Respiratory system 1-6 Flashcards
What is the purpose of the respiratory system?
Ensure all tissues receive the oxygen they need and disposes of the CO2 they produce.
How is pressure generated by gases?
By collision of molecules with the walls - more frequent and harder collisions, higher pressure
What is Boyles law?
the product of the pressure and volume for a gas is a constant for a fixed amount of gas at a fixed temperature.
PV = constant
What is Charles law?
if a given quantity of gas is held at a constant pressure, its volume is directly proportional to the absolute temperature. (Kelvin)
What is the universal gas law?
PV=RT
Allows calculation of how volume will change as pressure and temperature changes
How do gases behave when mixed with other gases?
Behave independently so each gas exerts a partial pressure
How do you calculate the partial pressure of each gas in a mixture?
The same fraction of the total pressure as the volume fraction of the gas in the mixture
What happens when gas comes in contact with water?
Water molecules evaporate and gas molecules dissolve.
What effect does evaporated water mixing with a gas have?
Exerts vapour pressure
How is the saturated vapour pressure achieved?
When molecules leave and enter water at the same rate.
What does the saturated vapour pressure depend on?
Temperature
What is the pressure of a gas in a liquid referred to as?
Tension - at equilibrium tension is the same as the partial pressure of gas in gas mixture
What does the tension of a gas in a liquid indicate?
How readily the gas will leave the liquid NOT how much gas is in the liquid
What does solubility determine?
The amount of gas which enters the liquid to establish a particular tension
content = solubility x tension
How does reactions of a gas with a component of liquid affect tension?
Reaction must complete before tension can be established
reacted gas + dissolved gas = content
How much oxygen must the blood pick up per minute at rest?
12 mmol
Explain how the lungs and blood are able to supply enough oxygen to the body.
300 million alveoli each surrounded by a capillary
Describe the differences between bronchi and bronchioles.
Bronchi have cartilage in walls and less smooth muscle
Describe the resistance and pressure of the pulmonary circulation
Low resistance and pressure.
Receives entire cardiac output
Why is it important that very little tissue fluid is formed by the pulmonary circulation?
Would fill space between alveoli and capillaries affecting gas exchange
How is air drawn into the lungs?
By increased volume of terminal and respiratory bronchioles as lungs expand in inspiration. Each breath draws a tidal volume into and out of the lungs
What effects ventilation?
Tidal volume and respiratory rate
Where does the nasal cavity lie?
Extends from the nostrils to posterior nares
What divides the nasal cavity?
septum - medial wall of each nasal cavity. Made of cartilage and bone
What makes up the lateral wall of the nasal cavity?
Bony projections lined by pseudo stratified columnar ciliated epithelium
How many tubinates and meatus do we have in the lateral wall of the nose?
3 - superior, middle and inferior
What are the functions of the nose?
Respiration - filters, humidifies and warms air
Smell
Receives local secretions from sinuses and nasolacrimal duct
How is the structure of the nose related to th function?
nostrils contain hairs which filter large particles
Epithelium moistened with mucus - traps particles
Cilia helps transport any trapped particels
Watery nasal secretions - water evaporates to humidify air
Vessels just below epithelium - warms air
Turbinates - slows airflow, helps mix air
How many paranasal sinuses are there and what are they called?
4 Frontal Ethmoid Maxillary Sphenoid
What epithelia line the sinuses?
pseudo stratified columnar ciliated containing goblet cells and glands
What are the potential paranasal sinuses function?
Extension of nasal cavity - humidification and warming of inspired air
Secretion of mucus to moisten nasal chamber
Lightening weight of skull
Buffer for trauma
Insulating sensitive structure from temp variations
What are the 3 parts of the pharynx?
Nasopharynx
Oropharynx
Laryngopharynx
Where is the soft pallete?
Between the nasopharynx and oropharynx
Where is the epiglottis?
Between the oropharynx and laryngopharynx
Where does the eustachian tube enter the pharynx?
Nasopharynx
What is the larynx?
Vocal cords act as a valve guarding the entrance to the trachea.
When is the larynx open/closed?
Open during respiration
Closed to protect LRT during swallowing
Initially closed then open during coughing reflex
What is the glottis?
2 vocal cords and the opening (aperture) between themm
What muscle moves the vocal cords?
The intrinsic muscle of the larynx
Does abduction or adduction open the glottis?
AB
What is the aperture of the glottis called?
rima glottidis
What nerve supplies the intrinsic laryngeal muscles?
Recurrent laryngeal nerve (branch of vagus)
Does not supply cricothyroid - superior laryngeal nerve
What symptoms may lesions of the recurrent laryngeal nerve cause?
Hoarseness of voice
Describe the course of the recurrent laryngeal nerve
Right - curves under sub clav. artery
Left - curves under aortic arch
Comes back up in the groove between the trachea and oesophagus
Where might URTIs spread?
sinuses via openings into nasal cavity and may result in sinusitis
Middle ear via eustachian tube
WHat disorders of the larynx may cause respiratory difficulty?
Oedema of the larynx
Tumours of the larynx
Aspiration of foreign body
Bilateral vocal cord paralysis
What disorders of the pharynx may cause respiratory difficulty?
