacement of alveolar air  gas composition in the alveoli varies
slightly during normal breathing prevent sudden changes in gas
concentrations and the pH of the blood
350 mL fresh air/breath reaches
alveoli ~ 1/7 of total lung
volume at the end of a quiet
inspiration
Alveolar Air Composition
•
Is different from the composition of the atmospheric air because:
– the alveolar air is only partially replaced by atmospheric air with each
breath
– oxygen is constantly being absorbed into the pulmonary blood from
the alveolar air
– carbon dioxide is constantly diffusing from the pulmonary blood into
the alveoli
– atmospheric air that enters the respiratory passages is humidified
even before it reaches the alveoli
Oxygen and carbon dioxide partial pressures in the expired air
•
Oxygen concentration in the
alveoli is controlled by
– the rate of absorption of
oxygen into the blood
– the rate of entry of new
oxygen into the lungs by the
ventilatory process
•
The alveolar PCO2
– increases directly in
proportion to the rate of
carbon dioxide excretion
– decreases in inverse
proportion to alveolar
ventilation
Types and patterns of ventilation
Name
Description
Examples
Eupnea
Normal quiet breathing
Hyperpnea
↑ respiratory rate and/or volume in
response to ↑ metabolism
Exercise
Hyperventilation
↑ respiratory rate and/or volume
without ↑ metabolism
Emotional hyperventilation
Hypoventilation
Decreased alveolar ventilation
Shallow breathing; asthma;
restrictive lung disease
Tachypnea
Rapid breathing;
usually ↑ respiratory rate with ↓ depth
Panting
Dyspnea
Difficulty breathing
(feel like ‘air hunger’)
Various pathologies or hard
exercise
Apnea
Cessation of breathing
Voluntary breath-holding;
depression of CNS control centers
Respiratory Membrane
1. Alveolar fluid with surfactant
2. Alveolar epithelium
3. Epithelial basement membrane
4. Thin interstitial space between
the alveolar epithelium and the
capillary membrane
5. Capillary basement membrane
6. Capillary endothelial cells
Has: 0.6 mm thickness
70 square meters
Pulmonary capillary diameter: 5 mm
Blood volume in pulmonary capillaries:
60 - 140 ml
Gas Diffusion Trough the Respiratory
Membrane
Depends on:
1.
2.
3.
4.
5.
The thickness of the membrane
• increased in pulmonary edema, fibrosis
The surface area of the exchange membrane
• decreased in emphysema
• increased during exercise when more capillaries are open
The diffusion coefficient of the gas in the substance of the membrane
The partial pressure difference of the gas between the two sides of the
membrane
The temperature
•
fairly constant in the body, therefore negligible
Diffusion Rate
D~
ΔP x A x S
d x MW
D = diffusion rate of the gas
ΔP = pressure gradient across the membrane
A = cross-sectional area
S = solubility coefficient of the gas
d = distance of diffusion
MW = molecular weight of the gas
The characteristics of the gas itself, S and MW, determine the diffusion
coefficient of the gas ~ S/ MW
Solubility Coefficient of a Gas
•
The partial pressure of a gas in a solution is determined not only by its
concentration but also by the solubility coefficient of the gas
• Henry’s law:
Partial pressure = Concentration of dissolved gas/ Solubility coefficient
•
Solubility coefficient (S) of a gas depends on the physical or chemical
attraction to water molecules; a higher attraction means a better solubility
and a lower partial pressure developed for a given concentration
Diffusing Capacity (DC) of the
Respiratory Membrane
Expresses the ability of the respiratory
membrane to exchange a gas between
the alveoli and the pulmonary blood
DC = volume of gas diffused in 1 minute
for a ΔP of 1 mm Hg
 allows the calculation of the diffusion
rate (DC x ΔP)
DC for O2
at rest = 21 ml/min/mm Hg
during exercise = 65 ml/min/mm Hg
DC for CO2
at rest = 400 - 450 ml/min/mm Hg
during exercise = 1200 - 1300
ml/min/mm Hg
Diffusion of O2 Through the
Respiratory Membrane
The blood Po rises almost to Po of the alveolar air by the time the blood
has moved a third of the distance through the capillary
2
2
PO2 in Alveoli, Blood and Tissues
The interstitial fluid PO2 depends on:
- the rate of the blood flow through the
tissue
- the rate of tissue metabolism
Diffusion of CO2 Through the
Respiratory Membrane
The blood Pco falls almost to Pco of the alveolar air by the time the
blood has moved a third of the distance through the capillary
2
2
PCO2 in Alveoli,
Blood and
