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Physiology of respiration
Respiration – principal and vital function of the respiratory system
• external respiration – exchange of the respiratory gases: atmosphere blood
• internal respiration - exchange of the respiratory gases: blood tissues
• cellular respiration – utilization of O2/ production of CO2 in the cell metabolism
• Respiration
• –function of: respiratory system - cardiovascular system – blood = the transport system
Other functions: vocalization, protection, acid-base balance, metabolic functions, water
and heat balance
atmosphere cells-metabolism
THE FUNCTIONS OF THE RESPIRATORYPASSAGEWAYS
A/ Conducting zone• upper respiratory passageways
– nasal cavity (+ paranasal sinuses)– (naso-) pharynx – larynx
• lower respiratory passageways(intrathoracic)– trachea– bronchi – terminal bronchioles
F: conduction, conditioning of the air
B/ Respiratory zone= lung parenchyma
– respiratory bronchioles– alveolar ducts– alveolar saccules– alveoli
F: exchange of the respiratory gases(air – blood)
Components of the respiratory system
- between trachea and alveoli the airways
divide 23 times
(23 generations of bronchi)
- bronchi
• primary bronchi – branches of trachea
(right, left)
• lobar (secondary) bronchi (3R + 2L)
• segmental...
- bronchioles
• increase in total cross section, and
eventually surface area for gas exchange
(2,5 cm2 → > 106 cm2)
Respiratory bronchiole
Alveolar sac
Tracheobronchial tree = trachea + bronchi
http://medicalpicturesinfo.com/wp-content/uploads/2011/09/bronchial-tree-4.jpg
Tracheobronchial tree - structure
⚫mucosa (innermost layer)
- epithelial cells with cilia
- goblet cells – produce mucus
⚫submucosa – slime glands
⚫smooth muscle
⚫cartilage
- ring- in bigger and medial bronchi
- fixate wall - prevents from collapse
- bronchioles
- lack cartilage
- in bronchoconstriction may cause major resistance to air flow
- the wall of bronchioles is formed especially smooth muscle
Airway smooth muscle
Facts:
• found in the trachea and along the bronchial tree (till terminal bronchioles)
• critically important in regulating bronchomotor tone of the airways
• secretes cytokines, chemokines and extracellular matrix proteins
• may serve as a potential new target for the treatment of chronic lung diseases
Regulation of the smooth muscles in the respiratory passageways
1/ nervous
2/ humoral (paracrine)
Regulation of the smooth muscles in the respiratory passageways
Autonomic nervous system (involuntary)
Parasympathetic nervous system – n. vagus (acetylcholine) – action already in rest
Effects:
- maintenance of basal tone of smooth muscles in airways
- bronchoconstriction (contraction of the smooth muscle)
- increased resistance to airflow
- increased mucous secretion
Sympathetic nervous system (noradrenaline) – no significant
- Adrenal medulla (adrenaline – beta receptors)
Effects:
- cause relaxation of the smooth muscle - dilation of the bronchi
- easier air flow (e.g. in stress, physical activity)
Local factors with bronchoconstricting effect
- histamine (released in allergic reactions)
- irritants in the air, cigarette smoke
Function of the conducting zone
- conduction and conditioning of the air - no gas diffusion between respiratory passageways and blood
• Warming to the body temperature (mainly in paranasal sinuses)- prevents cooling of body center
• Wetting (humidification, moisturizing)
- adding water vapor (diffusion of water through the mucosa)
- 100 % humidity
- prevents drying up of mucosa
- preserving integrity and function of cilia
- important for gas exchange in alveoli
• Filtering/ cleaning
out foreign material (dust, bacteria, etc.)
– by mucociliary transport
- mucosa covered by mucus - retain foreign material
- cilia of the mucosal epithelial cells beat with motion toward pharynx
- when mucus reaches pharynx - may be eliminated from the body
• nasal cavity
- efficient cleaning of the air by cilia
- efficient warming of the air (mainly in paranasal
sinuses)
• oral cavity
- also allows the breathing
- mostly in case of insufficient ventilation
through nasal cavity (e.g. edema of nasal
mucosa)
- no cilia – insufficient cleaning
- the air bypasses paranasal sinuses –
insufficient heating - irritation
http://t3.gstatic.com/images?q=tbn:ANd9GcQMmvwvKmgcUatUj
Q8A9dGvJPUIUAHutka6iCUs7P7PeXt7KagMsA
Protective mechanisms in the respiratory passageways
• inspired air – contains dust particles, microbes...
