Pathophysiology of the
respiratory system 
Structural properties of airways and lungs
Defense mechanisms of the respiratory system
Respiration and gas exchange
- ventilation & diffusion & perfusion
Pulmonary mechanics
Ventilation – perfusion (in)equality
Control of ventilation
The delicate structure-function coupling
of lungs
• The main role of the respiratory system
is to extract oxygen from the external
environment and dispose of waste
gases, principally carbon dioxide
– at the end of deep breath 80% of lung
volume is air, 10% blood and 10% tissue
• lung tissue spreads over an enormous area !
• The lungs have to provide
– a large surface area accessible to the
environment (tennis court area) for gas
exchange
– alveoli walls have to present minimal
resistance to gas diffusion
• Close contact with the external
environment means lungs can be
damaged by dusts, gases and infective
agents
– host defense is therefore a key priority for
the lung and is achieved by a combination
of structural and immunological means
3
Structure of airways
• There are about 23 (18-30) divisions
(223 i.e. approx. 8 millions of sacs)
between the trachea and the alveoli
– the first seven divisions, the bronchi
have:
• walls consisting of cartilage and smooth
muscle
• epithelial lining with cilia and goblet cells
• submucosal mucus-secreting glands
• endocrine cells - Kulchitsky or APUD
(amine precursor and uptake
decarboxylation) containing 5-
hydroxytryptamine
– the next 16-18 divisions the
bronchioles have:
• no cartilage
• muscular layer progressively becomes
thinner
• a single layer of ciliated cells but very few
goblet cells
• granulated Clara cells that produce a
surfactant-like substance
4
Wall structure of conducting conducting
airways and alveolar region
5
Alveoli
• There are approximately 300-400
million alveoli in each lung with the
total surface area is 40 - 80m2
• Cell types of the epithelial lining
– type I pneumocytes
• an extremely thin cytoplasm,
and thus provide only a thin
barrier to gas exchange, derived
from type II pneumocytes
• connected to each other by tight
junctions that limit the fluid
movements in and out of the alveoli
• easily damageable, but cannot divide!
– type II pneumocytes
• slightly more numerous than type I
cells but cover less of the epithelial
lining
• the source of type I cells and
surfactant
– macrophages 6
Alveolo - capillary barrier
• Alveolar epithelia
– type I and II cells
• Capillary
endothelium
– non-fenestrated
• Intersticium
– cells (very few!)
• fibroblasts
• contractile cells
• immune cells
(intersticial
macrophages,
mast cells, …)
– ECM
• elastin and
collagen fibrils
7
Pulmonary vasculature and lymphatics
8
• Lungs are the only organ through which all the blood (CO) has to pass!!!
• Lungs have a dual blood supply
– deoxygenated blood from the right ventricle via the pulmonary artery
– systemic (nutritional) supply throughout the bronchial circulation
• arises from the descending aorta
• bronchial arteries supply tissues
down to the level of the
respiratory bronchiole
• bronchial veins drain into the
pulmonary vein, forming part of
the physiological shunt observed
in normal individuals
• Drainage is provided by the four
main pulmonary veins (into the
left atrium)
• Lymphatics start in the interstitial
space between the alveolar cells
and the capillary endothelium of
the pulmonary arterioles
– the tracheobronchial lymph nodes are
arranged in five main groups:
• paratracheal, superior
tracheobronchial,
subcarinal, bronchopulmonary and
pulmonary
Defense mechanisms of the resp. tract
• These can be divided into two kinds of
mechanisms:
– physical
• humidification
• particle removal
– over 90% of particles greater than 10 μm
diameter are removed in the nostril or
nasopharynx (incl. most pollen grains which
are typically >20 microns in diameter)
– particles between 5 - 10 microns become
impacted in the carina
– particles smaller than 1 micron tend to
remain
• mucus
• particle expulsion
– by coughing, sneezing or gagging
– immunological
• humoral
• cellular
• Pulmonary disease often results from a
failure of the many defense
mechanisms that usually protect the
lung in a healthy individual 9
The ciliated epithelium
• Very important defense mechanism
• Each cell contains approx. 200 cilia
beating at 1000 beats per minute in
organized waves of contraction
• Each cilium consists of nine
peripheral pairs and two inner
longitudinal fibrils in a cytoplasmic
matrix
– nexin links join the peripheral pairs
– dynein arms consisting of ATPase
protein project towards the adjacent
pairs.
