Respiratory System Flashcards
In a healthy young subject (blood Hb concentration of 15g/dl), what is the concentration in atmospheric air for O2 and CO2?
(Symbol and value)
Fi02= 0.209 (20.9%)
FiCO2= 0.0004 (0.04%)
NB. subscript 2
In a healthy young subject (blood Hb concentration of 15g/dl), what is the partial pressure in alveolar air for O2 and CO2?
(Symbol and value)
PAO2= 13.3 kPa (100 mmHg) PACO2= 5.3 kPa (40 mmHg)
NB. subscript A and 2
In a healthy young subject (blood Hb concentration of 15g/dl), what is the partial pressure in arterial blood for O2 and CO2?
(Symbol and value)
PaO2= 13.3 kPa (100 mmHg) PaCO2= 5.3 kPa (40 mmHg)
NB. subscript a and 2
In a healthy young subject (blood Hb concentration of 15g/dl), what is the partial pressure in mixed venous blood for O2 and CO2?
(Symbol and value)
PvO2= 5.3 kPa (40 mmHg) PvCO2= 6.1 kPa (46 mmHg)
NB. subscript v and 2
What percentage of deaths in the UK are due to respiratory diseases?
20%
What are the main causes of respiratory related deaths?
Cancer Pneumonia Chronic obstructive pulmonary disease (COPD) Pulmonary circulatory disease Pneumoconioses Asthma Other respiratory diseases
What is the UK’s biggest cancer killer?
Lung cancer
Very small 5 year survival rate
COPD is expected to be the (number) biggest cause of mortality by 2020
3rd
What fraction of people visit their GP at least once a year because of a respiratory condition?
1/3
How are lung diseases classified?
AIRWAY DISEASES
Local obstruction
Generalised obstruction
SMALL LUNG DISORDERS (RESTRICTIVE)
Disease within the lung
Disease outside the lung
INFECTIONS
PULMONARY VASCULAR DISORDERS
List examples of airway diseases (local and generalised obstruction)
LOCAL Sleep apnoea (6x risk RTA) Laryngeal carcinoma Thyroid enlargement Vocal cord dysfunction Relapsing Polychondritis Tumours Post tracheostomy stenosis Foreign bodies Bronchopulmonary dysplasia
CHRONIC Asthma COPD Bronchiectasis Cystic Fibrosis Obliterative Bronchiolitis
List examples of small lung (restrictive) diseases (disease within/outside the lung)
WITHIN Sarcoidosis Asbestosis Extrinsic Allergic Alveolitis Fibrosing Alveolitis Eosinophilic pneumonia Idiopathic pulmonary fibrosis (35% increase in diagnosis 2000-> 2008, 3 year median survival)
OUTSIDE Pleural effusions Pneumothorax Scoliosis Respiratory muscle weakness Obesity (increases resp workload, increases i) Mesothelioma (asbestos)
List examples of lung infections
Tuberculosis (infection rate rising in London)
Infective bronchitis
Pneumonia
Empyema
List examples of pulmonary vascular disorders
Pulmonary emboli= clots in the lung may complicate immobility and be fatal e.g. associated with child birth, (more common >40y)
Pulmonary hypertension
What is the most common symptom associated with lung disease?
Breathlessness – also known as DYSPNOEA; a sensation of difficult, laboured or uncomfortable breathing
Cough Sputum production Haemoptysis Chest discomfort Wheeze or musical breathing Stridor (harsh/grating sound) Hoarseness Snoring history /Daytime sleepiness Weight loss Anorexia Fever
To aid diagnosis, what should you ask about (regarding lung diseases)?
Onset (acute, gradual)
Circumstances (on exertion, at rest, at night, lying flat, associated symptoms)
Degree
What may cause breathlessness?
Lung Disease
Heart Disease
Pulmonary Vascular Disease
Neuromuscular disease (e.g. diaphragm weakness
Systemic Disorders (e.g. anaemia, hyperthyroidism, obesity)
{Psychogenic Factors}
What are the 5 stages for MRC dyspnoea grading?
- Normal
- Able to walk and keep up with people of similar age on the level, but not on hills or stairs
- Able to walk for 1.5Km on the level at own pace, but unable to keep up with people of similar age
- Able to walk 100m on the level
- Breathless at rest or on minimal effort
What are the 2 main processes impaired by lung disease?
Disturbed gas exchange
Damaged respiratory mucosa
Outline gas exchange in the lungs
Small organisms meet their oxygen demand via diffusion, whereas larger organisms e.g. a resting adult cannot meet their requirements via diffusion alone
Breathing delivers warmed humidified air to specialised gas exchange surfaces
The heart delivers deoxygenated blood to the pulmonary capillaries
Gas exchange between the air and blood occurs by diffusion
How much oxygen does a resting adult need per minute?
250ml oxygen
Outline how damage to respiratory mucosa can lead to lung disease
Cell walls of epithelial cells are broken down, damaging and destroying the cilia so patients may have a reduced number of cilia as well as ineffective cilia
Damaged cilia are less effective at removing mucus from airways
How do enzymes lead to damaged respiratory mucosa?
Activity of enzymes e.g. neutrophil elastase – released from neutrophils which are attracted into the airways by cigarette smoke, bacterial products etc.
How is the respiratory system examined clinically?
Chest X ray
MRI
Spirometer
(Observation, palpating)
What does spirometry do?
Tests how well you can breathe
Can help diagnosis of different lung diseases e.g. COPD
Deep breath in, blow out as fast as possible into spirometer (small machine attached by a cable to mouth piece)
Why are some symptoms of lung disease hard to diagnose?
Overlap with lung and cardio conditions
Describe the nasal cavities
Nearly triangular cross-section
Fairly smooth medial and inferior walls
Elaborate lateral wall (respiratory epithelium covers 3 scroll-like plates of bones called conchae)
Nasal mucus and hair present
High resistance to airflow (because need to conserve heat and water)
Paranasal air sinuses present
How is nasal resistance affected by exercise?
During exercise, nasal resistance to flow means the respiratory muscles cannot propel air through the nose fast enough
Open-mouth breathing takes over with an increased loss of water and exposure to airborne particles
What do nasal mucus and hairs do?
Nasal mucus and hairs help exclude a range of airborne particles from flying insects to quite fine dust and particulate pollutants
Describe how nasal cavities are involved in inspiration and expiration
‘Conditioning the air’
Inspired air passes through these warm, moist plates-> become warmed and humidified
This protects lower parts of the respiratory tract from cold shock and drying
Nasal lining becomes cooled in this process so, during expiration, nasal lining cools the expired air and also retrieves water by condensation
Describe the paranasal air sinuses
Four sets of blind-ended ‘out-pocketings’ of the lateral walls of the nasal vaities
Slow air turnover
Little role in heat and water transfer
Probably function to:
- Reduce weight of facial bones
- Provide a ‘crumple zone’ in facial trauma
- Act as resonators for the voice
- Insulate sensitive structures from rapid temperature fluctuations
Why is infection of the maxillary sinus common?