Tongue falling back in unconscious patients
Sleep Apnoea
What disorders in the nose may cause respiratory difficulty?
Nasal polyps
What is the conducting portion of the respiratory tract?
nasal cavity to bronchioles
What is the respiratory portion of the resp tract?
Respiratory bronchioles and alveoli
What type of epithelia are in the terminal bronchioles?
Simple columnar with cilia but no goblets
What epithelia are in the resp bronchioles and alveolar ducts?
Simple cuboidal epithelium with Clara cells and a few sparsely scattered cilia
What type of epithelia are in the alveoli?
Simple squamous
What is olfactory?
Sense of smell
Axons run through the columnar epithelia pseudostratified and non-motile cilia.
No goblets
Contain bowmans glands - exocrine function
Which bronchus is more likely to be obstructed by a foreign body?
Right - more vertical
What happens to the cartilage surrounding the trachea with age?
Transforms to bone
Where is the trachealis muscle?
In the fibroelastic membrane
Why is the absence of cartilage in walls of bronchioles problematic?
It allows th air passages to constrict and almost close down when smooth muscle contraction becomes excessive eg in asthma and cause more difficulty with expiration than inspiration
What are Clara cells?
Interspersed between siliated cuboidal cells. secrete a surfactant lipoprotein which prevents the walls sticking together during expiration. Also secrete Clara cell protein
Where can Clara cell protein be measured?
In bronchoalveolar lavage fluid (if lowered - lung damage) in serum ( if raised - leakage across air-blood barrier
Why is it important there are no goblet cells in terminal bronchioles?
Narrow - prevent drowning in own mucus
Where can alveoli open into?
Resp. bronchiole
Alveolar duct
alveolar sac
alveolus
At what age do you stop developing alveoli?
8
What are alveolar walls like?
Have abundant capillaries
Supported by a basketwork of elastic and reticular fibres
Covering composed chiefly of type 1 pneumocytes
Have a scattering of intervening type II pneumocytes
What cell types are present in alveoli?
Type I (squamous) - 90% of surface area and permit gas exchange with capillaries
Type II cells (cuboidal) - cover 10% of surface area and produce surfactant
Numerous macrophages line alveolar surface (phagocytose particles)
What might cause obstruction of the pharynx to an unconscious patient?
Tongue falling back
A foreign body
Vomit
What are the 3 sections of the sternum?
Manubrium
Body
Xiphisternum
Describe the connection of the ribs to the sternum
1-7 conected via costal cartilage
8-10 connected via costal cartilage above them
11 and 12 floating ribs - end free in abdominal muscle
What are considered “typical ribs”?
3-9
Head, neck, tubercle, shaft, costal groove
2 articular facets separated by crest on head
Articular and non articular facets on tubercle
Describe the structure of the first rib
Shortest broadest and most curved. Head has single facet
How do the 11th and 12th rib differ to typical ribs?
Single facet on head and no tubercle and tapering anterior end
10th rib also has only a single facet on head
How many intercostal muscles are there in each space?
3- external, internal and innermost
What is the purpose of the costal groove?
Protection of the neurovascular bundle which runs along it
What are the intercostal nerves and where do they lie?
Anterior rami of thoracic spinal nerves T1-T12. Run between internal and innermost intercostal muscles. Supply the intercostal muscles in the corresponding space, the parietal plura and overlying skin
What is the intercostal arterial supply?
Thoracic artery -> posterior intercostal arteries
Internal thoracic artery -> anterior intercostal artery
anastomose to supply the muscles of each space, parietal pleura and overlying skin
What is the venous drainage of the thoracic wall?
Primarily into the Aqygos system -> SVC
Some into the internal thoracic vein
Which intercostal muscle is key in inspiration?
External - elevates ribs
Which ribs increase the thoracic lateral diameter in inspiration?
Lower
Which ribs increase the A-P diameter of the thorax?
Upper
What is the main muscle of inspiration?
Diaphragm - descends. Accounts for 70% of chest expansion in quiet respiration
What nerve supplies the diaphragm and what are its roots?
Phrenic nerve roots C3,4,5
What are the sensory functions of the phrenic nerve?
Both surfaces of diaphragm (margins of diaphragm receive innervation from intercostal nerves)
Mediastinal part of parietal pleura
Diaphragmatic part of parietal pleura
Explain how expiration is passive in quiet respiration
Elastic recoil of the chest wall and lungs
What is the function of the internal and innermost intercostal muscles?
forced expiration along with the abdominal muscles
What is the central compartment of the thoracic cavity called?
Mediastinum
What does the parietal pleura cover?
Bony thorax
Diaphragm
Mediastinum
What does the visceral pleura cover?
Lungs
Explain the sliding of pleural surfaces over each other
Film of fluid lubricates it but its surface tension resists the surfaces being pulled apart (forms a pleural seal)
Thus, when the thorax expands along with the parietal pleura -> the visceral pleura and lungs move with it -> the lungs expand
What are the contents of the pleural cavity?
Lungs
Costodiaphragmatic recess - pleural lined gutter surounds the upward convexity of the diaphragm
Where does the trachea start and end?