• risk – for the respiratory system and the body
• elimination by different protective mechanisms
– reflex
– nonreflex
Reflex mechanisms
• changes in breathing patterns, apnoic reflex, laryngoconstriction,
bronchoconstriction, the cough reflex, the sneeze reflex
Nonreflex mechanisms
• physical (filtration, humidification, warming, local immune mechanisms, mucocilliary
transport, surfactant, oxidative-antioxidant system, system of proteases and
antiproteases
The cough reflex, the sneeze reflex
• very forceful expiration – to clear the foreign matter out of the respiratory passageways
• stimulus – mechanical, chemical irritation of mucosa
– larynx, trachea, bronchi - cough
– nose - sneezing
• afferent fibres (n. vagus - cough, n. trigeminus – sneeze)
• reflex centre – medulla oblongata
• effector organs – muscles of respiration
Coughing and sneezing reflex involve a series of steps:
1. Inspiratory phase
– deep initial inspiration (2,5 l of air) – decrease in intrapleural and intrapulmonal
pressure
2. Expiratory phase
a/ compression
• epiglottis closes, vocal cords shut
• forceful contraction of expiratory muscles + accessory expiratory muscles
• the pressure in the lungs rises rapidly (to +27 kPa)
b/ expulsion
• vocal cords and the epiglottis suddenly open
• air explodes out under high pressure in the lungs
• the rapidly moving air - carries away the foreign matter
- velocity 150-280m/s (12 l/s)
- cough – through the mouth
- sneezing - through the nose
Production:
- in goblet cells in mucosa and submucosal glands
- 100 ml /24 h (85% are reabsorbed, 15% excreted)
Functions:
▪ mechanical barrier
▪ sticky – can trap the particles, microbes
▪ dilution of toxic substances
▪ optimal environment for cilia
▪ contribution for warming and wetting of the air
▪ contains immunoglobulin A (Ig A) - mucosal immunity
Sticky external layer
▪ thick mucus floats on the surface of the cilia
Watery internal layer
▪ periciliary fluid layer
http://www.ersnet.org/learning_resources_player/breathe/6_4/
8/10.-Review-pathophysiology-web-images/figure-3.jpg
Mucus in the respiratory passageways
Ciliary activity in the respiratory passageways
Mucociliary transport
cilia of the mucosal epithelial cells (50-300/cell)
beating causes the coat of mucus to flow slowly, at a velocity of a few millimeters per minute - mucus with the trapped particles moves in oral direction - when mucus reaches pharynx, may be spitted out
Optimal for ciliary activity:
- humidity >85%; temperature 18-40°C; pH 7-8
Decrease in ciliary activity:
- temperature in airways
- humidity in airways
- irritants – e.g. cigarette smoke
(initial increase, then decrease)
http://www.ersnet.org/learning_resources_player/breathe/6_4/
8/10.-Review-pathophysiology-web-images/figure-3.jpg
http://t0.gstatic.com/images?q=tbn:ANd9GcQkTr4lb97Y_yFl0PM
IE48XKCk_gmj65n5GoA6O-Qojmyd1Ew3_
Mechanical filtration depends on the size of particles
> 10 μm trapping by cilia, nasal cavity, pharynx
1 - 10 μm lower parts of respiratory passageways
0,5 - 1 μm can pass to respiratory bronchioles and alveoli –removal by phagocytosis
< 0,5 μm are not trapped, are expired back to the atmosphere
MECHANISM OF INSPIRATION AND EXPIRATION (VENTILATION)
- a cyclic, automatic process
1. inspiration
• air moves from the atmosphere into the lungs
• tidal volume - the volume air inspired in quiet
breathing VT – 500 ml
2. expiration
• the same volume air moves from the lungs into the
atmosphere
- external signs of breathing – movements of the chest and
abdomen
Inspiration and expiration
- the air flow into and out of the lungs is passive
- the main driving force for the air flow is the pressure
differences between the lungs and the atmosphere
Ventilationexchange of respiratory gasses between atmosphere and alveoli
Atmospheric pressureatmosphere
• the atmosphere (mass of air) exerts pressure
- depends on height column, height above see level
- at seal level approx. 100 kPa (1 atm, 760 mm Hg)
• the atmospheric pressure is lower in higher altitudes
- lower density of the air
- thinner layer of the atmosphere
• in physiology pressures in the body
are related the atmospheric pressure
e.g. if pressure in the lungs= 0,1 kPa,
it means, it is by +0,1 kPa higher than
atmospheric pressure
https://i.ytimg.com/vi/O37XuRkS5UE/hqdefault.jpg
• lungs – lined with a thin membrane
pleura visceralis („sticks“ to the lungs)
• the internal side of the chest is lined with
pleura parietalis („sticks“ to the chest wall)
• between both membranes is a thin space
(intra)pleural space
• the space is filled with small volume of fluid
Pleura, intrapleural space
The chest and lungs are elastic structures
lungs - exert an elastic recoil directed inwards
thorax - exerts an elastic recoil directed outwards
due to elastic recoil of the lungs and the
chest the pressure in intrapleural space
is lower than the pressure in
atmosphere (= it is subatmospheric)
by – 0,5 to –1,0 kPa in quiet breathing
The negative intrapleural pressure
prevents the lung to collapse
- it holds („pulls“) the lungs against the chest
wall
acts in inspiration and expiration
- lungs follow the chest movements intrapleural space –
negative pressure
Intrapulmonary (alveolar) pressure
- pressure inside the lungs (i.e. in the alveoli)
- when no air flows into/out of the respiratory passageways, the pressures in all
parts of the respiratory tree are equal to the atmospheric pressure
Physical laws in respiration and ventilation
• if two containers filled with air that differ in pressure are
connected, the air moves from the container with higher
pressure into the container with lower pressure
• pressure and volume of air within a closed system is
constant
– i.e. if the volume increases, the pressure
decreases and vice versaV
p
V
p
P1 p2
P1 > p2
Boyle's law
1. Contraction of the inspiratory muscles =
an active process
A. diaphragm - the main inspiratory
muscle
B. external intercostal muscles
- pull ribs up and out - cause further increase in chest volume
abdominal vs. costal breathing
C. accessory inspiratory muscles – active in forceful breathing
(m. sternocleidomastoideus, mm. scaleni, mm serrati ant.)
