5. respiratory system Flashcards
1
Q
what is the primary function of the respiratory system?
A
gas exchange between air and blood
2
Q
what are some functions apart from gas exchange of the respiratory system?
A
- regulation of blood pH (by changing CO2 levels)
- regulating blood pressure (by producing angiotensin converting enzyme)
- vocalisation
- olfaction (smelling)
- protection of respiratory surfaces from dehydration, temperature changes and pathogens.
3
Q
olfaction
A
the special sense through which smells (or odors) are perceived.
4
Q
what are the two structural divisions of the respiratory tract?
A
- upper respiratory system: nose to pharynx (shared with food)
- lower respiratory system: larynx to lungs (air only)
5
Q
what comprises the upper respiratory system?
A
nose to pharynx
*shared with food
6
Q
what comprises the lower respiratory system?
A
larynx to lungs
*air only
7
Q
what are the 2 physiological divisions of the respiratory tract; based on function?
A
- conducting zone (nose, pharynx, larynx, trachea, bronchi, bronchioles, terminal bronchioles)
- respiratory zone (respiratory bronchioles, alveolar ducts, alveolar sacs, alveoli)
8
Q
which 7 structures comprise the conducting zone of the respiratory tract?
A
- nose
- pharynx
- larynx
- trachea
- bronchi
- bronchioles
- terminal bronchioles
9
Q
which 4 structures comprise the respiratory zone of the respiratory tract?
A
- respiratory bronchioles
- alveolar ducts
- alveolar sacs
- alveoli
10
Q
how has the epithelium adapted throughout different parts of the respiratory tract?
A
a respiratory mucosa, with mucous cells and the mucus escalator, lunes the nasal cavity and the superior portion of the pharynx
a stratified squamous epithelium lines the inferior portions of the pharynx, protecting the epithelium from abrasion and chemical attack
a typical respiratory mucosa lines the conducting portion of the lower respiratory tract
in the finer bronchioles, the epithelium becomes cuboidal
the gas exchange surfaces (respiratory zone) consist of a delicate simple squamous epithelium. here the distance between the air and the blood in adjacent capillaries is generally less than 1µm
11
Q
what type of epithelium lines the nasal cavity and the superior portion of the pharynx?
A
a respiratory mucosa, with mucous cells and the mucus escalator
12
Q
what type of epithelium lines the inferior portions of the pharynx?
A
stratified squamous
a stratified squamous epithelium lines the inferior portions of the pharynx, protecting from abrasion and chemical attack
13
Q
what type of epithelium lines the conducting potion of the lower respiratory tract?
A
a typical mucosa
14
Q
what type of epithelium lines the bronchioles?
A
cuboidal
in the finer bronchioles, the epithelium becomes cuboidal
15
Q
what type of epithelium line the gas exchange surfaces (respiratory zone)?
A
simple squamous
the gas exchange surfaces consist of delicate simple squamous epithelium.
here the distance between the air and the blood in adjacent capillaries is generally less than 1 µm
16
Q
conducting zone epithelium
A
mostly lines by typical respiratory epithelium
= pseudostratified ciliated columnar epithelium with goblet cells
17
Q
goblet cells
A
produce mucus to trap inhaled particles
18
Q
ciliated cells of respiratory epithelium
A
ciliated cells move mucus towards the pharynx (expectorated/swallowed)
19
Q
what is the oropharynx and laryngopharynx lined by?
A
stratified epithelium
- to protect against abrasion from food
20
Q
oropharynx
A
The middle part of the throat, behind the mouth. The oropharynx includes the soft palate (the back muscular part of the roof of the mouth), the side and back walls of the throat, the tonsils, and the back one-third of the tongue.
21
Q
laryngopharynx
A
The laryngopharynx, also referred to as the hypopharynx, is the most caudal portion of the pharynx and is a crucial connection point through which food, water, and air pass. Specifically, it refers to the point at which the pharynx divides anteriorly into the larynx and posteriorly into the oesophagus.
22
Q
what epithelium is the respiratory zone lined by?
A
simple squamous
- minimises distance to capillaries for gas exchange
23
Q
functions of external nose and nasal cavity
A
- warm, moisten, and filter incoming air
- detect olfactory stimuli
- modify speech vibrations; resonance
*air enters through external nares (nostrils) into nasal cavity; nasal cavity continues posteriorly into pharynx
24
Q
external nose of respiratory tract
A
only external part of tract
held open by bones and cartilage
epithelium lined with hair to filter particles from incoming air
25
what divides the nasal cavity into left and right?
midline septum
26
what is the nasal cavity connected to?
paranasal sinuses
27
how many conchae project from lateral wall of nasal cavity?
3
28
nasal conchae
a long, narrow, curled shelf of bone that protrudes into the breathing passage of the nose in humans and various other animals.
29
what is beneath each of the 3 conchae?
a passageway - meatus
30
function of nasal conchae
(turbinates)
- spin air
- remove particles
- increase time for contact with mucosa and olfactory receptors
31
function of meatus
increase surface area for contact with mucosa
32
how do the nasal conchae and meatus warm and humidify air?
lines by respiratory epithelium which humidifies air
large plexus of blood vessels to warm air
33
pharynx
muscular tube that transmits air and food
34
3 anatomical regions of the pharynx
1. nasopharynx; (respiratory epithelium) from nasal cavity to tip of soft palate (uvula)
2. oropharynx; (stratified squamous epithelium) from uvula to epiglottis
3. laryngopharynx; (stratified squamous epithelium from epiglottis to oesophagus)
35
nasopharynx
respiratory epithelium
- from nasal cavity to uvula
36
epithelium of oropharynx
stratified squamous epithelium
- from uvula to epiglottic
37
epithelium of laryngopharynx
stratified squamous epithelium
- from epiglottis to oesophagus
38
uvula
The soft flap of tissue that hangs down at the back of the mouth (at the edge of the soft palate).
it helps prevent food and liquid from going up your nose when you swallow. It also secretes saliva to keep your mouth hydrated.
39
epiglottis
flap of cartilage located in the throat behind the tongue and in front of the larynx.
function is to close over the windpipe (trachea) while you're eating to prevent food entering your airway.
40
what prevents food from entering nasal cavity and larynx?
soft palate and epiglottis
41
function of tonsils
protect against infection
42
larynx
short passageway connecting the pharynx with the trachea
sound produced by air passing across vocal folds (voicebox)
closes off airway when swallowing
lies anterior in neck
43
what forms the larynx/voicebox
formed by 9 cartilages:
- 3 singular (epiglottis, thyroid, cricoid)
- 3 paired (arytenoid, cunieform, corniculate)
44
what are the names of the singular larynx cartilages?
1. epiglottis
2. thyroid
3. cricoid
45
what are the names of the paired larynx cartilages?
1. arytenoid
2. cunieform
3. corniculate
46
which cartilage of the larynx forms the 'adams apple' in males?
thyroid cartilage
47
epiglottis of larynx
leaf shaped cartilage
- forms a lid over the glottis during swallowing
48
cricoid cartilage of larynx
complete ring of cartilage
- landmark for making emergency airway
49
arytenoids cartilage of larynx
influence change in position and tension of vocal folds (true vocal cords)
50
trachea
'windpipe'
~12cm long and 2.5cm wide
lies anterior to oesophagus
proximally continues from circoid cartilage of larynx
C-shaped cartilages keep trachea patent
bifurcates into left and right primary bronchi at carina
lined by respiratory epithelium
51
from which cartilage of the larynx does the trachea continue from?
cricoid cartilage
52
carina
A ridge at the base of the trachea (windpipe) that separates the openings of the right and left main bronchi
53
bifurcation of trachea
left and right primary bronchi separated by carina (last tracheal cartilage)
carina particularly sensitive to mechanical stimuli and stimulated powerful cough reflex
right main bronchus wider and more vertical than left
54
which main bronchus is wider and more vertical?
right
55
what stimulates powerful cough reflex?
carina particularly sensitive to mechanical stimuli and stimulates powerful cough reflex
56
summarise the bronchial tree
1. primary bronchi; left and right, cartilage rings
2. secondary bronchi (lobar); 2 left and 3 right, cartilage plates
3. tertiary bronchi (segmental); one to each segment of the lung, cartilage plates
4. bronchioles; no cartilage, smooth muscle in walls
5. terminal bronchioles (end of conducting zone); simple cuboidal epithelium
6. respiratory bronchioles; start of respiratory zone
57
how many lobes in the left and right lung?
right= 3 lobes
left= 2 lobes
58
how many left and right lobar (secondary) bronchi?
2 left
3 right
59
which parts in the bronchial tree have cartilage plates?
primary bronchi
secondary (lobar) bronchi
tertiary (segmental) bronchi
*The trachea, or windpipe, is supported by C-shaped rings of hyaline cartilage, which help keep the airway open.
60
which bronchi have no cartilage?
bronchioles (smooth muscle in walls)
terminal bronchioles
respiratory bronchioles
61
which bronchi mark the end of the conducting zone of the respiratory tract?
terminal bronchioles
62
what epithelium line the terminal bronchioles?
simple cuboidal epithelium
63
what structure is the start of the respiratory zone?
respiratory bronchioles
64
what are the cluster called that alveoli form?
alveolar sacs
65
what surround alveolar sacs?
vast capillary network
66
how many alveoli does an adult lung have?