Opening is high up
What are the lower airways?
Trachea
Bronchi
Bronchioles (initially surrounded by smooth muscle, but end as respiratory bronchioles from which alveoli are direct or indirect buds)
What are the walls of the larynx, trachea and bronchi held open by?
Plates or crescents of cartilage
Non-mineralised, supporting but flexible
What are the nasal cavities and pharynx held open by?
Attachments to nearby bones
What do alveoli and bronchioles contain to prevent collapse?
Microscopic air spaces (alveoli and bronchioles) contain a surfactant phospholipid
Prevents collapse caused by surface tension forces
What is the role of the pharynx?
After air is conditioned, passes down back of nasal cavity
Final part of airway before oesophagus
What are the 3 parts of the pharynx?
Nasopharynx= posterior to nasal cavity (Eustachian tube opening)
Oropharynx= posterior to tongue, consists of lymphoid tissue
Laryngopharynx= after epiglottis
How is food channeled to the oesphagus?
Posteriorly along the oropharynx
What is the anatomy of the larynx?
Cartillagenous structure
Supported from roof of mouth by hyoid bone
Associated with lateral carotids
Superior and posterior to thyroid gland, superior to trachea
Entire structure is membrane lined (forms complete sheath inside trachea)
Arytenoid cartilage to control entry to larynx
Allows air into lower airways but excludes liquids and solids
What respiratory structure develops differently in men and women?
Larynx
What is the arytenoid cartilage?
Attached to vocal ligaments
Open and close entry to larynx
Act as sphincter (prevent entry to lower airways)
When is the arytenoid cartilage open and closed?
Open= during inspiration
Closed= during phonation
Vocal folds partially open and air is passed through= sound is made (mechanism of vocalisation in the mouth)
What is the role of the larynx?
Modulation of sound
Without larynx, voice would be monotonous and low pitch
What effect does the closure of the larynx vocal folds have on the thorax and abdomen?
Closure-> increased pressure in thorax and abdomen
Can lead to expulsive force (during sneezing, childbirth and vomiting)
What is the structure of the trachea?
Regular cartilage arrangement
Approx 20 horseshoe shaped cartilage rings (keep trachea open)
Rings= not continuous at posterior surface
Anterior surface lined with epithelium
Posterior surface consists of trachealis muscle (anterior to oesophageal muscle, needed for swallowing)
What is the tracheobronchial tree?
Bronchi held open by cartilage horseshoes and plates
Bronchiolar and alveolar surface tension reduced by surfactant
What is the surface marker for where the trachea branches?
Sternal angle at T4
What is the dimorphism between the primary bronchi?
Right side is larger and more vertical
-> More things inhaled into right lung
What do the secondary and tertiary bronchi do?
Secondary bronchi supply each lung lobe
Within each lobe, tertiary bronchi then supply each pulmonary segment
With branching of the bronchi, number of cartilage rings …… and amount of smooth muscle ……
With branching of the bronchi, number of cartilage rings DECREASE and amount of smooth muscle INCREASES
What separates the two pleural cavities?
Mediastinum
Central partition of tissue
What does the mediastinum contain?
Trachea Oesophagus Heart Great arteries and veins Various important nerves and lymph vessels
What is the pleura?
Thin, shiny, moist layer of tissue
Covers each lung and inside of pleural cavities
Allows each lung to slide smoothly within its pleural cavity during breathing
Describe the surfaces of each lung
Costal surface= convex, facing the ribs
Mediastinal surface= moulded to mediastinum
Diaphragmatic surface= inferior, concave
What is the diaphragm?
Sheet-like dome-shaped muscle
- Centre of dome bulges up because of pressure difference between pleural and abdominal cavities
Separates thoracic and abdominal cavities
Margin attached to costal margin
Highest in expiration
Where is the highest part of each lung?
Apex
2-3cm above clavicle in adult (in root of neck)
How do the chest wall muscles, diaphragm, ribs, pleural cavities, pleura and lungs have a role in breathing?
Contraction of diaphragm-> pulls domed centred down-> increases height of pleural cavities
Contraction of the intercostal muscles-> pulls ribs upwards towards relatively fixed first rib-> ribs slope down towards their anterior ends
Lifting movement-> expansion of pleural cavities (depth and width) -> decreased pleural pressure
Decreased pleural pressure means air flows through airways into lungs (which expand with increase in pleural cavity)
Lower part of each lung expands downwards to occupy much of the costo-diaphragmatic recess
Breathing normally passive
What is the costo-diaphragmatic recess?
Lowest region of each pleural cavity
In expiration, contains no lung because margin of diaphragm is pressed closely against lower part of rib cage
What are the diaphragm’s motor nerves?
C3, 4, 5
‘Keep the diaphragm alive’
What are airways?
Air-filled spaces/tubes which take air from outside to alveoli
What are alveoli?
Microscopic spaces lined by very thin simple squamous epithelium through which O2 and CO2 exchange takes place
What are alveolar capillaries?
On the pulmonary circuit
Bring deoxygenated blood from the right ventricle of the heart via the pulmonary trunk and pulmonary arteries
What are the upper airways?
Nasal cavities
Nasopharynx
Laryngopharynx
Larynx
What are the cellular layers separating alveolar air from blood?
Air Alveolar wall Epithelial basement membrane (Interstitial space) Capillary basement membrane Endothelial cells of capillary Blood
How thick is the alveolar-capillary membrane?
What does the interstitial space between the basement membranes between alveolar air and blood contain?
Pulmonary capillaries
Elastin
Collagen
How is the respiratory tract protected against drying, cold and inhaled particles?
Inspired air passes through the conchae are warmed and humidified on route
Protects lower parts of respiratory tract from cold, shock and drying
This process cools nasal cavities, so during expiration the expelled air is cooled and water is retrieved by condensation
Nasal mucus and hairs exclude airborne particles
During exercise, nasal resistance to air flow becomes too great and open mouthed breathing takes over (less protection)
How do alveoli resist collapse?
Trachea and bronchi are held open by cartilage
Bronchi are held open by cartilage horseshoes and plates
Bronchiolar and alveolar surfce tension reduced by surfactant
How is blood circulated through the lungs?
Double circulation in body (pulmonary for deoxy, systemic for oxy)
PULMONARY
Deoxygenated blood enters the right atrium via the inferior and superior vena cava
Atrial systole forces the blood into the right ventricle (through tricuspid valve)
Ventricular systole ejects the blood into the pulmonary trunk (through pulmonary valve) which branches in pulmonary arteries
Pulmonary arteries branch further into arterioles and capillaries within each lung-> carries blood close to alveolar so gas exchange can occur
Oxygenated blood returns to heart via venules and pulmonary veins which enter the heart at the left atrium
What is minute ventilation?
Volume of air expired in 1 minute (VE)
NB. E in subscript
What is respiratory rate?
Frequency of breathing per minute (RF)
NB. F in subscript
What is alveolar ventilation?