• Bending of the cilia results from a
sliding movement between adjacent
fibrils powered by an ATP-dependent
shearing force developed by the
dynein arms
– congenital absence of dynein arms
leads to immotile cilia. syndrome
• Mucus, which contains macrophages,
cell debris, inhaled particles and
bacteria, is moved by the cilia
towards the larynx at about 1.5
cm/min (the „mucociliary escalator“)
10
Respiratory tract secretions - mucus
• gelatinous substance (5 mm thick) consisting of acid and neutral polysaccharides
• relatively impermeable to water
– mucus floats on a liquid or sol layer that is present around the cilia of the epithelial cells
• secreted from goblet cells and mucous glands as distinct globules that coalesce
increasingly in the central airways to form a more or less continuous mucus
blanket
• under normal conditions cilia are in contact with the under surface of the gel
phase and coordinate their movement to push the mucus blanket upwards
– it may only take 30-60 minutes for mucus to be cleared from the large bronchi
– there may be a delay of several days before clearance is achieved from respiratory bronchioles
• reduction in mucociliary transport
– one of the major long-term effects of cigarette smoking
• contributes to recurrent infection and in the larger airways it prolongs contact with carcinogens
– air pollutants, local and general anaesthetics
– bacterial and viral infections
– congenital defects in mucociliary transport (characterized by recurrent infections and eventually
with the development of bronchiectasis)
• the 'immotile cilia' syndrome and cystic fibrosis: an abnormal mucus composition is associated with ciliary
dyskinesia
11
Humoral defense mechanisms
• Non-specific soluble factors
– characteristic for lungs
• α-Antitrypsin (α-antiprotease)
– present in lung secretions derived from plasma
– inhibits chymotrypsin and trypsin and neutralizes proteases and elastase
• Surfactant protein A (SPA)
– one of four species of surfactant proteins which opsonizes bacteria/particles, enhancing
phagocytosis by macrophages
– generally found on biological barriers
• Lysozyme
– an enzyme found in granulocytes that has bactericidal properties
• Lactoferrin
– synthesized from epithelial cells and neutrophil granulocytes and has bactericidal properties.
• Interferon (produced by most cells in response to viral infection)
– a potent modulator of lymphocyte function. It renders other cells resistant to infection by any
other virus.
• Complement
– present in secretions and is derived by diffusion from plasma
– in association with antibodies, it plays an important cytotoxic role
• Defensins
– bactericidal peptides present in the azurophil granules of neutrophils
12
Cellular defense mechanisms
• Pulmonary alveolar macrophages
– derived from precursors in the bone marrow and migrate to the lungs via the
bloodstream
– phagocytose particles, including bacteria, and are removed by the mucociliary
escalator, lymphatics and bloodstream
– dominant cell in the airways at the level of the alveoli
• comprise 90% of all cells obtained by bronchoalveolar lavage
– work principally as scavengers and are not particularly good at presenting antigens to
the immune system
• Dendritic cells
– form a network throughout the airways and are thought to be the key antigenpresenting
cell in the airway
• Lymphoid tissue
– the lung contains large numbers of lymphocytes which are scattered throughout the
airways. Sensitized lymphocytes contribute to local immunity through differentiation
into IgA-secreting plasma cells. IgG and IgE are found in low concentrations in airway
secretions from a combination of local and systemic production.
– In addition to these resident cells, the lung has the usual range of acute
inflammatory responses and can mobilize neutrophils promptly in response to injury
or infection and play a major part in inflammatory conditions such as asthma.
