Respiratory System Flashcards
What is the concentration of oxygen and carbon dioxide in the atmosphere?
Oxygen - 0.209 (20.9%)
Carbon dioxide - 0.0004 (0.04%)
What is the Partial pressure of oxygen in alveolar air, arterial blood and mixed venous blood, of a healthy subject with [Hb] 15g/dl?
Alveolar air (PAO2) = 13.3kPa Arterial blood (PaO2) = 13.3kPa Mixed venous blood (PVO2) = 5.3kPa
What is the Partial pressure of carbon oxide in alveolar air, arterial blood and mixed venous blood, of a healthy subject with [Hb] 15g/dl?
Alveolar air (PACO2) = 5.3kPa Arterial blood (PaCO2) = 5.3kPa Mixed venous blood (PVCO2) = 6.1kPa
What are the types of Respiratory diseases?
Airways diseases:
- Localised obstruction: e.g. foreign bodies, upper airway tumours, thyroid enlargement, obstructive sleep apnoea syndrome
- Generalised obstruction: e.g. Asthma, C.O.P.D, bronchiectasis, cystic fibrosis
Small lung/Restrictive disorders:
- Disease within lungs: e.g. Idiopathic pulmonary fibrosis, sardoicodosis, hypersensitivity pneumonitis, asbestosis
- Disease outside lungs: e.g. Pleural effusions, mesothelioma, pnerumothorax, Scoliosis, respiratory muscle weakness, obesity
Infections: e.g. Tuberculosis, infective bronchitis, Pneumonia/Empyema
Pulmonary vascular disorders: e.g. pulmonary emboli, pulmonary hypertension
What are the symptoms generally associated with respiratory disease?
- Breathlessness
- Cough
- Sputum production
- Haemoptysis (coughing blood)
- Chest discomfort
- Wheeze or musical breathing
- Stridor
- Hoarseness
- Snoring history/daytime sleepiness
- (weight loss, anorexia, fever)
How much Oxygen is need by a resting adult?
250ml/minute
Outline gas exchange.
- Action of breathing delivers warmed, humidified air to specialised gas exchange surfaces
- The heart delivers de-oxygenated blood to the pulmonary capillaries
- Gas exchange between air and blood occurs by diffusion
What is the process of diagnosis?
- Symptoms
- Take a history
- Examine respiratory system
What is the pathway of air in the respiratory system?
- Nasal/oral cavity
- Pharynx
- Larynx
- Trachea
- Bronchi
- Lungs
What is the function of mucosa?
To warm and humidify the air before it reaches the lungs
What is are the nerves supplying the nasal cavity?
- No motor only sensory
Cranial nerve V (trigeminal)
- Two branches: opthalmic and maxillary division
- General sensation e.g. temperature, irritation
Olfactory nerves:
- Top and back of cavity
- Near holes which allow nerves to pass into the skull to the olfactory tract
- Only sensing smell (chemical)
What are the paranasal air sinuses?
- Frontal sinus (in frontal bone, superior to eyes)
- Sphenoidal sinus (in sphenoid bone, at posterior and middle)
- Ethmoid air cells (underneath base of anterior skull, medial wall of orbit)
- Maxillary sinus (in cheek) Biggest
What is the function of a para-nasal air sinus?
- Lined with ciliated epithelium
- Drain into the nasal cavity
- Only if injected/clogged are they noticable e.g. opening of maxillary sinus is at the top which isn’t effective
- Important for lightening the skull and keeping strength
- Act as heat insulation at high and low temperatures
- Act as resonating chambers for the voice
- Physically protective for brain
What is the pharynx?
Area where the nasal and oral cavity come together, before the separation of the larynx and oesophagus.
Split into three:
- Nasopharynx: between base of skull and soft palate
- Oropharynx: between soft palate and superior border of epiglotis
- Laryngopharynx: beteen epiglotis and just before larynx
Describe the larynx.
- In anterior of neck
- Made of thyroid cartilage superiorly (thought thyroid is below it), then Cricothyroid ligament (where emergency tracheotomy is performed) before the Cricoid cartilage. After this it reaches the trachea.