Volume of air reaching the respiratory zone (Valv)
NB. alv in subscript
What is respiration?
The process of generating ATP either with an excess (aerobic) and a shortfall (anaerobic) of oxygen
What is anatomical dead space?
Capacity of the airways incapable of undertaking gas exchange
What is alveolar dead space?
Capacity of the airways that should be able to undertake gas exchange but cannot (e.g. hypoperfused alveoli)
What is physiological dead space?
Equivalent to the sum of alveolar and anatomical dead space
What is hypoventilation?
Deficient ventilation of the lungs
Unable to meet metabolic demand
Results in increased PO2- acidosis
What is hyperventilation?
Excessive ventilation of the lungs atop of metabolic demand
Results in reduced PCO2- alkalosis
What is hyperpnoea?
Increased depth of breathing (to meet metabolic demand)
What is hypopnoea?
Decreased depth of breathing (inadequate to meet metabolic demand)
What is apnoea?
Cessation of breathing (no air movement)
What is dyspnoea?
Difficulty in breathing/shortness of breath
What is bradypnoea?
Abnormally slow breathing rate
What is tachypnoea?
Abnormally fast breathing rate
What is orthopnoea?
Positional difficulty in breathing (when lying down)
What type of structure is the chest wall?
Chest wall= a rigid support structure composed mostly of the ribcage, sternum and intercostal muscles that naturally recoils outwards
What type of structures are the lungs?
Lungs= soft tissue structures are very elastic that naturally recoil inward (large SA for gas exchange)
What is the mechanical relationship between the chest wall, pleural membranes and the lung?
The chest wall has a tendency to spring outwards, and the lung has a tendency to recoil inwards
These forces are in equilibrium at end-tidal expiration (at functional residual capacity; FRC), which is the ‘neutral’ position of the intact chest
To further inspire (or expire), requires the equilibrium to be temporarily imbalanced
The lungs are surrounded by a visceral pleural membrane
The inner surface of chest wall is covered by a parietal pleural membrane
The pleural cavity is between the visceral and parietal pleura
The chest wall and lungs have their own physical properties that in combination dictate the position, characteristics and behaviour of the intact chest wall
What is the pleural cavity?
Between the visceral and parietal pleura
The gap between pleural membranes is a fixed volume and contains protein-rich pleural fluid
How can chest and lung recoil be expressed in equations considering inspiratory and expiratory muscle effort?
Chest recoil = lung recoil
Inspiratory muscle effort + chest recoil > lung recoil
Chest recoil
Why is the pleural cavity being breached a serious problem?
E.g. perforated or punctured
Bad because lung relies on the pleural fluid to operate normal lung mechanics
Thoracic wall-lung relationship is delicate (imbalance-> dysfunction)
E.g. haemothorax or pneumothorax
What is a haemothorax?
Accumulation of blood in the pleural cavity-> impedes lung function
Blood can’t enter pleural cavity as fast as air-> slow accumulation of fluid
Gradually reduces the space the lung has to inflate into, increases the effort required to inhaled to a given volume-> limits the overall volume achievable
Requires draining
What is pneumothorax?
Puncture in thoracic cavity that breaches the pleural cavity
‘Tension’ caused by normally negative pressure caused by constant inward recoil of the lung tissue
Outward recoil of the chest wall is suddenly compromised
This means the resistance (or link) between the two forces disappears
Allows lung to recoil and chest wall to expand
What is functional residual capacity (FRC)?
Lung volume at end of quiet expiration
RV+ERV = FRC
What is residual volume (RV)?
Lung volume at end of forced expiration
What is inspiratory reserve volume (IRV)?
Maximum amount of air that can be inhaled after normal inspiration
From TV to TLC
What is expiratory reserve volume (ERV)?
Maximum amount of air that can be exhaled after normal expiration
From TV to RV
What is tidal volume (TV)?
Volume of air breathed in or out during normal respiration
NB. T is subscript
What is total lung capacity (TLC)?
When taking maximum inspiration
TV+RV+IRV+ERV= TLC
What is vital capacity (VC)?
Amount of air that can be forced out of the lungs after maximal inspiration
IRV+VT+ERV= VC
NB. T (in VT) is subscript
What does peak flow test?
Tests airway resistance (how fast can air be expired)
What does time-volume curve test?
Tests airway resistance and FVC
What does flow volume loop test?
Tests airway resistance, flow rates, TV, IRV, ERV and FVC
What is transmural pressure?
Pressure inside - pressure outside = transmural pressures
-ve= leads to inspiration \+ve= leads to expiration
What is negative pressure breathing?
Palv is reduced below Patm
-> Healthy breathing
What is positive pressure breathing?
Patm is increased above Palv
-> Ventilation CPR
What is ventilation?
Quiet breathing
What is tidal breathing?
Predominantly diaphragm-induced (syringe movement)
What muscles are involved in maximum ventilation?
Full inspiratory muscle recruitment involved
Syringe and bucket handle movement
How does ventilation happen?
At FRC, mechanical forces of the lung are in equilibrium
Equilibrium needs to be imbalanced to generate airflow (and stimulate ventilation)
So atmospheric/intrapulmonary pressure is increased (positive pressure) or intrapleural pressure is decreased(negative pressure)
The respiratory musculature decrease intrathoracic pressure (diaphragm contracts downward towards the abdomen and the external intercostals pull the ribcage outwards and upwards) by creating a partial vacuum
Lung is elastic and expandable tissue stretches to fill the space (while maintaining intrapleural volume) assuming airway is clear
Which 3 pressures fluctuate and are important to determine whether inspiration or expiration?
Atmospheric pressure (Patm)
Intrapleural pressure (Ppl or PIP)
Intraalveolar pressure (PAlv)
(NB. After P, letters are subscript)
What is transmural pressure?
Pressure across tissues
Refers to the pressure inside relative to the pressure outside
What is transpulmonary pressure?
Difference in pressure between the alveolar sacs and the pleural cavity
PTP= Ppl-Palv
What is transthoracic pressure?
Difference between the pleural cavity and the atmosphere
PTT= Patm - Ppl
What is the transrespiratory system pressure?
Difference between the alveolar sacs and the atmosphere
PRS= Patm-Palv
At rest, when the lung capacity is at FRC, what is the PRS?
Transrespiratory system pressure
PRS= 0
Recoil forces of the lung tissue and chest wall are balanced
Volume can increase (inspiration > FRC) or decrease (expiration
How do you initiate inspiration in negative pressure breathing?
Inspiratory muscles contract (principally diaphragm and other deeper muscles)
Ppl (intrapleural pressure) decreases as the thoracic pleura expands
To prevent this decrease, in pressure the visceral pleura is pulled outwards which inflates the lungs (negative pressure breathing)
How do you initiate inspiration in positive pressure breathing?
Increase in alveolar pressure
Stimulates an expansion of lung tissue against the resistance of the thoracic wall
Leads to increased increased pleural pressure which causes an expansion of the chest wall (prevent Palv rising too high)
NB.