Starts at the border of the cricoid cartilage and ends by dividing into the right and left main bronchi at the carina (T4/5)
Describe the structure of the trachea.
Fibro-cartilaginous tube with 18-22 U shaped cartilages. Posteriorly, the trachealis muscle bridges the gap between the cartilage
What does the trachealis muscle do?
Construction and dilation of the trachea as air moves through it.
Stabilises the hyaline cartilage
Describe the main bronchi
Right - shorter, wider and more vertical. Splits into 3 lobar bronchi
Left - longer, more horizontal. Splits into 2 lobar bronchi
What do the lobar bronchi divide into?
Segmental bronchi - each of which supplies a bronchi-pulmonary segment
Describe the right lung.
3 lobes - upper, middle and lower.
2 fissures - horizontal and oblique
Describe the left lung
2 lobes - upper and lower
1 fissure - oblique
What is a bronchopulmonary segment?
An area of lung supplied by its own segmental bronchus and segmental branches of the pulmonary artery and vein
Describe the blood supply to the lungs
Bronchial arteries from the aorta supply the bronchial tree to the terminal bronchioles.
Pulmonary arteries carry deoxygenated blood from the right heart to the alveoli for oxygenation.
What is the hilum of the lungs?
The pulmonary vessels, main bronchus, nerves and lymphatics enter/exit via the hilum at the mediastinal surface of the lungs
Describe the borders of the areas of the mediastinum.
Between right and left pleural sacs
Anterior between body of sternum and fibrous pericardium
Middle between anterior and posterior
Superior bound superiorly by the thoracic inlet and inferiorly by plane passing though sternal angle and lover border of T4
Where are the oblique fissures in relation to the vertebra and costal cartilage?
Extend from spinous process of T2 to 6th costal cartilage
Where are the horizontal fissures in relation to the ribs and costal cartilage?
Extends from oblique fissure along border of 4th rib and costal cartilage
How does alveolar air differ to atmospheric air?
Less oxygen (13.3 kPa), more carbon dioxide (5.3 kPa)
What is the typical pO2 and CO2 in venous blood?
pO2 = 6.0 kPa
pCO2 = 6.5 kPa
this varies with metabolism
Why does oxygen diffuse into blood and carbon dioxide diffuse out?
pO2 is higher in alveolar gas than blood therefore moves out of the alveoli and into the blood. The opposite is true for CO2
What does diffusion in the lungs (and generally) depend on?
Area
gradients
Diffusion resistance (dependent on nature of the barrier and nature of the gas)
What are the diffusion barriers for O2 from the alveoli to the blood?
Through gas to the alveolar wall Epithelial cell of alveolus Tissue fluid Endothelial cell of capillary Plasma Red cell membrane (Gas to alveolar wall, 5 cell membranes, 3 layers of cytoplasm and 2 layers of tissue fluid. 0.6 micrometers)
How is the rate of diffusion of a gas through a gas linked to molecular rate?
rate is inversely proportional to molecular weight - big molecules diffuse slower therefore carbon dioxide is slower than oxygen
How is the rate of diffusion of a gas through liquid determind?
Rate is proportional to solubility. CO2 is much more soluble than O2 so diffuses 21 times faster
Which gas limits diffusion in the lungs?
Oxygen as carbon dioxide diffuses much faster than oxygen overall
How long do blood cells stay in capillaries?
1s. Oxygen exchange is complete in 0.5 seconds so plenty of leeway and gas diffusion is not limiting on the lung
What determines gas composition of the arterial blood/
Composition of alveolar air - same pO2 and CO2
How does ventilation occur?
Expansion of lungs increases volume of the respiratory bronchioles and alveolar ducts so air flows down the airways to them
How do you measure ventilation?
Using a spirometer, the subject breathes from a closed chamber over water whose volume changes with ventilation
What are the types of lung volume?
Tidal - volume in and out with each breath
Inspiratory reserve volume- extra volume that can be breathed in over that at rest
Expiratory reserve volume - extra volume that can be breather out over that at rest
Residual volume - volume left in the lungs at maximal expiration (cannot be measured by spirometer - use helium dilution)
Why do lung capacities not change with breathing pattern?
They are measured from fixed points in breathing cycle
What is vital capacity?
Biggest breath that can be taken - measured from max inspiration to max expiration. Approx 5l in typical adult. Often changes with disease
What is inspiratory capacity?
Biggest breath that can be taken from resting expiratory level. Approx 3l
What is functional residual capacity?
Volume of air in lungs at resting expiratory level. Typically 2l. (expiratory reserve + residual volume)
What is ventilation rate?
The amount of air moved in and out of a space per minute
Product of volume moved per breath and respiratory rate
How do you measure pulmonary ventilation rate?
Tidal volume x respiratory rate. Typically 8l/min at rest and can exceed 80l/min in exercise
What is dead space?
Space in airways where air is “wasted” as it does not reach the alveoli to exchange gas. Last air in and first out.
What is the alveolar ventilation rate?
The amount of air that actually reaches the alveoli. To calculate, need to allow for ‘wasted’ ventilation in dead spaces.
Pulmonary ventilation - dead space ventilation
What is physiological dead space?