13
Summary – lung defense
14
Respiration and gas exchange in the lungs
• ventilation = mechanical process
– breathing in narrower meaning
• diffusion = chemical process
– through alveolo-cappilary barrier
• perfusion = circulatory process
– circulation of blood in lungs
15
(1) VENTILATION & PULMONARY
MECHANICS
16
17
set by opposing recoil forces of the chest and lungs and the effort of respiratory muscles
Mechanika dýchání
• tlaky a tlakové gradienty
– tlak na povrchu těla (Pbs), většinou
totožný s atmosferickým (Pao)
– tlak v alveolu (Palv)
– „elastický“ tlak vyvíjený
parenchymem plic a povrchovým
napětím (Pel)
– tlak v pleurální dutině (Ppl)
– transpulmonální tlak = tlakový
rozdíl mezi alveolem a pleurální
dutinou (PL)
• PL = Palv - Ppl
– transtorakální tlak = rozdíl mezi
alveoly a tělesným povrchem (Prs),
určuje zda probíhá inspirium nebo
expirium
• Prs = Palv - Pbs
18
Ventilation
• pressure necessary to
distend lungs has to
overcome two kinds of
resistances
– DYNAMIC = airway resistance
(in the convection part of
airways)
– STATIC = elastic recoil (in the
respiratory part of airways
and lung parenchyma)
• energy requirements for
respiratory muscles to
overcome these two
resistances is normally quite
low (2-5% of a total O2
consumption)
• but increases dramatically
when resistance increases
(up to 30%)  subjective
perception as a dyspnea
19
Ventilation (breathing) as a mechanical process
20
• Inspiration
– an active process that results from the descent of
the diaphragm and movement of the ribs upwards
and outwards under the influence of the
intercostal muscles
• in resting healthy individuals, contraction of the
diaphragm is responsible for most inspiration
– respiratory muscles are similar to other skeletal
muscles but are less prone to fatigue
• weakness may play a part in respiratory failure
resulting from neurological and muscle disorders and
possibly with severe chronic airflow limitation
– inspiration against increased resistance may require
the use of the accessory muscles of ventilation
• sternocleidomastoid and scalene muscles
• Expiration
– follows passively as a result of gradual lessening of
contraction of the intercostal muscles, allowing the
lungs to collapse under the influence of their own
elastic forces (elastic recoil)
– forced expiration is also accomplished with the aid
of accessory muscles
• abdominal wall
Airflow
• Movement of air through the airways results
from a difference between the pressure in the
alveoli and the atmospheric pressure
– alveolar pressure (PALV) is equal to the elastic recoil
pressure (PEL) of the lung plus the pleural pressure
(PPL)
– positive PALV occurs in expiration and a negative
pressure occurs in inspiration
• During quiet breathing the sub-atmospheric
pleural pressure throughout the breathing cycle
slightly distends the airways
– during vigorous expiratory efforts (e.g. cough) the
central airways are compressed by positive pleural
pressures exceeding 10 kPa
– the airways do not close completely because the
driving pressure for expiratory flow (alveolar
pressure) is also increased
• When there is no airflow (i.e. during a pause in
breathing) the tendency of the lungs to collapse
(the positive PEL) is exactly balanced by an
equivalent negative PPL
21
The relationship between
maximal flow rates on
expiration and inspiration is
demonstrated by the maximal
flow-volume (MFV) loops
Elastic properties of the lung
22
• lungs have an inherent elastic property
that causes them to tend to collapse
generating a negative pressure within
the pleural space
– the strength of this retractive force relates
to the volume of the lung; for example, at
higher lung volumes the lung is stretched
more, and a greater negative intrapleural
pressure is generated
– at the end of a quiet
expiration, the retractive
force exerted by the lungs
is balanced by the
tendency of the thoracic
wall to spring outwards
• at this point, respiratory
muscles are resting and
the volume of the lung is
known as the functional
residual capacity (FRC)
the system of airway
elastic fibres
Anatomical – functional considerations explain
alveolar stability (due to alveolar interdependence
and collateral ventilation)
23
24
Elastic recoil is determined by two kinds of forces
• lung compliance (“distensibility”) = connective tissue
– a measure of the relationship between this retractive
force and lung volume
– defined as the change in lung volume brought about by
unit change in transpulmonary (intrapleural) pressure
(L/kPa)
• surface tension produced by the layer of fluid that lines
the alveoli
– determined by the cohesive (binding together)
forces between molecules of the same type
• on the inner surface of the alveoli
is fluid that can resist lung expansion
• there would be a lot of surface
tension because there is an air-water
interface in every alveolus
• if surface tension remained
constant, decreasing r during
expiration would increase P and
smaller alveolus would empty into large one (A)
– this collapsing tendency is offset by pulmonary surfactant
which significantly lowers surface tension (B)
25
Pulmonary surfactant
• Complex mixture of lipids
and proteins at the alveolar
cell surface (liquid – gas
interface) reducing surface
tension
– superficial layer made of
phospholipids (dipalmitoyl
lecithin)
– deeper layer (hypophase)
made of proteins (SP-A, -B, C,
-D)
• Surfactant maintains lung
volume at the end of
expiration
• Continually recycles
– influenced by many
hormones incl.
