Breathing & Gas Exchange Flashcards
What is the driving force that moves air in and out of the lungs?
Volume changes drives changes in pressure in the lung - this change in pressure sets up pressure gradients leading to movement of air in and out of the lungs.
At the end/start of a normal breath - Atmospheric pressure = Alveolar pressure
Inspiration - Atmospheric pressure > Alveolar pressure - driving air into the lungs
Expiration - Alveolar pressure > Atmospheric pressure
What force creates a balance/equilibrium in the thorax at the end of a normal breath?
Elastic recoil from the chest wall and lungs
Chest wall has an elastic recoil outwards
Lungs have an elastic recoil inwards
Result = opposing forces
Hence, at the end of a normal breath…
Lung elastic recoil inward = Chest wall elastic recoil outward
Equilibrium point sits at a slightly negative plural pressure - pressure in pleural cavity is slightly less than atmospheric
Outline the mechanical/muscular changes that take place in the thorax during inspiration.
- Inspiratory neural activation sent by brain to intercostals and diaphragm
- External intercostals diaphragm contract - diaphragm flattens and chest wall moves up and out
- Results in decreased pressure in the pleural space and decrease pressure in the alveolus
- Drives air into the lungs
Outline the mechanical/muscular changes that take place in the thorax during expiration.
- Normal expiration is a passive process - inspiratory neural activity stops
- Elastic recoil of lungs causes the thoracic volume to decrease
- Alveolar pressure exceeds atmospheric - driving air out of the lungs
What happens during large/forceful expiration?
Large/forced expiration is an active process
Requires active contraction of internal intercostals, diaphragm and abdominal muscles.
Clinical case - What causes breathlessness in COPD?
Decreased lung elastic recoil (important for expiration) + collapsed airways (obstruction) - fight against both these forces to drive adequete expiration
What are 4 potential causes of disrupted inspiration/expiration?
Inspiration and expiration may be disrupted by:
1. Airflow obstruction – lower or upper (COPD, asthma)
2. Weakness of respiratory muscles (MND, advanced respiratory disease, diaphragm failure)
3. Lung tissue damage (emphysema component of COPD)
4. Thoracic cage disorders (ankylosing spondylitis, kyphoscoliosis)
What are the different regions of the brain that play a role in regulation respiration?
- Cortex - cognitive control of breathing
- Pons - controls the rate/speed of involuntary breathing
- Medulla - centre that involuntary drive to breathe
What are the three groups of neurons in the brain stem that are involved/required for breathing?
Outline the feedback loop that is responsible for setting the respiratory rhythm.
Feedback loop setup up in the medullary neurons (VRG and DRG)
- Inspiratory neurons activated - drive inspiration, inhibit expiration but also activates expiratory neurons
- Expiratory neurons activated - inhibit inspiration and in turn drive expiration
Cycle repeats - sets the basal rhythm
Note that this is a measured system - large inspiration is followed by large expiration - e.g. increased activation in inspiratory neurons will drive a similar increase in expiratory neurons.
What are four things that could change the basic breathing pattern?
- Inhaled noxious substances
- Speech/volition
- Sleep
- Exercise
What are the lung and chemo- receptors that provide feedback to respiratory rhythm generator?
Lung receptors:
1. Slowly Adapting Receptors
2. Rapidly Adapting Receptors
3. C-fibre endings
Afferent nerve fibres carried in vagus - removal results in much larger and longer breaths (reverse when stimulated)
Chemoreceptors
1. Central chemoreceptors
2. Peripheral chemoreceptors
How do the slow adapting receptors (SARs), also called stretch receptors, regulating breathing rhythm?
Mechanoreceptors that send a signal to the medulla telling it that the lung is stretched/inflated and that expiration should be intiated.
Slow response & slower return to baseline
Example Hering-Breuer reflex - equal expiration to inspiration
How do the rapidly adapting receptors (RARs), also called irritant receptors, regulating breathing rhythm?
Located in the airway epithelium – respond to lung inflation (mechanoreceptors similar to SARs) and chemicals - present in the trachea and large bronchi (higher up in the lungs)
Trigger cough reflex, mucus production and bronchoconstriction - response to remove substances in the airway - changes breathing pattern as well
Rapid response and rapid return to baseline
Receptors are antagonised during COPD - to bronchodilate and mucus production - Inhaled Long-acting Muscarinic Antagonists
How do C-fibre endings regulating breathing rhythm?
Found much further down the lungs
What do the central and peripheral chemoreceptors measure?
These chemical levels are then signalled to the medulla in order to regulate breathing
Peripheral - Rapid response
Central - Slow response
What terminology is used to describe high, normal and low O2 and CO2 levels?
How do central chemoreceptors detect changes in pCO2?