Serial dead space (volume of airways measured by nitrogen washout, typically 0.15l) and distributive dead space (other parts of the lungs that do not support gas exchange - dead or damaged alveoli or alveoli with poor perfusion, typically 0.17 l)
Must be completely filled with air at each breath
How do you calculate dead space ventilation?
dead space vol x resp rate
Approx how much inspired air is “wasted”?
one third. Almost 2/3 in rapid shallow breathing. Less is wasted in slow deep breathing but is most work so at rest we adopt an intermediate rate and depth
What work must be done during breathing?
Move the lungs and thorax and move air through the airways
What would happen to the lungs if taken out of the thorax?
Collapse
What holds the lungs at a larger volume in the thorax?
Pleural seal created by a thin layer of fluid between the visceral and parietal pleura. Changes volume as thorax does
What is pneumothorax?
Collection of air in the pleural space. Forms if the integrity of the pleural seal is broken - lungs collapse
Describe the equilibrium of forces in the thorax.
Lungs pull up and in
Thoracic cage pulls out
Passive stretch of diaphragm pulls down
How does the resting expiratory level occur?
All forces in balance. Like a set of springs - if disturbed will spring back to the resting expiratory level.
What way do the muscle fibres in the diaphragm run?
Medial to lateral - contraction flattens it
What is forced expiration?
Breathing out beyond resting expiratory level. Requires force exerted by abdominal muscles. Inspiration to resting level is then passive
What requires the most work in quiet breathing?
Stretching the lungs unless diaphragm cannot easily move into abdomen because of pregnancy, obesity or corsets
What is lung compliance?
The stretchiness of the lungs
Volume change per unit pressure change
Higher compliance means easier to stretch
What makes the lungs elastic/stiff?
Airways have elastic walls but compliance is reduced by surface tension of lining fluid - interactions between molecules at surface of a liquid. Makes the surface resist stretching.
What chemicals decrease surface tension?
Detergents. Disrupt interactions between surface molecules. Lungs have a mixture of detergents called surfactant produced by type 2 alveolar cells
How does the action of surfactant change as lung volume changes?
Reduces surface tension when lungs are deflated but not when fully inflated so little breaths are easy and big breaths are hard
Why is hysteresis important in the lungs?
The energy put into stretching a film of surfactant is not all recovered when the film recoils. This loss is greatest when tidal volume is max. This is why little breaths are best
How is a bubble created?
Film of fluid surrounds a gas and shrinks to compress gas until equilibrium between tension and pressure
What is Laplace’s law?
Pressure = 2 x surface tension/radius
Therefore big bubbles have low pressure, little bubbles have high pressure
What is the law of bubbles?
If a big bubble is connected to a small bubble air will flow from high pressure to low so small bubble collapses into big.
‘Big bubbles eat little bubbles’
By the law of bubbles, larger alveoli should ‘eat’ little alveoli. How come this does not occur?
As alveoli get bigger, surface tension in their walls increases because surfactant is less effective so pressure stays high and stops them eating the little ones
Describe Respiratory Distress Syndrome.
Babies born prematurely have too little surfactant so lungs are very stiff. They have few, large alveoli and breathing and gas exchange is compromised.
Give mum steroids if premature labour expected - promotes surfactant production
Why do small tubes have high resistance?
Poiseulles law -
How does the anatomy of the lungs reduce the high tension that should occur in the airways due to their small tubes?
At each branch the increase in the number of airways in parallel compensates for the increase in their resistance. The smaller the tubes get, the lower the resistance actually becomes in the airways - highest resistance in trachea and lowest in small airways so breathing is easy however the slightest change in small airways diameter has major effects on the effort required to push air through them
What limits forced expiration?
Small airways are narrowed as the lungs are compressed, resistance dramatically increases and air is trapped in the alveoli as the resistance in the airways is too large. (airways are not totally obstructed)
What is obstructive airway disease?
If the small airways are narrowed by disease eg asthma or chronic bronchitis, resistance increases much earlier in expiration. Breathing out can become very difficult
What do lung function tests assess?
The mechanical condition of the lungs
Resistance of the airways
Diffusion across the alveolar membrane
How might lung function be inferred non invasively?
From the lungs: Volumes Pressures/flows Composition Measured from the mouth
How is volume measured?
Spirometer - vital capacity by max inspiration and expiration
What limits maximum inspiration?
Compliance of the lungs
Force of inspiratory muscles
What might limit maximum expiration?
Increasing airway resistance
Lungs compressed
How does a single breath spirometry work?
Subject fills lungs from atmosphere and breathes out as far and fast as possible through a rapid responding spirometer
What is a vitalograph trace?
Plot of volume expired vs time
Initial rapi rise tails to a plateau
What is FEV1.0?
Volume expired in the first second. Affected by how quickly air flow slows down so less if airways narrowed. Usually >70% FVC
What is FVC?
the maximum volume that can be expired from full lungs. Typically 5l in adult
Why might the lungs be difficult to fill?
Stiff (potentially due to fibrous tissue)
Weak
Problem with chest wall
What effect will stiff lungs have on the FVC and FEV?
Start less full so FVC will be reduced but air will come out normally so FEV will be >70% FVC
How does obstructive deficit affect ventilation?