Expiration Inspiration
Mechanism of inspiration
2. increase in chest volume
- by 0.5 L in quiet breathing
- diaphragm contraction (approx. 75% of chest expansion) in quiet breathing
- by contraction it descends by 1-1,5 cm / chest volume + 250 - 350 cm3
- forceful breathing - stronger contraction - it descends by 6 -10 cm, chest volume+ 2-3000 cm3
3. increase in chest volume
- the interpleural negativity „pulls“
parietal pleura outwards
- decrease in intrapleural pressure – becomes more negative
4. lungs expand - decrease in intrapulmonary pressure
– becomes lower than atmospheric
5. the air moves
- from the place with higher pressure (atmosphere)
- to the place with lower pressure (lung)
- until the pressures get equal (= end of inspiration)
Before inspiration inspiration
Mechanism of expiration
• a quiet expiration is passive
(i.e. it does not require
muscle contraction)
1. inspiratory muscles are relaxed
- the diaphragm moves upwards, ribs move downwards
(because of their elastic recoil)
2. chest size decreases
3. pressure in intrapleural space gets increased (less negative)
4. intrapulmonary pressure exceeds atmospheric pressure
5. air moves
- from the place with higher pressure (lung)
- to place with lower pressure (atmosphere)
- expiration is terminated when the pressures in lungs/atmosphere are equal
expiration
Forceful expiration
• active process = requires muscle contraction
Expiratory muscles1. internal intercostal muscles
- move ribs downwards
- further decrease in thoracic volume
2. accessory expiratory muscles – abdominal muscles, chest muscles
expiration
Recapitulation
- characterize mechanism of inspiration in 6 steps
1. contraction of the inspiratory muscles
- diaphragm, external intercostal muscles
2. increase in chest volume
3. decrease of intrapleural pressure - becomes more negative
4. increase of lung volume
5. decrease in intrapulmonary pressure
6. the air moves - from the place with higher pressure (atmosphere) - to the place with lower pressure (lung) - until the pressures get equal (end of inspiration)
- after expiration / prior to next inspiration
- all the respiratory muscles are relaxed
- the pressure of air in the lungs = atmospheric pressure
Relaxation position of the chest
- increase volume of the air - active process
- decrease volume (expiration) - active process
- starting position for breathing – the least work of
breathing muscles
- in the lung is volume equal to functional residual
capacity (FRC = ERV+RV)
Non-relaxation positions
1. inspiratory positions
- during inspiration, when inspiratory muscles
are contracted
2. expiratory positions
- during expiration, when expiratory muscles
are contracted
- inspiratory and expiratory position are a
result of respiratory muscle activity
(contraction)
• Inspiration
- starting from relaxation position is active (quiet respiration)
- activity = contraction of inspiratory muscles
• Expiration
- above relaxation position is passive (quiet respiration)
- relaxation of inspiratory muscles
• Expiration
- starting from relaxation position is active (forced expiration)
- activity = contraction of expiratory muscles
• Inspiration
- up to relaxation position is passive (forced breathing)
- relaxation of expiratory muscles
FRC
Relaxation position of the chest
- respiratory muscles (inspiratory and expiratory) are relaxed
- pressure of the air in the lungs = atmospheric pressure
- volume in the lungs = functional residual capacity (FRC)
Pneumothorax
• „a hole“ in the pleura
– due to injury of chest wall, lung disease, etc.
• the intrapleural cavity communicates with the atmosphere
• air enters the intrapleural space
• an increase of the intrapleural pressure
• lack of underpressure, that prevents the collapse of lungs – the lung collapses
• decreased effectiveness of breathing – the lung fails to expand
Pressures in the respiratory system
Intrapleural pressure – quiet breathing
• beginning of inspiration: - 0,5 kPa
• beginning of expiration: - 1,0 kPa
Intrapleural pressure - forceful breathing
• end of inspiration – more negative values
• end of expiration – may be a positive
beginning beginning
of inspiration of expiration
0
-1
0
0,5
0
Intrapulmonary (alveolar) pressure
• inspiration – negative values
a) at the beginning of inspiration – chest expands, decrease of the intrapulmonary pressure
b) later during inspiration - air moves into the lungs – pressure progressively increases (from negative values to zero value)
• expiration – positive values
c ) at the beginning of expiration – chest volume reduces, increase in the intrapulmonary pressure
d) later during expiration - air moves out of lungs – progressive decrease pressure (from positive values to zero value)
Volume of air in the lungs
- increase during inspiration, decrease during expiration
inspiration exspiration
ab
c
d
LUNG VOLUMES AND CAPACITIES
- the most common pulmonary function test
- the patient is breathing into a spirometer - he follows the doctor´s instructions how to
breathe: quiet breathing, maximum inspiration, hold the breath, ....
- a record is obtained and evaluated (manually or by a computer)
The functional lung examination (spirometry)
Pulmonary volumes
• tidal volume (TV, VT) - 500 ml–volume of normal inspiration (or expiration)
• expiratory reserve volume (ERV) - 1000 ml– largest additional volume that can be forcefully
exhaled after tidal expiration
• inspiratory reserve volume (IRV) - 2500 ml– largest volume that can be forcefully inspired over
normal inspiration
• residual volume (RV) 1000 - 2000 ml– the volume of air remaining in the lungs after the
most forceful expiration
- collapse volume CV 500 -1000 ml- minimal volume MV 500 -1000 ml
VC
IRV
ERV
VT
IRV
IC
VT VC TLC
ERV
FRC
RV CV
MV
inspiratory capacity IC = VT + IRVexpiratory capacity EC = VT +ERVvital capacity
VC = VT + ERV + IRV = 4000 ml- maximum volume that can be expired after max. inspiration
VT = 15% VCIRV = 60% VCERV = 25% VC
total lung capacity TLC = VC+ RV - maximal volume of the air in the lungs
functional residual capacity FRC=RV + ERV- the volume in the lungs in relaxation position of the chest- at the after quiet expiration / before next inspiration
Lung capacities
Pulmonary volumes and capacities depend on body size
- greater in large and athletic people than in small and asthenic people
- about 20 to 25 % lower in females than in males
VENTILATION AND ITS CHANGES
Minute lung ventilation V
• tidal volume (VT) 500 ml
– volume of inspired/expired air in quiet breathing
• respiratory rate - frequency of breathing (f)
– number of inspirations in quiet breathing (or expirations)
– usually expressed per minute: 10 – 18/min
(VT)
(f)
the volume of air moved into (or out of) the lungs per minute
in quiet breathing 5 – 9 l/ min
.