Tissues
Effect of blood flow and metabolic
rate on body tissues PCO2
Pulmonary pathologies that
affect alveolar ventilation and
gas exchange
Hypoxia
•
Hypoxic hypoxia: low arterial PO2 (high altitude, alveolar hypoventilation)
•
Anemic hypoxia: decrease in total amount of O2 bound to Hb (blood loss,
anemia, CO poisoning)
•
Ischemic hypoxia: reduced blood flow in tissue
•
Histotoxic hypoxia: failure of cell to use O2 due to poisoning (cyanide)
Regulation of Ventilation
Regulation of Ventilation
•
Breathing is a rhythmic process that usually occurs without voluntary
command
•
Skeletal muscles do not contract spontaneously, but after receiving
impulses from somatic motor neurons, controlled by the CNS
•
There is a central pattern generator (CPG) with intrinsic rhythmic activity
(network of neurons with unstable membrane potentials) in the medulla
oblongata that controls the respiratory muscles
Central Pattern Generator
•
•
•
"Central pattern generators (CPGs) can be defined as neural networks
that can endogenously (i.e. without rhythmic sensory or central input)
produce rhythmic patterned outputs" or as "neural circuits that generate
periodic motor commands for rhythmic movements“
CPGs have been shown to produce rhythmic outputs resembling normal
"rhythmic motor pattern production" even in isolation from motor and
sensory feedback from muscle targets
To be classified as a rhythmic generator, a CPG requires:
1. two or more processes that interact such that each process
sequentially increases and decreases
2. that, as a result of this interaction, the system repeatedly returns to its
starting condition
Respiratory Center
•
The primary control center for ventilation lies in the medulla, where the
rhythm of ventilation is set
 Respiratory neurons in the medulla (CPG) control I and E
– dorsal respiratory group (DRG) – inspiratory (I) neurons
– ventral respiratory group (VRG) – expiratory (E) neurons and accesory
inspiratory (I+) neurons (active during forced breathing)
 The rhythmic pattern of breathing arises from a network of
spontaneously discharging neurons
• Neurons in the pons (pneumotaxic and apneustic centers) influence the
rate and depth of ventilation
•
Ventilation is subject to modulation by various chemical factors (CO2, O2,
H+), stretch receptors from lungs and respiratory muscles, and by higher
brain centers
Central chemoreceptors
Organization of the Respiratory
Center
Peripheral chemoreceptors
Dorsal Respiratory Group
•
Plays the most fundamental role in the control of respiration
•
Located
– within the nucleus of the tractus solitarius (NTS, sensory termination
of vagal and glossopharyngeal nerves)
– in the adjacent reticular substance of the medulla
•
Integrates sensory information from:
– peripheral chemoreceptors
– respiratory-related receptors in the lungs and airways
Dorsal Respiratory Group
•
Emits repetitive bursts of inspiratory neuronal action potentials towards:
• the motor neurons of the phrenic and spinal nerves
• the neurons of VRG
•
The inspiratory signal is a ramp signal that increases steadily for about 2 s,
then it ceases abruptly for the next 3 s
 causes a steady increase in the volume of the lungs during inspiration
Rhythmic Activity of DRG
I neurons stop firing
• Gradual recruitment of skeletal muscle fibers
(diaphragm)  rib cage expands smoothly
• In forced breathing I+ are activated by the
increased activity of DRG inspiratory neurons
• Elastic recoil of inspiratory muscles and
elastic lung tissue
• E neurons in VRG act during active
expiration
Pneumotaxic Center
•
Located dorsally in the nucleus parabrachialis of the upper pons
•
Controls the “switch-off” point of the inspiratory ramp
 limits inspiration and increases the rate of breathing:
A strong pneumotaxic signal can increase the rate of breathing to 30 to 40
breaths per minute, whereas a weak pneumotaxic signal may reduce the
rate to only 3 to 5 breaths per minute
Ventral Respiratory Group
•
Located about 5 mm anterior and lateral to the DRG, in the nucleus
ambiguus rostrally and the nucleus retroambiguus caudally
•
Is primarily motor
•
Remains almost totally inactive during normal quiet respiration
•
When high levels of ventilation are required, respiratory signals spill over
into the VRG from the basic oscillating mechanism of the DRG
Ventral Respiratory Group
•
Has three regions:
– the rostral region (Botzinger complex), E, drives the expiratory action
