Pathophysiology of the respiratory system II
Pulmonary gas exchange
Oxygen cascade
Hypoxemia – causes
– hypoventilation / diffusion impairment / shunt / VQ mismatch
Ventilation – perfusion (in)equality
Pulmonary circulation – hypoxic pulmonary vasoconstriction
Respiratory insufficiency
Control of ventilation
Restrictive diseases – examples of gas exchange limiting ones
Gas exchange in lungs
• main function of respiratory system – gas exchange between
blood and outside environment – is governed by temporally
changing requirements of organism for O2
– maintained in optimum by regulation of intensity of ventilation (see
further)
• requirements defined mainly by consumption of ATP and its
replenishing by mitochondria
– oxidative phosphorylation
– other O2 consuming processes
• alveolo-capillary gas exchange takes place from alveolus to blood
by simple diffusion through alveolar septum, lung intersticium
and capillary wall
– in the past physiologist believed
it was an active transport
• driving force for O2 (and reciprocally for CO2) is the gradual
decrease of its partial pressure, i.e. concentration gradient
between inhaled air, blood and tissues:
– partial pressure = the pressure that the gas would have if it alone
occupied the same volume at the same temperature
Functional classification of airways
3
Functional classification of airways
• Conducting airways (= anatomical dead space)
• nose (mouth)
• larynx
• trachea
• main bronchi & bronchioles
– gas conduction, warming, defense
• Acinar airways (= respiratory space)
• respiratory bronchioles
• alveolar ducts & sacs
• alveoli
– gas exchange
• The concept of acinus
– the functional 3-D unit - part of parenchyma - in
which all airways have alveoli attached to their wall
and thus participating in gas exchange
3-D acinus – gas exchange unit
• structure following each
individual terminal bronchiole
– 3 generations of branching of
resp. bronchiole and subsequent
approx. 8 generations of
branching of alveolar dusts
– every pulmonary lobule (=
anatomical term) contains 10 -
30 acini
Lobule (=morphological unit, 3-5 acini) vs. acinus (=functional unit)
Lung development in humans (from birth until maturity 20‐fold
increase in gas-exchange surface area)
(Kajekar R. 2007. Environmental factors and developmental outcomes in the lung. Pharmacol Therap 114:129–145)
Pulmonary gas exchange as an ultimate purpose of breathing
• Alveolar ventilation
• at rest there is a constant rate of carbon dioxide generation in the body
and rate of the diffusion in the lungs
– while pattern of flow in conductive airways (both upper and lower airways, i.e. dead
space) varies between turbulent / transitional / laminar (depending on Reynolds
number – see elsewhere), in alveoli gas moves across by diffusion
– CO2 production can be lowered by cooling the body
– CO2 production increases by exercise or in pathology
• therefore PACO2 is more ore less constant (or fluctuates very little)
• all of the CO2 exhaled by the body comes from gas exchanging areas of the
lung, that is ventilated alveoli
• the PACO2 is equivalent to the PaCO2 (complete diffusion)
• (1) The alveolar ventilation equation – describes the
‘mechanics’
– allows us to calculate alveolar ventilation rate
– V'A = (V'CO2/PaCO2) * K = ~4.2 L/min
• thus the alveolar ventilation is proportional to the rate of carbon dioxide
exhaled by the body (V'CO2) and inversely proportional to the PaCO2
• instructive in understanding the influence of alveolar ventilation on the
partial pressure of arterial carbon dioxide
– for example, if V'A is doubled, the PaCO2 is halved
– if alveolar ventilation (V'A) is halved, the PaCO2 will double
Exchange of gas between the alveolus and the respiratory
bronchiole occurs purely by random diffusion
• There are minimal changes between inspirium and expirium
– breathing in and out doesn’t completely replenish the stale air in the lungs
– in fact most of the volume of the lungs stays in the lungs, and each breath
dilutes fresh air in the functional residual capacity (FRC) of the lung
• At rest, with a typical tidal volume VT (the depth of each breath) of around
500 ml, 150 ml is lost in dead space (VD), and the remaining 350 mL is
mixed into the much larger 2350 mL existing FRC
– so, it’s not a matter of breathing in, exchanging gases and breathing out
• The process of gas exchange goes on continuously, and breathing is just the
mechanism for removing a little stale air and adding a little fresh stuff
• Therefore, VA is a tidal volume (VT) minus the dead space (VD)
• (2) The alveolar gas equation –
describes the interdependency
of alveolar gases
– describes the concentration of gases
in the alveolus and demonstrates, that
their dynamic is interconnected
– PAO2 = (0.21 x (760 - 47)) - (PaCO2 x 1.25) =
~100 mmHg
• basically the two gases compete for partial pressures
– if one increases, other must decrease
• normally PaCO2 in mixed venous blood (i.e.