Vmin = f x VT
Maximum ventilation (Vmax) – the ventilated volume of air when an individual is
breathing as deeply and as quickly as possible (by maximum forceful respiratory effort)
• e.g. in physical activity
Vent max = frequency max x Volume max
Average values
- max frequency: 40 – 50/min.
- max volume: approx. 4500 ml
- respiratory rate
- (can increase by 30 times)
quiet
forceful
frequencymax
volumemax
.
2. alveolar dead space
- involves alveoli where no gas exchange takes place
- in a healthy human:
- all alveoli serve for gas exchange
- alveolar dead space = 0
- in people with a lung disease - alveoli are malfunctioning
- alveolar dead space > 0 (problem in diffusion or perfusion of alveoli)
- parts of respiratory passageways where no significant gas exchange occurs
between lungs and blood
- the volume of the air in the dead space - VD
1. anatomical dead space – approx. 150 ml
= conductive part of airways
Total (physiological) dead space = anatomical dead space + alveolar dead space
Dead space
• volume of air that reaches alveoli per minute (and serves for the gas exchange
between blood and alveoli)
• it can be calculated as:
alveolar ventilation = alveolar volume x frequency of breathing
= (tidal volume – dead space) x frequency of breathing
Example
tidal volume VT = 500 ml
frequency of breathing f = 12/min
dead space VD = 150 ml
minute ventilation Vmin = VT x f = 500 x 12 = 6000 ml/min
alveolar ventilation VA min = (500 – 150) x 12 = 4200 ml/min
1800 ml/min – remain in dead space
Alveolar ventilation (VA)
- more air is supplied for gas exchange if the inspiratory volume is higher
(increase is less pronounced if the breathing rate gets higher)
VT /ml frequency min. ventilation/ml VD-dead space/ml alveolar ventilation/ml
500 12 6000 150x12=1800 350x12 = 4200
Ventilation can be increased by an increase of
- the inspiratory volume (deeper breathing)
- frequency of breathing (faster breathing)
- both frequency and volume
Question: Does it matter whether there is an
increase in frequency or inspiratory volume?
– alveolar ventilation depends on frequency of breathing and tidal volume
VT /ml frequency min. ventilation/ml VD-dead space/ml Alveolar ventilation/ml
1000 12 12 000 150 x 12=1800 10 200
500 24 12 000 150 x 24=3600 8 400
• eupnea
- easy, free respiration, as is observed normally under resting conditions
- normal frequency 12-18/ min
- normal tidal volume 500 ml
Changes:
1. frequency of breathing
• tachypnea – increased frequency of breathing, rapid breathing
• bradypnea – decreased frequency of breathing, slow breathing
2. volume of an inspiration
• hyperpnea – an increase of tidal volume, deep breathing
• hypopnea – a decrease of tidal volume, shallow breathing
Ventilation and its changes
Hypoventilation
- lower ventilation that does not meet the metabolic needs
- CO2 production is higher than its elimination
- CO2 content in blood is increased – hypercapnia (pCO2 > 6,5 kPa)
- respiratory acidosis may occur
- in blood excess of acids
- pH of blood is lower than 7,36
Hyperventilation
- higher ventilation that exceeds the metabolic requirements
- CO2 is removed by lungs at higher than normal rates
- decrease of CO2 in blood – hypocapnia (pCO2 < 5 kPa)
- may result in respiratory alkalosis
- in blood excess of bases
- pH of blood exceeds 7,44
• forced expiratory volume (FEV)
- maximal forced expiration after a maximal inspiration
(= forced expiration of vital capacity)
- normal duration: max 3 s
• forced expiratory volume per 1s (FEV 1)
- the volume expired in the first second of maximal expiration after a maximal inspiration
- normal value: 80 - 85% of VC
- FEV1 is the most frequently used index for assessing airway obstruction,
bronchoconstriction or bronchodilation
e.g. in asthma the FEV1 is lowered
DIFFUSION OF GASES FROM ALVEOLI INTO BLOOD
Blood supply of the respiratory system
- function - pulmonary circulation
- nutrition - from systemic circulation
1. The pulmonary circulation
– right ventricle
– pulmonary artery
– alveolar capillary network
– pulmonary vein
– left atrium
• carries blood for oxygenation
= perfusion of alveoli
• rich capillary network surrounding alveoli – serves blood oxygenation
Pulmonary circulation
Distribution of blood – not equal
1. influence of hydrostatic pressure– in vertical position - difference between the highest and the lowest
point 30 cm → corresponds to 23 mmHg
– apical parts - BP lower about 15 mmHg than in heart level
– heart level - BP lower about 8 mmHg than in lung bases
2. alveolar pressure– the highest in apical parts - higher than BP → blood flow during
systole only
– heart level - lower (+ higher hydrostatic pressure) - higher blood flow
– base of lungs - the lowest - lower than BP (systolic and diastolic) - all the capillaries are open
Ventilation-perfusion ratio• ideal = 1 (ventilation = perfusion), 0.8 acceptable
Blood supply of the respiratory system
2. The bronchial circulation
• a. bronchialis (branch of aorta) – carries oxygenated blood
• provides oxygen and nutrients to the respiratory passageways and lungs
- the atmosphere exerts atmospheric pressure- pressure of individual gasses is proportional to their content (%)
Dalton's lawpartial pressure of a gas
= atmospheric pressure x percent of the gas
e.g. if the atmospheric pressure is 100 kPa
O2 content in atmosphere 21% partial pressure of O2 = 100 x 0,21=21 (kPa)
CO2 content in atmosphere 0,04 % partial pressure of CO2=100 x 0,0004=0,04 (kPa)
Partial pressures of the respiratory gases
N2 O2
Composition of atmosphere (inspired air):
N2 78 %
O2 21 %
CO2 0,04 %
H2O vapour 0,5% (non constant component)
atmosphere
CO2
Importance?