of the caudal region
– the intermediate region, I, has somatic motorneurons whose fibers
mediate the enlargement of the pharynx, larynx and other structures
– the caudal region has premotor neurons that synapse motorneurons
innervating accessory muscles of expiration
Mechanisms of Rhythmic Output
•
The firing pattern of respiratory-related neurons (I, E) is determined by
both intrinsic membrane properties (ion currents) and patterned synaptic
input (excitatory and inhibitory postsynaptic potentials)
Because of reciprocal
inhibition between the
early-burst neuron and
the late-onset
inspiratory neuron, only
one can be maximally
active at a time
Chemical Control of Ventilation
•
The respiratory system regulates the arterial levels of O2, CO2 and pH
•
At the same time, these parameters are exerting the most important
control on breathing via two sets of chemoreceptors:
– peripheral chemoreceptors,
stimulated mainly by hypoxia
located in aortic and carotid bodies (glomus cells)
- central chemoreceptors,
stimulated mainly by increased plasma PCO2
and acidosis (low pH)
located in the medulla (ventral surface)
Hypoxia
•
Monitored by carotid and aortic bodies (peripheral chemoreceptors)
•
Changes in oxygen concentration have virtually no direct effect on the
central chemoreceptor, due to the fact that hemoglobin is able to release
enough oxygen to body tissues even when the pulmonary Po changes from
a value as low as 60 mm Hg up to a value as high as 1000 mm Hg
2
O2 Sensor of the Carotid Body
•
Glomus cells in the carotid body are
equipped with a gated K+ channel that has
an extracellular O2 sensor (KO2)
•
When the sensor is activated by normal
arterial levels of O2, the channels open 
K+ leaves the cell, hyperpolarizing the
membrane
•
When arterial O2 decreases  closure of K+
channels  cell depolarization  opening
of voltage-gated Ca2+ channels  ↑ [Ca2+]i
 exocytose with vesicles containing
dopamine  action potential in sensory
neurons  respiratory control centers 
↑ventilation
Chemosensitivity of the Carotid Body
H+ Concentration
•
It is believed that hydrogen ions may
be the only important direct stimulus
for central chemoreceptors
•
However, hydrogen ions do not easily
cross the blood-brain barrier 
changes in blood pH have less effect
in stimulating the chemosensitive
neurons than do changes in blood
carbon dioxide
•
pH has little effect on peripheral
chemoreceptors; acidosis increases
their sensitivity for hypoxia
Carbon Dioxide
•
Carbon dioxide: main respiratory regulator
by a potent indirect effect on the central
chemoreceptor
•
Increased PCO
-
has little effect on peripheral
chemoreceptors; however, acts faster
through this pathway, and increases their
sensitivity for hypoxia
-
CO2 passes easily through the blood-brain
barrier
-
central chemoreceptors detect
CO2induced H+ concentration in brain
cerebrospinal fluid (CSF)
2
Central chemoreceptor monitors CO2 in cerebrospinal fluid
Chemoreceptor Reflex
Nervous Modulation of Respiratory
Output
•
•
PO2, PCO2 and pH are the major parameters that feed back on the
respiratory control system
Apart from these, there are two other major sources that provide input
(through IX and X up to DRG) for regulation of ventilation:
– Stretch and chemical/irritant receptors, monitor the size of the
airways and the presence of noxious agents
• Pulmonary stretch receptors (PSR) are mechanoreceptors that
detect changes in lung volume; example: the Hering-Breuer reflex
• Irritant receptors, very sensitive to chemical stimuli (serotonin,
bradykinin, prostaglandins, histamine, cigarette smoke etc.)
– Higher CNS centers, coordinate ventilation with other behaviors
(speaking, sniffing, regulating temperature, chewing, swallowing,
vomiting)
Hering-Breuer Inflation Reflex
•
•
One of the first examples of negative feedback in physiology (1868)
Lung inflation inhibits the output of phrenic motor neurons, protecting the
lungs from overinflation
•
How?
Lung inflation  stretch receptors from bronchi and bronchioles are
stimulated  vagi  inhibition of DRG in a similar manner with
pneumotaxic influences  amplitude of inspiration decreases,
respiratory rate increases = the reflex maintains a constant alveolar
ventilation
The information provided by the sensor may be used by the medulla for
choosing a combination of tidal volume and respiratory rate that
minimizes the work of breathing