- Intrapleural volume fixed and resistant to change (because its a fluid and not a gas)
- Intrapleural pressure not equal from base to apex (base pressure is -3 cmH20, apex is -7 cmH20)…. So average is -5 cmH20
What factors affect lung volumes and capacities?
Body size (height affects more than weight)
Sex (male larger than female)
Age (older= more diseased)
Disease (pulmonary, neurological)
Fitness (innate e.g. born in Andes, training)
What effect does obstructive disease have on RV, TV, IRV, ERV, TLV, FRC, VC?
↔↑RV ↔↑TV ↓↔IRV ↓↔ERV ↔↑ TLC ↔↑FRC ↓↔VC
What effect does restructive disease have on RV, TV, IRV, ERV, TLV, FRC, VC?
↓ RV ↔↓TV ↓IRV ↔↓ERV ↓TLC ↓FRC ↓VC
Describe the respiratory tree
Airway network of progressively bifurcating smaller tubes across 23 ‘generations’
Air is warmed, humidified, slowed and mixed as it passes down the respiratory tree
What is the conducting zone of the respiratory tree?
Where the velocity dramatically slows as the cross-sectional area increases
Functions= defence (mucus secreted), speech (vocal folds in larynx) and preparation of air for gas exchange (warming and humidifying)
16 generations
No gas exchange
150ml in adults at FRC
ANATOMICAL DEAD SPACE
What is the respiratory zone of the respiratory tree?
Respiratory bronchioles have occasional sacs off the sides that provide a surface for gas exchange
Further down the airway the concentration of these alveolar sacs increases dramatically
These respiratory sacs are called alveoli (parenchymal tissue of the airways)
7 generations
Gas exchange
350ml in adults
Air reaching here is equivalent to ALVEOLAR VENTILATION
What is non-perfused parenchyma?
Alveoli without a blood supply
No gas exchange
0ml in adults
ALVEOLAR DEAD SPACE
Parenchyma = functional subunit
What is dead space?
Generic term that describes parts of the airways that don’t participate in gas exchange
What is physiological dead space?
Anatomical + alveolar dead space
What is anatomical dead space?
Entirety of the conducting airways and upper respiratory tract
Can’t be measured using standard spirometry, use dilution test
How is a dilution test carried out?
Known volume of inert gas (e.g. helium) that is inspired and expired into a closed circuit
After enough breathing to equilibrate it with the air already in airway-> measure sample of the original volume for concentration of inert gas
To calculate VD use:
Ratio of inert gas to original concentration
Spirometry data
NB. Tubing connected to the airway increases the volume of anatomical dead space
What is alveolar dead space?
Includes respiratory tissues unable to participate in gas exchange, usually due to absent or inadequate blood flow
Healthy individuals, volume is effectively 0
What is physiological dead space?
Sum of anatomical and alveolar dead space volumes
How does alveolar ventilation happen?
Primary function of breathing (or mechanical ventilation)
Increasing depth of breathing is more effective at increasing alveolar ventilation
What is the value of alveolar ventilation during tidal (subconscious) breathing?
Equal to the difference between tidal volume and dead space
Valv= VT - VD
For every generation further down the airway, what happens to pressure and velocity of airflow?
Divergence in path associated with 50% decrease in pressure and velocity of airflow
Why you can’t get a longer snorkel to swim deeper?
More dead space (snorkel functions as extension of lung)
This means more times greater than resting TV and typical TLC
Poiseuille’s law:
Resistance= 8nl/πr4 (n with arrow down)
Boyle’s= P gas is proportional to 1/(v gas)
What does there need to be to ensure effective and sustainable gas exchange?
Ventilation= fresh sample of atmospheric air (alveolar ventilation) in the alveolar sac
Perfusion= Adequate perfusion (pulmonary capillary)
Need to be in close proximity (shorter diffusion distance)
What happens when there is a proportional imbalance between ventilation and perfusion ?
Compromise pulmonary gas exchange
Ventilated alveoli with no blood supply= wasted ventilation
Pulmonary capillaries that perfuse non-ventilated alveoli= wasted perfusion
Where in the lung is ventilated more readily and why?
Ventilation (V)in healthy upright individual…
Base ventilates more readily
Because of effect of gravity on the transpulmonary pressure
Makes the basal lung tissue more compliant (distensible)
Explain the difference between transpulmonary pressure in the apex, base and middle of the lung
APEX
PA > Pa > Pv
MIDDLE
Pa > PA > Pv
BASE
Pa > Pv > PA
How does perfusion (Q) vary in the lung?
Gravity affects distribution of blood flow
As pulmonary circulation flows at a low pressure, the vessels perfusing the base of the lung receive a greater proportion of blood flow (least resistant)
At rest, apex receives very little perfusion
How can the ratio of ventilation to perfusion be interpreted?
Ideally, blood would only flow to ventilated parts of the lung
Ratio shows ventilation volume per litre of perfusion
High V/Q associated with poorly perfused regions
Low V/Q associated with poorly ventilation regions
What factors alter the V/Q ratio?
Exercise stimulates increased cardiopulmonary effort to increase oxygen supply to meet escalating demand in the skeletal musculature
So RF, VE and Q increase proportionately
Increased force of ventilation-> improves apical ventilation-> increased pressure in the pulmonary circulation-> increases perfusion of apical capillary beds
Slight discrepancy between the base and apex of the lung, more subtle than at rest
What role does gravity have on ventilation and perfusion?
Favours V and Q of the basal lung versus the apical lung
Where in the lung is more likely to have ‘wasted perfusion’ and ‘wasted ventilation’?
Basal lung has ‘wasted perfusion’
Apical lung has ‘wasted ventilation’
What are common lung function tests?
Volume-time curve
Peak expiratory flow
Flow-volume loop
How does the volume-time curve work?
PROTOCOL
- Patient wears nose clip
- Patient inhales to TLC
- Patient wraps lips round mouthpiece
- Patient exhales as hard and fast as possible
- Exhalation continues until RV is reached or six seconds have passed
- Visually inspect performance and volume time curve- repeat if necessary
- Look out for:
a. Slow starts
b. Early stops
c. Intramanouever variability
How does peak expiratory flow work?
PROTOCOL
- Patient wears nose clip
- Patient inhales to TLC
- Patient wraps lips round mouthpiece
- Patient exhales as hard and fast as possible
- Exhalation doesn’t have to reach RV
- Repeat at least twice (take highest measurement)
How does flow-volume loop work?
- Patient wears noseclip
- Patient wraps lips round mouthpiece
- Patient completes at least one tidal breath
- Patient inhales steadily to TLC
- Patient exhales as hard and fast as possible
- Exhalation continues until RV reached
- Patient immediately inhales to TLC
- Visually inspect performance and volume time curve and repeat if necessary
Look out for:
a. Inconsistencies with clinical picture
b. Interrupted flow data
List common airway problems
Mild obstructive disease Severe obstructive disease Restrictive disease Variable extrathoracic obstruction Variable intrathoracic obstruction Fixed airway obstruction
What is the shape of the curve for mild obstructive disease?