pulmonary artery and the same in alveolus) is 40
mmHg
• if PaCO2 doubles (e.g. hypoventilation) then PAO2 falls
in half, i.e. 50 mmHg
Pulmonary gas exchange as an ultimate purpose of breathing
Transport of gases in blood
• CO2 can be considered to be in simple solution in the
plasma, the volume carried being proportional to its
partial pressure (physically dissolved)
• O2 is carried in chemical combination with
hemoglobin in the red blood cells, and the
relationship between the volume carried and the
partial pressure (physically dissolved fraction) is not
linear
– in physiological PaO2 (90mmHg/12kPa) and normal
hemoglobin there is nearly 100% Hb saturation
• if PaO2  1OkPa saturation do not significantly decreases
– saturation measured by pulsion oxymetry
• O2 diffuses to tissues according to demands of
mitochondria
– for adequate production of ATP jpO2 in tissues have to be >
0.13kPa (1mmHg) = critical oxygen tension
• organism needs oxygen:
–  250ml/min  350l/day in rest
– much more (10x) during exercise
Oxygen in the body
• there are no significant O2 stores in the
body
• lasts for  5min
– therefore breathing has to be continuous
process
– disruption means
• life-threatening emergency (<5min)
– reversible vision loss in7s, unconsciousness in
10s
• clinical death (5-7min), event. brain death
• death of the whole organism (>10min)
• 85-90% used in aerobic metabolism in ATP
production
– maintenance of ion gradients
– muscle contraction
– chemical synthetic reactions
• remaining processes are less sensitive to
PaO2
– hydroxylation of steroids
– detoxification of xenobiotics in liver
– synthesis of NO ( vasodilation)
– degradation of haem by hemoxygenase
OXYGEN CASCADE IN THE BODY
Oxygen cascade – progressive drop of oxygen content
• reasons for normal gradual decrease of PO2 between air and
blood:
– competition with CO2 in alveoli
• up to the atmospheric pressure
– see alveolar gas equation
– less that 100% diffusion across alveolo-capillary membrane
• irregularity of its thickness and change in the rate of lung perfusion
• lower solubility of O2 compared to CO2
– physiological right-left shunt
• mixing of oxygenated and deoxygenated blood
– nutritional supply of large airways by aa. bronchiales and their drainage to v.
pulmonalis
– drainage of vv. coronarie and thebesian veins into left atrium and other
chambers
– phyiological ventilation-perfusion inequality
– physiologically a small fraction of abnormal Hb
• Met-Hb
• COHb
– various oxygen extraction by tissues
• pathological agravation in any if these steps contributing to
drop of oxygen tension can cause hypoxia
– hypoxic (= hypoxemia)
– anemic
– circulatory
– histiotoxic
Normal values of blood gases in various parts of circulation
Quantitatively
• (1) inhaled atmospheric air
– 21% O2, 0.03% CO2, 78% N2, water gases 0.6% and the rest other gases (argon,
helium, ..)