• physically dissolved respiratory gases in the blood exert partial pressure
Diffusion - in partial pressure gradient (pO2 and pCO2)
https://www.boundless.com/biology/textbooks/boundless-biology-textbook/the-respiratory-system-39/gas-exchange-across-respiratory-surfaces-220/basic-principles-of-gas-exchange-833-12078/
Composition of alveolar air
inspired air (= atmospheric) → alveoli
But, alveolar air does not have the same concentrations of gases as atmospheric air.
1. the inspired air is mixed with the air from previous expiration = the alveolar air is only partially replaced by atmospheric air with each breath
2. in alveoli - oxygen is constantly diffusing into the blood from the alveolar air + carbon dioxide is constantly diffusing from the blood into the alveoli
3. dry atmospheric air that enters the respiratory passages is humidified even before it reaches the alveoli
Composition of the expired air
alveoli → expired air
But, the composition is not equal:
• the expired air is mixed with the air from previous inspiration
• is changed during expiration
from: Guyton textbook of medical physiology
Atmospheric air
O2 - 21%
CO2 - 0.04%
Alveolus
O2 - 14% 13.3kPa
CO2 - 5.6% 5.3 kPa
Expiration
O2 - 16.3%
CO2 - 3.8%
venous blood in pulmonary artery
O2 - 5.3kPa
CO2 - 6.1 kPa
arterial blood in pulmonary veins
O2 - 12.6 kPa
CO2 - 5.3 kPa
Diffusion of gasses – depends on
1. the pressure gradient of the respiratory gasses (difference of partial pressures in the
blood and alveoli)
– O2: 13,3 – 5,3 =8 (kPa)
– CO2: 6,1 – 5,3 = 0,8 (kPa)
2. thickness of the respiratory
(alveolocapillary) membrane
(0,6 – 0,8 mm)
1. alveolar epithelium (+ surfactant)
2. basement membrane
3. capillary endothelial membrane
http://www.hakeem-sy.com/main/files/Respiratory-membrane--colored2_0.jpg
Diffusion of gasses – depends on
3. diffusion area = the surface of the respiratory membrane (adults – 70 m2)
– decrease to 1/3 – gas exchange is impaired in rest
– exercise – even a small decrease can be detrimental
4. diffusion coefficient – depends on solubility and molecular weight of gas
– CO2 diffuses about 20 times as rapidly as O2
The respiratory membrane’s diffusing capacity
- is the volume of a gas that will diffuse through the membrane each minute for a
partial pressure difference of 1 mmHg (0,133 kPa)
= the ability of the respiratory membrane to exchange a gas between the alveoli
and the pulmonary blood
- it is affected by all factors mentioned above
- diffusing capacity for CO2 is 20x higher than for O2 (21 ml, 400 ml at rest)
Alveolar surface tensionSurfactant
Alveoli - water / air interface
• inside - air
• outside – interstitial fluid and blood
• the water molecules on the surface of the water have a
strong attraction for one another (drop of water)
• as a result, the water surface tends to contract
• surface tension - force caused by water molecules on
air/water interface
• due to surface tension alveoli tend to collapse and to
force air out
http://www.sciencehq.com/chemistry/surface-tension.html
Inspiration
• diameter of alveoli increases
Expiration
• diameter of alveoli decreases
i.e.
• Increased tendency of alveoli to collapse
• in case of a collapse a higher breathing effort
would be needed to expand the alveoli
Law of Laplace-the tendency of alveoli to collapse is
- directly related to the surface tension- inversely related to the alveolar diameter
-i.e.- objects with high surface tension and small diameter tend to collapse
P =____2T
r
P – collapsing pressure of alveolusT – surface tensionr – diameter of alveoli
http://clinicalgate.com/surfactant-agents/
• a substance that covers alveoli in thin monolayer
• reduces surface tension
• prevents collapse of alveoli
• produced and re-uptaken by type II pneumocytes
• a complex mixture of lipids and protein
(mainly dipalmitoylphosphatidylcholine)
Surfactant
http://casopis.vesmir.cz/files/obr/nazev/1996_630_03/type/html
Inspiration
• diameter of alveoli increases
• molecules of surfactant get more apart
• surface tension increases
Expiration
• diameter of alveoli increases
• molecules of surfactant get closer to
each other
• surface tension decreases
- decreased diameter of the alveoli (expiration)
- more molecules of surfactant / surface area
- more powerful effect of surfactant,
- i.e. lower surface tension,
- i.e. lower tendency to collapse
Effects of surfactant
1. alveoli do not collapse in expiration
2. this reduces the effort required by the respiratory muscles to expand the lungs
3. smaller alveoli do not empty into larger one
Expansion of lungs at birth
• at birth – alveoli are kept collapsed and are filled by the amniotic fluid
• the first breath of a newborn: 3-7 kPa of negative inspiratory pressure (in normal breathing:
-1,0 kPa) is required to open the alveoli and inflate the
• the surfactant becomes spread in alveoli after the 1st breath
• once the alveoli are open, further respiration is effected with relatively weak changes in
intrapleural pressure (normal values)
Respiratory distress syndrome (RDS)
• a condition when lungs of a newborn baby tend to collapse after each expiration
• extreme effort is required for inspiration
• often due to insufficient surfactant production
• mostly a problem of pre-term babies
- production of surfactant starts in last 1-3 months of gestation
- if there is risk of preterm birth, the mother is treated with corticoids that trigger production of
surfactant
Lung compliance
• the extent to which the lungs will expand for each
unit increase in pressure
= how easy it is to inflate the lungs
• normal values + 0,1 kPa → + 200 ml