Displaced to the left (indented exhalation curve)
RV and TLC are higher than normal
Because of mild breakdown in lung parenchymal tissue and hyperinflation of lungs
More air retained in lungs at RV (can’t be emptied)
Mild ‘coving’ (indentation) on the expiratory loop that suggests obstruction of the smaller airways
What is the shape of the curve for severe obstructive disease?
Shorter curve
Displaced to the left
Indented exhalation curve
Like mild, except the features of the loop are more pronounced
The RV is larger (more hyperinflation) and the ‘coving’ is deeper
Also, the height of the curve is lower, showing a lower peak expiratory flow rate (due to obstruction)
What is the shape of the curve for restrictive disease?
Displaced to the right
Narrower curve
Overall shape of the curve is preserved, however it is narrower on the x-axis (indicating a smaller TLC) and shorter on the y-axis (indicating impaired flow rates for inspiration and expiration)
What is the shape of the curve for the variable extrathoracic curve?
Blunted inspiratory curve (bottom too short)
Otherwise normal
This curve shows a complete normal expiratory curve, but an impeded (flattened) inspiratory curve
This is due to an obstruction outside thorax (perhaps the upper airway)
What is the shape of the curve for the variable intrathoracic curve?
Blunted expiratory curve (top too short)
Otherwise normal
This curve shows a complete normal inspiratory curve, but an impeded (flattened) expiratory curve
This is due to an obstruction within the thorax (perhaps the trachea)
What is the shape of the curve for the fixed airway obstruction?
Loop shows mixed characteristics of variable intra and extra obstruction
Blunted inspiratory and expiratory curves
Otherwise normal
What part of the lung/chest is in a partial vacuum?
Pleural cavity
What are the different mechanical forces involved in tidal and maximal ventilation?
Tidal breathing is predominantly diaphragm-induced (syringe movement)
Maximum ventilation involves full inspiratory muscle recruitment (syringe and bucket handle movement)
In gas transport/exchange, how are descriptions denoted?
I.e. how would you say volume of carbon monoxide bound to haemoglobin in the alveolar blood?
Prefix e.g. P, F, S, C, Hb
Middle (subscript) e.g. I, E, A, a, v (with line across top), P, D
Suffix e.g. O2, CO2, N2, Ar, CO, H20
SO…..
HbACO (A subscript)
In gas transport/exchange, what are these prefixes; P, F, S, C, Hb?
P= partial pressure (kPa or mmHg)
F= fraction (% or decimal)
S= Hb saturation (%)
C= content (mL)
Hb= volume bound to Hb (mL)
In gas transport/exchange, what are these middle (subscript) initials; e.g. I, E, A, a, v (with line across top), P, D
I= inspired
E= expired
A= alveolar
a= arterial
v (with line across top)= mixed venous
P= peripheral
D= dissolved
In gas transport/exchange, what are these suffixes; e.g. O2, CO2, N2, Ar, CO, H20?
O2= oxygen
CO2= carbon dioxide
N2= nitrogen
Ar= argon
CO= carbon monoxide
H20= water
List the key gas laws relevant in gas transport
Henry Fick Dalton Boyle Charles
‘Charles found Henry drinking beer’
What is Dalton’s law?
The pressure of a gas mixture is equal to the sum of partial pressures of gases in that mixture
Describes the pressure composition of the atmosphere
What is Fick’s law?
Molecules diffuse from regions of high conc to low conc at a rate
PROPORTIONAL TO:
P1-P2= the conc gradient
A= surface area for exchange
D= diffusibility of the gas
INVERSELY PROPORTIONAL TO:
T= thickness of the exchange surface
Describes factors affecting diffusion of molecules across a membrane
What is Henry’s law?
At a constant temperature, the amount of given gas that dissolves in a given type and volume of liquid is:
DIRECTLY PROPORTIONAL TO:
a= solubility of the gas
P= partial pressure of gas in equilibrium with that liquid
Describes how gas solubility in blood is proportional to pressure
What is Boyle’s law?
At a constant temperature, the volume (V) of a gas is indirectly proportional to the pressure (P) of the gas
Describes how gas volume decreases with increasing pressure
What is Charles’ law?
At a constant pressure, the volume (V) of a gas is proportional to the temperature (T) of that gas
Describes how gas volume increases with increasing temperature
What is atmospheric gas made up of?
- 2% nitrogen
- 9 % oxygen
- 9% argon
- 04% carbon dioxide
- 01% neon, xenon, helium and hydrogen
What is the barometric pressure (PB) at sea level?
101.3 kPa (760 mmHg)
How can the partial pressure of a gas (PGas) be calculated within a mixture?
Barometric pressure x gas proportion (as decimal) = kPa
E.g. 101.3 kPa x 0.209 = 21.2 kPa
= PO2 at sea level
What percentage of oxygen is in supplemental/therapeutical oxygen and how is it administered?
Up to 100%
Nasal cannula or full face mask
Depending on the concentration and flow rate of therapeutical oxygen, how much could the fraction of inspired oxygen (FI02) be increased to?
Above 60%
So amount of oxygen that will dissolve in the blood increases
What happens when noxious or polluted air is inspired?
Dangerous
Low oxygen in the mixture or chemicals that interrupt normal physiology (e.g. CO)
What happens to barometric pressure as altitude increases?
Ambient PB reduces
Fractions in inspired air are unchanged but reduced overall pressure
So PBIO2 at sea level= 21.2 kPa
PBIO2 at 4000m= 61.3 kPa
BUT still 20.9% oxygen
I.e. 20.9% of a smaller cake
What PO2, PCO2 and PH20 are found at sea level, in the conducting airways and in the respiratory airways
DRY AIR AT SEA LEVEL
PO2= 21.3
PCO2= 0
PH20= 0
CONDUCTING AIRWAYS
PO2= 20
PCO2= 0
PH20= 6.3
RESPIRATORY AIRWAYS
PO2= 13.5
PCO2= 5.3
PH20= 6.3
All in kPa
Air is warmed, humidified, slowed and mixed down respiratory tree
What is the total oxygen delivery at rest?
16ml/min
What is resting VO2?
Approx 250ml/min
Why is there a need for a more effective transport mechanism for oxygen than just relying on dissolved oxygen?
Total oxygen delivery at rest=16ml/min
Resting VO2= approx 250ml/min
Dissolved oxygen alone is not enough
Describe a monomer of haemoglobin
Ferrous iron ion (Fe 2+, haem-) at the centre of a tetrapyrrole porphyrin ring
Connected to a protein chain (-globin)
Covalently bonded at the proximal histamine residue
What are the 4 variants of haemoglobin
Alpha chain + haem = Hbα
Beta chain + haem = Hbβ
Delta chain + haem = Hbδ
Gamma chain + haem = Hbγ
How many monomers of haemoglobin form a haemoglobin molecule?
4-> tetramer
So can carry 4 oxygen molecules
What are the 3 most common variants of haemoglobin tetramer molecules?