- Thyroid has no posterior, but Cricoid is a whole ring
- Cartilage controls the vocal ligaments, opening and shutting, determining what enters into the larynx (air)
How is sound made?
- Air is forced between the vocal ligaments in the larynx.
- Speed determines volume, distance between ligaments is pitch
- Words are made with the mouth, teeth, tongue etc
Describe the trachea.
- Held open by cartilage C-shaped rings, and has soft tissue posteriorly to allow the opening of the oesophagus behind it
- About 20 rings holding it open at all times
- Rings allow flexibility
Describe the tracheobronchial tree.
- Starts at the end of the larynx
- Bifurcates at carina at T4/5
- Unequal bifurcation due to slight right sided position (because of aorta)
- The primary bronchus on left is slightly longer, and right more vertical and shorter (clinical relevance for foreign objects)
- Primary divides into secondary which goes into the lobes
- Secondary divides into tertiary which goes into bronchopulmonary segments
- Cartilage in all bronchi though less and less
- After tertiary, bronchioles which have smooth muscle walls so can open and close. Terminal bronchioles end in alveolar sacs
Describe the dome of the diaphragm.
- Dome comes up to 5th intercostal space/level of male nipple (for someone lying down)
- But attached to the costal margin
What is the pleura made up of?
- Visceral (on the lung)
- Parietal (on the chest wall)
What areas are available to the lung for expansion?
- Right lung: Area inferior to its base (larger at posterior)
- Left lung: Area inferior to its base (larger at posterior) and area in front of the heart
What enters/exits the lung at the hilum?
- Pulmonary artery
- Pulmonary vein
- Lymph vessels and nodes
- Bronchi
- Pulmonary plexus (autonomic nerves)
- Bronchiole arteries
What is a bronchopulmonary segment?
The smallest functional unit of the lung. (each receive discrete air and blood supply)
Right lung: 10
Left lung: 8/9 (can be fusion)
Where does gas exchange take place?
Alveoli
Why does gas exchange take place?
Difference in partial pressure of oxygen in atmospheric air (100mg) and in the alveoli (40mg) drives exchange
What is the lymph system for the lungs called?
Bronchomediastinal trunk/system
Ascend with the trachea and enter the venous system.
Right - Subclavian and lower part of internal jugular
Left - Thoracic duct
Describe the structure of the diaphragm.
- Muscular around the edges
- Tendonous in the middle
Allows more efficient increase in volume of the thorax as it can flatten.
Connected to heart by the pericardium so heart also moves down to some degree.
What passes through the diaphragm?
- Inferior vena cava (in tendon as it’s low pressure so can’t resist other pressure e.g. muscle contraction) (T8)
- Oesophagus (T10) in muscle
- Descending aorta (T12)
What innervates the diaphragm?
Phrenic nerves, arising from C3,4,5 in the neck.
What is the relation between the two major nerves in the thorax and the lung?
Phrenic passes hilum anteriorly
Vagus passes hilum posteriorly
What movements do the ribs and diaphragm do for inspiration?
Ribs move outward, and the sternim is moved superiorly
Diaphragm moves down and flattens
What role do the abdominal muscles play in breathing?
- In forced expiration the muscles push upward
- Abdominal muscles are used in important actions, along with the diaphragm, such as coughing, vomiting etc.
Define Minute ventilation.
Volume of air expired in one minute (VE) or per minute
Define Respiratory rate (RF)
The frequency of breathing per minute
Define Alveolar ventilation (Valv)
The volume of air reaching the respiratory zone
Define Respiration
The process of generating ATP either with an excess of oxygen (aerobic) and a shortfall (anaerobic).
Define anatomical dead space
Capacity of the airways incapable of undertaking gas exchange
Define alveolar dead space.
Capacity of airways that should be able to undertake gas exchange but cannot (e.g. hypoperfused alveoli)
Define Physiological dead space.