If airways are narrowed lungs will still be easy to full but resistance will increase in expiration so air will come out more slowly and FEV will be reduced but FVC will be relatively normal
What is a flow volume curve?
Plot of volume expired against flow rate derived from vitalograph
Why is flow rate of expiration maximum when lungs are full?
Airways stretched so resistance minimum.
What limits the PEFR? (Peak Expiratory Flow Rate)
The largest airways in the lungs
How does an obstruction/narrowing in the airways effect the flow rate of expiration?
Same PEFR but more rapid fall in the flow rate falls
How might PEFR be measured and why is it often used for screening test for airway narrowing?
Simple cheap device that can be easily used at home by blowing into it.
Why are flow volume curves used to indicate airway narrowing?
Very sensitive
Can also discriminate between large and small airway narrowing
How is residual volume in the lungs measured?
Helium dilution. Helium is not normally present in air and is insoluble in blood. If a known concentration is breathed in starting at FRC, you can measure how much the concentration is reduced by mixing with air already in the lungs. Need to know to measure airway disease
What is nitrogen washout used for?
Measure serial dead space in the lungs
indirectly measure ventilation perfusion matching
Describe the nitrogen washout test.
Subject takes one normal breath of pure oxygen, breathes out via meter measuring % nitrogen. Initially only oxygen is expired from the airways. Then mixture of oxygen and air (inc nitrogen) from alveoli. Volume expired at transition is serial dead space.
How do you measure diffusion conductance?
Difficult to measure directly how easily oxygen diffuses into the blood so carbon monoxide is used because binding to Hb means no partial pressure in mixed venous blood.
Measure how easily CO crosses from alveolar air to blood. Measure pCO in the air sample, how much is exhaled and can then figure out how much perfuses.
How much oxygen does a person need in 1 minute at rest?
12 mmol
Why is haemoglobin necessary?
To transport oxygen which is not very soluble in water - at 13.3kPa it dissolves 0.13 mmol/l. Haem used because it reacts with oxygen reversibly - oxygenation not oxidation
What does a dissociation curve show?
The reversibility of oxygen binding
amount of oxygen bound vs pO2.
Tells you how much oxygen will be bound or given up.
Generally expressed as a percentage of amount of O2 bound at saturation as amount bound is dependent on amount of pigment
How is chemical binding saturated?
Above a given pO2
What is the structure of haemoglobin?
Tetramer - 2 alpha and 2 beta subuniits each containing one haem + globin. Overall structure has variable quaternary structure. May be tense (T) - does not readily bind to O2 or relaxed (R) - readily binds
When is haemoglobin in its T state?
Low pO2. Hard to bind first O2 but as it does, changes to R state so next is easier
What shape is the oxygen dissociation curve?
Sigmoidal. Initially shallow but binding facilitates further binding so the curve steepens rapidly as pO2 rises until saturation
At what pO2 is haemoglobin saturated?
above 8.5kPa (compare to alveolar 13.3kPa)
half at 3.5-4kPa
0 at 1kPa
How much haemoglobin is in the blood?
2.2mmol/l and each caries 4 O2 therefore oxygen content is 8.8mmol/l
What is the pO2 in the tissues?
Around 5kPa - haemoglobin 65% saturated so leaves around 3mmol/l.
How can extra O2 be released from haemoglobin into cells?
Higher capillary density allows the pO2 to be lower (cannot generally fall below 3kPa)
The mood of haemoglobin depends on pH - more relaxed in alkaline, more tense in acidic conditions. Tissues have lower pH and higher temp (same effect).
Up to 70% of bound O2 can be given up, about 27% normally.
What is the Bohr effect?
In more acidic conditions (lower pH) the dissociation curve shifts along the pO2 axis - shifts right. Hb binds less O2 at a given pO2
Compare carbon dioxide and oxygen in the blood.
Carbon dioxide is more soluble and reacts chemically with water. More CO2 in the blood - almost 3 times as much. CO2 plays a major part in controlling blood pH
How much CO2 dissolves in water at pCO2 5.3kPa and what effect does this dissolution of CO2 have on the blood?
1.2mmol/l. Forms H+ and HCO3- reversible reaction in equilibrium - dependent on concentration of reactants and products. If pCO2 rises, pH falls (more H ions) if pCO2 falls, pH rises.
What else other than CO2, maintains the HCO3 equilibrium in the plasma?
Sodium hydrogen carbonate stops nearly all CO2 from reacting so pH is alkaline
What is the standard ratio of hydrogen carbonate to dissolved CO2 in blood that maintains the pH?
20:1 maintains pH 7.4
Other than oxygen, what does haemoglobin bind to that is usually in the blood?
hydrogen ions bind to the globin increasing the reaction of CO2 with H2O to produce more H+ and HCO3-
When HCO3 leaves the red blood cell, what is exchanged for it?
Chloride
Why is the HCO3 conc in plasma so high?
CO2 reacts with H2O in the RBC forming H+ and HCO3-. H+ binds to globin causing the reaction to continue in a forwards direction to try and reach equilibrium. HCO3 then leaves the RBC in exchange for Cl-. The reaction continues increasing the HCO3 conc. Dependent on how much H+ binds to Hb and excretion by kidneys.