glucocorticoids
• lung maturation in pre-term
newborns
26
Pulmonary surfactant adsorption to the interface and surface film formation : Processes that may contribute to
transport of surface active surfactant species to the interface include 1) direct cooperative transfer of surfactant
from secreted lamellar body-like particles (LB) touching the interface, 2) unravelling of secreted LB to form
intermediate structures such as tubular myelin (TM) or large surfactant layers that have the potential to move and
transfer large amounts of material to the interface, and 3) rapid movement of surface active species through a
continuous network of surfactant membranes (so-called surface phase) connecting secreting cells with the
interface.
Perez-Gil J , Weaver T E Physiology 2010;25:132-141©2010 by American Physiological Society
Abnormalities of elastic properties
• change of lung compliance
–  in pulmonary emphysema, aging ( TLC, 
FRC,  RV)
–  in interstital disease (TLC,  FRC,  RV),
e.g. pulmonary fibrosis or bronchopneumonia
• lack of surfactant (TLC,  FRC,  RV)
– infant or adult respiratory distress syndromes
(IRDS or ARDS, resp.), i.e. lung collapse
– lung edema (damages surfactant)
• diseases that affect the movement of the
thoracic cage and diaphragm
– marked obesity
– diseases of the thoracic spine
• ankylosing spondylitis and kyphoscoliosis
– neuropathies
• e.g. the Guillain-Barré syndrome)
– injury to the phrenic nerves
– myasthenia gravis
28
Forced expiration - dynamic compression
• In forced expiration, the driving
pressure raises both the PALV and
the PPL
– between the alveolus and the
mouth, a point will occur (C)
where the airway pressure will
equal the intrapleural pressure,
and airway compression will occur
– however, this compression of the
airway is temporary, as the
transient occlusion of the airway
results in an increase in pressure
behind it (i.e. upstream) and this
raises the intra-airway pressure so
that the airways open and flow is
restored
• the airways thus tend to vibrate at
this point of 'dynamic compression'
29
Dynamic compression in various situations
• The respiratory system is
represented as a piston with
a single alveolus and the
collapsible part of the
airways within the piston
• C, compression point; PALV,
alveolar pressure; PEL, elastic
recoil pressure; PPL, pleural
pressure.
– (a) at rest at functional
residual capacity
– (b) forced expiration in normal
subjects
– (c) forced expiration in a
patient with COPD
31
Airflow pattern as a result of change in
airway diameter  resistance
• From the trachea to the periphery, the airways
become smaller in size (although greater in number)
– the cross-sectional area available for airflow increases as
the total number of airways increases
– the flow of air is greatest in the trachea and slows
progressively towards the periphery (as the velocity of
airflow depends on the ratio of flow to cross-sectional
area)
• in the terminal airways, gas flow occurs solely by diffusion
• The resistance to airflow is very low (0.1-0.2 kPa/L in
a normal tracheobronchial tree), steadily decreasing
from the medium size to small airways
• Airway tone is under the control of the autonomic
nervous system
– bronchomotor tone is maintained by vagal efferent nerves
– many adrenoceptors on the surface of bronchial muscles
respond to circulating catecholamines
• sympathetic nerves do not directly innervate them!
32
Airway resistance
• Ohm´s law:
– flow is inversely
proportional to
resistance
• Poiseuille’s law:
– determinants od resistance
• This means that the most
important variable here is the
radius
• Overcoming increased resistance
requires forced expiration
33
Airflow resistance - bronchoconstriction
• theoretical amplifying effect of
luminal mucus on airflow
resistance in asthma. (a)
According to Poiseuille’s law,
resistance to flow (R) is
proportional to the reciprocal of
the radius (r) raised to the fourth
power. (b) Without luminal
mucus, bronchoconstriction to
reduce the airway radius by half
increases airflow resistance 16fold.