Equivalent to the sum of alveolar and anatomical dead space
Define Hypoventilation.
Deficient ventilation of the lungs; unable to meet metabolic demand (increased PCO2 - acidosis)
Define Hyperventilation
Excessive ventilation of the lungs atop of metabolic demand (results in decreased PCO2 - alkalosis)
Define Hyperpnoea
Increased depth of breathing (to meet metabolic demand)
Define Hypopnoea
Decreased depth of breathing (inadequate to meet metabolic demand)
Define Apnoea
Cessation of breathing (no air movement)
Define Dyspnoea
Difficulty breathing
Define Bradypnoea
Abnormally slow breathing rate
Define Tachypnoea
Abnormally fast breathing rate
Define Orthopnoea
Positional difficulty in breathing (when lying down)
Explain the mechanical relationship between the chest wall and the lung.
- Chest wall has tendency to spring outwards
- Lung has a tendency to recoil inwards
- Forces are at equilibrium at end-tidal expiration (Functional residual capacity; FRC) which is neutral position of the intact chest
- To further inspire (or expire) requires equilibrium to be temporarily imbalanced
What is the Pleural membrane?
- Lungs are surrounded by visceral pleural membrane
- Inner surface of chest wall is covered by a parietal pleural membrane
- Pleural cavity between them is a fixed volume and contains protein-rich pleural fluid
What could cause a breach in the pleural cavity?
- Intrapleural bleeding causing a haemothorax
- Perforated chest wall/punctured lung causing a Pneumothorax
What is the tidal volume (TV)?
The volume of air inspired during normal, relaxed breathing (about 500ml)
What is Inspiratory reserve volume (IRV)?
The additional air that can be forcible inhales after the inpiration of a normal tidal volume (about 3100ml)
What is the Expiratory reserve volume (ERV)?
The additional air that can be forcibly exhaled after the expiration of a normal tidal volume (about 1200ml)
What is Residual volume (RV)?
The volume of air still remaining in the lungs after the expiratory reserve volume in exhaled (about 1200ml)
What is the total lung capacity (TLC)
The maximum amount of air that can fill the lungs. (about 6000ml)
TLC= TV+IRV+ERV+RV
What is the vital capacity (VC)?
The total amount of air that can be expired after fully inhaling. (about 4800ml) Varies according to age and body size.
VC= TV+IRV+ERV
What is the inspiratory capacity (IC)?
The maximum amount of air that can be inspired. (about 3600ml)
IC= TV+IRV
What is the functional residual capacity (FRC)?
The amount of air remaining in the lungs after a normal expiration. (about 2400ml)
FRC= RV+ERV
What factors affect Lung volumes and capacities?
- Body Size (height and shape)
- Sex (male or female)
- Disease (pulmonary, neurological)
- Age
- Fitness (innate, training)
What are the two types of breathing in relation to pressure?
- Negative pressure breathing: Palv is reduced below Patm e.g. healthy breathing
- Positive pressure breathing: Patm is increased above Palv e.g.ventilation, CPR
What is transmural pressure?
Transmural pressure = P inside - P outside
Transrespiratory pressure = pressure across airways, lungs, chest wall
- Negative transrespiratory pressure will lead to inspiration
- Positive transmural pressure leads to expiration
Describe the process of ventilation.
- Increased volume of thorax, lowers pressure
- Air moves into the lungs, down pressure gradient
- Recoil of alveoli increases pressure
- Air moves out of the lungs, down pressure gradient
Describe the conducting zone.
- Bronchi and bronchioles
- 17 generations
- No gas exchange
- Typically 150ml in adults FRC
- Anatomical dead space
Describe the respiratory zone.
- Alveoli
- 7 generations
- Gas exchange
- Typicall 350 ml in adults
- Air reaching here is equivalent to alveolar ventilation
Describe non-perfused parenchyma.
- Alveoli without blood supply
- No gas exchange
- Typically 0ml in adults
- Called alveolar dead space
What reversible procedures would increase or decrease dead space?
