respiratory physiology: ventilation and perfusion Flashcards
what determines respiratory airflow?
the pressure difference between mouth and alveoli
what causes flow?
either an upstream rise (positive pressure breathing) or a downstream fall in pressure (negative pressure breathing)
what is positive pressure breathing?
generating a higher pressure in the mouth forcing air into the lungs
ventilation
what is negative pressure breathing?
generating a lower pressure in the lungs causing air to move into them from the mouth
normal breathing
Pip
intrapleural pressure/ intrathoracic pressure
Palv
alveolar pressure
Ptp
transpulmonary pressure
Patm
atmospheric pressure
Pip at rest
already negative due to counter recoil of chest wall/ alveoli and slight suction of excess fluid into lymphatic channels
what happens at inspiration?
Inspiratory muscles contract
Pip becomes more negative
increases difference between Palv and Pip which increases Ptp
alveolar volume increases so Palv decreases and increases the difference between Patm and Palv
What is Ptp
synoymous with alveolar wall distension
the larger Ptp is the greater the alveolar wall distension
What happens at expiration?
inspiratory muscles relax
Pip becomes less negative
decreases difference between Palv and Pip, decreasing Ptp
If Ptp is smaller the alveolar wall recoils due to elastin and collagen fibres
alveolar volume decreases causing Palv to increase and so increase the difference between Patm and Palv.
what is alveolar interdependence?
outer alveoli are affected by the change in intrapleural pressure
which affects the next alveoli and the next row until the inner depths of the lung
where is the visceral pleura?
membrane attached to lungs
where is the parietal pleura?
membrane attached to chest wall
what is between the visceral and parietal pleura?
intrapleural cavity/ space
what are the types of pneumothorax?
spontaneous
trauma
tension
what happens in a tension pneumothorax?
membrane breaks and there is infiltration of air into the thoracic cavity, it only comes in, it cannot leave. It compresses the heart and vessels causing cardiac tamponade
what happens in a pneumothorax?
the pleural seal breaks and air enters and gets trapped causing lung collapse
airway resistance
it is difficult to quantify in the conduction zone
what affects airway resistance?
branching, narrowing, dispensable, compressible airways
type of airflow
what are the different types of airflow through the airways?
laminar - linear
turbulent
transitional
what defines the changes in types of airflow?
reynold’s number
what is reynold’s number?
defines the airflow and is based on density of fluid, velocity, diameter of tube and viscosity of fluid
poiseuille’s law
resistance is directly proportional to viscosity of fluid and the length of tube and inversely proportional to the 4th power of radius (r^4) of tube
what conditions are associated with changes in tube radius?
asthma
bronchitis
croup
who are at greater risk of conditions affecting airway resistance/ radius?
children
why are children at greater risk of conditions affecting airway resistance/ radius?
smaller airways
higher resting respiratory rates
what can trigger contraction of smooth muscle in bronchi?
PGD2 - prostaglandins LTC4 - leukotrienes histamines released during type 1 hypersensitivity TXA2 serotonin alpha adrenergic agonists ACh low pp of CO2
what can cause an asthma attack
contraction of bronchial smooth muscle
how does bronchial muscle contraction occur?
trigger binds to muscarinic receptor (GPCR)
release calcium via IP3 into cell
forms calcium and calmodulin complex
activates myosin light chain kinase
myosin light chain (regulatory protein) around myosin head is phosphorylated by kinase and activates contraction
what mediates dephosphorylation of myosin?
myosin light chain phosphotase
what causes bronchiodilation
noradrenaline
adrenaline
B2 agonist - salbutamol
asthma
type 1 hypersensitivity
allergic or immediate hypersensitivity
develop IgE antibodies in response to harmless antigens
mechanism of asthma - type 1 hypersensitivity - initial allergen encounter
allergen is inhaled, ingested, injected or contact
antigen presenting cells pick up and present the allergen and adaptive immune response by B cells forming plasma cells to make IgE to allergen
IgE enter circulation and bind to mast cells in tissue
what happens in type 1 hypersensitivity on subsequent allergen encounter
allergen inhaled, ingested, injected or by contact
binds to IgE on mast cell
cross linking causes mast cell degranulation and release histamine, cytokines/ chemokines and leukotrienes (vasoreactive amines)
compliance
high = good low = bad
how is compliance measured
as volume per unit of pressure change
mLcmH2O-1)
value varies as lungs inflate
pressure volume pathway
is different taken during expiration and inspiration
what is average compliance of both lungs?