http://web.carteret.edu/keoughp/LFreshwater/CPAP/Ventilation/ventilation_class_notes.htm
Lung compliance
• depends on:
– elasticity of lung tissue (the ability of the lung to recoil after it has been inflated) –
inverse relation
• normal lungs: balance between compliance and elasticity
– higher – e.g. in emphysema – loss of alveoli
(loss of tissue) - results in difficulty to resume the shape of the lung during
expiration
– lowered – e.g. in fibrosis – stiffness of the lung - results in difficulty to expand
the lung during inspiration
http://web.carteret.edu/keoughp/LFreshwater/CPAP/Ventilation/ventilation_class_notes.htm
Static compliance
• the curve of relaxation pressures
Dynamic compliance
TRANSPORT OF O2 IN THE BLOOD
1/ Physically dissolved O2
• the amount depends on the partial pressure of O2 in lungs
• 3 ml /l of blood – under normal pressure conditions
(more in hyperbaric chambers)– Henry's law - the amount of dissolved gas in a liquid is proportional to its partial pressure above the liquid
• it exerts the partial pressure of O2 in blood
2/ Chemically bound O2
• bound to haemoglobin (oxygenated Hb) – attached to Fe2+
• fully saturated 1 g hemoglobin – carries 1,34 mL O2 (Hüfner number)
• oxygen-carrying capacity (ml O2/l blood) = Hüfner number x Hb concentration (g/l)
Oxygen haemoglobin saturation = % of oxygenated Hb from total Hb
Normal values
1. arterial blood 97-100% (95%)
2. venous blood 75%
▪ amount (%) of oxygen attached to hemoglobin
(saturation of Hb) depends on the partial
pressure of oxygen
Oxygen – hemoglobin
association-dissociation curve
(O2 equilibrium curve)
▪ relates oxygen partial pressure in blood and
hemoglobin saturation
▪ the higher pO2, the more O2 is bound to Hb
▪ the curve has sigmoidal shape
▪ at the beginning –slow increase (the first
molecule of O2 binds with difficulties, later
change in spatial conformation of Hb - easier
combination)
▪ then sharp increase - i.e. in rather low pO2 is
blood relatively well saturated with O2
Oxygen equilibrium curve
- flat in higher pO2, i.e. rather high saturation within a broad range of pressures
Normal values
▪ arterial blood (A)
▪ pO2 12-13,3 kPa (90-100 mm Hg)
▪ saturation 95% (100%)
▪ venous blood (V)
▪ pO2 5,3 kPa (40 mm Hg)
▪ saturation 75%
▪ arteriovenous (AV) difference – ca.20%
▪ during physical activity▪ increase in AV difference – up to 50%
▪ high altitudes
▪ low pO2
▪ 6 000 m: 4,5 kPa = 34 mm Hg
▪ therefore lower Hb saturation
▪ as a compensation the Er count is rising
http://www.physiologyweb.com/figures/physiology_graph_sLCVoxW1Ww7uMYapMyDLnHYZN5gCKV8v_oxyhemoglobin_dissociation_curve.html
Factors that affect combination of O2 and Hb
i.e. affect the affinity of Hb to O2
i.e. affect the oxygen equilibrium curve:
1. pCO2
2. pH
3. temperature
4. content of 2,3 biphosphoglycerate in Ery(2,3-BPG – product of Ery metabolism)
Oxygen equilibrium curve
effect of pH changes
Affinity of Hb to O2 is decreased
=O2 is more easily released from the bound to Hb
pCO2*
pH
temperature
2,3 DPG
= shift to right and down (e.g. in tissues)
Affinity of Hb to O2 is increased
= O2 is released from bound with Hb less easily
pCO2
pH
temperature
2,3 DPG
= shift to left and up (e.g. in the lungs)
* Bohr effect: increasing concentration of CO2 reduces the oxygen affinity of Hb
TRANSPORT OF CO2 IN THE BLOOD
CO2 - main product of metabolism (98%)
- diffuses from tissues into blood, then transported as:
1. Physically dissolved CO2
- arterial blood 30 ml, venous 35 ml/L (5 %)
2. Chemically bound (15-20 %)
- to hemoglobin – carbaminohemoglobin
- to plasma proteins - carbaminoproteins
- CO2 bound to hemoglobin – decreases the affinity to O2 (Bohr effect)
- and vice versa – Haldane effect
- lungs: more O2 lowers the affinity for CO2 (which is released)
- tissues - CO2 produced in tissues binds to hemoglobin – decreases affinity
for O2 (released from hemoglobin)
3. Bicarbonate ions (75-80 %)
- after diffusion into erythrocytes CO2 reacts with water
CO2 + H2O → H2CO3 → H+
+ HCO3-
(catalysed by bicarbonate dehydratase)
- H+
is bound by Hb (Hb buffer)
- HCO3-
diffuses into plasma (and functions as a part of bicarbonate buffer)
(and Cl -from plasma enters erythrocytes, this ion change is referred to as = Hamburger effect)
- in lung the reactions occurs in reverse order
The CO2 equilibrium curve
• shows the dependence of total blood CO2 in
all forms and pCO2
- the higher the blood partial pressure of CO2,
the more CO2 is transported
• CO2 is in an inverse association with pO2:
• less O2 allows more CO2 to load (in tissues)
Normal values of pCO2
normocapnia - arterial blood – 5,3 kPa (40 mm Hg)
- venous blood – 6,1 kPa (45 mm Hg)
hypercapnia – increase of pCO2
hypocapnia – decrease of pCO2
hyperventilation - excessive ventilation causing of pCO2 and of pO2
hypoventilation - excessive ventilation causing of pCO2 and of pO2
- binding of O2 to hemoglobin tends to displace CO2 from the blood into alveoli
(Haldane effect)
- more O2 shifts the curve downwards and to the right
REGULATION OF BREATHING
= REGULATION OF VENTILATION
➢ Ultimate goal of respiration
– to maintain proper concentrations of oxygen, carbon dioxide, and hydrogen ions in the tissue
• adequate ventilation in minimal possible energy consumption
+ ventilation must be adjusted to perfussion
➢ Modulated parameters:
mechanics of breathing + aerodynamics
➢ Components of regulation:
➢ frequency and depth of breathing, reflexes, voluntaryventilation
➢ final efectors: respiratory muscles
Regulation of respiration – the respiratory centre
medulla oblongata and pons – the respiratory center
reciprocal inhibition
expiratory neurons