- Increase: Ventilation
- Decrease: Tracheostomy
What is Pouseuilles’s Law?
Resistance = 8ηl/πr^4
π x radius ^4
What is Boyle’s Law?
P(Gas) is proportional to 1/V(Gas)
Volume of a gas is inversely proportional to pressure
Describe the mechanics of ventilation.
- Diaphragm has a pulling force in one direction (like syringe)
- Other respiratory muscles move upward and outwards (like bucket handle)
Both act to increase the volume of the thorax, and decrease the pressure.
On a graph what does the pressure/volume of the intact lung show?
- Equal to the independent chest wall + independent lung
- Sigmoid function (S shaped)
- So larger change in pressure is required to have a small change in volume at the extremes (total lung capacity, residual volume)
What is the method of a volume-time lung function test?
Patient wears noseclip
- Inhale to TLC
- Wraps lips around mouth piece
- Exhale as hard and fast as they can
- Continue exhaling till RV is reached or 6 seconds have passed
- Visually inspect performance on graph
What effect do restrictive and obstructive disorders have on the volume-time lung function test?
Restrictive: Lower FVC, lower FEV1, Higher FEV1/FVC ratio, lower forced expiratory time (FET)
Obstructive: Lower FVC, much lower FEV1, lower FEV1/FVC ratio, higher gorced expiratoy time (FET)
FEV1 = volume expired in 1 minute
How is peak expiratory flow measure?
Spirometer:
- Patient wears noseclip
- Patient inhales to TLC
- Patient wraps lips round mouthpiece
- Patient exhales as hard and fast as possible (don’t have to reach RC)
- Repeat twice and use highest
What are the factors taken into account to assess peak expiratory flow measure?
- Gender
- Height
- Age
What is the method of doing a Flow-volume loop?
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 to RV
- Immediately inhales to TLC
How do restrictive and obstructive diseases affect the flow-volume loop?
- Restrictive: Displaced to the right, shorter, narrower curve
- Severe obstructive: Shorter curve, displaced to the left, indented exhalation curve
- Mild obstructive: Very slightly shorter curve, displaced to the left, indented exhalation curve
How do different types of obstruction affect the flow-volume loop?
- Variable extrathoracic obstruction: Blocks inhalation. Blunted inspiratory curve, otherwise normal
- Variable intrathoracic obstruction: Blocks exhalation. Blunted expiratory curve, otherwise normal
- Fixed airway obstruction: Affects both. Blunted inspiratory and expiratory curve, otherwise normal
Explain the regional differences in ventilation and perfusion of the lung.
Gravity favours ventilation and perfusion of the basal lung versus the apical lung
What is the Dalton gas law?
Pressure of a gas mixture is equal to the sum of the partial pressures of gases in that mixture
What is the Fick gas law?
Molecules diffuse from regions of high concentration to low concentration at a rate proportional to the concentration gradient, the exchange surface area and the diffusion capacity of the gas. It is inversely proportional to the thickness of the exchange surface.
What is the Henry gas law?
At a constant temperature, the amount of a given gas that dissolves in a given type and volume of liquid is directly proportional to the partial pressure of that gas in equilibrium with that liquid.
What is the Boyle gas law?
At a constant temperature, the volume of a gas is inversely proportional to the pressure of that gas.
What is the Charles gas law?
At a constant pressure, the volume of a gas in proportional to the temperature of that gas.
What differences are there in the composition of room air, oxygen therapy, smoke and air at high altitude?
- Room air: 78% nitrogen, 21% oxygen, 0.9% argon, 0.04% CO2
- Oxygen therapy: 40% nitrogen, 59% oxygen etc
- Smoke/house fire: Less oxygen, more CO2, some CO
- High altitude: Same proportions but smaller volume
What changes occur from the atmospheric air to the respiratory airways?
- Slowed
- Warmed
- Humidified
- Mixed
PO2 decreases + PCO2 increases in respiratory airways, PH2O increases n conducting airways
What is the total oxygen delivery at rest on solubility alone? What’s needed?