~500 million
- form honeycomb structure with very large surface area
67
gas exchange
gas exchange occurs by diffusion across alveolar and capillary walls
= respiratory epithelium
68
simple squamous epithelium type 1 and 2 cells lining alveoli
type I; involved in gas exchange
type II; secrete surfactant
69
surfactant
lines the alveoli to lower surface tension, thereby preventing atelectasis during breathing.
a complex mixture of lipids and proteins that lines the alveoli, the tiny air sacs in the lungs, and reduces surface tension, preventing them from collapsing and making breathing easier
**produced and secreted by alveolar type II cells
70
what are the lungs separated by?
mediastinum
71
pleural membrane of lungs
parietal + visceral
The outer layer is called the parietal pleura and attaches to the chest wall. The inner layer is called the visceral pleura and covers the lungs, blood vessels, nerves, and bronchi.
72
pleural cavities of lungs
potential space between pleural membrane layers containing pleural fluid
73
pleural fluid
prevents friction; causes layers of pleural membrane to adhere to one another
= surface tension
74
components right lung
superior, middle, inferior lobes
oblique, horizontal fissures
75
components of left lung
superior and inferior lobes
oblique fissure
76
oblique and horizontal fissures
horizontal; only in the right lung, separates the right upper and middle lobes
oblique; bilateral structures in both lungs separating the lung lobes
77
hilum of lungs
the wedge-shaped area on the central portion of each lung, located on the medial (middle) aspect of each lung. The hilar region is where the bronchi, arteries, veins, and nerves enter and exit the lungs.
bronchi
pulmonary arteries (deoxygenated blood)
pulmonary veins (oxygenated blood)
lymphatics
nerves
78
what is the thoracic cage comprised of?
- ribs and costal cartilages
- sternum
- thoracic vertebrae T1-T12
79
which vertebrae comprise the thoracic cage?
T1-T12
80
viscera
The soft internal organs of the body, including the lungs, the heart, and the organs of the digestive, excretory, and reproductive systems.
81
function of thoracic cage
- protects viscera
- attachment site of muscles of respiration
- facilitates respiration
82
when does air move into lungs?
when pressure inside lungs (alveolar pressure) is less than atmospheric pressure
83
inspiration vs expiration
inspiration;
->thoracic cavity expands
-> lung expands
-> interpulmonary pressure decreases
= draws air in
expiration
-> decrease in volume of thoracic cavity
-> lung contracts
-> interpulmonary pressure increases
= air expelled
84
inspiration vs expiration energy requirements
inspiration requires energy (muscle contraction)
expiration is passive (elastic recoil)
85
what is the main muscle of respiration?
diaphragm
86
diaphragm
- main muscle of respiration
- large dome-shaped musculotendinous sheet
- separates thorax from abdomen
- supplied by phrenic nerve (C3, 4, 5)
- contraction; descends/flattens increases size of thoracic cavity (inspiration)
- relaxation (expiration) passive
87
what nerve supplies the diaphragm?
phrenic nerve (C3, 4, 5)
88
where are intercostal muscles found?
lie between the ribs (intercostal spaces)
89
what are the 3 intercostal muscle layers?
-> external intercostal
-> internal intercostal
-> innermost intercostal
90
which intercostal muscle layer elevate ribs during inspiration?
external intercostal muscles
91
lateral and anterior increase in volume of thoracic cavity
Rib Cage Movement: During inspiration, the external intercostal muscles contract, lifting the ribs upwards and outwards. This increases the lateral (side-to-side) dimension of the thoracic cavity.
Elevation of the Sternum: The sternum moves upward and forward, increasing the anterior-posterior (front-to-back) diameter of the thoracic cavity. This is primarily due to the action of the scalene muscles, which lift the first two ribs, and the external intercostals, which elevate the other ribs.
92
sternum
or breastbone is a long flat bone located in the central part of the chest. It connects to the ribs via cartilage
93
what are the 2 primary muscles of inhalation?
1. external intercostal muscles
2. diaphragm
94
what are the accessory muscles of inhalation?
1. sternocleidomastoid muscle
2. scalene muscles
3. pectoralis minor muscle
4. serratus anterior muscle
95
what are the accessory muscles of exhalation?
1. internal intercostal muscles
2. transversus thoracis muscle
3. external oblique muscle
4. rectus abdominus
5. internal oblique muscle
96
what is the function of the lungs?
it is the job of the lungs to bring in fresh air rich in oxygen needed to fuel the body
and
to expel the waste gas (CO2) produced from cells in the body
97
what is the movement of air in and out of the lungs coupled to?
movement of air in and out of the lungs is coupled to cellular respiration
98
breathing rate and tidal volume
Breathing Rate: The person is taking approximately 12 breaths per minute, with each breath moving 500 milliliters (ml) of air (this is also referred to as tidal volume).
Tidal Volume (500 ml/breath): The volume of air moved in or out of the lungs with each breath.
99
ventilation rate at rest
At rest, the ventilation rate is about 6 liters per minute (L/min). This means the total volume of air moving in and out of the lungs per minute is 6 liters.
100
PO2 at rest
PO₂ = 100 ± 2 mmHg: This is the partial pressure of oxygen in arterial blood, which is around 100 mmHg at rest. This is a normal value for oxygen saturation in the blood after gas exchange occurs in the lungs.
101
PCO2 at rest
PCO₂ = 40 ± 2 mmHg: This is the partial pressure of carbon dioxide in arterial blood, which is around 40 mmHg at rest. This indicates the balance between CO₂ production and removal, and reflects the efficiency of ventilation and gas exchange.
102
gas exchange of O2 vs CO2
~250 ml/min O2 consumed
~200 ml/min CO2 expired
103
how does breathing maintain blood gas homeostasis?
[O2, CO2 and pH]
changes in PCO2 and PO2 are minimal during exercise, except extreme exercise
ventilation increases during exercise to maintain blood gas homeostasis
104
how is CO2 transported in body?
CO₂ is carried in the blood, mainly as bicarbonate ions, and is transported back to the lungs.
105
how does CO2 lower blood pH?
CO₂ is converted into carbonic acid in the blood, which dissociates into hydrogen ions (H⁺) and bicarbonate ions (HCO₃⁻).
The hydrogen ions (H⁺) are responsible for lowering the blood pH, making it more acidic.
Bicarbonate helps to buffer this acidity, but when too much CO₂ is present, the buffering capacity is overwhelmed, leading to a drop in pH.
This is why high levels of CO₂ lead to respiratory acidosis—a condition where blood pH becomes too acidic due to an excess of CO₂.
106
how does breathing regulate o2 and co2 levels?
The body constantly monitors CO₂ levels in the blood through chemoreceptors in the brain and in blood vessels (especially in the carotid arteries). When CO₂ levels rise (such as after exercise), these sensors signal the respiratory center in the brainstem to increase the rate and depth of breathing.
This rapid breathing helps remove excess CO₂ from the blood, returning its levels to normal.
Similarly, when oxygen levels drop, the body increases breathing to take in more O₂.
107
what is partial pressure?
if a container filled with more than one gas, each gas exerts pressure. The pressure of anyone gas within the container is called its partial pressure.
'sum of the partial pressure (mmHg) or tensions (torr) of a gas must be equal to total pressure'
108
what is the atmospheric pressure at sea level?
at sea level atmospheric pressure
=760mmHg (barometric pressure)
*Pb(760)
=PN2+PO2+PCO2+PAr+other gases
109
how does partial pressure of a gas relate to the fraction of gas in mixture and the barometric pressure?
Pgas=Fgas x Pb
110
how would you calculate the partial pressure of O2 in air if there was 21%?
PO2=0.21 x 760 = 159mmHg/torr
*760=atmospheric/barometric pressure
111
how would you calculate the partial pressure of oxygen in the trachea? (21%O2)
in airways; air warmed and humidified (becomes saturated with water vapour)
water vapour partial pressure at body temperature= 47mmHg
PIO2
= (Bp-PH2O) x FO2
= (760-47) x 0.21
= 150mmHg/torr in trachea
112
partial pressures of alveolar and blood gases
pulmonary artery mixed venous blood
PVO2=40
PVCO2=46
pulmonary veins
PpVO2=102
PpVCO2=40
anatomic dead space
PIO2=150
PICO2=0
PAO2=102
PACO2=40
113
values for the partial pressures of o2 and co2 in mixed venous blood
(pulmonary artery)
PVO2 = 40mmHg
- low level indicated that o2 has been consumed by tissues and blood returning to lungs has relatively low o2 content
PVCO2= 46mmHg
- amount of co2 produced by tissues during metabolism and carried back to lungs for removal
114
values for the partial pressures of o2 and co2 in pulmonary veins
PpVO2= 102mmHg
- blood that has been oxygenated in the lungs; high o2 partial pressure here reflects successful oxygen exchange in lungs
PpVCO2= 40mmHg
- after co2 has been removed in the lungs, the levels are significantly lower than in mixed venous blood
115
values for the partial pressures of o2 and co2 in anatomic dead space
PIO2= 150mmHg
- partial pressure of oxygen in inspired air; o2 level in air before reaching lungs (at sea level under normal atmospheric conditions)
PICO2= 0mmHg
- partial pressure of CO2 in inspired air; ideally the co2 content is close to 0
116
values for the partial pressures of o2 and co2 in alveolar gas
PAO2= 102mmHg
- reflects o2 available for diffusion into blood; since atmospheric pressure is 760mmHg and o2 content is ~21% it is consistent that the alveolar o2 partial pressure is close to the inspired o2 pressure (150mmHg)
PACO2= 40mmHg
- similar to co2 pressure in pulmonary veins; reflects that co2 has diffused out of the blood into the alveoli to be exhaled
117
dead space
anatomic dead space is the part of the respiratory system where gas exchange does not occur, such as the trachea and bronchi. The inspired air (PIO₂ = 150 mmHg and PICO₂ = 0 mmHg) is similar to what you breathe in, but these gases don't participate in the exchange of gases in the lungs.