HbA (2 Hbα & 2 Hbβ)= Adult Hb; 98%
HbA2 (2 Hbα & 2 Hbδ)= Adult Hb normal variant; ~2%
HbF (2 Hbα & 2 Hbγ)= Foetal Hb; trace amounts
What does it mean that haemoglobin is an allosteric protein?
As more molecules of oxygen bind, there is a greater attraction for other oxygens to bind
Cooperativity-> high affinity
What is methahaemoglobin?
If the ferrous iron (Fe 2+) is further oxidised by nitrites (-> Fe 3+, ferric form) then the haemoglobin becomes methaemoglobin (MetHb)
MetHb doesn’t bind oxygen so can cause functional anaemia
- Normal Hct
- Normal PCV
- Impaired O2 capacity
Describe the oxygen dissociation curve
Relationship between PO2 and oxygen in solution is simple and linear BUT Hb is more efficient than this
Across the physiological range of the lungs, Hb remains almost fully saturated (very shallow relationship)
At respiring tissues, there is a steep relationship (between PO2 and Hb saturation)
Why is haemoglobin very efficient at loading oxygen in the lungs and unloading oxygen at respiring tissues?
Lungs: LARGE change in PO2 = SMALL change in HbO2
Tissues: SMALL change in PO2 = LARGE change in HbO2
What causes a rightward shift in the oxygen dissociation curve?
Increased temperature
Acidosis (Bohr effect)
Hypercapnia
Increased 2,3- DPG
What causes a leftward shift in the haemoglobin oxygen dissociation curve?
Decreased temperature
Alkalosis
Hypocapnia
Decreased 2,3- DPG
What is the PO2 on the oxygen dissociation curve that corresponds to 50% binding called?
P50
Used as an index of oxygen affinity
Found on one of the steepest parts of the ODC (so highly susceptible to changes)
What is the normal P50 for adult Hb?
3.3 kPa
What haemoglobin concentration does the oxygen dissociation curve assume?
15g/dL
What causes the haemoglobin concentration to change?
Polycythaemia= condition where concentration of RBCs in the blood is much higher than normal, usually when the Hct/PCV is >55%
Anaemia
NB. severely anaemic patient may still have a normal pulse oximetry because can still fully saturate their Hb
.
Carbon monoxide= colourless, odourless poisonous gas (usually due to incomplete fuel combustion)
Why does CO affect haemoglobin concentration?
Hb has a greater affinity for CO than oxygen (250 times greater)
Hb will preferentially bind CO in the lungs, which reduces the number of binding sites for oxygen-> reducing oxygen content in the blood (causing a functional anaemia)
Also, binding CO pushes Hb into the tense state, reducing its ability to unbind any oxygen it is carrying
NB. Inhaling gas solution of 0.2% CO will occupy 80% haem binding sites
What does the HbCO dissociation curve look like?
HbCO ODC is displaced downwards (less capacity to bind O2) and leftwards (greater affinity for bound oxygen)
How does polycythaemia affect haemoglobin concentration?
RBC conc is much higher than normal
This stretches the ODC upwards, meaning that for a given PO2 there is no change in HbO2 saturation but a marked increase in blood oxygen content
How does anaemia affect haemoglobin concentration?
ODC pushed downwards as there is a lower concentration of haemoglobin, markedly reducing the overall oxygen-carrying capacity of the blood
Pulse oximetry may be same (can fully saturate their Hb)
What is the principal factor controlling the haemoglobin-oxygen relationship?
The partial pressure of dissolved oxygen
Although small by proportion (1.5%) it is pivotal in O2 transport
What does the ODC of foetal haemoglobin look like?
Greater affinity than adult HbA to ‘extract’ oxygen from mothers blood in placenta
So ODC shits to left
What does the ODC of myoglobin look like?
Much greater affinity than adult HbA to ‘extract’ oxygen from circulating blood and store it
So ODC shifts very far to left (almost vertical by Y axis), more left than foetal haemoglobin
What does foetal haemoglobin (HbF) consist of?
2 alpha chains
2 gamma chains
Greater affinity for oxygen than adult haemoglobin
In utero, HbF proportion is dominant (switches to HbA post-partum)
What is the P50 for HbF?
2.4 kPa
Why does methaemoglobin only occur in low quantities in healthy people?
Redox reactions constantly liberating or binding electrons
What is methaemoglobinaemia?
MetHb concentration is >1%
Functional anaemia (Hct and PCV normal, oxygen carrying capacity impaired)
100% MetHb would result in death (dissolved oxygen can’t support metabolic demands)
Familial methaemoglobinaemia is genetically recessive medical condition-> blue tinge of skin
What is myoglobin (Mb)?
Not a haemoglobin variant
Another oxygen-binding molecule
Consists of a haem molecule bound to a protein chain
What are the main differences between Mb and Hb?
Mb is a monomeric molecule (i.e. one haem group, one protein chain and one molecule of bound O2
Mb is a principally a storage molecule (Hb is a transport molecule) found in myocytes (myoglobin)
Why is meat fresh red/pink in colour?
High concentration of myoglobin
What is the P50 for Mb?
Very low
Approx 0.37 kPa
In respiratory gas transport, how is mixed venous blood involved in oxygen loading?
Blood in the venous circulation is often referred to as deoxygenated, despite the blood still containing 75% of the oxygen that arterial blood has
So known as mixed venous, and by using the symbol v̄
Blood retains 75% of its oxygen because metabolic demand for oxygen is low at rest
Using the ODC, this gives a PVO2 of 5.3 kPa (40 mmHg)
PAO2 is 13.5 kPa, and when deoxygenated blood reaches the respiratory exchanges surface it rapidly equilibrates with alveolar gas (0.25 s)
Oxygen passively diffuses down a concentration gradient (Fick’s Law)
During oxygenation, it passes from the alveolar space, into the pulmonary epithelial cells, into the interstitial space, into vascular endothelial cells, into the plasma, into red blood cells, and then binds to molecules of Hb that are not fully saturated
After equilibration, post-alveolar PaO2 is equal to PAO2 (which is 13.5 kPa) and SaO2 will be 100%
Post-alveolar venules converge into pulmonary veins but some deoxy blood enters circulation from bronchial venous drainage (before draining into the left atrium and being pumped into the systemic circulation)
This deoxygenated blood dilutes the PaO2 to 12.7 kPa (95 mmHg) and the SaO2 to 97%
In total, oxygen content (CaO2) is still slightly more than 20 mL/dL which is a delivery rate of about 1000 mL/min (assuming a cardiac output (Q̇) of 5 L/min)
In respiratory gas transport, how is mixed venous blood involved in oxygen unloading?