16ml per minute
250mL per minute is requires at rest. To increase this number specialist binding proteins are needed. (Haemoglobin)
Describe the features of Haemoglobin.
- Four monomers; Each a Ferrous iron ion (Fe2+, valency of 2) at centre of tetrapyrrole porphyrin ring, connected to a protein chain.
- Genes responsible for coding the globin chain can produce four variants:
- Alpha chain (main)
- Beta chain (variant of main)
- Gamma chain (foetal heamoglobin)
- Delta chain
- Capable of carrying 4 O2 molecules
- 3 Common variants:
- HbA (2 alpha, 2 beta); Adult Hb; 98%
- HbA2 (2 alpha, 2 delta); Adult Hb; 2%
- HbF (2 alpha, 2 gamma) Foetal Hb; trace amounts
- Haemoglobin in toxic, and so is carried in red blood cells.
How does Haemoglobin change when binding to oxygen?
Cooperative binding:
- Haemoglobin has a low affinity for oxygen at the beginning
- As more O2 binds the affinity increases
Allosteric protein:
- As O2 binds the structure of the protein changes, and creates a binding site for 2,3-DPG which binds and changes the protein from relaxed to tense, to promote dissociation of O2.
What is methaemoglobin?
- When Fe2+ is oxidised to Fe3+ valency and cannot bind oxygen
- Can cause functional anaemia (i.e. normal Haematocrit, normal PCV but impaired O2 capacity)
- Nitrites oxidise Hb into ferric MetHb
- Can be genetically caused
What is the oxygen dissociation curve?
- At low PO2 Hb has a low affinity for O2 and so more dissociation (in tissues)
- At high PO2 Hb has a high affinity for O2 and so more association (in alveoli)
What is P50?
The partial pressure at which 50% of Hb is saturated.
The higher the P50, the lower the affinity for O2.
What conditions cause more dissociation of O2 from Hb? (decreased affinity)
- Increased temperature
- Acidosis
- Hypercapnia (high CO2 levels)
- Increased 2,3-DPG levels.
Happens in exercise, allows more O2 to be released at the same partial pressure.
What conditions cause more association of O2 from Hb? (increased affinity)
- Decreased temperature
- Alkalosis
- Hypocapnia
- Decreased 2,3-DPG
How does anaemia affect the oxygen dissociation curve? Why?
- Same shape as normal, but lower total O2 in blood (downward shift)
- Less haemoglobin available to carry O2
What could cause an increase in the total O2 in blood?
- Polycythaemia (abnormally high [Hb])
Blood-doping, over production of red blood cells. (increase haematocrit)
How does carbon monoxide affect the oxygen dissociation curve?
- Hb has higher affinity for CO than O2
- CO occupies binding sites, so less O2 circulates
- CO changes affinity of Hb for O2, so it is at a higher affinity.
The curve moves downward and to the left.
How does foetal haemoglobin differ from adult haemoglobin in the oxygen dissociation curve?
- Greater affinity than adult Hb, so that it can take O2 from mother’s blood in the placenta.
- Curve is to the left of normal adult Hb
How does myoglobin differ from normal haemoglobin in the oxygen dissociation curve?
- Single monomer in the muscle
- Much greater affinity that adult Hb so it can take O2 from circulating blood and store it
- Curve is to the left, not sigmoid but hyperbolic
What is the saturation of mixed venous blood?
75%
What is the PO2 of blood before and after going through the lungs?
Before: 5.3kPa (40mmHg)
After: 13.5kPa (101mmHg)
After passing the lungs, what is;
- Saturation of O2 in artery
- Volume of O2 bound to Hb
- Content of O2 dissolved
- Content of O2 in artery
- SO2 = 100%
- HbO2 = 20.1mL/dL
- CDO2 = 0.34mL/dL
- CaO2 = 20.4mL/dL
Why is the PO2 of the blood which returns to the left atrium not the same as what leaves the lungs?
- Bronchiole circulation drains into the pulmonary vein
- So loss of PO2 slightly (97%)
What is the importance of the PO2 of blood?