(c) A small increase in mucus
thickness (tM), which reduces the
radius of the airway by only onetenth,
has a negligible effect on
airflow in the unconstricted
airway (compare with panel a). (d)
With bronchoconstriction, the
same amount of luminal mucus
markedly amplifies the airflow
resistance of this airway
34
Airflow obstruction
• In patients with severe
COPD, limitation of
expiratory flow occurs even
during tidal breathing at rest
• To increase ventilation these
patients have to breathe at
higher lung volumes and
also allow more time for
expiration by increasing flow
rates during inspiration,
where there is relatively less
flow limitation
• Thus patients with severe
airflow limitation have a
prolonged expiratory phase
to their respiration
35
VÝMĚNA PLYNŮ V PLICÍCH & POMĚR
VENTILACE-PERFÚZE
36
Functional classification of airways
• Conducting airways (=
anatomical dead space)
• nose (mouth)
• larynx
• trachea
• main bronchi & bronchioles
– gas conduction, warming
• Acinar airways (= respiratory
space)
• respiratory bronchioles
• alv. ducts & sacs
• alveoli
– gas exchange
• Pulmonary acinus
– the functional 3-D unit – a part
of the parenchyma in which all
airways have alveoli attached to
their wall and thus participating
in gas exchange
37
Koncept acinu
• 3-D struktura následující po terminálním bronchiolu
– 3 úrovně větvení resp. bronchiolu a násl. cca 8 větvení alveolárních duktů,
– každý plicní lalůček (anatomický pojem) tak vyplňuje 10 - 30 acinů
– vzhledem k tomu, že kyslík (pouze) difunduje (neproudí) a tedy mění svůj
koncentrační gradient směrem k periferii acinu, je tento koncept důležitý
pro pochopení ventilačně – perfúzní nerovnováhy
Výměna plynů v plicích
• hlavní funkce dýchacího systému –
výměna plynů mezi okolím a krví – je
podřízena časově variabilním nárokům
organismu na O2
– udržovány v optimálním rozmezí zejm.
regulací intenzity ventilace
• nároky jsou určeny spotřebou ATP a jeho
nahrazováním mitochondriemi (ox.
fosforylací)
• alveolo-kapilární výměna plynů probíhá z
alv. prostoru do krve prostou difuzí přes
stěnu alveolu, plicní intersticium a stěnu
kapilár
• hnací silou dodávky O2 (a recipročně CO2)
je postupný pokles jeho parciálního tlaku,
tj. koncentrační gradient mezi
vdechovaným vzduchem, krví a tkáněmi:
– parciální tlak = tlak, který by plyn měl
pokud by byl ve směsi sám
Výměna plynů v plicích
40
• důvody poklesu PO2:
– difuze v acinárních cestách a
postupný pokles gradientu
– kompetice s CO2 v alveolu (do
výše atm. tlaku)
• alveolární rovnice plynů
– rozpustnost =  100% difuze
přes alveolo-kapilární
membránu
– fyziologický pravo-levý zkrat
• míchání okysličené a
neokysličené krve (aa.
bronchiales a vv. coronarie)
– fyziologicky malá část Hb jako
Met-Hb a COHb
– postupné spotřebovávání v
průběhu acinu
Kvantitativně
• (1) vdechovaný atmosférický vzduch
– 21% O2, 0.03% CO2, 78% N2, vodní páry 0.6% a zbytek tvoří
další plyny (argon, helium, ..)