• atm. pressure 760 mmHg (101 kPa)
• PO2: 0.21 x 760 = 160 mmHg
• analogically PCO2 = 0.3mmHg
• (2) alveolar air (mixture of inhaled and exhaled air)
– PAO2 = 100mmHg (13.3kPa), PACO2 = 40 mmHg (5.3kPa)
• PAO2 in alveolus slightly lower than atmospheric due to higher CO2 content in alveolus
(diffusion from blood)
• (3) arterial blood
– PaO2 = 90mmHg (12kPa), PaCO2 = 45 mmHg
• diffusion of oxygen not 100% and there is also physiological shunt
• (4) venous blood
– PvO2 = 30 - 50mmHg
air (P) alveolar (PA) arterial (Pa) venous (Pv)
O2 21kPa/150mmHg 13.3 kPa/100mmHg 12kPa/90mmHg 5.3kPa/40mmHg
CO2 0.03kPa/0.3mmHg 5.3kPa/40mmHg 5.3kPa/40mmHg 6.0kPa/45mmHg
Hypoxemia (low PaO2) - classification
• (1) Low inspired oxygen
– e.g. high altitude hypoxemia
• low PaO2 due to low PAO2 with low atmospheric pressure and
normal FiO2
– gas mixture with low O2
• (2) Hypoventilation (low V'A)
– low PaO2 due to low PAO2 with normal atmospheric
pressure and normal FiO2
• (3) Diffusion impairment
– low PaO2 with normal PAO2 with normal atmospheric
pressure and normal FiO2 (increased P(A-a)O2)
• (4) R-L shunt
– low PaO2 with normal PAO2 with normal atmospheric
pressure and normal FiO2 (increased P(A-a)O2)
• (5) Ventilation perfusion inequality
– low PaO2 with variable PAO2 with normal atmospheric
pressure and normal FiO2
(2) Hypoventilation as a cause of hypoxemia
(low PaO2 + hypercapnia)
• normally PaCO2 in mixed venous blood (i.e. pulmonary
artery and the same in alveolus) is 40 mmHg
• if PaCO2 doubles (e.g. hypoventilation) then PAO2 falls
in half, i.e. 50 mmHg (more than PaCO2 rise since RQ is
0.8)
• can we restore the PAO2?
– using alveolar gas equation you can calculate what the
inspired fraction of oxygen should be to bring it back to
normal
• i.e. PAO2 100mmHg = (FiO2 ?? x (760 - 47)) - (PaCO2 80mmHg x
1.25) = ~0.28, i.e. 28%
• examples – typically extra-pulmonary
– respiratory CNS generator
• congenital, drug overdose, CNS injury, metab. alkalosis,
encephalitis, …
– neuromuscular
• myasthenia gravis, ALS, muscular dystrophy, cervical spinal cord
injury, …
– chest wall
• deformities, injury, obesity, …
(3) Diffusion impairment as a cause of hypoxemia
(low PaO2 + normocapnia)
• due to
– shortening of the time blood
spends in pulmonary capillary
• extreme exercise
• hyperkinetic circulation
• increased velocity of pulmonary
circulation
– thickened alveolo-capillary
barrier
• PaO2 typically normal at rest, but
hypoxemia appears in exercise
Fick's Law: V'gas = D * A * ΔP/T
• V'gas = Rate of gas diffusion
across permeable membrane
• D = Diffusion coefficient of that
particular gas for that membrane
• A = Surface Area of the
membrane
• ΔP = Difference in partial
pressure of the gas across the
membrane
• T = Thickness of the membrane
Oxygen is perfusion-limited
Gases do not diffuse across a homogeneous barrier
22
Examples of disease leading to diffusion impairment
• Interstitial lung diseases
– Idiopathic pulmonary fibrosis
– Hypersensitivity Pneumonitis
– Sarcoidosis
– Pneumoconiosis
• Note, very often the diffusion
impairment combines with V/Q
mismatch
(4) Right to left shunt as a cause of hypoxemia
(low PaO2 + normocapnia + large A-a gradient)