- Isn’t enough to sustain life
- Role is changing the affinity of Hb for oxygen
After passing the tissue, what is;
- Saturation of O2 in artery
- Volume of O2 bound to Hb
- Content of O2 dissolved
- Content of O2 in artery
- SO2 = 75%
- HbO2 = 15mL/dL
- CDO2 = 0.14mL/dL
- CaO2 = 15.1mL/dL
What is the Oxygen flux?
Amount of oxygen lost = 5ml/dL
250ml of oxygen per ml/min
How is CO2 transported?
- Very soluble, crossed membrane and dissolves into plasma
- Some CO2 will move into the red blood cell
Most CO2 transported as bicarbonate, HbCO2 more prevalent in mixed venous blood (i.e. when not bound to O2)
What happens to CO2 in red blood cells?
- Carbonic anhydrase accelerates reaction of CO2 and H20
- Produces H2CO3 which dissociates
- Bicarbonate is moved out of cell, Chloride shift compensates to maintain resting potential (Cl- entry with H20 through AE1 transporter)
- Hb bind CO2 at the amine ends of protein chain, to give HbCO2
- H+ binds to amines in the Hb chain to buffer the inside of the erythrocyte
What happens to CO2 in the plasma?
- Slowly binds to water to form carbonic acid (HCO3)
- Carbonic acid dissociates into H+ and HCO3- (bicarbonate)
- Some H+ will bind to plasma proteins to buffer pH
What is the Partial pressure of CO2 in the arterial and venous blood, and the Content of CO2 in the arterial and venous blood?
PaCO2 = 5.3 kPa (40mmHg) PvCO2 = 6.1 kPa (46mmHg)
CaCO2 = 48.5 mL/dL CvCO2 = 52.4 mL/dL
What is the CO2 flux?
Amount of CO2 gained = 4ml/dL
200ml CO2/min
How long are red blood cells next to the respiratory membrane?
0.75 seconds
How does cardiac output affect the exchange of gases?
- Pulmonary transit time is shorter
- Manages to diffuse in time during exercise
- About 0.25 seconds for O2, and less for CO2
Describe ventilation and perfusion mismatching.
- Due to gravity, blood flow is less to the apical area than basal.
- Intrapleural pressure at the base of lung is higher (less negative) so it is easier to ventilate.
- Ventilation/perfusion ration is low at the base than apical.
Describe the structure of the airways.
- Trachea: Cartilage C shaped rings to allow for oesophagus, divides into two
- Bronchi: C shaped cartilage rings to allow for constriction and dilation
- Bronchioles: Smooth muscle, connect to alveoli
What are the basic functions of the airways?
- Conduit to: conduct O2 to the alveoli, conduct CO2 out of the lung. (gas exchange)
- Facilitated by: mechanical stability (cartilage), control of calibre (smooth muscle) and protection and cleansing
Describe the organisation of the airway in a transverse section.
- Cartilage sections around outside (not a full ring, as they are offset)
- Air way smooth muscle, sometimes with the terminal end of submucosal glands
- Blood vessel
- Ciliated cells, goblet cells
- Mucus and cilia
- Airway lumen
List the different cell types in the airways.
- Lining cells e.g. ciliated, intermediate, brush, basal
- Contractile cells e.g. smooth muscle (airway and vasculature)
- Secretory cells e.g. goblet (epithelium), mucous, serous (glands)
- Connective tissue e.g. fibroblast, interstitial cell (elastin, collagen, cartilage)
- Neuroendocrine e.g. nerves, ganglia, neuroendocrine cells, neuroepithelisl bodies
- Vascular cells e.g. endothelial, pericyte, plasma cell (and smooth musce)
- Immune cells e.g. Mast cell, dendritic cell, lymphocyte, eosinophil, macrophage, neutrophil
Describe the release of mucin from goblet cells.
- When stimulated, the mucin granules (in a highly concentrated form) fuse with the surface of the cell
- This forms a pore which attracts water
- As more and more water accumulates the mucin granules change to take it on into a liquid form which spreads from the pore onto the surface
- The volume of the mucous expands greatly
Describe the production of mucous from a submucosal gland.