118
how does ventilation during moderate activity (i.e. walking) compare to during strenuous activity?
moderate:
- increase in ventilation (10L/min), balances o2 intake and co2 removal
strenuous:
- significant increase in ventilation (160L/min) to meet high o2 demands and expel the excess co2
119
what can be said about breathing regulation in terms of differing levels of activity?
breathing regulation is continuous
chemoreceptors in the brain and arteries (carotid) monitor o2, co2 and pH levels, providing feedback to regulate breathing rate and depth
120
what value is ventilation at rest?
~6L/min
121
how does gas exchange compare in moderate vs strenuous exercise?
moderate:
~800ml/min o2 consumed
~750ml/min co2 expired
strenuous:
~5000ml/min 02 consumed
~6000ml/min co2 expired
122
how do the different components of the respiratory tract function in the movement of air into the body?
nasal cavity/paranasal sinuses
- filer, warm, humidify air and detect smells
pharynx
- conducts air to larynx, chamber shared with digestive tract
larynx
- protects opening to trachea and contains vocal cords
trachea
- filters air, traps particles in mucus, cartilages keep airway open
bronchi
- filters air, traps particles in mucus, cartilages keep airway open
lungs
- responsible for air movement through volume changes during movements of ribs and diaphragm, include airways and alveoli
alveoli
- at as sites of gas exchange between air and blood
123
what is the site for an emergency airway?
a hollow needle is inserted into the throat, just below the Adam's apple (thyroid cartilage). This is called a needle cricothyrotomy
124
what type of muscle is the diaphragm?
skeletal muscle (dome shaped)
- major inspiratory muscle
125
how does inspiration and expiration correspond with being active or passive? (quiet breathing)
inspiration= active
expiration= passive
126
in what way is inspiration active?
diaphragm contracts downwards pushing abdominal contents contents outwards; external intercostals pull ribs outwards and upwards
127
how is expiration in quiet breathing passive?
through elastic recoil
128
how does inspiration and expiration correspond with being active or passive? (strenuous breathing)
inspiration= active
expiration= active
129
how does inspiration change between quiet and active breathing?
greater contraction of diaphragm
(1cm in quiet breathing--> up to 10cm during strenuous breathing) and external intercostals.
inspiratory accessory muscles active
e.g. sternocleidomastoid, alae nasi, genioglossus
130
what are some inspiratory accessory muscles?
sternocleidomastoid (elevates sternum)
scalenus-posterior, middle, anterior (elevate and fix upper ribs)
parasternal intercartilaginous muscles (elevate muscles)
alae nasi
genioglossus
131
which accessory inspiratory muscle elevates the sternum?
sternocleidomastoid
132
what are some of the expiratory accessory muscles?
internal intercostals (depress ribs)
abdominal muscles (depress lower ribs, compress abdominal contents)
rectus abdominis
external oblique
internal oblique
transversus abdominis
133
which internal intercostal is not involved in the muscles of expiration?
parasternal intercartilaginous muscles
134
how does expiration compare in quiet vs strenuous breathing?
abdominal muscles (rectus abdominus, interna oblique, external oblique, transversus abdominus) active
internal intercostal muscles oppose external intercostals by pushing ribs down and inwards
135
which abdominal muscles are involved in the active expiration of strenuous breathing?
1. rectus abdominus
2. internal oblique
3. external oblique
4. transversus abdominus
136
what is the alveolar (PA) and barometric (PB) pressure at the beginning of inspiration?
PA=0
PB=0
137
what effect does the contraction of inspiratory muscles have on thoracic volume and pleural pressure?
increases thoracic volume so pleural pressure becomes more negative
*increase in transpulmonary pressure
138
what effect does lung expansion have on alveolar volume and pressure?
alveolar volume increases
alveolar pressure becomes negative (below barometric pressure)
139
what does the negative PA caused by lung expansion and alveolar volume increase cause?
negative alveolar pressure (PA) is below barometric pressure (PB), therefore aur flows into alveoli- from higher to lower pressure.
140
what marks the end of inspiration?
muscles stop contracting and the thorax and alveoli stop expanding
PA=PB (no flow)
141
what happens to the values of pleural and transpulmonary pressure in expiration?
thoracic volume decreases
Ppl and PL values return to pre-inspiration values.
- pleural pressure becomes more +ve
- decrease in transpulmonary pressure
142
what happens to the thorax and lungs during expiration?
thorax and lungs recoil
- elastic recoil pressure
143
what effect does they recoil of the thorax and the lungs have on the air in alveoli?
(elastic recoil pressure)
air in alveoli compressed
144
what effect does the compression of the alveoli during expiration have?
alveolar pressure becomes greater than barometric pressure and air flows out of lungs
145
tidal volume (VT)
amount of air exchanged in a single normal breath
the amount of air that moves in or out of the lungs with each respiratory cycle.
(about same for both males and females- ~500ml)
146
inspiratory reserve volume (IRV)
the amount of air that can be forcibly inhaled after a normal tidal volume
(larger in males than females- 3300ml vs 1900ml- reflecting greater lung capacity)
147
expiratory reserve volume (ERV)
he volume below the tidal end-expiratory level that can be forcefully expired from the lungs
(larger in males due to larger lung volumes- 1000ml vs 700ml)
148
residual volume (RV)
the air that remains in the lungs after maximum forceful expiration. In other words, the air volume cannot be expelled from the lungs, thus causing the alveoli to remain open at all times
(slightly larger in males- 1200ml vs 1100ml)
149
total lung capacity (TLC)
combines all values (RV, ERV, IRV, VT)
6000ml in males
4200ml in females
150
function of upper airways
conduct air to lung
1. humidify (saturate with water)
2. warm (to body temp)
3. filter
*dry air would damage epithelial cells and agitate airways
151
how do the upper airways filter air?
upper airways to bronchioles are lined by pseudo-stratified ciliated, columnar epithelium
inhaled particles stick to mucus; mucus moved towards mouth by beating cilia
152
how does the number, diameter and surface area change throughout the respiratory tree?
airways branch into smaller and more numerous bronchioles until terminating in a group of alveoli.
each division results in an increase in number, a decrease in diameter and an increase in surface area.
153
what forms the anatomic dead space?
conducting airways
- do not participate in gas exchange
154
what is the volume of the conducting airways?
150ml
*30% of average breath
(bronchi containing cartilage and nonrespiratory bronchioles)
155
volume of respiratory airways?
~2500ml
(bronchioles with alveoli where gas exchange occur- from terminal bronchioles to alveoli)
156
how much of an average breath is in the conducting airways?
30%
157
how long are respiratory airways; bronchioles with alveoli- from terminal bronchioles to alveoli?
~5mm
158
what is a respiratory unit?
respiratory unit= gas exchanging unit
basic physiological unit of the lung consisting of respiratory bronchioles, alveolar ducts and alveoli
159
roughly how many alveolar sacs are there in an adult?
~300-400million alveolar sacs
160
shape, diameter and composition of alveoli
shape= polygonal
diameter= ~250µm
composition= type 1 and type 2 epithelial cells
161
type 1 and type 2 epithelial cells of alveoli
type 1:
occupy 97% of surface area of alveoli- primary site of gas exchange
type 2:
(septal cells), occupy 3% of alveolar surface area, produce pulmonary surfactant- reduces surface tension
alveolar macrophages; removal of debris
162
alveolar macrophages
Immune cells that remove debris and pathogens from the alveoli.
These macrophages engulf and digest foreign material (a process known as phagocytosis). They also secrete cytokines and other molecules that help modulate inflammation and immune responses within the lungs. Additionally, after they digest material, they can migrate up to the upper airways and be cleared from the respiratory tract.
163
type 2 epithelium of alveoli
Type II cells are responsible for producing pulmonary surfactant, a substance that reduces surface tension in the alveoli. Pulmonary surfactant allows the alveoli to stay open by preventing the collapse of the alveolar walls, particularly during exhalation.
164
what percentage of alveoli is type 1 vs type 2 epithelium?
type 1= 97%
type 2= 3%
165
what characteristics make alveoli perfectly designed for gas exchange?