200ml air per 1cmH2O
why is there a difference in the pressure-volume pathway for inspiration and expiration?
differences in pressure applied to surfactant and recruitment of alveoli in inspiration and derecruitment in expiration
what is the pressure- volume pathway called?
hysteresis
what limits increase in pressure and volume in the lungs?
elastic limit of chest wall
what happens to compliance in Emphysema?
increases - left shift
what happens to compliance in fibrosis?
decreases - right shift
what does increased compliance suggest?
emphysema/ obstructive disease
what does decreased compliance suggest?
fibrosis/ restrictive disease
compliance curve
Ptp on x axis and Vol on y axis
emphysema
destruction of alveolar walls - large air spaces that are no cleared of air on exhalation - air trapping . destruction of elastic fibres reduced elastic recoil gas exchange decreases O2 diffusion decreases O2 levels in blood drop
signs/ symptoms of emphysema
mild exercise causing breathlessness
barrel chest
what causes emphysema?
consistent exposure to irritants - smoke, dust, chemical irritants
genetic predisposition due to alpha 1 antitrypsin deficiency
what is emphysema part of ?
along with chronic bronchitis they are the 2 main causes of COPD
what is chronic bronchitis?
inflammation of bronchial tubes and excessive mucus production causing coughing and SOB
what are the diseases making up COPD?
chronic bronchitis
emphysema
what is surfactant?
lipoprotein secreted by type 2 alveolar cells
part of the liquid film lining alveoli
what does surfactant do?
lowers surface tension
increases compliance
improves work of breathing
why is surfactant clinically important?
infant respiratory distress syndrome and acute respiratory distress syndrome
what happens in IRDS?
surfactant not produced until 4 months gestation and not sufficiently until 7 months gestation or later
what happens in ARDS?
reduction in surfactant production through injury to type 2 alveolar cells
what is matched in the process of breathing and respiration?
ventilation and perfusion
what is ventilation rate?
4-6L/min
what is pulmonary blood flow?
4-6L/min
ventilation/ perfusion
V/Q = 0.8-1.2
what is the problem with ventilation/ perfusion matching?
there are regional differences so ventilation and perfusion need to be matched at the alveolar - capillary level
ventilation distribution in healthy lungs
at start of inspiration, alveoli at the base of the lung are smaller and so have more capacity to expand - therefore ventilation to these areas is greater over the whole breathing cycle .
perfusion distribution in healthy lungs
perfusion pressure falls if above level of heart and increases if below it . Blood flow increases steadily from apex to base .
maximum PAP
pulmonary artery pressure
25/10mmHg
ventilation-perfusion matching
greater ventilation at bottom of lung and greater perfusion at bottom of lung so they are generally well matched
problems with V/Q matching
affects O2 and CO2 transfer
pulmonary shunt
passage of deoxygenated blood from right side of heart to left without participation in gas exchange in the pulmonary capillaries. There is no ventilation and pulmonary arterial blood is not oxygenated
Alveolar dead space
no perfusion
alveolar gas is the same as room air, containing not CO2
no blood flowing through their adjacent pulmonary capillaries
severe ventilation/ perfusion abnormalities
pulmonary shunt
alveolar dead space
less severe ventilation/ perfusion abnormalities
respiratory problems that produce a fall in FRC and compliance
how does reduced FRC effect ventilation?
reduced volume causes reduced compliance due to increased airway resistance, airway collapse and lung collapse
causes apexes and mid-zones to have higher compliance and so ventilation becomes higher at the apex
affect of falling FRC on V/Q matching
greater ventilation at apex of lung but greater perfusion remains at bottom of lung and so there is a mismatch - resulting in inadequate ventilation to oxygenate blood in base of lungs - hypoxia
what is the importance of ventilation/ perfusion matching
efficient gas exchange requires them to be well matched
what are the stages involved in carbon dioxide and oxygen transport?
ventilation external respiration Gas transport internal respiration cellular respiration
what happens in ventilation?
gas exchange between atmosphere and alveoli
what happens in external respiration?
O2 and CO2 transfer between alveoli and blood
what happens in gas transport?
O2 and CO2 carried in blood between alveoli and tissues
what happens in internal respiration?
O2 and CO2 transfer between blood and tissues
what happens in cellular respiration?
O2 utilisation and CO2 production by tissues
how many divisions are there of the respiratory tree?
23
which divisions are conduction airways?
1-16
tidal flow generated by respiratory muscles
which divisions are respiratory exchange?
