Applied respiratory physiology - inc humidification Flashcards
Define saturated vapour pressure
the maximum pressur exerted by the evaporated molecules above the liquid at equilibrium
Define humidity
The amount ofwater vapour present in the air
Absolute humidity - the mass of water molecules present per unit of volume g/cm^3
Relative humidity - the percentage of actual humidity relative to maximal humidity possible (saturation point) at a given temperature
What effect does temperature have on humidity
The saturated vapour pressure or maximum pressure exerted by evaporated molecules above a liquid at equilibrium is higher at higher temperatures i.e. when water is hot it has a higher saturated vapour pressure and increased potential humidity. Note it is not the air temperature but the water temperature in the air that matters - this is because when the water molecules have more energy they evaporate more readily –> but when they cool they clump together and liquid forms (dew point)
Explain how a cloud is formed
he greater the partial pressure of water in the air, the less dense it is and so the more humid air will rise. As air rises the effect of the earth’s gravitational field becomes lower, spreading the molecules further apart and decreasing the atmospheric pressure. This process of expansion requires energy and so the air cools. As the saturated air cools down its constituent water molecules now contain less energy and condensation occurs. The water condenses out (onto dust and other hygroscopic particles present in the air) and becomes visible as cloud. The humidity of the air decreases as the water condenses out and the air becomes denser. It therefore stops rising and an evaporation/condensation equilibrium is reached between the surrounding air and the floating body of water in the form of a cloud.
How is air humidified in the respiratory tract
Nose - inferior turbinates. As cold air passes over the inferior turbinates it si warmed to 36 degrees. Additional water vapour is added fro the moist lining of the mucosa. By the time it reaches large bronchi it is fuly saturated 44mg/L giving partial pressure of 6 kPA
Why is humidity a probem when considering medical gasses
- Gasses are manufactured as dry as possible to eliminate ice and water damage to valves and regulators
- Artificial airways bypass normal humidification
Why is moisture important to the respiratory tract
- Ciliary function and mucous transport - prolonged dry gas causes tenacious secretions –> mucous plugging and susbsequent hypoventilation
- Dry gas will increase humidification by the lower respiratory tract causing heat loss - this also has a detrimental effect on cilia function
Heat loss from respiration - how would you calculate it?
Heat loss from warming inspired air = ventilation x specific heat capacity x temperature rise
Humidifying air = ventilation x water required x specific latent heat of vapourisation
Aggreagted is 10% fo total heat loss for adults
Advantages of a HME filter?
Inexpensive
Disposable
passive
Efficient enough to work for 24 hours
What makes up a HME filter and how does it work?
Seal unit, hygroscopic material e.g. calcium chloride or silica gel whcih condenses the gas meating the surface simultaneously heating it via the latent heat of condensation and with the next inspiration this is reversed
A 0.2 micrometer filter renders the itnerface impermeable to bacteria and viruses avoiding contamination of circuits
What is the efficiency with HME filters
80%
Disadvantages of a HME filter?
Passive - therefore not 100% efficient and loss of heat ad moisture does occur over time
Filter adds dead space and resistance
Dead space can range from 8mL in paediatrics to 100mL in adult. Resistance 2cmH20 - also add a dam to secretions increasing work of braething
What is the principle of water bath humidifers?
Dry gas is bubbled through a water bath causing humidification as energy is conveyed to water molecules which are then evaporurated
What is is the problem with a passive water bath
Inspired gas is bubbled through a unheated water bath therefore humidification is limited by SVP at a lower temperature. Humidification will therefore not be 100% when raised to 37 degrees. Effect exacerbated by cooling of water bath seconddary to latent heat of vapoourations after water vapourised
Explain why a active humidification with a water bath may be ideal?