Central chemoreceptors – pCO2 moving across the blood brain barrier – increase levels of H+ levels in CSF – impacts neurons in the medulla
What is a clinical example of when chemical control fails to help regulate breathing?
In patients with severe COPD - hypoxia and CO2 increase - resulting in chronic hypercapnia - results in loss of central chemoreceptor sensitivity
Hypoxia is required to create the drive to breath
But when too much O2 is delivered - drive to breathed is abolished - resulting in further hypoventilation and increases in pCO2 - resulting in acidosis / respiratory failure – death
Solution
Delivering controlled oxygen – deliver oxygen but not remove the hypoxemic respiratory drive– COPD range of intervention – 88-92% (normal level is 94%)
What are some examples of depressants that influnece respiratory rate?
Anaesthetics - almost all
Analgesics - opioids (morphine and its analogues)
Sedatives (anti-anxiolytics, sleeping tablets) -
benzodiazapines (diazepam, temazepam, etc.)
Clinical examples: Recreational drug overdose, procedural sedation
What are some examples of stimulants that influnece respiratory rate?
Primary action:
Doxapram - not used anymore - reliance on ventilation
Secondary action:
Beta 2- agonists (bronchodilators) - can also increase respiratory drive
Can problems in breathing patterns arise from the cortex of the brain?
Yes, breathing pattern disorders (e.g. stacking breaths) – can be triggered by anything that effects normal breathing (nasal blockage, pain, irritable cough, infection), which then results in a conscious adaptation of the normal breathing pattern, and sometimes this pattern kicks in and replaces the normal breathing pattern
Treatment – going to the physiotherapist to control breathing again
Why can breathing be problematic when we sleep?
During sleep:
1. Respiratory drive decreases (loss of wakefulness drive)
- Reduction in metabolic rate
- Reduced input from higher centres such as pons and cortex
2. Loss of tonic neural drive to upper airway muscles
Consequences of loss of wakefulness drive:
Patients with pre-existing respiratory conditions will first sense/feel respiratory problems first during sleep
What happens to the tonic level of activity to the muscles of the upper airway during sleep? Why is this important for sleep aponea?
Phasic - fluctuating levels of muscle activity in the upper airway to help airflow inwards
Tonic - constant level of activity to keep the airway open
Hence, during sleep there is a loss of tonic activity to upper airways. Hence, in patients that are obese/overweight, increase pressures/weight on the upper airway can make it collapse - increasing liklihood of obstruction - resulting in sleep apnoea
What happens to the tonic level of activity to the muscles of the upper airway during sleep?Why is this important for sleep aponea?
Phasic - fluctuating levels of muscle activity in the upper airway to help airflow inwards
Tonic - constant level of activity to keep the airway open
Hence, during sleep there is a loss of tonic activity to upper airways. Hence, in patients that are obese/overweight, increase pressures/weight on the upper airway can make it collapse - increasing liklihood of obstruction - resulting in sleep apnoea
How does sleep apnoea normally present?
Sleep Apnoea (cessation of breathing)
Body’s response to airway closure is to wake up to increase muscle tone – significantly impacts sleep quality
Risk factors: obesity, alcohol, nasal obstruction, anatomical anomalies
Important cause of traffic accidents
Solution - Sleep apnoea machine – creates air pressure that pushes air through the obstructed airway
How are our lungs adapted to maximise gas exchange?
Large surface area, rich blood supply (high SA of contact + maintains conc. gradients), thin walls and moist surface - all faciliate gas exchange
Note - We have extensive branching in both the bronchial and arterial anatomy. But blood vessels branch more than bronchi so we have bigger airspaces with smaller vessels
Is more oxygen dissolved in the plasma or bound to hemoglobin?
Most Oxygen is carried by Haemoglobin rather than dissolved
What is Haemoglobin? How does it bind to O2?
A tetramer: 2 alpha and 2 beta subunits
Each subunit has a Haem group - A porphyrin with a central Ferrous atom: binds O2
Combines loosely with Oxygen
Binding alters its shape and charge - results in cooperative binding - means that the affinity of binding O2 increases with each successively bound O2 molecule = Allosteric Effect
What factors ensure that oxygen is bound to Hb in the lungs and release in O2 deprived tissue?
Ultimately we want Hb to take up O2 in the lung and liberate O2 at the tissues
Increase CO2, Increase H+ (low pH), increase temp and 2,3-DPG - cause a right shift in O2 dissociation curve = favouring release of O2 at lower O2 concentrations
Reverse is applicable to the high O2 environments - favouring uptake
Is the transfer of gas in the lungs 100% efficient?