(ventral respiratory group)
1. inhibit inspiratory neurons
2. cause active expiration
inspiratory neurons
(dorsal and ventral respiratory group)
- their stimulation causes inspiration
- generator of respiratory activity
pneumotaxic centre
-inhibits the apneustic centre (switches-off inspiration)
- affects duration of the inspiration
apneustic centre – stimulates inspiratory neurons
- bursts of action potentials in the respiratory centre
- travel to the respiratory muscles and cause their contraction
Activity of respiratory centre is influenced by
pneumotaxic centre
apneustic centre
respiratory centre
expiratory neuronsinspiratory neurons
cortex (voluntary control of breathing)
subcortical structures (limbic system -
emotions, hypothalamus - temperature)
receptors in respiratory
passageways
(mechano, thermo, chemo)
peripheral and central
chemoreceptors
other
receptors
spinal
cord
respiratory
muscleslung stretch
receptors
muscle spindles
Chemical regulation of respiration
• active already under conditions of normal pO2 a pCO2 (generate action potentials)
• hypoxia and hypercapnia increase stimulation of the receptors that subsequently
stimulate inspiration centre
(via vagus and glossopharyngeus nerves)
• more pronounced stimulation if both hypoxia and hypercapnia occurs
Peripheral chemoreceptors= small islets of sensory cells in
• aorta – glomus aorticum (aortal bodies)• a. carotis – glomus caroticum (carotid bodies)
- well perfused, sensitive to pO2 (! the only O2
sensing locality) and pCO2
K-channels sensitive to O2
- In the presence of O2 –channels openned –hyperpolarisation
- ↓ in O2 – channels closed –stop of K+ outflow -depolarization
Central chemoreceptors
• ventral part of medulla oblongata
• sensitive to changes of H+ concentration
in cerebrospinal fluid
• H+ from blood cannot pass BBB
• CO2 diffuses from blood to cerebrospinal fluid freely and reacts with water
CO2 + H2O → H2CO3 → H+
+ HCO3-
• central chemoreceptors
– indirect and delayed effect (after 20-30 s)
– more powerful than peripheral chemoreceptors (80% of response)
• in very high concentrations of CO2 in inspired air, CO2 has inhibitory effect –decrease of ventilation – death may occur
Stretch receptors in the lungs
• mechanoreceptors – sensitive to stretching, speed of air, etc.
The Hering Breuer reflexes
• Inflation reflex
– passive inflation of air into the lungs – inhibits ventilation
– a reflex triggered to prevent overinflation of the lungs
– inflation stimulates the lung – inflation receptors
– their activity increases (more frequent action potentials that travel via n. vagus to the inspiratory neurons in respiratory center)
– if lung inflation is large - the inspiratory neurons are inhibited (reflex)
– inspiratory muscles relax - expiration starts
• Deflation reflex
– passive deflation of air from the lungs – stimulates inspiration
Voluntary regulation of respiration
• frequency and depth of breathing – can be voluntarily regulated
(action potential travels by tr. corticospinalis, involuntary breathing – tr.
bulbospinalis)
• voluntary apnoea – is eventually broken by autonomous regulatory
mechanism, that stimulate inspiration (chemoreceptors)
• breaking point
– hypoxia pO2 9,3 kPa (in arterial blood)
– hypercapnia pCO2 6,6 kPa (in arterial blood)
Central hypoventilation syndrome = Ondine´s curse
-congenital (acquired) respiratory disorder of automatic breathing
-patient can breathe only voluntarily
-problems during sleep – tracheotomy, mechanical ventilation
Respiration in high altitudes
• high altitudes
• aviation
• with increasing altitude
– atmospheric pressure decreases (not %O2)
– significantly decreases pO2
(atmosph., alveoli, blood)
altitude
(m)
atm. pressure
(mm Hg)
pO2 saturation
(art. blood)
0 760 159 97%
3 300 524 110 90%
6 600 349 73 73%
9 900 225 47 24%
13 200 141 29
16 600 87 18
Acute hypoxia (mountain sickness)
- mainly in not acclimatized people
- 2500 m – first symptoms (10-25% people)
- deeper breathing
- tachycardia
- 3000 - 4000 m (4500 - 50-85%)
- hypocapnia, alcalosis due to hyperventilation
- mental and physical fatigue
- headache, nausea
- euphoria, decreased judgement, memory
- impaired sensory perception
- impaired discrete motor movements
- pulmonary oedema
- 5 500 m – cramps
- 7 000 m – coma, death
Acclimatization to low p02 (after 2-3 weeks)
• increased lung ventilation
– pO2 – stimulates the peripheral chemoreceeptors
– increase of ventilation
– subsequently pCO2 – respiratory alkalosis
– subsequently – an increase in bicarbonate excretion by kidney
– balance of pH reestablished
• increased erythrocyte count
– haemoglobin – increase to 200 g/l
– increased total blood volume by 20-30 %
(thus also the ability to transport O2)
• increased erythrocyte count
The other compensatory mechanisms
1. increase of 2,3 DPG in erythrocytes
– decrease of Hb affinity to oxygen
2. increase in diffusion capacity of the lungs (approx. 3x)
– increased blood flow through capillaries
– expansion of the capillaries
– due to increased inspiratory volume – alveoli expand more in inspiration
– result: larger surface area for gas exchange
3. improved blood flow in peripheral tissues
4. growth of increased numbers of systemic circulatory capillaries
– in the non-pulmonary tissues – angiogenesis
– mainly in active tissues (muscle)
5. cellular acclimatization
• better ability to utilize O2 despite decreased pO2
• the count of mitochondria grows
• increases concentration of enzymes for oxidative reactions
RESPIRATION UNDER WATER
Low depths• usage of snorkel - tube maximally 35 cm long, inner diameter