1. large surface area (~100m^2)
2. very thin walls (mean 0.5µm)
*good diffusion characteristics
166
how is the surface area of alveoli and the size of the walls?
surface area = ~100m^2
wall= 0.5µm
167
what are the two separate blood supplies to the lungs?
1. pulmonary circulation:
2. bronchial circulation
168
pulmonary circulation
brings deoxygenated blood from heart to lung and oxygenated blood from lung to heart then rest of body
169
bronchial circulation
brings oxygenated blood to lung parenchyma
170
lung parenchyma
lung parenchyma refers to the functional tissue of the lungs, including the alveoli and the small airways, where gas exchange occurs
the lung parenchyma itself requires oxygenated blood
171
lymphatic system role in the lungs
in defence and the removal of lymph fluid
172
what is the total blood volume in the pulmonary circulation? what is this in comparison to the total?
500ml
10% of total
173
how does the blood volume in the alveolar-capillary network differ during rest and exercise?
rest= 75ml
exercise= 150-200ml
174
why does the blood volume in the alveolar-capillary network increase during exercise as compared to at rest?
(from 75ml to 150-200ml)
due to recruitment of new capillaries secondary to an increase in pressure and flow.
175
how do pulmonary arteries compare to the systemic circulation?
thin walled
highly compliant
larger diameter
low resistance
176
hoe is the network described where gas exchange occurs?
gas exchange occurs through dense mesh-like network of capillaries and alveoli.
177
what is the distance between alveoli and red blood cell?
1-2 µm
178
what 3 things does the 1-2 µm between alveoli and red blood cell include?
1. type 1 alveolar epithelial cell
2. capillary endothelia cell
3. basement membrane
179
how quickly can red blood cells pass though capillaries?
in <1s
(sufficient time for co2 and o2 gas exchange)
180
what are the gas gradients of the pulmonary circuit and the systemic circuit?
[gases move down their pressure gradients]
pulmonary:
o2 enters blood - co2 leaves
systemic:
o2 leaves blood - co2 enters
181
is o2 or co2 more diffusible?
co2 is more diffusible
182
does o2 or co2 have a larger pressure gradient?
pressure gradient for o2 is much bigger than for co2
183
how does the partial pressure of o2 compare between alveolar air and venous blood of pulmonary capillaries? comment on pressure gradient
alveolar air PO2: 100mmHg
venous blood PO2: 40mmHg
pressure gradient for oxygen between the alveolar air and venous blood is 60mmHg; this large gradient drives oxygen from the alveoli into the blood
*venous blood returning from body tissues
184
how does the partial pressure of co2 compare between alveolar air and venous blood of pulmonary capillaries? comment on pressure gradient
alveolar air pco2: 40mmHg
venous blood pco2: 46mmHg
pressure gradient for co2 between venous blood and alveolar air is only 6mmHg; although this gradient is smaller compared to o2 it is still sufficient for co2 exchange as co2 is more soluble in plasma and diffuses more easily than o2
185
how does the partial pressure of o2 compare between arterial blood and tissues in systemic capillaries? comment on pressure gradient
arterial blood po2: 100 mmHg
tissues po2: <40 mmHg
pressure gradient for o2 between arterial blood and tissues is greater than 60 mmHg, favouring the diffusion of oxygen from blood to tissues.
*partial pressure of o2 in tissues is low because tissues are consuming o2 and is high in arterial blood because blood is coming from lungs
186
how does the partial pressure of co2 compare between arterial blood and tissues in systemic capillaries? comment on pressure gradient
arterial blood pco2: 40 mmHg
tissues pco2: >46 mmHg
pressure gradient for co2 between tissues and arterial blood is around 6mmHg which is relatively small but sufficient for co2 to diffuse as is diffuses more easily because its more soluble
187
why is the partial pressure of co2 in tissues high (>46mmHg)?
because co2 is a waste product of metabolism
188
how do the diffusion rates of o2 and co2 compare?
Oxygen needs a higher pressure gradient to overcome its lower solubility and to diffuse efficiently.
Carbon dioxide, because it is more soluble, can diffuse more easily even with a smaller gradient
189
how does movement of gas occur throughout the respiratory system?
movement of gas throughout the respiratory system occurs via diffusion
190
what do unique anatomical and physiological properties do respiratory and circulatory systems contain to facilitate gas diffusion?
1. large surface area for gas exchange
2. large partial pressure gradients
3. gases with advantageous diffusion properties
4. specialised mechanisms for transporting o2 and co2 between lungs and tissues
191
in what 2 ways is o2 transported?
1. dissolved
2. bound to haemoglobin (Hb)
192
what percentage of o2 in blood is in the dissolved form?
only a small %
193
what is the amount of dissolved o2 in blood proportional to?
to its partial pressure
194
for each mmHg of po2 how much dissolved o2 is in blood?
each mmHg of po2 there is 0.003ml o2 in blood
195
how does the proportions of dissolved o2 differ in arterial blood?
pao2 = 100mmHg
0.3ml o2/100ml
= 3ml o2/L of blood
196
is transport of o2 in dissolved form adequate for body's requirements?
transport of o2 in dissolved form is NOT adequate for body's requirements, even at rest
197
explain how the transport of o2 in dissolved form is not adequate for body's requirements- even at rest
at rest cardiac output (CO)
= 5L/min
3ml o2/litre of blood x 5
= 15ml/min
*tissue requirements at rest 250ml o2/min
during strenuous exercise CO
= 30L/min
3ml o2/litre of blood x 30 (CO)
= 90ml/min
*tissue requirements may need 3000 ml o2/min
198
what is the major transport molecule for o2 and where is it found?
Haemoglobin (Hb) is the major transport molecule for o2 found in red blood cells
199
what type of compound is a heme group?
iron porhyrin compound
200
what is the structure of haemoglobin?
4x heme groups joined to globin protein
201
what does the globin protein on haemoglobin consist of?
2 alpha chains and 2 beta chains
- polypeptide chains
202
in which state is the iron contains in the heme groups?
reduced ferrous form
(Fe+++)
203
where is the binding site of o2 on haemoglobin?
the reduced ferrous iron (Fe+++)
204
how many haemoglobin molecules/ red blood cell?
280 million Hb molecules / red blood cell
205
how quick is binding and dissociation of o2 with Hb? why is this necessary?
binding and dissociation of o2 with Hb occurs in milliseconds to facilitate transport
- necessary because red blood cells in capillaries for only 1s
206
what does the oxyhaemoglobin dissociation curve illustrate?
curve illustrates relationship between PO2 in blood and number of o2 molecules bound to Hb
a graphical representation of the relationship between the amount of oxygen bound to haemoglobin and the partial pressure of oxygen in the blood.
207
significance of the oxyhaemoglobin dissociation curve
flat portion:
drop in po2 from 100 to 60 mmHg has minimal effect on Hb saturation
steep portion:
large amount of o2 is released from Hb with only a small change in po2 facilitating release into tissues
208
what are the two distinct portions of the oxyhaemoglobin dissociation curve?
1. flat portion (high PO2 range)
2. steep portion (low PO2 range)
209
what is the flat portion of the oxyhaemoglobin dissociation curve?
when po2 is high, (60-100mmHg- po2 range seen in lungs)
a drop in po2 has minimal effect on the Hb saturation.
this means that Hb remains highly saturated with o2 even as the po2 decreases within this range.
this flatness ensures that even if there's a slight drop on o2 availability (such as in high altitudes or mild respiratory issues), Hb will still carry most of the o2, helping to maintain o2 delivery to tissues.
210
what is the steep portion of the oxyhaemoglobin dissociation curve?
occurs at lower po2 levels (20-60mmHg- po2 range seen in tissues)
small changes in po2 lead to significant changes in haemoglobin saturation.
steep part is crucial because it facilitates the release of o2 from Hb into tissues.
when the po2 drops slightly in this range, Hb readily unloads o2- ensuing tissues receive the o2 they need (particularly in areas with higher metabolic demand)
211
how does the oxyhaemoglobin dissociation curve explain the efficiency of o2 delivery?
allows for efficient o2 loading in the lungs (at high po2) and efficient o2 unloading in tissues (at low po2)
212
buffering effect of oxyhaemoglobin dissociation curve
the flat portion buffers against moderate reductions in po2 (e.g. during ascent to high altitudes) by ensuring that haemoglobin is still saturated
213
tissue oxygenation of oxyhaemoglobin dissociation curve
steep portion maximised o2 delivery to tissues- even with small changes in po2; especially important in areas with high metabolic activity (e.g. exercising muscles)
214
oxygen saturation of haemoglobin
o2 saturation (SaO2) refers to the amount of o2 bound to Hb relative to maximal amount that can bind
215
how many o2 atom can each Hb molecule bind?
up to 4
216
what would 100% saturation of Hb be?
all heme groups of Hb molecules fully saturated with o2
217
what is the total o2 capacity / litre of blood?
211ml o2/ 1L of blood
1Hb combines with 1.39ml o2
~150g Hb/L blood
150 x 1.39 = 208 ml o2/L blood
+ ~3ml/L (dissolved component)
= 211ml/L
218
what is used in clinic to measure o2 saturation measured?
pulse oximeters
219
how does a pulse oximeter measure o2 saturation?
measures ratio of absorption of red and infrared light by oxyHb and deoxyHb
220
what is the ratio of expired co2 to o2 uptake called?
respiratory exchange ratio
221
in normal healthy conditions how many ml/min of co2 is produced?