Arterial blood leaving heart remains unchanged (after oxygen loading) until it reaches systemic capillary beds, where tissue PO2 is considerably lower than PaO2
This gradient promotes diffusion of oxygen from the plasma into the endothelial cells, into interstitium, respiring cells, and mitochondria
As soon as the PaO2 starts to decrease, oxygen unloads from Hb (according to the ODC) and follows the dissolved oxygen down the concentration gradient and out of the circulation
Once the blood enters the venous circulation the PO2 has been reduced 5.3 kPa and SV̄O2 to 75%
CaO2 is reduced to 15 mL/dL, which is a 5 mL/d reduction from the pre-capillary vessel
In respiratory gas transport, how is mixed venous blood involved in oxygen flux?
Assuming a 5 L/min cardiac output, this represents a 250 mL/min rate of oxygen utilization
This is termed the oxygen consumption and is denoted by V̇O2
Blood is then returned to the right side of the heart where it is pumped back to the lungs and the cycle restarts
In respiratory gas transport, how is mixed venous blood involved in carbon dioxide loading?
CO2 is much more soluble (about 20x greater) than oxygen and diffuses into plasma very quickly
But in an aqueous solution (like plasma) CO2 will combine with H2O to form carbonic acid (H2CO3)
H2CO2= a weak acid that dissociates into a proton (H+) and bicarbonate (HCO3-)
Although very slow, this can cause the pH to fall significantly below the tightly regulated set-point of 7.4
Like oxygen, CO2 diffuses down the concentration gradient, so when plasma PCO2 begins to rise, CO2 begins to diffuse into erythrocytes
Once inside, the conversion of CO2 and H2O to carbonic acid is accelerated by the enzyme carbonic anhydrase
Bicarbonate is pumped out of the erythrocyte by an AE1 exchanger, which imports chloride ions to maintain membrane electroneutrality
The influx of chloride is associated with an influx of H2O – keeps the cell hydrated (water pumped out cell in form of bicarbonate)
To prevent an intracellular decrease in pH, excess protons are buffered by globin chains of haemoglobin molecules– certain residues are active proton accepters (e.g. Histamine)
Some intraerythrocytic CO2 binds to haemoglobin, but not to the haem molecule like oxygen; instead it combines with the amine group and the N-terminal of globin chains (-NH2 to -NHCOOH) adding a carboxyl group
When this occurs the haemoglobin molecule becomes carbamino-haemoglobin (HbCO2)
In respiratory gas transport, how is mixed venous blood involved in carbon dioxide unloading?
Similar to oxygen, CO2 in solution will diffuse into the alveoli first, which will trigger the reversal of all of the other binding mechanisms
Bicarbonate will re-enter erythrocytes and be re-associate with H+ to form carbonic acid, which the carbonic anhydrase enzyme will convert back into CO2 and H2O
Less oxygen bound, the more carbon dioxide will bind (and vice versa)
How long are pulmonary transmit time and gas exchange time?
Pulmonary transmit time= 0.75s
Gas exchange time= 0.25s
Oxygen less soluble, takes slightly longer
What is the main difference between carbon dioxide and oxygen transport?
The major difference between oxygen and carbon dioxide transport is that CO2 is much more soluble (about 20x greater) and diffuses into plasma very quickly
BUT in an aqueous solution (like plasma) CO2 will combine with H2O to form carbonic acid (H2CO3); a weak acid that dissociates into a proton (H+) and bicarbonate (HCO3-)
Very slow reaction but can cause the pH to fall significantly below the tightly regulated set-point of 7.4
What enzyme catalyses the reaction from CO2 and H2O to carbonic acid?
Carbonic anhydrase
Catalyses the reaction by a factor of 5000x and subsequent H2CO3 dissociates into H+ and HCO3- ions
Summarise how respiratory gases are transported in the blood
O2 transported in solution (~2%) or bound to Hb (~98%)
CO2 transported in solution, as bicarbonate (HCO3-) and as carbamino compounds (e.g. HbCO2)
What is the basic structure of the airways?
Conduit pipes to:
Conduct oxygen to the alveoli
Conduct carbon dioxide out of the lung
Cartilaginous or alveolar
What facilitates the functions of the airways?
Mechanical stability (cartilage)
Control of calibre (smooth muscle)
Protection and ‘cleansing’
How many generations of branches are there from trachea to alveolar sacs?
23
Cartilage quantity decreases
Smooth muscle increases
NB. cartilage ring incomplete and slightly offset, smooth muscle and nervous innervation complete
Why are the C shaped cartilages not set?
If set and stacked, there would be less tensile strength
This means can’t see the whole C
What happens to mucus when muscle contracts?
Muscle contracts-> squeezes mucus onto airway surface
Unknown process
What type of airways cells are found in ….?
Lining Contractile Secretory Connective Neuroendocrine Vascular Immune
Lining= ciliated, intermediate, brush, basal
Contractile= smooth muscle (airways, vasculature)
Secretory= goblet, mucous, serous
Connective= fibroblast, interstitial cell (elastin, collagen, cartilage)
Neuroendocrine= nerves, ganglia, neuroendocrine cells, neuroepithelial bodies
Vascular= endothelial, pericyte, plasma cell (and smooth muscle)
Immune= mast cell, dendritic cell, lymphocyte, eosinophil, macrophage, neutrophil
What do goblet cells contain?
Mucin granules
What do ciliated cells contain?
Many mitochondria
What cells are in the submucosal glands in the airway?
Mucous and serous acini
What is secreted by mucous and serous cells?
Mucous cells secrete mucins (mucin granules contain mucin in highly condensed form)
Serous cells secrete antibacterials (e.g. lysozyme)
Glands also secrete salt and water (Na ions and Cl ions)
What is the function of epithelial cells?
Secretion of mucins, salt and water
(Mucus + plasma , mediators etc.)
Physical barrier
Production of inflammatory and regulatory mediators (NO, CO, chemokine, cytokines, proteases, prostaglandins)
What is the ciliary structure?
9 + 2 arrangements of microtubules
Metachronal rhythm (beats out of sync-> moves mucus in one direction instead of backwards and forwards)
Mucus flakes= could be artefact of imaging or just how it works in people without lung conditions
With conditions-> thick mat of mucus
Describe the response of the smooth muscle in airways to inflammation
Structure- hypertrophy, proliferation
Tone (airway calibre)- contraction, relaxation
Secretion (mediators, cytokines, chemokines)
What is the secretory response of smooth muscle cells to inflammation?
Inflammation-> bacterial products and cytokines which act on smooth muscle cell
NOS-> NO
COX-> prostaglandins
Inflammatory cells recruitment (chemokines
cytokines and adhesion molecules)
What is the humoral control of the function of the airway cells?
Regulatory and inflammatory mediators:
- Histamine
- Arachidonic acid metabolites (e.g. prostaglandins, leukotrienes)
- Cytokines
- Chemokines
Reactive gas species
- Proteinases
Describe the tracheo-bronchial circulation (of the airway circulation)
1-5% of cardiac output
High blood flow (100-150 ml/min/100g tissue)
Bronchial arteries arise from sites on:
Aorta, intercostal arteries and others
Blood returns from tracheal circulation via systemic veins
Blood returns from bronchial circulation to both sides of heart via bronchial and pulmonary veins
Contributes to warming and humidification of inspired air
Clears inflammatory mediators and inhaled drugs
Provides airway tissue and lumen with inflammatory cells
Supplies airway tissue with proteinaceous plasma
Describe the 3 types of nerve that control the function of airway cells
Parasympathetic- cholinergic (ACh)
Sympathetic- adrenergic (adrenaline and noradreanline)
Sensory
What do cholinergic neurons do to control airways?