• fraction of the cardiac output that bypasses normal
circulatory pathways
– oxygen-poor blood from the right heart flows in the left heart
without passing through functional, ventilated alveoli
• physiologically this happens due to bronchial circulation
and thebesian veins draining into left ventricle
• Anatomical causes of increased right-to-left shunting
– intrapulmonary: pulmonary arteriovenous malformations
– extrapulmonary: right-to-left intracardiac shunts
• patent ductus arteriosus
• septal defects
• Pathological causes of increased right-to-left shunting
– poorly ventilated alveoli
– fluid filled alveoli
• Hypoxemia caused by right-left shunts prototypically
cannot be corrected by oxygen therapy
(5) Ventilation-perfusion inequality as a cause of hypoxemia
(low PaO2 + hypercapnia)
• Alveolar air composition the partial pressures of oxygen and carbon dioxide in any given
alveolar unit are largely determined by the relative rates of ventilation and perfusion of
that alveolus
• Ventilation-perfusion mismatch is by far the most common cause of arterial hypoxaemia
• For efficient gas exchange it is important that there is a match between ventilation of
the alveoli (VA) and their perfusion (Q)
– in ideal alveolus V/Q ration = 1
• Effect of the V/Q ratio on Alveolar Gas Tensions
• V'/Q' ratio of alveoli within even a healthy lung is not uniform
– regional variation within the lung when an individual is standing upright
– the action of gravity results in a vertical gradient of both blood flow and ventilation in the
upright lung
• athough both blood flow and ventilation are lowest at the lung apex and highest in the base, the vertical
gradient for blood flow is wider than that for ventilation
• The effect of an increased dead space (V/Q ratio > 1) can usually be overcome by a
compensatory hyperventilation of normally perfused alveoli
– alveolar hyperventilation reduces the alveolar PCO2 and considerable diffusion of CO2 leads to
a proportional fall in the carbon dioxide content of the blood
• An increased R-L shunting (VA/Q ratio < 1) results in arterial hypoxaemia that cannot be
effectively compensated for by hyperventilation
• In advanced disease with V/Q mismatch this compensation cannot occur, leading to
increased alveolar and arterial PCO2, together with hypoxaemia which cannot be
compensated by increasing ventilation
Normal lung - relationship between ventilation and perfusion
• There is a wide variation in the VA/Q ratio to some extent already in
healthy subjects
– tendency for ventilation not to be matched by perfusion towards the apices, with the
reverse occurring at the bases
• physiological dead space in apexes (VA/Q = 3.3)
• physiological shunt in bases (VA/Q = 0.7) – lower PAO2, higher PACO2 and lower pH
• All the blood from various lung regions mixes, however, quantitative
contribution of the blood from bases of the lungs is much greater!
Example of a distribution of ventilation-perfusion ratios
VA and Q measured with the multiple inert gas infusion technique. [Left] healthy subject,
[Middle] COPD type A (i.e. emphysema), [Right] COPD type B (i.e. chronic bronchitis).