200mlco2/min produced
222
how many molecules of co2 is expired by lungs for every 100 o2 molecules entering in normal healthy conditions?
80
(80 molecules co2 expired by lungs for every 100 molecules of o2 entering)
223
in which 3 forms and what percentage is co2 carried in blood?
1. 7% dissolved
2. 23% bound to Hb
3. 70% converted to bicarbonate
224
in what form is the majority of co2 carried in the blood?
70% is converted to bicarbonate
225
what is the co2 to hco3- reaction pathway?
h2o + co2 <-> h2co3 <-> h+ + hco3-
226
what is the intermediate in the co2 to bicarbonate ion pathway?
carbonic acid; h2co3
227
what does the co2 to hco3- pathway play a critical role in regulating?
in regulation of h+ ions and in maintaining acid-base balance in body
228
what determines the direction and speed of the carbon dioxide to bicarbonate reaction pathway?
concentration gradients
229
what are chemoreceptors?
sensory receptors that detect chemical changes in the surrounding environment
230
what do chemoreceptors detect in the respiratory system?
detect changes in po2, pco2 and pH in blood
231
hypoxic environment
low o2 environment
(high altitude)
232
hypercapnic environment
high co2 environment
233
what are peripheral chemoreceptors?
small, highly vascularised bodies in region of aortic arch and carotid sinuses
234
how is information sent from peripheral chemoreceptors to the NTS?
via glossopharyngeal and vagus nerves
234
NTS
nucleus tractus solitarius
(nucleus in brainstem)
235
baroreceptors vs chemoreceptors
The chemoreceptors are sensitive to acidosis and produce vasoconstriction of the vessels. Stimulation of the chemoreceptors also produces tachycardia. The baroreceptors are pressure receptors that respond to changes in the arterial wall due to fluctuations in blood pressure.
236
what do peripheral chemoreceptors respond to?
decreases in PO2 (hypoxia)
237
what are the stages that occur within body involving the chemoreceptors in a hypoxic environment?
1. reduction in arterial po2
2. peripheral chemoreceptors stimulated
3. neural signals sent from carotid and aortic bodies to NTS in brainstem
4. ventilation increases to restore po2 levels
238
what is the ventilatory response to hypoxia?
the body's response to increase breathing when o2 levels drop
239
at what po2 level does the ventilatory response to hypoxia have an effect?
below 60mmHg
(hyperventilation)
240
how does the body response to hypoxia above ~60mmHg?
as po2 in blood decreases there is little/no change in rate of ventilation until po2 falls below ~60mmHg
suggests that body is relatively insensitive to small reduction in o2 levels
241
what is the po2 threshold for hyperventilation?
once po2 drops below ~60mmHg, the body responds with progressive hyperventilation
due to the activation of chemoreceptors in the carotid and aortic bodies which detect the low o2 levels in blood
242
role of chemoreceptors
carotid bodies (located in carotid arteries) and aortic bodies (located near aorta) are key in detecting changes in blood o2 levels.
these chemoreceptors stimulate the respiratory centres in the brain to increase ventilation when po2 drops
243
po2's role in moment-moment breathing control
po2 does not play a large role in moment-moment control of normal breathing (when po2 levels are within normal range)
body primarily regulates ventilation based on levels of co2 and pH in blood
hypercapnia (high co2) and acidosis (low pH) are more important for maintaining breathing under normal/non-hypoxic conditions
244
what are central chemoreceptors?
central chemoreceptors are clusters of neurones in the brainstem that are activated when pco2 is increased (hypercapnia) or pH decreased
245
what are the stages which take place in body when there is an increase in arterial pco2?
1. increase in arterial pco2
2. central chemoreceptors (brainstem neurones) stimulated
3. signals processed and information passed on to neuronal clusters in brainstem involved in generating breathing
4. ventilation increases to restore pco2 levels
246
how does ventilatory response to hypercapnia compare to that of hypoxia?
very small changes in pco2 have large effects on ventilation unlike o2
247
where does the hypercapnic response originate?
hypercapnic response originates in central chemoreceptors in brainstem
248
what plays major role in moment to moment control of breathing?
hypercapnic response (pco2)
249
what are mechanoreceptors?
sensory receptors that detect changes in pressure, movement and touch.
250
what do mechanoreceptors detect in the respiratory system?
movement of lung and chest wall
e.g. during inspiration mechanoreceptors detect inflation of lungs and movement of chest outwards
251
what other things to mechanoreceptors in respiratory system respond to?
mechanoreceptors in respiratory system don't just respond to changes in the lungs and chest wall during breathing (like inflation during inspiration).
they also integrate information about other body movement,
e.g. posture and locomotion
252
what are the stages of respiratory mechanoreceptor activation?
1. inflation of lungs activates mechanoreceptors
2. neural signals sent via vagus verve to NTS (in medulla oblongnata) in brainstem
3. ventilation adjusted accordingly
253
via what nerve are respiratory mechanoreceptor signals sent to NTS in brainstem?
vagus nerve
254
what activates respiratory mechanoreceptors?
inflation of lungs
255
where is the information from mechanoreceptors and chemoreceptors received?
NTS
nucleus tractus solitarius in brainstem
* series of neurons whose cell bodies form a roughly vertical column of grey matter in the medulla oblongata of the brainstem
256
what type of neurones process the respiratory information from mechanoreceptors and chemoreceptors in the brainstem?
respiratory neurones
257
what generates the rhythm of breathing?
the cluster of respiratory neurones in brainstem
*the rhythmic signal is sent to the respiratory muscles
258
4th ventricle in brainstem
the fourth ventricle is a diamond-shaped cavity located dorsal to the pons and upper medulla oblongata and anterior to the cerebellum
receives CSF from the midbrain aqueduct (of Sylvius) and drains this fluid to the subarachnoid space via its median (Magendie) and lateral foramina (Luschka).
259
when are inspiratory vs expiratory neurones active?
inspiratory neurones
= active during inspiration
expiratory neurones
= active during expiration
260
what are rhythm generating neurones?
cluster of respiratory neurones in brainstem generate rhythm of breathing
the rhythmic signal is sent to the respiratory muscles
inspiratory neurones: active during inspiration
expiratory neurones: active during expiration
261
what muscles do the respiratory muscles activate?
intercostal muscles
diaphragm
262
what are the 3 respiratory groups in brainstem?
1. pontine respiratory group
2. ventral respiratory group (rhythm generating neurones)
3. dorsal respiratory group (NTS)
263
which respiratory group is the rhythm generating neurones?
ventral
*"respiratory group" refers to distinct groups of neurons within the brainstem that control breathing. Specifically, these groups are involved in regulating the rhythm, depth, and rate of respiration.
264
which respiratory group is the NTS?
dorsal
*The Nucleus Tractus Solitarius (NTS) is a key part of the respiratory system, specifically within the dorsal respiratory group (DRG)
265
at what point does the phrenic nerve exit the spinal cord?
at cervical spinal cord level 3-5
C3-C5
*innervates diaphragm
266
which nerve innervates the diaphragm?
phrenic nerve
267
which nerves innervate the intercostal muscles?
nerves exiting thoracic spinal cord
268
output from brainstem to respiratory muscles
- brainstem neurones produce rhythmic output
- rhythmic neural signals sent to spinal cord
- phrenic nerve exits spinal cord at cervical spinal cord level 3-5
- phrenic nerve innervates diaphragm
- nerve exiting thoracic spinal cord innervate intercostal muscles
269
what shape is the oxyhaemoglobin dissociation curve?
s-shaped
(>60mmHg an increase/decrease in PO2 has minimal effect on Hb saturation)
* steep slope at low partial pressures of oxygen and a more gradual slope at higher partial pressures.
270
function of the lungs
to oxygenate blood
271
how do the lungs oxygenate blood?
by brining inspired air into close contact with o2-poor blood in the pulmonary capillaries
(promote efficient gas exchange)
272
function of trachea and bronchia
trachea:
conducts inhaled air into the lungs
bronchia:
distribute air within the lungs
273
control of airway function
centres in the brain and CNS as well as in the spinal cord regulate afferent and efferent pathways to coordinate lung function
this implies regulation of musculature, blood vessels and glands of the airways
274
afferent vs efferent neurones
Afferent neurons carry information from sensory receptors found all over the body towards the central nervous system, whereas efferent neurons carry motor information away from the central nervous system to the muscles and glands of the body in order to initiate an action
275
afferent nerves (respiratory)
send information to the CNS; mostly sensory stimuli from lungs to CNS
276
efferent nerves
receive information from CNS; regulation of muscle contraction, glands secretion
277
what do afferent nerves in the airways regulate?
serve to regulate breathing pattern, cough, and airway autonomic neural tone
278
what do chemoreceptors and nocireceptors respond to?