Principle motor control of airway (constriction)
Cholinergic nerves-> ACh onto muscarinic receptors on:
- Blood vessels
- Smooth muscle cells
- Submucosal glands
Why do the airways rely on the adrenal gland?
Little/no adrenergic nerves
List cells in regulatory-inflammatory cells in airways
Eosinophil Neutrophil Macrophage Mast cell T lymphocyte Structural cells e.g. smooth muscle, may also be regulatory-inflammatory cells
List mediators in regulatory-inflammatory cells in airways
Histamine Serotonin Adenosine Prostaglandins Leukotrienes Thromboxane PAF Endothelin Cytokines Chemokines Growth factors Proteinases Reactive gas species
What functions do the mediators have on on regulatory-inflammatory cells in airways?
Smooth muscle (airway, vascular: contraction, relaxation)
Secretion (mucins, water etc.)
Plasma exudation
Neural modulation
Chemotaxis
Remodelling
What respiratory diseases are associated with loss of airway control?
Loss of control-> respiratory disease
Asthma, COPD, cystic fibrosis
Airway inflammation, airway obstruction
Airway remodelling
What is the prevalence of asthma, COPD and CF?
Asthma – 5% of population
COPD – 4th cause of death in UK/USA
CF – 1:2000 Caucasians
What is asthma?
Increased airway responsiveness to a variety of stimuli -> airway inflammation and obstruction
Airway obstruction varies over short periods of time, is reversible
Dyspnea, wheezing, coughing
Varying degrees (mild to severe)
Airway inflammation-> re-modelling
Bronchoconstriction
What is bronchoconstriction?
Airway wall is thrown into folds, mucus plug in lumen
What is the mucosa in the lung?
Epithelium and underlying matrix
What is the structure of the mucosa?
From the large conducting airway to the alveoli
The structure is optimised for gas exchange (s.a. approximately size of tennis court)
Gas exchange units form a sponge-like structure which are intimately linked with the airways
The cross-sectional area of the lung increases peripherally
The gas exchange units are linked with surfactant
What lines the gas exchange units and why?
Surfactant
Phospholipid-rich surface active material that prevents lung collapse on expiration (immunological functions)
Secreted in the peripheral link and accounts for about 1 wine glass of fluid
Forms a very thin layer covering the respiratory units
Without it, the surface tension of the different gas exchange units will increase-> collapse of the lung
Describe the healthy lung?
HEALTHY LUNG
Epithelium forms a continuous barrier, isolating the external environment from the host
Produces secretions to facilitate mucociliary clearance
Protects underlying cells as well as maintain reduced surface tension
Metabolises foreign and host-derived compounds which may be carcinogenic – important for smokers
Releases mediators – controls number of inflammatory cells that reach the lung
Triggers lung repair processes
Describe the lung in COPD?
IN COPD
Increased number of goblet cells (known as hyperplasia) and increased mucus secretion
Between the goblet cells, ciliated cells push the mucus towards the throat
What proportion of epithalial cells are the goblet cells?
1/5
In large, central and small airways
What do goblet cells do?
Synthesise and secrete mucus
Mucus is complex, very ‘thin’ sol phase overlays cells, thick gel phase at air interphase
What happens to goblet cells in smokers?
Goblet cell number at least 2x
Secretions increase
More viscoelastic secretions
What does the modified gel phase do?
Traps cigarette smoke particles but always traps and harbours microorganisms
Enhances chance of infection
What does mucus contain?
Mucin proteins, proteoglycans and gycosaminoglycans, released from goblet cells and seromucous glands
Serum-derived proteins, such as albumin and alpha 1-antitrypsin, also called alpha 1-proteinase inhibitor, an inhibitor of polymorphonuclear neutrophil proteases
Antiproteases synthesised by epithelial cells e.g. secretory leucoprotease inhibitor
Antioxidants from the blood and synthesised by epithelial cells and phagocytes - uric acid and ascorbic acid (blood), glutathione (cells)
What is the purpose of mucin proteins, proteoglycans and glycosaminoglycans in mucus?
Gives mucus viscoelastcity
What is the purpose of serum-derived proteins e.g. albumin in mucus?
Combats microorganism and phagocyte proteases
What is the purpose of antiproteases in mucus?
Combats microogranism and phagocyte proteases
What is the purpose of antioxidants from the blood in mucus?
Combats inhaled oxidants e.g. cigarette smoke, ozone
Counteracts excessive oxidants released by activated phagocytes
What percentage of epithelial cells are ciliated cells?
80%
Found in large, central and small airways
How do cilia beat?
Metasynchronously
Push mucus forward engaging when vertical
Then circle around to original position in order to prevent the movement of the mucus backward as well as forward
Tips of cilia in sol phase of mucus pushes mucus towards epiglottis
Usually swallowed but expectorate
What happens to ciliated cells in smokers with bronchitis?
BRONCHIOLAR CILIATED CELLS
Depleted
Beat asynchronously
Reduced mucus clearance, bronchitis and respiratory infections occur
Airways obstructed by mucus secretions
Which lung condition associated with COPD is more easily reversed than other illnesses?
Bronchitis
Describe small airways
reduces peripheral gas exchange)
What are clara cells?
Club cells (non-ciliated, bronchiolar exocrine epithelial cells)
In large, central and small airways, bronchi and bronchioles
Found in most conducting and transitional airways (they increase proportionally distally)
What is the role of clara cells?
Metabolism, detoxification and repair
Contain phase I (incl. cytochrome P450 oxidases) and phase II enzymes
Major role of these enzymes is in xenobiotic metabolism (metabolism of foreign compounds deposited by inhalation)
Phase I enzymes are designed to metabolise foreign compounds into a format that enables phase II enzymes to react and neutralise the toxic agent
What is the problem with Phase I enzymes in clara cells?
Phase I enzymes are designed to metabolise foreign compounds into a format that enables phase II enzymes to react and neutralise the toxic agent; BUT they often activate a precarcinogen to a carcinogen
E.g: Benzopyrene (BP) is a precarcinogen in the particulate tar phase of cigarette smoke
One cytochrome P450, labelled CYPIA1 (also called aryl hydrocarbon hydroxylase), oxidases BP to benzopyrene diol epoxide (BPDE) which is a potent carcinogen
Phase II enzymes include glutathione S-transferase, which enables conjugation of BPDE to a small molecule that neutralises its activity
Why is CYPIA1 (one cytochrome P450) dangerous for smokers?
Smokers with lung cancer have a polymorphism of CYPIA1 that results in high levels (extensive metabolism -> extensive production of potent carcinogen)