Variation is dependent on kidneys as RBC is generally constant
How does the body buffer pH change?
If acid is produced, this reacts with HCO3 to form CO2 which is breathed out
The less O2 Hb is bound to, the more H+ binds to it so more bound in venous blood therefore there is more HCO3 in plasma
What controls arterial dissolved CO2?
Alveolar pCO2 - affects pH
How is the increased amount of CO2 in venous blood buffered?
Less O2 bound to Hb so more H+ bound, so more CO2 converted to H+ + HCO3-.
As both pCO2 and [HCO3] increase, pH does not change much
If CO2 picked up from the body reacts to form H+ + HCO3-, how is it removed by the lungs?
Hb picks up O2 so gives up H+ which reacts with HCO3 to form CO2 and it is breathed out
What else does CO2 react/bind with in the blood (other than water)?
Proteins - carbamino compounds. This contributes to CO2 transport but not acid base balance (not that significant)
How much CO2 in total is in the arterial blood (dissolved and reacted)?
21.5mmol/l
How much CO2 in total is in the venous blood (dissolved and reacted)?
23.5mmol/l
How much CO2 is created by the body?
10mmol
What forms does CO2 travel as?
80% HCO3
11% carbamino compounds
8% dissolved
What is a rise/fall in pCO2 called?
hyper/hypocapnia
What is a fall in pO2 called?
Hypoxia
What might cause a decrease in pCO2 and and an increase in O2?
Increase in ventilation with no change in metabolism (hyperventilation)
At what pO2 is saturation of Hb significantly reduced?
8kPa
Why is a change in pCO2 harmful?
Affects plasma pH - acidic
pH=pKa + log ([HCO3-]/(pCO2 x o.23))
What effect does a fall in blood pH below 7 do?
Lethally denatures enzymes
What effect does a rise in plasma pH above 7.6 do?
Free calcium concentration falls enough to produce fatal tetany - Loss of H+ ions bound to plasma proteins enables Ca2+ to bind instead…
What is respiratory acidosis?
Fall in pH due to hypercapnia from hypoventilation - can cause fatal tetany
(respiratory alkalosis is the opposite)
How is plasma pH maintained if pCO2 changes?
Compensated for by change in [HCO3] by the kidneys. This takes 2-3 days
What is metabolic acidosis?
Tissues produce acid which reacts with HCO3 causing a fall in pH. Can be compensated for by increasing ventilation rate - Lower pCO2 maintains ratio
What is metabolic alkalosis?
Rise in [HCO3] eg after vomiting, causes a rise in pH. Can be compensated to a degree by decreasing ventilation
What monitors arterial pO2?
Peripheral chemoreceptors in the carotid bodies and aortic bodies
What changes occur in the body due to a large fall in pO2?
Increased breathing
Changes in heart rate
Diversion of blood flow to the brain
What detects changes in pCO2?
Peripheral chemoreceptors but they are rather insensitive.
Central chemoreceptors in the medulla of the brain are much more sensitive and cause negative feedback control of breathing - small rises in pCO2 increases ventilation…
HOw do central chemoreceptors know of the changes in pCO2 in the arteries?
Respond to changes in the pH of CSF which is separated from the blood by the blood-brain barrier but it’s pCO2 is determined by arterial pCO2 - elevated pCO2 drives it across the barrier
What controls the [HCO3] in the CSF?
Choroid plexus cells. Fixed in short term. but persisting changes in pH are corrected by the cells
What is the equation for the ventilation perfusion ratio?
Alveolar ventilation/Blood flow
What causes diffusion impairment between the alveoli and blood?
Problems with the alveolar capillary membrane:
- Fibrotic lung disease: thickened alveolar membrane slows gas exchange
- Pulmonary oedema: fluid in the interstitial space increases diffusion distance
- Emphysema: destruction of alveoli reduces surface area for gas exchange
What are the 2 types of respiratory failure?
1 - Not enough oxygen enters the blood but CO2 removal is not compromised
2 - Not enough oxygen enters the blood and not enough CO2 leaves it
How is oxygen saturation of haemoglobin in arterial blood measured and what should it be?
Pulse oximeter
>95%
How are blood gases analysed?
Arterial blood sample obtained by arterial stab (usually from radial artery) and the sample is put through a blood gas analyser
What are the symptoms of type 1 respiratory failure?
Breathlessness
Exercise intolerance
Central cyanosis
What is type 1 respiratory failure?
Ventilation perfusion mismatch. Some alveoli are poorly perfused so there is poor uptake in some alveoli that cannot by compensated by increase in others
What might cause type 1 respiratory failure?
Fibrosis - fibrosing alveolitis, extrinsic allergic alveolitis, pneumoconiosis, asbestosis Pulmonary oedema Pneumonia Consolidation Early stages of acute asthma Pulmonary embolism
What are the symptoms of type 2 respiratory failure?
Poor respiratory effort
Chest wall problems
Hard to ventilate lungs
What might cause poor respiratory effort?
Respiratory depression - adverse drug reaction to narcotics
Muscle weakness due to upper/lower motor neurone problems
What might cause chest wall problems?