up to 2 cm (smaller diameter - increase in resistance to airflow → increases the work of breathing)
• increase of VD
Deep diving
1. Increased pressure acts on the chest
2. Compression of inspired gases
3. Effect of high partial pressures of individual gasses on the body
4. Decompression sickness
1. Increased pressure acts on the chest
• atmospheric pressure (0 m) 760 mm Hg ( cca 100 kPa)
• column of seawater 10 m thick
– exerts hydrostatic pressure + 760 mm Hg (+ 100 kPa)
-descend beneath the sea - the pressure around considerably increases
-to keep the lungs from collapsing - air must be supplied at very high pressure to keep them inflated
2. Compression of inspired gases
• Boyle´s law: pressure x volume of gasses = constant
• if the pressure increases, the volume decreases
• inspired air is denser
• higher density of the inspired air – higher resistance in airways – high
effort in breathing
• compression of the atmospheric air is inappropriate for breathing - we
need another mixture of gases
3. Effect of high partial pressures of individual gasses on the body
Nitrogen
• under normal atmospheric pressure – no effects on the human body (about 1 L is dissolved in the body)
• under high pressure – narcotic effect (at 40 m approx. in 1 h)
– similar to the effects of alcohol
– loss of judgement
• 50-60 m: tiredness
• 60-80 m: impaired motor abilities
• more than 80 m: significant deficit of mental and physical abilities
• mechanism of the narcotic effect of nitrogen
– nitrogen is dissolved in fat (membranes, nerves)
– causes abnormal ion conductivity
– decrease in nerve excitability
Oxygen• major increase in the content of physically dissolved O2 in blood
• tissues are exposed to extremely high pO2
• oxygen „intoxication“ – nausea
– muscle twitching
– abnormalities of vision, disorientation
– seizures, coma (in 30-60 min)
faster in physical activity
• mechanism of the adverse oxygen effects
– increased production of free oxygen radicals (superoxide, hydroxyl)
– increased oxidation of membrane lipids
– oxidation of intracellular enzymes – metabolic abnormalities
Carbon dioxide
• diving in depth does not increase pCO2 the in alveoli
• if CO2 is expired into water – no problems occur
• closed system (re-breathing apparatus)
– progressive increase in CO2 content of the inspired air
– at the beginning – stimulatory effect – increased ventilation
– later – suppressed ventilation
– lethargy, narcosis, loss of consciousness
• mechanism of the carbon dioxide effect
– pCO2 over 80 mm Hg – supression of the respiratory centre
– respiratory acidosis – malfunction of the enzymes
4. Decompression sickness
• if a diver has been beneath the sea long enough - large amounts of nitrogen (mainly,
but not exclusively) are dissolved in the body water and in the fat
• when the diver suddenly comes back to the surface of the sea, significant quantities of
nitrogen bubbles can develop in the body (inside the cells, in extracellular space)
• can damage in almost any area of the body
• first, only the smallest vessels are blocked by
minute bubbles
• but as the bubbles coalesce, progressively larger
vessels are affected
• Boyle’s law - increase in volume of the air in
alveoli - rupture of the lungs - gas embolism
• symptoms
– pain in the joints – arms, legs
– nausea, paralysis, loss of consciousness
– embolia of a.pulmonalis: lung oedema, dyspnoea, death
-e.g. Buhlmann tables ZH-L12 -depth 36 m, duration of diving 30 min - decompression9 m – 2 min6m – 5 min3 m – 15 min
Decompression tables
Tank decompression
• tanks with compressed air or breathing mixture
– first stage valve – gas of reduced pressure leaves to
the mask
– demand valve – the demanded volume is released
into the mask
• exhalation into the sea
Helium-Oxygen Mixtures in Deep Dives
-helium replaces nitrogen
-lower narcotic effect
-lower solubility in tissues
-lower density – lower resistance in respiratory passageways
-low O2 content (1%)
-suffcient to supply tissues
-prevents seisures
SCUBA diving
Other functions of the respiratory system
1. Vocalization - larynx = „voice box“
– air moving across vocal cords createsvibrations - speech, laughing, shouting (communication, emotions)
2. Protective function
• prevents foreign material (microbes, dustparticles, etc.) to enter the body through mucosal lining of the respiratory tract
• (e.g. by the ciliary activity, immune cells and molecules)
http://choirly.com/wp-content/uploads/2012/03/vocal-folds.jpg
http://media.gettyimages.com/photos/vocal-cords-the-intensity-of-
voice-sound-depends-on-the-pressure-of-picture-id541323641
3. Maintenance of the acid-base balance • i.e. maintenance of constant pH 7,4 in the body
• by the rate of CO2 removal from the body via the expired air
• (acid base balance is maintained also by the kidney and blood buffer systems)
4. Water Balance• the inhaled air is saturated with water; the water is lost on exhalation
• a minor pathway of water loss in humans
5. Heat Balance• respiration - minor pathway of heat loss in humans
http://i.cbc.ca/1.1549934.1418313236!/httpImage/image.jpg_gen/derivatives/16x9_1180/hi-cold-
breath-03881746.jpg
Disorders of the respiratory system
- results of functional lung examination help in diagnosis of:
1. Restrictive lung diseases
• increased lung stiffness
• causing incomplete lung expansion
• volumes are lower
• e.g., fibrosis, alveolar damage, pleural effusion
2. Obstructive lung disorders
• diseases of the lung where the bronchial tubes become narrowed
• making it hard to move air in and especially out of the lung
• prolonged expiration, lower ERV
• normal lung capacity
• e.g. asthma attacks, emphysema, bronchitis