1. exogeneous chemicals
2. inflammatory mediators
3. physical stimuli (e.g. cold air)
279
nociceptors
Specialized peripheral sensory neurons known as nociceptors alert us to potentially damaging stimuli at the skin by detecting extremes in temperature and pressure and injury-related chemicals, and transducing these stimuli into long-ranging electrical signals that are relayed to higher brain centers.
280
where do efferent nerves receive information from?
from CNS
281
what do parasympathetic efferent nerves control in respiratory system?
1. bronchocontriction (upper airways)
2. mucus secretion (acetylcholine on M3 receptor)
282
what is the acetylcholine receptor?
M3/muscarinic 3 receptor
283
mucus secretion via efferent nerves
Parasympathetic (Cholinergic): Acetylcholine from the vagus nerve acts on M3 muscarinic receptors on epithelial cells and submucosal glands, stimulating mucus secretion. It also causes bronchoconstriction via smooth muscle contraction.
Sympathetic (Noradrenergic): Norepinephrine acts on β2 adrenergic receptors, causing bronchodilation and inhibiting mucus secretion.
284
cholinergic
relating to or denoting nerve cells in which acetylcholine acts as a neurotransmitter.
285
what do the sympathetic efferent nerves innervate in respiratory system?
blood vessels and glands
286
branches of autonomic nervous system
sympathetic
parasympathetic
287
how does the autonomic nervous system play a significant role in regulating the respiratory system?
parasympathetic nervous system promotes bronchoconstriction and mucus secretion via muscarinic receptors (primarily M3)
sympathetic nervous system causes bronchodilation and reduces mucus secretion via β2-adrenergic receptors
288
parasympathetic control of respiratory system
parasympathetic nervous system is primarily mediated by the vagus nerve, which releases acetylcholine (ACh) as its neurotransmitter
ACh acts on muscarinic receptors (mainly M3) in bronchial smooth muscle glands
when acetylcholine binds to the M3 receptors on bronchial smooth muscle, it causes bronchoconstriction, leading to the narrowing of the airways
acetylcholine also stimulates goblet cells and submucosal glands, increasing the production of mucus in the respiratory tract, which helps in trapping foreign particles
289
what can efferent signals be?
sympathetic and parasympathetic divisions of the autonomic nervous system (ANS) are part of the efferent pathway because they carry signals away from the central nervous system (CNS) to target organs, muscles, or glands.
290
what is the primary nerve involved in parasympathetic NS of respiratory system
The parasympathetic nervous system is primarily mediated by the vagus nerve, which releases acetylcholine (ACh) as its neurotransmitter.
291
which neurotransmitter is related to parasympathetic nervous system
acetylcholine
292
which receptors does ACh act on? respiratory system
ACh acts on muscarinic receptors, mainly M3 receptors, in bronchial smooth muscle and glands.
These receptors, primarily M3, are involved in smooth muscle contraction and mucus secretion. M1 receptors also play a role in neurotransmission in the ganglia.
293
effects of parasympathetic control of respiratory system
When acetylcholine binds to the M3 receptors on bronchial smooth muscle, it causes bronchoconstriction, leading to the narrowing of the airways.
Acetylcholine also stimulates goblet cells and submucosal glands, increasing the production of mucus in the respiratory tract, which helps in trapping foreign particles.
294
cholinergic vs adrenergic
Adrenergic Receptors binds catecholamines namely epinephrine and norepinephrine. Cholinergic Receptors binds to acetylcholine
295
norepinephrine vs epinephrin
Norepinephrine is continuously released into circulation at low levels while epinephrine is only released during times of stress. Norepinephrine is also known as noradrenaline. It is both a hormone and the most common neurotransmitter of the sympathetic nervous system. Epinephrine is also known as adrenaline.
296
sympathetic nervous system control of respiratory system
primary nerve= sympathetic nerve (adrenergic)
mainly uses noradrenaline (norepinephrine) as its neurotransmitter which acts on adrenergic receptors.
sympathetic nerves do not directly innervate bronchial smooth muscle but influence blood vessels and glands in the respiratory system.
In the airways, noradrenaline binds to beta-2 adrenergic receptors (β2 receptors) on the bronchial smooth muscle, leading to bronchodilation, which relaxes the smooth muscle and opens up the airways.
Sympathetic stimulation leads to a decrease in mucus secretion in the respiratory tract, as it acts to prepare the body for the “fight or flight” response, where rapid breathing and less obstruction to airflow are beneficial.
The sympathetic system generally leads to relaxation of the airways (bronchodilation) and decreased mucus production, which facilitates increased airflow and oxygen delivery to tissues during times of physical exertion or stress.
Beta-2 adrenergic receptors (β2 receptors): These receptors are present in bronchial smooth muscle, and their activation causes bronchodilation.
Sympathetic stimulation also influences alpha-1 adrenergic receptors on blood vessels in the respiratory tract, leading to vasoconstriction and reducing blood flow to non-essential areas during stress.
297
primary nerve of sympathetic nervous system
sympathetic nerve
298
receptors involved in sympathetic control of respiratory system
Beta-2 adrenergic receptors (β2 receptors): These receptors are present in bronchial smooth muscle, and their activation causes bronchodilation.
Sympathetic stimulation also influences alpha-1 adrenergic receptors on blood vessels in the respiratory tract, leading to vasoconstriction and reducing blood flow to non-essential areas during stress.
299
sympathetic effects on respiratory system
1. Bronchodilation:
In the airways, noradrenaline binds to beta-2 adrenergic receptors (β2 receptors) on the bronchial smooth muscle, leading to bronchodilation, which relaxes the smooth muscle and opens up the airways.
2. Decreased Mucus Secretion:
Sympathetic stimulation leads to a decrease in mucus secretion in the respiratory tract, as it acts to prepare the body for the “fight or flight” response, where rapid breathing and less obstruction to airflow are beneficial.
300
what do sympathetic nerves of respiratory system innervate?
Sympathetic nerves do not directly innervate bronchial smooth muscle but influence blood vessels and glands in the respiratory system
301
parasympathetic and sympathetic effects on the respiratory system
The sympathetic system generally leads to relaxation of the airways (bronchodilation) and decreased mucus production, which facilitates increased airflow and oxygen delivery to tissues during times of physical exertion or stress.
The parasympathetic system, therefore, generally leads to constriction of the airways (bronchoconstriction) and increased mucus production as part of the body's defense mechanism against irritants and pathogens.
302
inhibitory vs excitatory NANC
inhibitory:
nerves relax airway smooth muscle (NO and VIP)
excitatory:
nerves cause neuro-inflammation due to tachykinin release (substance P and neurokinin A)
303
NANC
non-adrenergic non-cholinergic (nerves)
304
inhibitory NANC nerves
responsible for relaxing airway smooth muscle
305
what neurotransmitters are in the inhibitory NANC pathway?
1. Nitric oxide (NO)
2. Vasoactive intestinal peptide (VIP)
306
nitric oxide (NO)
involved in the inhibitory NANC pathway
acts as a vasodilator and bronchodilator; helps relax smooth muscle in the airways, promoting bronchodilation
307
vasoactive intestinal peptide (VIP)
involved in inhibitory NANC pathway
contributes to smooth muscle relaxation, playing a role in bronchodilation.
released by non-adrenergic nerves and can cause relaxation of airway smooth muscle through VIP receptors.
308
excitatory NANC nerves
involved in promoting bronchoconstriction and can contribute to neuro-inflammation
309
which neurotransmitters are involved in the excitatory NANC pathways?
1. substance P
2. neurokinin A
310
substance P and neurokinin A
involved in excitatory NANC pathways
tachykinins; family of neuropeptides that cause smooth muscle contraction (contributing to bronchoconstriction)
tachykinins also play a role in inflammation and pain sensation in the airways, contributing to neuro-inflammation
311
tachykinins
(substance P and neurokinin A) involved in excitatory NANC pathway
a family of neuropeptides that cause smooth muscle contraction (contributing to bronchoconstriction)
also play a role in inflammation and pain sensation in the airways (contributing to neuro-inflammation)
Neuro-inflammation due to tachykinin release is a key factor in conditions like asthma and chronic obstructive pulmonary disease (COPD), where there is increased airway inflammation and bronchoconstriction
312
what is a key factor in conditions like asthma and COPD?
Neuro-inflammation due to tachykinin release is a key factor in conditions like asthma and chronic obstructive pulmonary disease (COPD), where there is increased airway inflammation and bronchoconstriction
313
non-adrenergic non-cholinergic pathways
The term NANC refers to nerves that are not adrenergic (not using noradrenaline) and not cholinergic (not using acetylcholine).
These NANC nerves can be both inhibitory and excitatory, and they are important in regulating airway tone in a way that complements the actions of the sympathetic and parasympathetic nervous systems.
-> Inhibitory NANC nerves (using NO and VIP) relax the airway smooth muscle.
-> Excitatory NANC nerves (using Substance P and Neurokinin A) can lead to bronchoconstriction and inflammation, contributing to airway narrowing.
314
what is the function of the mucus layer?
1. acts as a protective layer or barrier against pathogens or particles
2. maintains the liquid environment needed to carry out an effective gas exchange
315
goblet cells
Goblet cells are situated in the epithelium of the conducting airways, often with their apical surfaces protruding into the lumen: secrete mucin and create a protective mucus layer
316
goblet cells and mucus glands
[both play a role in the production of mucus, which serves to trap and clear foreign particles, pathogens, and irritants from the airways.]