Scoliosis/kyphosis
Trauma
Pneumothorax
Why might it be difficult to ventilate the lungs?
High airway resistance
COPD
Asthma
What is emphysema?
Destruction of lung tissue (alpha 1 antitrypsin) Changes in compliance Ventilation perfusion mismatch Affects oxygen supply Type 1 resp failure initially
What pO2 is diagnosed as acute hypoxia?
<8 kPa
What are the acute effects of type 2 respiratory failure?
pCO2 rises, pO2 falls
Breathlessness - some compensation but poor ventilation due to disease may prevent full compensation
What is COPD?
Chronic obstructive pulmonary disorder. Type 2 resp failure. Slowly progressive, does not change markedly over several months. Most of the lung function is fixed although some reversibility can be produced by bronchodilator or other therapies.
What are the symptoms of COPD?
Dyspnoea and cough
What are some component disorders of COPD?
Emphysema
Chronic bronchitis
Asthma
What are the causes of COPD?
Cigarette smoking
Coal mining
Anti protease deficiency
What is the basic problem of COPD?
Lung inflammation
Where are the sites of pathology in COPD?
Changes in large airways, small airways, lung parenchyma, pulmonary arteries
How is COPD diagnosed?
Reduced FEV1 and FEV1/FVC ratio which does not change markedly over several months
What are some causes of COPD?
Smoking
Environmental factors
Genetic predisposition
What is the mechanism of COPD?
Airway and systematic inflammation Alveolar destruction Hyperinflation Respiratory muscle inefficiency Skeletal muscle dysfunction
What are the consequences (symptoms) of COPD?
Airway obstruction Dyspnoea Exercise limitation Nutritional depletion Respiratory failure
What are the impacts of COPD on a persons life?
Mobility Health status Mood Exacerbation Hospitalisation Death
How do you investigate COPD?
History Chest xray FEV1 Other lung function tests (vol, loop, TLCO) High resolution CT scan
What is the treatment of COPD?
Stop smoking
Promote effective inhaled therapy - Bronchodilators/inhaled steroids
Provide pulmonary rehabilitation for all who need it
Use non-invasive ventilation
Exacerbation management
Oxygen therapy
What is the pattern of decline in chronic lung disease?
Health status
Functional performance
Symptoms
Hospital admissions
What is the MRC dyspnoea scale?
Shows degree of breathlessness related to activities by grade
What are the physiological benefits of pulmonary rehabilitation?
Muscle mass Fibre CSA Mitochondria density Capillarisation Mitochondria Enhanced performance Reduced dyspnoea
What are the pulmonary causes of respiratory failure?
Hypoventilation
Ventilation/perfusion imbalance
Alveolar/capillatry diffusion block: Pulmonary oedema, fibrosing alveolitis
True shunt - VSD, av malformation
What microbial flora is common in the upper respiratory tract?
Viridans streptococci Neisseria spp Anaerobes Candida sp Less common: Streptococcus pneumonia, streptococcus progenies, haemophillus influenza, Peudomonas, escherichia coli
What are the defences of the upper respiratory tract?
Muco-ciliary clearance mechanisms, nasal hairs, ciliated columnar epithelium
Cough and sneezing reflex
Resp mucosal immune system lymphoid follicles of the pharynx and tonsils, alveolar macrophages, secretory IgA and IgG
How are acute and chronic bronchitis caused?
Acute: viruses and bacteria. May lead to pneumonia
Chronic: Not primarily infective. Exacerbations have been associated with many organisms but the role of infection remains controversial
What is pneumonia?
Infection of pulmonary parenchyma with consolidation
Involves the distal airspaces and results in inflammaatory exudation
Fluid filled air spaces and consolidation (heavy and stiff lung)
Gas exchange is impaired resulting in local and systemic manifestations
How is pneumonia classified?
Clinical setting
Presentation
Organism
Lung pathology
What is the most common cause of pneumonia?
Streptococcus pneumoniae
What is lobar pneumonia?
Confluent consolidation involving a complete lung lobe
Most often due to Streptococcus pneumonia
Usually community acquired with acute onset
What is the pathology of lobar pneumonia?
A typical acute inflammatory response. Exudation of fibrin rich fluid
Neutrophil infiltration
Macrophage infiltration
How is pneumonia resolved?
Antibodies lead to opsonisation, phagocytosis of bacteria
What is bronchopneumonia?
Infection starting in airways and spreading to adjacent alveoli and lung tissue
Most often seen in the context of pre-existing disease. The consolidation is patchy and not confined by lobar architecture.
How can bronchopneumonia be caused?
Complication of viral infection
Aspiration of gastric contents
Cardiac failure
COPD
How is acute bacterial pneumonia treated?
Target the most common pathogens
Amoxicillin (mild to moderate)
Co-amoxiclav if severe
What is the outcome of acute pneumonia?
Resolution by organisation (fibrous scarring) Complications : - Lung abcess - Bronchiectasis Empyema (pus in the pleural cavity)
What investigations diagnose pneumonia and determine the pathogen?