Temperature of water bath raised to allow for increased humdification as SVP will be higher, less cool air causing tenacious secretions and cilia paralysis
Draw different configurations of water baths
- No fluid warming configuration
- Fluid warmed to 35 degrees
- Fluid warmed to 45 degrees
- Effect of warming coil in the elephant trunk to the patient
What is a water trap in the context of humidification equipment
Water baths in active heating produce very humdified gas that subsequently cools as it leaves the chamber and enters the circuit limb going to the patient and can cause a reduntant pool of water in the tubing
What are the different approaches to how much to heat a water bath
Unheated - incomplete humidification, and energy still lost and secretions still affected by cool air
Heated to 40 degrees - minimises the risk of scalding the patietn airways but ideal for microbial growth
Heated to 60 bacterial contamination risk low but gas must now be carefully monitored to prevent airway scalding
What are aerosols
Small particles of liquids or solids suspended in carrying gas including dusts, bacteria, yeast, water drolets
For liquid medications to enter the alveoli as an aerosol what conditions are required
Stability of the aerosol - to remain in suyspension
Penetration is dependent on particle size - <3 micrometres and less than 1 micrometre the most ideal. Smaller than this the particles will be exhaled without effect
Particles or droplets 5-10micromtres deposit where when inhaled
upper airways
Particles 1-3 micrometres deposit where when inhaled
Alveoli
What is an atomiser
Jet or gas driven nebiuliser - high flow gas over a capillary tube immersed in fluid being nebilised
How is a gas different ot a vapour?
How does a vapouriser basically work?
Draw a vapouriser
What is the SvO2 of each of these locations
Jugular vein
Renal vein
Hepatic vein
IVC
SVC
Muscles
ugular vein (55%)
◦ Renal vein (81%)
◦ Hepatic vein (66%)
◦ IVC (71%)
◦ SVC (79%)
◦ Muscles (72%)
PO2 of mixed venous blood
40mmHg
How does PO2 related to SVO2
- The PO2 describes the proportion of dissolved oxygen (PO2 × 0.03)
- The PO2 also determines the SvO2 (usually 70-75%) according to the shape of the oxygen-haemoglobin dissociation curve in mixed venous blood
◦ This curve is slightly right-shifted (compared to arterial blood) because of the Bohr effect
How do you calculate blood oxygen content?
- Total blood oxygen content = (SvO2 × ceHb × BO2) + (PvO2 × 0.03)
◦ ceHb = the effective haemoglobin concentration
◦ PvO2 = the partial pressure of oxygen in mixed venous blood
◦ 0.03 = the content, in ml/L/mmHg, of dissolved oxygen in blood
◦ BO2 = the maximum amount of Hb-bound O2 per unit volume of blood (normally 1.39)
◦ SvO2 = oxygen saturation of mixed venous blood
Mixed venous blood oxygen is determined by what factors according to the Fick principle?
(CO = VO2 / CaO2 - CvO2):
◦ Arterial oxygen content: decreased arterial oxygenation will produce a decreased SvO2
◦ VO2, the oxygen consumption rate: decreased VO2 will produce an increased SvO2
◦ Cardiac output: a decreased cardiac output will produce a reduced SvO2
What is the normal PaCO2
40mmHg
What are the factors affecting partial pressure of CO2 in mixed venous blood
VCO2 = cardiac output x (CvCO2 - CaCO2)
As CaCO2 and CvCO2 are directly proportional/linearly related to their partial pressures this can be used
PCO2 = VCO2 / MV
Therefore PvCO2 will be dependent on CO, VCO2 and PaCO2
What factors increase rate of CO2 production? or decrease it?