V/Q mismatch largely contributes to the A-a difference of oxygen
• Blood form various zones mixes with
largest contribution of that from lung
bases
– therefore alveoli with lower V/Q affect the
arterial PaO2 more (PaO2 ~97 mmHg)
– on the contrary, ventilation does not differ
that much, therefore PO2 in expired air is
~100 mmHg
Ventilation-perfusion inequality (mismatch)
• VA/Q inequality (mismatch) is significantly
increased in many lung diseases and contributes
to their pathophysiology
–  VA/Q ratio (i.e.  dead space)
• e.g. pulmonary embolism
–  VA/Q ratio (tj.  pulmonary shunt)
• obstructive diseases
• lung collapse
• optimalisation of  VA/Q - vasoconstriction
reflex
– vessels around hypoventilated part of the lung contract
– but!!! see obstructive diseases  development of
pulmonary hypertension
Hypoxic pulmonary vasoconstriction (HPV)
• a physiological phenomenon in which small pulmonary arteries
constrict in the presence of alveolar hypoxia (low oxygen levels)
• a homeostatic mechanism that is intrinsic to the pulmonary
vasculature
– intrapulmonary arteries constrict in response to alveolar hypoxia,
diverting blood to better-oxygenated lung segments, thereby
optimizing ventilation/perfusion matching and systemic oxygen
delivery
• chronically happens with low V/Q ratio (and event. in long-lasting
hypoventilation)
• mechanisms
– in response to alveolar hypoxia, a mitochondrial sensor dynamically
changes reactive oxygen species and redox couples in pulmonary artery
smooth muscle cells (PASMC)
– this inhibits potassium channels, depolarizes PASMC, activates voltagegated
calcium channels, and increases cytosolic calcium, causing
vasoconstriction
– sustained hypoxia activates rho kinase, reinforcing vasoconstriction,
and hypoxia-inducible factor (HIF)-1α, leading to adverse pulmonary
vascular remodeling and pulmonary hypertension (PH)
– this pre-capillary PH leads to right heart remodelling – cor pulmonale
• primary role is in the non-ventilated fetal lung, HPV diverts blood to
the systemic vasculature
RESPIRATORY INSUFFICIENCY
Oxygen cascade completed – 4 causes of hypoxemia
V/Q mismatch –
causes difference
in PO2 between
pulmonary
capillaries and
pulmonary vein
Hypoxemia dif. dg.
Respiratory insufficiency
• there 4 (or 5) causes of basically all types of respiratory disorders
can lead to RI
– severity of disease is graded according to its effect on gas exchange
• the aim of the respiration is to maintain optimal values of blood
gases by way of their exchange with
environment, therefore the main criteria
of resp. insufficiency are blood gases values
– ↓paO2 (hypoxemia) is a constant component of RI
• a thus decrease of Hb saturation
– pulsion oxymetry!
– ↑paCO2 (hypercapnia) sometimes, often normo- or even hypocapnia
• classification of resp. insufficiency
– type I or partial or hypoxemic (↓paO2 10 kPa and normo or
↓paCO2)
• failure of oxygenation
– type 2 or global or ventilatory (↓paO2 8kPa and ↑paCO2 6 kPa)
• failure of mechanical ventilation
– compensated – normal blood pH (compensatory increase of hydrogen carbonates)
– decompensated – decrease of blood pH < 7,36 (respiratory acidosis)
Aetiology and consequences of RI
Respiratory insufficiency
• extra-pulmonary causes of low paO2
(hypoxemia/hypoxia) are not usually classified as RI
– cardiovascular (heart disease with right-to-left shunt)
– circulation hypoxia
• classification of RI
– latent RI: normal blood gases at rest, abnormal during
exercise
– manifest RI: blood gases pathological in rest
• time course:
– acute: abrupt onset
• aspiration of foreign body, pneumothorax, asthma attack
– chronic: slowly progressing, variable compensation
• COPD, lung fibrosis, cystic fibrosis
– chronic with acute exacerbations:
• COPD
• diagnostics of resp. insufficiency
– examination of blood gases and acidbase
balance (Astrup)
• arterial blood (a. radialis, a. cubitalis, a.