Sputum gram stain and culture of - oral flora
Chest x-ray
Look for antigens in urine and antibody in blood
Describe viral pneumonia
Damage to cels lining the airways/alveoli by the virus and immune system
Fluid filled air spaces interferes with gas exchange
Mild to severe
Severe - necrosis/haemorrhage in the lung parenchyma
Patchy or diffuse ground glass opacity on chest x-ray
What causes influenza?
RNA virus who’s genetic makeup changes constantly through mutations. Can also acquire large genetic elements - have lead to epidemics and pandemics
When is infection of influenza severe?
Pregnancy and immunocompromised. Offer antiviral drugs
What is hospital acquired pneumonia?
Pneumonia occurring 48 hrs after hospital admission approx 15% of all hospital acquired infections
Common in ITU and ventilated patients and post surgical.
What organisms cause hospital acquired pneumonia?
Enteric Gram negative bacteria (E. coli) Pseudomonas Anaerobes S aureus MRSA
Usually require treatment with broad spectrum antibiotics
What is aspiration pneumonia?
Aspiration of exogenous material or endogenous secretions into the respiratory tract
Mixed infection - viridans streptococci and anaerobes
Who commonly gets aspiration pneumonia?
Patients with neurological dysphagia, epilepsy, alcoholics, drowning
At risk groups - nursing home residents and drug overdose
What are the symptoms of pneumonia?
Fever/chills/sweats/rigors Sough Sputum- clear / prudence / rust coloured / haemoptysis Dyspnoea Pleuritic chest pain Malaise Anorexia and vomiting Headache Myalgia Diarrhoea
What are the specific chest signs of pneumonia?
Bronchial breath sounds Crackles Wheeze Dullness to percussion Reduced vocal resonance
What are the investigations of pneumonia?
CXR
O2 saturation and blood gases
FBC, WCC, platlets
Urea LFT and CRP
What are useful markers of pneumonia?
WCC (>20 or <4) indicates severe disease
CRP useful in assessing response to treatment
Radiology - very reliable - rarely radiological signs can lag behind clinical characteristics
What microbiological samples can be taken to investigate pneumonia?
Sputum Nose and throat swabs or NPAs Endo Tracheal aspirates Broncho Alveolar Lavage fluid (BAL) Open lung biopsy Blood culture Urine (to detect antigens of legioella / pneumococcus) Serum (acute and convalescent sera)
What microbiological investigations of pneumonia can be done?
Macroscopy Microscopy - gram stain, acid fast Culture - bacteria and viruse PCR - resp viruses Antigen detection (legionella) Antibody detection (serology)
What is the CURB 65 prognostic index?
Confusion (AMT 7)
RR (>30)
Blood pressure (65 yrs old
Add 1 point if yes for each criteria - if score >2, hospitalisation +/- ITU referral advised
What is the management of a patient with pneumonia?
Depends on severity and co-morbidities
Supportive treatment
Antibiotics - cover most likely organisms
Review patient - change if microbiology results or poor responses
What antibiotics are given for pneumonia?
Penicillin class (amoxycillin) are the first choice
Penicillin + Clavulanic acid for severe infections (co-amoxiclav)
Legionella pneumonia - treat with Levofloxacin
Other typical organisms treat with Tetracyclines or Macrolides
Poor response / atypical presentation - discuss with microbiology
What preventative measures can be taken against pneumonia?
Immunization - flu vaccine (high risk), pneumococcal vaccine (x2). Given to patients with co-morbidities /increased risk of pneumococcal disease
Chemoprophylaxis - Oral penicillin / erythromycin to patients with higher risk of lower resp tract infections (asplenia, dysfunctional spleen, immunodeficiency)
When would you inform ITU of a case of pneumonia?
Respiratory failure Rising pCO2 Worsening metabolic acidosis Hypotension despite fluid resuscitation Age and quality of life and co-morbidities determine decision
How is a final diagnosis of pneumonia made?
High index of suspicion
Teamwork (physician, microbiologist, pathologist)
Broncho-alveolar lavage
Lung biopsy (with lots of special stains)
How common is cystic fibrosis?
1 in 2500 live caucasian births
What are the problems associated with cystic fibrosis?
Viscid bronchial secretions
Early infections - H influenza and S aureus
Later, Pseudomans auruginosa and Burkholderia cepecia
(more susceptible to disease)
What is PneumoCystis Pneumonia?
Opportubistic Pneumonia affecting immunosuppressed patients
Pneumocystis jirovecii -> acute alveoli tis
Treat with cotrimoxazole
How is PneumoCystis Pneumonia diagnosed?
Specimens Induced sputum BAL Lung Bx PCR to detect P jiroveci DNA
What is whooping cough and what causes it?
Disease of the reps tract caused by Bordetella pertussis
Starts with cold like symptoms, develops into bouts of severe coughing followed by characteristic whoop or vomiting for 2-3 months
How is whooping cough spread and who is most at risk?
Droplet spread
Most dangerous <1yr
Older children and adults have prolonged cough
How is whooping cough diagnosed and treated/prevented?
Specimens for diagnosis - per nasal swabs, nasopharyngeal swabs or aspirates. Culture/PCR
Treat with erythromycin
Prevention with childhood vaccination
Vaccination of pregnant mothers (28-30 weeks)