- ↑production: hypermetabolic state (MH);
◦ exercise, fever, pregnancy - ↓production: ↓T°C; anaesthesia
How is minute ventilation ralted to PCO2
- pCO2 = Vco2/MV
What is PEEP
- The maintenance of positive pressure at the end of expiration
WHat is baseline PEEP
3mmHg when breathign through your nose
Physiological consequences of PEEP in the heart - RV
‣ Reduced preload - due to increased intrathroacic pressure
‣ Increased afterload reducing stroke volume - increased pulmonary vascular resistance due to increased intrathoracic pressure occurring in West zone 1 and 2 where increased alveolar pressure exceeeds venous pressure.Leads to preferential blood flow to diseased lung in heterogenous disease
‣ IV septum displacement can reduce LV compliance - can be significant in an already pressure overloaded RV
‣ Can exacerbate a R->L shunt intracranial
Physiological consequences of PEEP on LV heart
◦ LV - decreased preload and decreased afterload (reduced LV transmural pressure reducing myocardial work) with generally decreased cardiac output especially if hypovolaemia
‣ Decreased preload from bulging of the septum from dilated RV
‣ Decreased afterload - LV transmural pressure and wall stress, pressure gradient from thoracic to abdominal aorta improving flow
What 4 major factors does PEEP change in the lung
- Lung recruitment
- Compliance
- Increased mean alveolar pressure
- Dead space
How is lung recruitment affected by PEEP 2
‣ Prevents cyclic de-recruitment/atelectasis on expiration - raising FRC above closing volume
* Trauma
◦ Decreased atelectrauma and VILI
◦ Decreases bio trauma from alveolar collapse and release of inflammatory mediators
◦ Minimised denitrogenation atelectasis with high FiO2
* Improved FRC
◦ It increases the FRC above the closing volume which becomes more important with age, meaning that in expiration gas exchange can continue to occur as there is no collapse (i.e.increased total gas exchange surface)
◦ Creating an oxygen resevoir
◦ Improved V/Q matching - reduced shunt potentially
How is mean airway/alveolar pressure changed by PEEP
2 positive, 2 negative
‣ Displaces interstitial fluid improving gas exchange
‣ Improved partial pressure of gasses —> increased oxygenation via increased capillary-alveoli interface (recruitment and fluid displacement) and partial pressure
‣ Risk of overdistension and barotrauma increases —> cytokine leak and neutrophil retention
* Overinflation of non dependent alveoli or focal areas of unaffected lung
‣ Can impair lymphatic drainage - pulmonary oedema and pneumonia resolution
* Neutrophil retention in pulmonary capillaries
How does PEEP affect static compliance
‣ Depending on the portion of the static pressure volume relationship curve increasing the PEEP may either improve recruitment and improve lung compliance or over-distend and worse. For most who do not already have auto-PEEP and PEEP is being newly applied it will move inspiration at the start of tidal volume breathing towards the steeper portion of the volume pressure curve
‣ If improved compliance —> improved WOB. Less effort to trigger if improved compliance
How does PEEP affected dynamic compliance
‣ Dynamic compliance effect - Decreased turbulent flow on inspiration through increased airway diamtre creating less resistance on inspiration (more on expiration though depending if stenting open and obstruction), and improved lung compliance at moderate volumes
How does PEEP change dead space
◦ The change in dead space via the chosen device to deliver PEEP will also have an increase or a decrease in minute ventilation
‣ Additionally increased dead space due to decreased flow in West’s zones 1 (PA > Pa > Pv)
How does PEEP affect the brain
◦ Raised ICP if high PEEP - only with impaired cerebral autoregulation, PEEP above 15 appears to be where this is signifciant
How does PEEP affect the kidney 4
◦ Water retention - ADH release/vasopressin related to atrial stretch
◦ Aldosterone secondary to dropped systemic BP
◦ Sodium retnetion - ANF release drops due to reduced preload —>water and salt retention
◦ Decreased renal perfusion and GFR - cardiac output drop, increased renal vein pressure
How does PEEP affect the gut 3
◦ Decreased hepatic perfusion and decreased metabolic clearance of drugs
‣ Due to increased intrathoracic pressure —> decreased hepatic artery and portal venous flow and subsequent liver congestion and LFT changes
◦ Decreased splanchnic perfusion - reduced mortality and poor gastric emptying
◦ Decreased gastric perfusion - stress ulcers
What effect does 100% FiO2 have on a pneumothorax
Relative composition of air in a pneumothorax - partial pressures will depend on the pressure within the pneumothorax
- 78% nitrogen
- 21% oxygen
- 1% Argon/Co2
Diffusion out of a pneumothorax depends on Ficks laws of diffusion and will be equivalent to partial pressure
If we first calculate the effect of breathing air for diffusion gradient to alveoli vs 100% FiO2
Then compare this to blood as this will be the additional source of reabsorption
The solubility coefficient of N2 is poor, requiring 2x the partial pressure of O2 to dissolve
Why does gas flow into the pleural space if there is a hole
- Pleura separated by thin layer of pleural fluid –> surface tension keeping membranes apposed, balanced between elastic recoil (natural tendancy to collapse) and elastic recoil of the chest leaves normal intrapleural pressure -2.5 -6 cmH20
Once air enters the pleural space what happens to lung mechanics?