femoralis)
• arterialised blood (ear lobe)
• capillary blood (fingers) – imprecise
– parameters:
• blood pH – normally 7.36-7.44
– i.e.[H+] = 35-44 nM
• paO2 – partial pressure of oxygen
– 10-13 kPa (75-95 mmHg)
• paCO2 – partial pressure of carbon dioxide
– 4.8-6 kPa (36-45 mmHg)
• HCO3 – hydrogen carbonates
– 22,0-26,0 mmol/l
• BE – base excess
– normally 0
• SatO2 – saturation of Hb (normally > 90%)
• Mean PvO2
– 6 kPa (45 mmHg)
• Mean PvCO2
– 6.1 kPa (46 mmHg)
36
Generalized hypoxia
• = deficiency of O2 in the organism (paO2 10kPa/75mm Hg)
• types:
– (1) hypox(emi)c hypoxia =  arterial PO2 - leads to central cyanosis
• causes of hypoxemia
–  PO2 in inspired air (PO2 (high altitude, low FiO2)
– hypoventilation due to damage of respiration center
– diffusion impairment (fibrosis, emphysema)
– anatomical shunting of non-oxygenated blood (heart)
– ventilation-perfusion mismatch
– (2) anemic hypoxia = normal arterial PO2
•  concentration of hemoglobin
– anemia, leukemias
• abnormal hemoglobin with low ability to bind oxygen
– carbonylhemoglogin (COHb )
– methemoglobin
– - (3) circulatory hypoxia = normal arterial PO2 – leads to peripheral cyanosis
• decreased cardiac output
• decreased of systemic blood pressure
• (local tissue ischemia)
• microcirculation defects
– - (4) histotoxic hypoxia – normal arterial PO2 ,  venous PO2
• Intoxication with cyanides, cobalt, …)
pO2
kidney
erythropoetin
Blood marrow
erytropoesis
Sugar
Lipids
Proteins
cell
+ O2 CO2
CO2
H2O
mitochondria
mitochondria
Histotoxic hypoxia
Hypoxic hypoxia
O2
Circulation hypoxia (ischemic)
Anemic hypoxia
Intermittent, chronic intermittent and chronic hypoxia
• Intermittent hypoxia
– an effective stimulus for evoking the respiratory, cardiovascular, and
metabolic to some extent beneficial
• they may provide protection against disease as well as improve exercise
performance in athletes
• Long-term consequences of chronic intermittent hypoxia (such
as OSA) may have detrimental effects
– hypertension, cerebral and coronary vascular problems
–  right ventricular heart mass, pulmonary
vascular remodeling and pulmonary hypertension
– developmental and neurocognitive deficits and neurodegeneration
• Chronic hypoxia induces proliferation of the vasculature due to
angiogenesis (up-regulation of VEGF) but can also change the
integrity of vessels, leading to changes in vascular
permeability (e.g. contribution to acute mountain sickness)
Hypoxia and gene transcription
• The ability of hypoxia to
promote persistent
adaptations is due in
part to its ability to
induce changes in gene
transcription
• The regulation of the
expression of a wide
variety of genes involved
in hypoxic adaptations is
largely due to activation
of a hypoxia-sensitive
transcription factor,
hypoxia-inducible factor
1 (HIF-1)
– HIF-1 is a heterodimer
of HIF-1 alpha and HIF-1
beta
– oxygen levels directly
regulate the expression
of the HIF-1 component
in a dose-dependent
manner
According to the severity and duration of exposure, intermittent hypoxia (IH) may have either beneficial effects,
involving pre- and postconditioning, or detrimental effects as in sleep apnea. It is not clear whether pre/postconditioning-like
phenomena occur during chronic exposure and contribute to the differential
susceptibility between patients for IH-related consequences and/or to the age-related decline in mortality
observed in sleep apnea patients
41
Multidimensional classification of lung diseases
• basically each pulmonary disease can be classified un
multiple aspects
– whether it causes a ventilator impairment and of what kind –
spirometry and other kinds of tests
• obstructive (FEV1) vs. restrictive (FVC, TLC)
– whether it causes a gas exchange impairment and of what
kind – blood gas analysis
• 4 causes hypoxemia (hypoventilation, diffusion, R-L shunt, V/Q
mismatch)
– whether it combines with hyper-, normo- or hypocapnia
• hypoxemic (type 1, partial) vs. hypercapnic (type 2, global) RI
– whether it affects ABB and which way - ABG
• respiratory acidosis vs. alkalosis
– what kind of symptoms they produce
• cough / dyspnea / cyanosis / change of breathing pattern
CONTROL OF RESPIRATION