No, the partial pressure of oxygen in arterial blood is lower than the alveolus - ideally it should be equal if gas exchange was 100% efficient
This is due to shunting and dead space
How does blood shunting impact gas exchange in the lungs? Two types
Shunts - movement of deoxygenated blood into the oxygenated system - oxygen level in aorta is lower than in pulmonary veins
Anatomical shunts
- Veins that drain the into the left side of the heart - Thebsian veins
- Some blood from bronchial circulation also enters the oxygenated circulation
Physiological shunts
Physiological shunts (V) and alveolar dead space (Q) - Not all lung units have the same ratio of ventilation (V) to blood flow (Q) - imbalance between the two
Leading to V/Q mismatch
What is physiological dead space?
Physiological dead space = anatomical dead space + alveolar dead space
Anatomical dead space - represents the conducting airways where no gas exchange takes place - e.g. trachea - areas of circulation but no gas exchange
Alveolar dead space - alveolar areas where there is insufficient blood supply for gas exchange to take place - practically non-existent in healthy young but appears with age and disease
Not normally a cause of disease - normal physiology
What is the ventilation to perfusion ratio?
V/Q - ratio of ventilation and perfusion
If ventilation = perfusion then will get perfect gas exchange (shunting aside…)
In the lung naturally have V/Q mismatch with overall less blood and air going to the top of the lung due to gravity.
But we still have relatively more airflow to perfusion at the top of the lung. Conversely we have increase perfusion relative to ventilation at the bottom.
Consequence
1. Higher PO2 at the top of the lungs
2. Lower PO2 at the bottom of the lung -
How does oxygen saturation change during hypoventilation and hyperventilation?
During hypoventilation - blood O2 saturation decreases but does not decrease in proportion to the reduction in ventilation rate
During hyperventilation - blood O2 saturation does not increase even though the partial pressure of O2 in the lungs increases - Hb fully saturated
What happens to CO2 levels in alveoli during hypoventilation?
If there is lower ventilation, then CO2 accumulates in the alveolar space meaning less can be removed from the blood
Reduced gradient - resulting in increased plasma CO2 - changes are proportionate
Reduction in ventilation by half, doubles plasma CO2
What does the following graph try to show?
Changes in plasma gas concentrations (O2 and CO2) in response to changes in ventilation
Low ventilation/hypo - low O2 and increased CO2 (due to reduced conc. gradient)
High ventilation/hyper - high O2 (but plateaus) and CO2 is low (plateaus)
Does plasma CO2 change more dynamically than O2?
Yes, it is more responses to changes in ventilation rates.
CO2 curve is steeper (does not follow sigmoidal shape as O2) - CO2 does not bind/associate with Hb, meaning that there is no cooperative binding.
Hence, hypo and hyperventilation results in significant changes on CO2
How does a V/Q mismatch in the lungs result in in low plasma O2? What are possible causes of a V/Q mismatch?
V/Q mismatch - occurs when not enough O2 in the alveoli comes into contact/exchanges with the blood
Potential causes…
1. Conditions that thicken the alveolar wall or narrow and block small airways
2. Lung infection such as pneumonia (increases CO2 in alveoli but does not impact plasma CO2)
3. Bronchial narrowing such as asthma and COPD (although they can also progress to hypoventilation and type 2 resp failure)
4. Interstitial lung disease
4. Acute lung injury
All of these reduce the contact/exchange of O2 in the alveoli in the lungs (V) with the circulating blood (Q) - leading to a mismatch
Example - pneumonectomy no V/Q mismatch as supply = demand but O2 saturation can be effected when there is a higher O2 demand on the body
How does a V/Q mismatch effect arterial O2 and CO2 levels?
- Blood leaving areas of low V/Q ratio has Low PaO2 & High PaCO2 - low exchange
- High PaCO2 stimulates ventilation
- ‘Extra’ ventilation goes to areas of normal lung and areas with high V/Q ratio
- But extra ventilation can’t push O2 content much higher than normal. BUT extra ventilation in high V/Q areas can remove sufficient CO2.
- Blood from both areas mixes - O2 levels are not compensated by extra ventilation (still low) but CO2 levels are normal.
Because CO2 is more dynamic?
How do we treat the hypoxia in VQ mismatch?
Super-saturate O2 in the areas of V/Q mismatch - supplemental oxygen
Note this deals with one part of the equation (ventilation) but not the perfusion element, which could also be causing problems - e.g. in a pulmonary embolism the lungs are not receiving sufficient blood supply
What are the two types of respiratory failure? How do they differ?
Respiratory Failure - Low PaO2
Two main types:
a) Type 1 Respiratory Failure - PaO2 is low and PaCO2 is normal - caused by V/Q mismatch
b) Type 2 Respiratory Failure - PaO2 is low and paCO2 is high - hypoventilation
When is non-invasive ventilation typically used?