- Individual components (acini)
- Produced by collecting duct, secreted by ciliated duct and spread by cilia
- Serous acini at periphery secrete antibacterials and watery mucous
- Mucous acini secrete mucus
- Glands also secrete water and salts (e.g. Na+, Cl-)
Describe the structure and movement of cilia.
- 9+2 arrangements ( 9 doublets form a ring, and 2 in the middle)
- Dynein arms (on doublets) slide over each other causing the backward and forward motion of the cilia
- Mitochondria in the cell provide the ATP
- About 200 cilia for one ciliated cell
- The co-ordinated movement of areas of cilia so that some beat while others recover so that mucus moves along
What are the functions of the aiway epithelium?
- Secretion of mucins, water and electrolytes
- Movement of mucus by cilia (mucociliary clearance)
- Physical barrier
- Production of regulatory and inflammatory mediators:
- NO (by NO synthase, possibly to control cilia movement)
- CO (by hemeoxygenase, may be antibacterial)
- Arachidonic acid metabolites e.g. prostaglandins
- Chemokines e.g. interleukin-8
- Cytokines e.g. GM-CSF
- Proteases
Describe the function of smooth muscle in the airways.
Important for:
- Structure
- Tone: Calbibre - Contraction and relaxation
- Secretion: Some mediators, cytokines, chemokines
In inflammation, there is reaction:
- e.g. in Asthma, there is hypertrophy due to cell proliferation. Contribute to tone so there is a greater force of contraction. Big upregulation of NOS and COX (to produce NO and prostaglandins), cytokines and chemokines which recruit inflammatory cells.
Describe the airway vasculation of the tracheo-bronchial circulation.
- 1-5% cardiac output
- Perfusion to the tissue is among highest in the body
- Bronchial arteries arise from many sites on aorta, intercostal arteries and others
- Blood returns from tracheal circulation via systemic veins
- Blood returns from bronchial circulation to both sides of the heart via the bronchial and pulmonary veins
- Large plexus of vessels underneath the epithelium
What are the functions of the tracheo-bronchial circulation?
- Good gas exchange
- Contributes to warming of inspired air
- Contributes to humidification of inspired air
- Clears inflammatory mediators
- Clears inhaled drugs (good/bad, depending on drug)
- Supplies airway tissue and lumen with inflammatory cells
- Supplies airway tissue and lumen with proteinaceous plasma
Outline the mechanism of plasma exudation in the airways.
- Under normal conditions the post-capillary venules can contract, pulling cells away from each other allowing plasma to leak
- Artificially this can be demonstrated by stimulating the sensory neuron (with motor function) innervating it or using inflammatory mediators e.g. histamine from mast cells, platelet activating factor (PAF)
Describe how the airways are controlled.
- Nerves: parasympathetic (cholinergic), sensory
- Regulatory and inflammatory mediators: histamine, arachidonic acid metabolites (e.g. prostaglandins, leukotrienes), cytokines, chemokines
- Proteinases (e.g. neutrophil elastase)
- Reactive gas species (e.g. O2-, NO)
Describe the innervation of the airways.
Constriction:
- Sensory nerves detect foreign object and stimulates parasympathetic reflex
- Impulse travels to brainstem (through vagus nerve)
- Parasympathetic (cholinergic) motor pathway causes constriction of smooth muscle (also causes mucus secretion and possibly vasodilation)
Relaxation:
- Sympathetic sensory nerves relay information and synapse at a cervical thoracic ganglion
- Efferent nerve releases NO as a transmitter to smooth muscle causing relaxation
- Also, sympathetic stimulation of adrenaline release relaxes smooth muscle in airways
What inflammatory cells are/can be present in the airways?
- Eosinophils
- Neutrophils
- Macrophages
- Mast cells
- T-lymphocytes
Structural cells e.g. smooth muscle
What mediators are produces by the inflammatory cells?