& ITS DISORDERS
43
Control of respiration
• central chemoreceptors in
medulla oblongata
• peripheral chemoreceptors in
aorta and glomus caroticum (via
n. glossopharyngeus and vagus)
– active when PaO2 below 10kPa
– activation supported by
hypercapnia
• pulmonary mechanoreceptors
Central chemoreceptors
45
• sensitive to PaCO2 (and subsequent formation of
H+ in CF)
• H+ cannot go through hematoencephalic barrier
therefore response to other than respiratory
acidosis slower
– increase in [H+] due to metabolic acidosis (e.g. diabetic
ketoacidosis) will subsequently increase ventilation with a
fall in PaCO2 causing deep (Kussmaul) respiration
• very quick adaptation to acute or intermittent
hypercapnia, however, gets adapted to chronic
hypercapnia due to HCO3- in cerebrospinal fluid
– problem in COPD
• they adjust to hypercapnia and hyperventilation ceases
• -in these patients hypoxaemia is the chief stimulus to respiratory
drive
• oxygen treatment may therefore reduce respiratory drive and
lead to a further rise in PaCO2
Peripheral chemoreceptors - oxygen senzors
• Glomus caroticus and aortic bodies - sensitive to change
of PaO2
– decrease of 02 in these cells closes K+ channels 
depolarization   intracellular Ca2+  excitation 
activation of the respiratory centre
• When hypoxemia is not accompanied with hypercapnia,
activation of this sensors is when PaO27,3 kPa (55 mm
Hg)
Respiratory stimuli
• Coordinated respiratory
movements result from
rhythmical discharges arising
in interconnected neurones in
the reticular substance of the
brainstem (medulla
oblongata), known as the
respiratory centre
– via the phrenic and intercostal
nerves to the respiratory
musculature (principal and
aucilliary respiratory muscles)
- the pulmonary blood flow of 5 L/min carries 11 mmol/min (250 mL/min) of oxygen from the
lungs to the tissues
- ventilation at about 6 L/min carries 9 mmol/min (200 mL/min) of carbon dioxide out of the
body
- normal PaO2 is between 11 and 13 kPa (83 - 98 mmHg)
- normal PaCO2 is 4.8-6.0 kPa (36-45 mmHg)
Respiratory centres
• Respiratory centre is formed by
several groups of neurons:
– The basic automatic rhytm of respiration
is due to activity of Dorsal Respiratory
Group (DRG) — inspiration neurons –
efferent impulses go to diaphragma and
inspiration intercostal muscles
• DRG also obtain afferent stimuli from the
peripheral chemoreceptors and several
pulmonary receptors
– Ventral Respiratory Group (VRG)
contains both inspiration and expiration
neurons
• inactive during to normal ventilation,
increased ventilation leads to their
activation
Higher respiratory centres
• Medulla
– quiet inspiration
– —effort inspiration and forced expiration
• Pons - Pneumotaxic and apneustic
centres can modulate depth of
ventilation and its frequency
– Apneustic centre:
• supports inspiration by the activity of
inspiration neurons
– Pneumotaxic centre:
• antagonises apneustic centre
• inhibition of inspiration
• Ventilation can be modulate by cortex,
limbic systém and hypothalamus
(emotions and diseases).
Apnea
• suspension of external breathing
• causes
– voluntarily achieved (free diving)
– drug-induced (e.g. opiate toxicity)
– during sleep
• mechanically induced (e.g. OSA)
• infants (sudden death)
– central apnea syndromes
• periodical breathing
• Cheyne-Stokes breathing
– patients with cardiac failure
– consequence of neurological disease or
trauma
Obstructive sleep apnea (OSA)
52
• Episodic obstructions of airflow during sleep due to airway blockade
– breathing pauses can last from a few seconds to minutes
– may occur 30-60 times or more an hour
– typically, normal breathing then starts again, sometimes with a loud snort or
choking sound
• During apnea deep sleep shifts to light sleep
– as a result, the quality of sleep is poor, which makes one tired during the day
(excessive daytime sleepiness)
• Commonly undiagnosed, typically overweight adults
• Risks – due to intermittent hypoxia with significant Hb desaturation to
levels as low as 50%
– changes in the neurons of the
hippocampus and frontal cortex
– hypertension
– coronary artery disease
– type 2 diabetes
– depression
– sleepiness-related accidents
53