• atmosferický tlak je 760 mmHg (101 kPa)
• parc. tlak O2 (PO2): 0.21 x 760 = 160 mmHg
• analogicky PCO2 = 0.3mmHg
• (2) alveolární vzduch (směs vdechovaného a
vydechovaného vzduchu)
– PAO2 = 100mmHg (13.3kPa), PACO2 = 40 mmHg (5.3kPa)
• parc. tlak O2 v alveolu je o něco nižší něž v atmosféře kvůli
většímu zastoupení CO2 v alveolu (vydechovaný vzduch)
• (3) arteriální krev
– PaO2 = 90mmHg (12kPa), PaCO2 = 45 mmHg
• difuze kyslíku není 100% a navíc existuje fyziologický zkrat
• (4) venózní krev
– PvO2 = 30 - 50mmHg
41
vzduch (P) alveolární (PA) arteriální (Pa) venózní (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
Transport plynů krví
• krví (ve vazbě na Hb a fyzikálně
rozpuštěný) je kyslík dodáván do
všech částí těla, kde difunduje do
tkání
– při fyziologickém PaO2
(90mmHg/12kPa) a fyziologickém
hemoglobinu je téměř 100%
saturace
• a do poklesu PaO2 na 12kPa
saturace významně neklesá
– saturace měřena pulzní oxymetrií
• rozhodující je množství v
mitochondriích
– pro dostatečnou produkci ATP je
nutné pO2 v tkáních > 0.13kPa
(1mmHg) = kritická tenze kyslíku
• organizmus potřebuje kyslík:
– cca 250ml/min  350l/den v klidu
– při zátěži mnohem více
Význam kyslíku v organizmu
• v těle neexistují větší zásoby kyslíku
• stačí cca na 5min
– dýchání a dodávka kyslíku tkáním je proto
nepřetržitý děj
– jeho úplné přerušení znamená
• ohrožení života (<5min)
– reverzibilní ztráta zraku za cca 7s, bezvědomí
za cca 10s
• klinickou smrt (~5-7min), event. smrt mozku
• smrt organizmu (>10min)
• 85-90% využito v aerobním metabolizmu
při výrobě ATP na
– udržení iontových gradientů
– svalová kontrakce
– syntézy
• pro zbytek procesů je pokles pO2 méně
kritický
– hydroxylace steroidů
– detoxikace (hydroxylace) cizorodých látek
v játrech
– syntéza oxidu dusnatého ( vazodilatace)
– degradace hemu hemoxygenázou
Sumárně: plíce jako součást „O2 dráhy“
Ventilace a perfúze plic
• vztah mezi ventilací a perfuzí plic je
variabilní
– do jisté míry i u zdravých lidí
• rozdíly mezi apexem a bazí plíce
– apex: ventilace alveolů s redukovanou
perfuzí (tzv. fyziologický mrtvý prostor,
VA/Q = 3.3)
– báze: perfuze alveolů s redukovanou
ventilací (fyziologický zkrat, VA/Q = 0.7)
• ventilačně perfuzní (VA/Q) nepoměr se
významně zvyšuje u některých plicních
nemocí a zodpovídá za jejich projevy
–  VA/Q poměru (tj.  mrtvého
prostoru)
• např. plicní embolie
–  VA/Q poměru (tj.  plicního zkratu)
• obstrukční nemoci plic
• kolaps plíce
• optimalizace  VA/Q - vazokonstrikční
reflex
– cévy okolo méně ventilované části plíce
se kontrahují
– ale!!! viz důsledky obstr. nemocí
45
Ventilation-perfusion inequality
46
CONTROL OF RESPIRATION
& ITS DISORDERS
47
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
48
Central chemoreceptors
49
• sensitive to PaCO2 (and subsequent
formation of H+ in CF)
• H+ cannot go through
hematoencephalic barrier therefore
response to olther 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 - 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 Pa02
– 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)
50
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) 51
- 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)
52
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
53
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).
54
Dyspnea (breathlessness)
• on physical exertion is normal and
not considered a symptom unless the
level of exertion is very light, such as
when walking slowly
• although breathlessness is a very
common symptom, the sensory and
neural mechanisms underlying it
remain obscure
• the sensation of breathlessness is
derived from at least three sources:
– changes in lung volume
• sensed by receptors in thoracic wall
muscles signalling changes in their length
– the tension developed by contracting
muscles
• this can be sensed by Golgi tendon organs
• tension developed in normal muscle can
be differentiated from that developed in
muscles weakened by fatigue or disease
– central perception of the breathing
effort
55
common causes of dyspnea
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
57
Obstructive sleep apnea (OSA)
58
• Flow of air pauses or decreases during sleep because the
airway has become narrowed, blocked, or floppy
– breathing pauses can last from a few seconds to minutes
– may occur 30 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 hypoxia
– changes in the neurons
of the hippocampus and
frontal cortex
– hypertension
– coronary artery disease
– type 2 diabetes
– depression
– sleepiness-related
accidents
59