Goblet cells produce small amounts of less viscous mucus that primarily serves to trap particles and protect the airway epithelium. present in the pseudostratified columnar epithelium of the airways. The mucus is mainly composed of mucins (glycoproteins). Goblet cells play a crucial role in the mucociliary clearance system, in which mucus is moved by cilia to the throat
Mucus glands, located deeper in the airway wall, produce larger volumes of more viscous mucus that serve to lubricate and protect the airways, especially in response to irritation or infection. larger, multicellular structures composed of glandular cells that produce and secrete mucus. glands contain serous cells (that produce a watery, enzyme-rich secretion) and mucous cells (that produce thicker, mucus-like secretions).
317
mucus glands
Mucus glands, located deeper in the airway wall, produce larger volumes of more viscous mucus that serve to lubricate and protect the airways, especially in response to irritation or infection. larger, multicellular structures composed of glandular cells that produce and secrete mucus. glands contain serous cells (that produce a watery, enzyme-rich secretion) and mucous cells (that produce thicker, mucus-like secretions).
318
goblet cells
Goblet cells produce small amounts of less viscous mucus that primarily serves to trap particles and protect the airway epithelium. present in the pseudostratified columnar epithelium of the airways. The mucus is mainly composed of mucins (glycoproteins). Goblet cells play a crucial role in the mucociliary clearance system, in which mucus is moved by cilia to the throat
319
how does the nervous system regulate mucus secretion?
decreased by sympathetic NS
increased by parasympathetic NS, inflammatory mediators & chemical/physical stimuli
320
what increases mucus secretion in respiratory system?
parasympathetic NS, inflammatory mediators and chemical/physical stimuli
321
what decreases mucus secretion?
sympathetic NS
322
what physiological effect does the endogenous ligand histamine have in respiratory function?
broncho-constriction
323
what physiological effect does the endogenous ligand acetylcholine have in respiratory function?
broncho-constriction
324
what physiological effect does the endogenous ligand adrenaline have in respiratory function?
broncho-dilation
325
what physiological effect does the endogenous ligand cysteinyl leukotrienes have in respiratory function?
broncho-constriction
326
what physiological effect does the endogenous ligand prostanoids have in respiratory function?
broncho-constriction/dilation
(depending on cellular context and receptor)
327
which endogenous ligands effect broncho-constriction?
1. histamine
2. acetylcholine
3. cysteinyl leukotrienes
4. prostanoids
328
which endogenous ligands effect broncho-dilation?
1. adrenaline
2. prostanoids
329
receptor target, expression, cellular effect and physiological effect of histamine of respiratory function
H1
smooth muscle
increases intracellular Ca+2
broncho-restriction
330
receptor target, expression, cellular effect and physiological effect of acetylcholine of respiratory function
M3
smooth muscle
increases intracellular Ca+2
broncho-constriction
331
receptor target, expression, cellular effect and physiological effect of adrenaline of respiratory function
β2AR
smooth muscle
increases intracellular cAMP
broncho-dilation
332
receptor target, expression, cellular effect and physiological effect of cysteinyl leukotrienes of respiratory function
CysLT1/CysLT2
mucosa/immune cells
increases intracellular Ca+2
broncho-constriction
333
receptor target, expression, cellular effect and physiological effect of prostanoids of respiratory function
TxA2, PGD2, PGF2a, PGF2
smooth muscle, immune cells
several cellular effects
broncho-constriction/dilation (depending on cellular context and receptor)
334
receptor targets of prostanoids?
1. TxA2
2. PGD2
3. PGF2a
4. PGF2
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asthma
obstructive lung disease
chronic inflammatory condition with acute exacerbations
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treatment of asthma
bronchodilators and anti-inflammatory agents
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relevance of asthma
asthma related deaths very low (<2% lung disease related deaths in UK); still a significant cause of premature death and a great proportion of people living with the condition
>5.2m people have asthma (1 in 5 households in UK)
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how many people in UK have asthma?
>5.2m people have asthma (1 in 5 households in UK)
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how is asthma defined?
as a recurrent reversible airway obstruction with attacks of wheeze, cough and shortness of breath
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wheeze
whistling sound when breathing
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what triggers asthma attack?
generally triggered by external/environmental stimuli
some genetic factors may influence the predisposition or severity of the pathology
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hyperplasia and hypertrophy
Hyperplasia is an increase in the number of cells, while hypertrophy is an increase in the size of cells.
During hypertrophy, the cells enlarge as they fill with more cytoplasm. This can lead to an increase in the strength or function of the tissue. During hyperplasia, new cells are formed as existing cells divide.
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impact of inflammation of airways in asthma
infiltration of inflammatory cells
tissue hyperplasia/hypertrophy
mucus secretion
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bronchial hyper-reactivity of asthma
abnormal sensitivity to irritants, allergens or changes in air temperature or humidity
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impact recurrent but reversible airways obstruction of asthma
wheezing
acute severe asthma attack very difficult to reverse, can be fatal
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structural changes in asthma
1. smooth muscle cell hypertrophy/hyperplasia and contraction
2. oedema
3. mucus hypersecretion
4. epithelial damage
5. infiltration of inflammatory cells/inflammation
6. bronchial hyper reactivity
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oedema
build-up of fluid in the body which causes the affected tissue to become swollen
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bronchial hyper-reactivity
abnormal sensitivity to a wide range of stimuli
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what can trigger asthma symptoms (due to bronchial hyper-reactivity)?
pet dander
dust mites
moulds
pollens
respiratory infections
exercise
cold air
tobacco smoke and other pollutants
stress
alcohol
other food/drug allergies
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what drugs allergies can trigger asthma symptoms?
aspirin and other non-steroidal anti-inflammatory medications (NSAIDS)
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NSAIDS
non-steroidal anti-inflammatory medications
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how is asthma diagnosed?
respiratory function tests
use of spirometry to measure FEV1/FVC and measurement of peak flow
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what is used to measure peak flow?
peak flow meter (PEFR)
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FEV1
forced expiratory volume in 1 second
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what should FVC be in healthy condition?
<3s
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FVS
forced vital capacity
(a persons forced maximal expiration following full inspiration)
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what does the ratio FVE1/FVC show?
used to access lung function
about 70-80% in adults
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what value does asthma reduce?
FEV1
numerous cells and mediator play a part in this response; drug treatment must take this into account
*forced expiratory volume in 1s
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what two phases do asthma attacks consist of?
1. early/immediate
2. late/delayed
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immediate phase asthma attack
- fast onset after contact with allergen/stimuli
- activation of mast cells
= bronchospasm
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late phase asthma attack
- onset after hours of immediate phase
- progressive inflammatory response
- infiltration and activation of Th2 cells and eosinophils
= airway inflammation and hyper-reactivity
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what does the immediate phase of asthma attack lead to?
bronchospasm
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what does late phase asthma attack lead to?
airway inflammation and hyper-reactivity
364
what cells are activated in immediate phase of asthma attack?
mast cells
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what cells are activated in late phase of asthma attack?
Th2 cells
easinophils
366
what two mechanisms of asthma do drugs target to treat?
1. bronchoconstriction
2. inflammatory response
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bronchodilators vs anti-inflammatory agents as anti-asthmatics?
bronchodilators = relievers
anti-inflammatory agents = preventers
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relievers of asthma
bronchodilators
work by promoting smooth muscle relaxation;
by stimulating β2-adrenoceptors/their 2nd messenger systems/by blocking the constricting cholinergic effects
369
what 3 things to bronchodilators (relievers) stimulate in the treatment of asthma?
1. β2-adrenoceptors
2. their 2nd messenger systems
3. blocking the constricting cholinergic effects
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give an example of a β2 agonist bronchodilator (asthma reliever)
Salbutamol (Ventolin)
short acting β2 agonist; duration ~4-6hrs; mainly inhaled but also available orally.
Terbutaline (Bricanyl)
short acting β2 agonist
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give an example of a muscarinic antagonist bronchodilator (asthma reliever)
Ipratropium (Atrovent)
short acting non-selective muscarinic antagonist (M1, M2, M3); 2-5hr duration
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give an example of a methylxanthine bronchodilator (asthma reliever)
Theophylline/aminophylline
increases cAMP & cGMP levels by inhibiting phosphodiesterase (PDE)
373
what is a type of bronchodilator (asthma reliever) apart from β2 agonist, muscarinic antagonist, and methylxanthines?
cysteinyl leukotriene
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what pathway do beta-agonists and methylxanthines both involve?
cyclic AMP (cAMP) pathway
mechanisms of action of beta-agonists (e.g. salmeterol) and methylxanthines (e.g. theophalline) both involve cAMP pathway but act at different points
375
how to the actions of beta-agonists compare to those of methylxanthines?
beta-agonist activate adenylyl cyclase directly through G2 protein activation, leading to production of cAMP from ATP
methylxanthines inhibit PDE, preventing cAMP breakdown and therefore maintaining elevates cAMP levels
both increase cAMP levels, leading to activation of PKA and bronchodilation (relaxation of airway smooth muscle)
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how do beta agonists increase cAMP levels?
in activating adenylyl cyclase directly through Gs protein activation leading to cAMP production from ATP
(bind to β-2 adrenergic receptors on airway smooth muscle--- stimulates Gs protein --- activates adenylyl cyclase ---- adenylyl cyclase converts ATP to cAMP)
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how do methylxanthines lead to increase in cAMP levels?
by inhibiting PDE, preventing breakdown of cAMP
378
how does PKA cause bronchodilation?