- Histamine
- Serotonin
- Adenosine
- Prostaglandins
- Leukotrienes
- Thromboxan
- Platelet activating factor (PAF)
- Endothelin
- Cytokines
- Chemokines
- Growth factor
- Proteinases
- Reactive gas species
What effects do mediators have on the airway?
- Smooth muscle contraction or relaxation (both airway and vascular)
- Secretion (mucins, water etc)
- Plasma exudation
- Neural modulation
- Chemotaxis
- Remodelling
Outline respiratory diseases which result in a loss of airway control.
- Asthma, Chronic obstructive pulmonary disease (COPD) and cystic fibrosis
- Causes airway inflammation, obstruction and remodelling
What are the features of Asthma?
- Clinical syndrome characterised by increased airway responsiveness to a variety of stimuli (e.g. allergens, emotional upset, cold air etc)
- Airway obstruction varies over short periods of time and is reversible (spontaneously or with drugs)
- Common symptoms: dyspnoea, wheezing and cough (varying degrees: mild to severe)
- Airway inflammation can lead to remodelling:
Increased mucus with inflammatory cells embedded in it (eosinophils), thickening of basement membrane, epithelial fragility, increased size of glands and smooth muscle mass, vasodilation, cellular infiltrate of eosinophils. - Airway wall thrown into folds due to bronchi constriction, lumen narrows and fills with mucus
Outline the pathophysiology of asthma.
- Epithelial fragility exposes sensory nerves which causes cholinergic reflex
- This causes bronchoconstriction and mucus hypersecretion and vasodilation
- Inflammatory cells produce mediators and with time there is hypertrophy of smooth muscle, increases plasma exudation, angiogenesis etc.
- Fibroblasts add to basement membrane causing thickening
How does the surface area of the airways change?
Increases peripherally (almost exponentially)
Describe the epithelial layer.
- Forms a continuous barrier for protection from external environment
- Produces secretions to facilitate clearance via mucociliary escalator, and protect underlying cells as well as maintain reduced surface tension (alveolae)
- Metabolises foreign and host-derived compounds
- Releases mediators
- Triggers lung repair process
What cell types form the epithelial layer? What changes in patients with COPD?
- Normally: Columna ciliated cells, basal cells and goblet cells
- COPD: increase number of goblet cells (hyperplasia) and increased mucus secretion
Describe the features of goblet cells.
- found in large, central and small airways
- normally 20% of epithelium
- synthesise and secrete mucis
- In smokers: goblet cell number almost double, secretions increase and are more viscoelastic
- This increases the amount of cigarette particles and microorganisms trapped so greater chance of infection
Describe the features of ciliated cells.
- Found in large, central and small airways
- Normally form 80% of epithelium
- Cilia beat metasynchonously
- In smokers: ciliated cells are depletes, beat asynchronously, found in bronchioles, unable to transport thickened mucus which leads to infection and bronchitis.
Describe how the patency of small airways are maintained, and the effect of disease.
-
What cell types are present in respiratory bronchioles?
- Bronchiolar ciliated cells: increased in smokers and COPD, beat synchronously to move mucus up to epiglottis and clear trapped debris, cells etc
- Clara/Club cells: 20% epithelial cells (lower in smokers), secretory cells, detoxification, involved in repair as progenitor cells
What cell types are present in the alveolar unit?
- Type 1 epithelial cells:
- Large cells (~80μm)
- Very thin to allow gas exchange
- Type 2 epithelial cells:
- Cuboidal, small (~10μm) but highest in number
- Secrete surfactant to decrease surface tension
- Repair/progenitor cells
- Precursor of type 1 cells
- Capillary endothelium
- Macrophage
- Stromal cells (myo) fibroblasts:
- Make extracellular matric
- Collagen, elastin to give elasticity and compliance
- Divide to repair
What is the function of the pores of Kohn?
Holes in the alveoli which regulate the pressure across the lung and allow air to move between alveoli so that pressure is equal.
What is the ration of type 1 to type 2 cells?
1:2