17-23
passive diffusion by partial pressure gradients
passive diffusion
exchange of CO2 and O2 occurs by this, it is governed by dalton’s and Henry’s law
what is Dalton’s law?
how gases move down their concentration gradient by diffusion
what is Henry’s law?
how the solubility of a gas relates to its diffusion
Dalton’s law
to do with partial pressure
how is partial pressure calculated?
pressure exerted by a gas in a mixture
% in the mixture x ambient pressure (overall pressure) e.g. 21% O2 in air x atmospheric pressure (750mmHg) = 157mmHg§
role of Dalton’s law in lungs
gases move from high partial pressure to lower partial pressure, so O2 moves down airways and CO2 moves up .
O2 moves from alveoli to blood and CO2 from blood to alveoli
determines the exchange of CO2 and O2 between atmosphere and lungs, lungs and blood and blood to tissue cells
henry’s law
the quantity of a gas dissolved in liquid is proportional to partial pressure of the gas and solubility of the gas .
The higher the partial pressure and the higher the solubility of the gas the more gas will stay in solution
partial pressure in solution = partial pressure in gas phase
what happens if you double partial pressure of a gas in gas phase?
double the amount of gas will be dissolved for a simple solution
external respiration
diffusion of O2 and CO2 between air in alveoli and blood in pulmonary capillaries
converts deoxygenated blood to oxygenated
CO2 into alveoli and O2 into blood
what type of process is external respiration?
passive/ independent
another name for external respiration
perfusion
internal respiration
exchange of O2 and CO2 between systemic capillaries and tissue cells
converts oxygenated to deoxygenated blood
CO2 into blood and O2 into cells
what type of process is internal respiration?
passive/ independent
what is the major determinant of oxygen in the blood?
partial pressure of O2
how much oxygen is dissolved in plasma?
1.5% of inhaled O2
oxygen carriage system
haemoglobin
deoxyhaemoglobin + oxygen –> oxyhaemoglobin
haemoglobin increases the total quantity of oxygen in blood greatly doesn’t change partial pressure of oxygen because partial pressure measures dissolved oxygen
haemoglobin
globin protein 4 polypeptides 2 alpha and 2 beta 4 haem groups pigment one on each polypeptide
haem group
porphyrin ring surrounding an iron ion (Fe 2+ - ferrous ion) linked to a globin chain
binding to haemoglobin
each haem binds 1 molecule of oxygen - O2
binding is reversible
process of binding
as the first oxygen binds the haemoglobin changes shape and becomes looser
making binding of the next oxygen easier
full saturation - binding of 4th oxygen is harder because there are fewer spaces available
how much oxygen can 1g of haemoglobin hold?
1.34mL
oxygen saturation curve
indicates that the saturation of haemoglobin depends on the partial pressure of oxygen
high pp = high saturation of haemoglobin
low pp = low saturation of haemoglobin
what happens at the tissues?
as partial pressure of oxygen falls the saturation of haemoglobin falls because it unloads oxygen
the bohr effect
in tissues that need more oxygen the local environment moves the curve to the right by helping unloading of oxygen
how does the bohr effect work
as tissue metabolism increases lactic acid and CO2 concentration increase causing:
CO2 + H2O H2CO3 H+ + HCO3-
the H+ ions bind to haemoglobin and alter its structure decreasing its oxygen carrying capacity
what happens in the lungs?
alveolar environment has high pp of oxygen and low of CO2 so is alkalotic and so moves the curve to the left and aids uptake of oxygen
solubility of CO2 in plasma
25 times more soluble than O2 in plasma still has specialised transport systems
what forms is CO2 carried in?
dissolved in plasma
bicarbonate
carbamino compounds
results in a CO2 content curve
Proportions of different carbon dioxide carriage methods
HCO3-
carbamino
dissolved
CO2 in the red cell
CO2 + H2O <> H2CO3 <> H+ +HCO3-
Bohr effect: H+ + Hb.O2 <> Hb.H+ + O2
CO2 + Hb.NH2 <> H+ + Hb.NH.COO- (carbamino)
The H+ needs buffering
Haldance effect
works in tandem with the bohr effect to enhance CO2 transport
Haldane effect in tissues
haemoglobin gives up O2
Affinity for CO2 increases (left shift)
greater CO2 carriage
Haldane effect in lungs
haemoglobin gives up CO2
Affinity for CO2 decrease - right shift
Haemoglobin binds oxygen
how the bohr and haldane effect work together
bohr = O2 unloading/ loading enhanced by CO2 loading/ unloading Haldane = CO2 loading/ unloading enhanced by O2 unloading/ loading
how are smooth muscles relaxed?
To relax myosin is dephosphorylated and Calcium and extruded from the cell into sarcoplasmic reticulum
what does kinase do?
phosphorylates
how do bronchodilators work?
bronchodilator causes release/ activation of protein kinase A
which phosphorylates the myosin light chain kinase which
deactivates it causing smooth muscle relaxation