◦ Air enters pleural space
‣ Simple pneumothorax - air enters until pressure intrapleural is 0 OR until hole is closed
‣ Tension –> via a one way valve in the lung –> intrapleural pressure rises
◦ Air entry into intrapleural space –> lost surface tension and negative pressure causing dissociation between chest wall resting state and lung resting state
‣ Chest cavity expands outwards
‣ Lung collapses –> towards resting state, if intrapleural pressure rises above atmospheric pressure (1 way valve) compressive resistance to alveoli exacerbates collapse
If air enters into the pleural space causing a pneumothorax how does this impact volumes, compliance, work of breathing, gas exchange adn perfusion?
◦ Lung collapse causes
‣ Reduced lung volumes, reduced vital capacity
‣ This may be below closing capacity
◦ Increased work of breathing
‣ Lung compliance is poor at postitive intrapleural pressure –> increased work of breathing
‣ Falling PO2 and rising PCO2 –> stimulation of central and peripheral chemoreceptors increasing work of breathing without much increase in TV
◦ Gas exchange
‣ Reduced partial pressure of oxygen - due to V/Q mismatch in atelectatic segments, anatomical shunts (if pneumothorax is >25% of hemithorax) and alveolar hypoventilation
‣ Reduced ventilation causes rise in PCO2
◦ Perfusion
‣ Lung perfusion stops when alveolar pressure rises and lung volume drops
How is perfusion affected by a simple pneumothorax
◦ Lung collapse causes
‣ Reduced lung volumes, reduced vital capacity
‣ This may be below closing capacity
◦ Increased work of breathing
‣ Lung compliance is poor at postitive intrapleural pressure –> increased work of breathing
‣ Falling PO2 and rising PCO2 –> stimulation of central and peripheral chemoreceptors increasing work of breathing without much increase in TV
◦ Gas exchange
‣ Reduced partial pressure of oxygen - due to V/Q mismatch in atelectatic segments, anatomical shunts (if pneumothorax is >25% of hemithorax) and alveolar hypoventilation
‣ Reduced ventilation causes rise in PCO2
◦ Perfusion
‣ Lung perfusion stops when alveolar pressure rises and lung volume drops
How is gas exchange affected by a simple pneumothorax
◦ Lung collapse causes
‣ Reduced lung volumes, reduced vital capacity
‣ This may be below closing capacity
◦ Increased work of breathing
‣ Lung compliance is poor at postitive intrapleural pressure –> increased work of breathing
‣ Falling PO2 and rising PCO2 –> stimulation of central and peripheral chemoreceptors increasing work of breathing without much increase in TV
◦ Gas exchange
‣ Reduced partial pressure of oxygen - due to V/Q mismatch in atelectatic segments, anatomical shunts (if pneumothorax is >25% of hemithorax) and alveolar hypoventilation
‣ Reduced ventilation causes rise in PCO2
◦ Perfusion
‣ Lung perfusion stops when alveolar pressure rises and lung volume drops
How is work of breathing affected by a simple pneumothorax
◦ Lung collapse causes
‣ Reduced lung volumes, reduced vital capacity
‣ This may be below closing capacity
◦ Increased work of breathing
‣ Lung compliance is poor at postitive intrapleural pressure –> increased work of breathing
‣ Falling PO2 and rising PCO2 –> stimulation of central and peripheral chemoreceptors increasing work of breathing without much increase in TV
◦ Gas exchange
‣ Reduced partial pressure of oxygen - due to V/Q mismatch in atelectatic segments, anatomical shunts (if pneumothorax is >25% of hemithorax) and alveolar hypoventilation
‣ Reduced ventilation causes rise in PCO2
◦ Perfusion
‣ Lung perfusion stops when alveolar pressure rises and lung volume drops
With tension pneumothorax what happens from a respiratory perspective