Common treatment for COPD exacerbations with type 2 respiratory failure. Also useful for neuromuscular diseases and thoracic wall diseases
Uses a tight fitting mask (CPAP), no need to sedate and intubate - Increases ventilation efficiency
What are the three responses the body uses to react to changes in plasma H+?
How is bicarbonate formed? What is the bicarbonate buffer system?
CO2 in the blood reacts with water to form carbonic acid, catalysed by carbonic anhydrase. Carbonic acid then dissociates to form H+ and bicarbonate
HCO3- can help soak up extra H+ in the blood
Knowing this chemical reaction we can write a expression for Ka using CO2, H+ and HCO3- –> shows us that CO2 is proportionate to H+, whereas HCO3- is inversely proportionate to H+
What are the different types of acid-base disturbance? Think about Ka expression for H+, CO2 and HCO3-
Two causes of acidemia [H+] > 44 nmol/L– high CO2 (respiratory) or low bicarbonate (metabolic)
Note - acidosis and acidemia are different
Acidemia - state of low pH
Acidosis – something that causes an academic state
Two causes of alkalaemia [H+] < 36 nmol/L
- low CO2 (respiratory) or high bicarbonate (metabolic)
What are the compensation mechanisms for the different types of acid base disturbance?
Physiological response to the disturbance – compensation - always the opposite mechanism used to compensate
Acidemia
1. Respiratory acidemia - Increase bicarbonate – metabolic compensation – performed by the kidney
2. Metabolic acidemia - Decrease CO2 – respiratory compensation – increase the breathing rate to reduce CO2
Alkalemia
1. Respiratory alkalemia - Low CO2 – decrease bicarbonate production by kidneys
2. Metabolic alkalemia - High bicarbonate – decrease breathing rate to increase CO2
What algorithm should be used to classify acid-base disturbance?
- Decide whether it is an acidemia or alkalaemia
- Look at the levels of PaCO2 and HCO3- to see whether they are abnormal - is it respiratory or metabolic
- Decided whether the change in PaCO2 or HCO3- a cause or a compensation.
a) Acidemia - high CO2 = cause but low CO2 = respiratory compensation
b) Acidemia - Low HCO3- = cause but high HCO3- = metabolic compensation
c) Alkelemia - low CO2 = cause but high CO2 = respiratory compensation
d) Alkelemia - High HCO3- = cause but low HCO3- = compensation
What happens to free [Ca2+] when plasma [H+] falls?
- As plasma [H+] falls, H+ dissociate from the side-chains of plasma proteins
- Proteins now have a greater negative charge, so bind more Ca2+
- Total plasma [Ca2+] is unchanged at ~2.2 mM, but since more Ca2+ is protein-bound, the free Ca2+ concentration falls
Basically H+ decreases - more H+ released from protein - more Ca2+ binds to proteins - lower free Ca2+
Why does excessive vommiting cause metabolic alkalemia?
Vomiting – gastric juice lose/acid is pumped out – stimulates gastric acid production , which requires H+ and Cl- to be pumped into the stomach lumen but movement of Cl- into the cell drives movement of HCO3- out into the blood
Another factor is that repeated vomiting reduces the plasma volume, so that the bicarbonate is contained in a smaller volume: ‘contraction alkalaemia’.
Why are type I diabetics prone to keto acidemia?
Failure of insulin results in increased fatty acid breakdown to form ketone bodies - used as an energy source
Ketone bodies - acetoacetic acid and 3-hydroxybutyric acid
At physiological leveles these ketone bodies can be buffered but in uncontrolled type I diabetes, they’re levels are very high resulting in keto-acidemia
Acetoacetic acid - not very stable - decarboxylates to form acetone - creates characteristic smell
What is the anion gap?
AG= ([Na+] + [K+]) – ([Cl-] + [HCO3-])
Difference between the two most common cations in the plasma (Na+ and K+) minus the two most common anions (Cl- and HCO3-)
Increase anion gap - indicates that one of the anions (e.g. HCO3-) have been used up (levels decreases) to buffer an acid
Important diagnostic tool for a metabolic acidosis
Example - Salicylic acid - mops up HCO3- –> resulting in an increased anion gap
What are the metrics that a blood gas monitor measures?
Do all healthy people have similar blood gas measurments?
Yes, same measurments but it’s the utilisation of the gases that differs
What are the two types of bicarbonate measurment?
Actual bicarbonate: Calculated with actual H+ and pCO2 values
Standard bicarbonate: Calculated with actual H+ and a pCO2 of 5.3kPa (normal pCO2)
Standard bicarbonate is therefore only influenced by metabolic effects
Allows you to discern if an acidaemia is purely respiratory or metabolic - if standard bicarbonate is normal than higher actual bicarbonate is simply due to increase CO2