(cAMP activates PKA- protein kinase A)
PKA causes bronchodilation by phosphorylating and inhibiting myosin light-chain kinase (MLCK); normally cause smooth muscle contraction--- therefore inhibition of MLCL leads to relaxation of smooth muscle resulting in bronchodilation
379
what is the result of ACh binding to M3 muscarinic receptors on airway smooth muscle cells?
when acetylcholine binds to M3 muscarinic receptors on airway smooth muscle cells, it initiates a signalling cascade which leads to bronchoconstriction
380
summarise the signalling cascade that occurs when ACh binds to M3 receptors
1. ACh activates the M3 muscarinic cholinergic receptor, which is couples to the Gq protein
2. Gq protein activates phospholipase C (PLC), which converts PIP2 into IP3 and DAG
3. IP3 binds to receptors on ER, leading to release of Ca+2 into cytoplasm
4. calcium binds to calmodulin, forming calcium-calmodulin complex
5. complex activates myosin light-chain kinase (MLCK)
6. MLCK phosphorylates myosin light chains (MLC), which activate myosin ATPase leading to smooth muscle contraction and resulting in bronchoconstriction
381
how do muscarinic antagonists stop bronchocontriction?
block the activation of the M3 muscarinic receptors; prevent acetylcholine from activating M3 receptors
(prevents the cascade that leads to bronchoconstriction)
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glucocorticoids for asthma treatment
(anti-inflammatory agents)
main drugs used for anti-inflammatory action in asthma; not bronchodilators but effective in preventing the progression of chronic asthma.
383
how do glucocorticoids act?
- by inhibiting the production of prostanoids, leukotrienes and cytokines
- decrease release of cytokines particularly those released by Th2 lymphocytes
384
how are glucocorticoids administered?
by inhalers (not nebulised)
[frequently combined with long-acting β2-adrenoceptor agonists]
384
what are glucocorticoids frequently combined with?
[frequently combined with long-acting β2-adrenoceptor agonists]
385
give glucocorticoid example
1. beclomethasone
2. fluticasone
main one is beclomethasone but in severe cases high potency glucocorticoids like fluticasone are used
386
use of cysteinyl-leukotriene receptor agonists in asthma treatment
(anti-inflammatory agent)
- infiltrated immune cells release cysteinyl-leukotrienes that act at CysLT1 and CysLT2 receptors found in the respiratory mucosa and infiltrating inflammatory cells
- they relax airways in mild asthma and normally are used in combination with salbutamol/another reliever inhaler
387
what are cysteinyl-leukotriene receptor antagonists used in combination with?
normally are used in combination with salbutamol/another reliever inhaler
388
what is an example of a cysteinyl-leukotriene receptor antagonist?
montelukast
(most commonly 'lukast' used drug in asthma treatment; is given orally; antagonist of CysLT1)
389
what is montelukast an antagonist of and how is it administered?
antagonist of CysLT1
given orally
390
biologic treatments of asthma
consist of monoclonal antibodies (mAbs) that target either IgE antibodies or other mediators of the inflammatory response (Il-5)
391
when are biologic treatments of asthma particularly effective?
to treat severe allergic asthma that cannot be controlled with glucocorticoid inhalers alone
392
how do biologic treatments of asthma work?
by reducing inflammatory effect mediated by mast cells, eosinophils and basophils
393
how are biologic asthma treatments administered?
by injection or intravenous drip
394
6 UK approved biologics for the treatment of asthma?
1. mepolizumab (nulala)
2. reslizumab (cinqaero)
3. benralizumab (fasenra)
4. omalizumab (xolair)
5. dupliumab (dupixent)
6. tezepelumab (tezspire)
395
acetylcholine effect on airways
induces bronchoconstriction and mucus secretion
396
adrenaline/epinephrine effect on airways
induces bronchodilation
397
atropine effect on airways
blocks acetylcholine dependent bronchoconstriction
398
atorpine
used in the respiratory system primarily for bronchodilation and reduction of respiratory secretions, which can help manage conditions like asthma, COPD, and other situations requiring airway management.
[Atropine is a muscarinic antagonist (also known as an anticholinergic drug) that works by blocking the action of acetylcholine at muscarinic receptors, which are a type of receptor found in various parts of the body, including the heart, smooth muscles, and glands.
Atropine specifically blocks muscarinic receptors (especially the M3 receptors) in the parasympathetic nervous system. By doing so, it inhibits the effects of acetylcholine, which is a neurotransmitter that promotes the "rest and digest" response, such as increasing secretion, constricting airways, and slowing heart rate.]
399
histamine effects on airways
increases bronchoconstriction and inflammatory response
400
mepryamine effect on airways
blocks histamine dependent bronchoconstriction
401
histamine effect in respiratory system
Histamine is a potent bronchoconstrictor, meaning it causes the smooth muscles in the airways (bronchi and bronchioles) to contract. This results in narrowing of the airways, which can lead to difficulty breathing and wheezing, especially in conditions like asthma or allergic rhinitis.
Histamine plays a central role in the pathophysiology of allergic reactions and asthma, and its effects are primarily mediated by H1 receptors in the respiratory system. Management often involves the use of antihistamines and other medications to alleviate the symptoms of histamine-induced airway constriction and inflammation.
402
effect of mepryamine on airways
Mepryamine is an antihistamine (also known as a H1 receptor antagonist), primarily used to treat allergic conditions such as allergic rhinitis, urticaria (hives), and hay fever. Like other antihistamines, mepryamine works by blocking H1 histamine receptors, which prevents histamine from binding and exerting its effects on various tissues, including the respiratory system.
Mepryamine, as an H1 receptor antagonist, has a bronchodilatory effect (relaxing the airways), reduces mucus production, and can help reduce swelling and inflammation in the airways. It is effective for treating allergic conditions like hay fever and allergic asthma by blocking histamine’s action on H1 receptors in the respiratory system, improving airflow and reducing symptoms such as wheezing and nasal congestion.
403
acetylcholine pathway in airways
Parasympathetic (Cholinergic) Stimulation (via the vagus nerve, ACh, M3 receptors) leads to bronchoconstriction.
(The parasympathetic control of the respiratory system is mediated primarily by the vagus nerve, which originates from the brainstem (medulla oblongata). The vagus nerve carries parasympathetic fibers to the lungs.)
404
where is adrenaline/epinephrine produced?
produced and released by the adrenal medulla, which is the inner part of the adrenal glands located above the kidneys.
(It is a hormone and neurotransmitter that is part of the body's response to stress or danger.)
405
adrenaline/epinephrine pathway in airways
Adrenaline/Epinephrine is produced by the adrenal medulla and released into the bloodstream.
It circulates and acts on β2 adrenergic receptors on bronchial smooth muscle.
Activation of β2 receptors leads to the activation of cAMP and PKA, resulting in bronchodilation (smooth muscle relaxation).
The overall effect is an increase in airway diameter, improving airflow and making it easier to breathe, particularly in stressful or high-energy situations.
406
primary benefit of using inhaled glucocorticoids in the management of asthma
reduction in airway inflammation
[They inhibit the release of inflammatory mediators (like histamine, leukotrienes, and cytokines) and reduce the activation of inflammatory cells such as mast cells, eosinophils, and T-cells.]
407
montelukast
Montelukast is a leukotriene receptor antagonist (LTRA) used in the treatment of asthma and allergic rhinitis. It works by blocking the action of leukotrienes, which are inflammatory mediators involved in the pathophysiology of asthma, particularly in the bronchoconstriction and inflammation that occur during an asthma attack.
408
montelukast mechanism of action
Montelukast works by blocking CysLT1and CysLT2 receptors, preventing the action of leukotrienes like LTC4, LTD4, and LTE4.
This reduces bronchoconstriction, inflammation, and mucus production, which are key components of asthma pathophysiology.
It provides long-term control of asthma symptoms and can be used as add-on therapy to other medications like inhaled corticosteroids (ICS) for better management of asthma.
409
what acts by blocking H1 receptors?
meptryamine
H1 receptor antagonists (antihistamines) block the effects of histamine at H1 receptors, thereby alleviating allergic symptoms like itching, sneezing, and swelling. First-generation antihistamines tend to cause drowsiness, while second-generation antihistamines are typically non-sedating and preferred for long-term allergy management.
410
histamine, mepriamine, acetylcholine, atropine and adrenaline/epinephrine target receptors
histamine= histamine receptors
mepryamine= H1 receptor
acetylcholine= M3 receptors
atropine= muscarinic receptors
adrenaline/epineprhine= beta-2 adrenergic receptor
411
bombesin and airways
Bombesin can induce bronchoconstriction in the lungs,
(neuropeptide)
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