◦ With tensioning pneumothorax the icnreasing pressure causes ipsilateral lung collapse –> shunting, V/Q mismatch adn worsening hypoxia –> contralateral lung compression compromises gass exchange further
Worsening collapse
Worsening work of breathing due to having to overcome positive pressure in the chest at baseline to move air
Worsening V/Q mismatch
Increasing shunt
With increasing pressure West Zone 2 increases and eventually West zone 1 with rising intrapulmonary pressure
Reduction in pulmonary blood flow
Cardiovascular consequences of a pnuemothorax transforming into a tension pneumothorax
◦ Compression of vena cava and right atrium –> reduced preload and decreased SV
◦ Compression of aorta –> increased afterload and reduced stroke volume
◦ Cardiac arrest due to hypoxia and above
◦ Compression of ventricles increased transmural pressure gradient and increased contracility
How is pneumothorax physiology different to a pleural effusion?
When a pneumothorax is present, the pleural pressure increases as it does with the presence of a pleural effusion. However, with a pneumothorax the pressure is the same throughout the entire pleural space if it is not loculated. In contrast, with a pleural effusion there is a gradient in the pleural pressure due to the hydrostatic column of fluid. Accordingly, the pleural pressure with a pleural effusion in the dependent part of the hemithorax is much greater than it is in the superior part of the hemi thorax. IN a pneumothorax the upper lobes are affected mroe than than lower lobes as suually the pressure int he apices is more negative than the bases, therefore when all symmetrical atmospheric pressure the increase in pressure is greater in the apex.
Diaphragmatic work is greater with pleural effusions
What are the cardiovascular consequences of hypoxia
- Pulmonary circulation vasoconstriction - increased afterload (normal value 100-200 dynes/sec/cm and doubles with severe hypoxia over 5 minutes)
- Systemic circulation vasodilation - in arteriolar beds (in response to local hypoxia) which is combatted by the more powerful systemic symapthetic response
- Coronary and cerebral vasodialtion remain marked
- Sympathetic driven response
◦ Hypertension - mild - slighty temporised by systemic vasodilation
◦ Increased cardiac output
◦ Tachycardia
◦ (Vagal tone also increases but to a lesser degree) - Eventually the brain becomes hypoxaemic and respiratory drive is depressed, thereby removing respiratory compensation and resulting in increasing acidosis, failure of the Na.K.ATPase pumps in most cells, cell lysis and death.
What acid base changes occur with hypoxia
- Mild hypoxaemia results in a respiratory alkalosis (respiratory stimulant)
- Hypoxia results in both fixed and volatile acid-base disturbances in severe cases
◦ Anaerobic metabolism results in lactate production
◦ Production of fixed acid results in a base deficit, and a low bicarbonate
◦ Drop in pH further stimulates the respiratory centre - Hypoxia and metabolic acidosis stimulate ventilation and hypocarbia
How are other organ systems affected by hypoxia - other than heart, lungs
Brain - cerebral vasodilation, ischaemic reflex if severe
Renal release of EPO, decrease in diuresis and natriuresis
Liver decreases O2 consumption
Reduced blood flow as part of symathetic response to gut. kdineys. skin
Release of hypxoia inducible factors stimulates immune cells to produce inflammatory cytokines
What are the 4 causes of hypoxia to cells
Hypoxaemic hypoxia
Anaemic hypoxia
Ischaemic hypoxia
Histotoxic hypoxia - failure to utilise oxygen
In hypoxaemic hypoxia what are the 4 causes
- Reduced oxygen delivery to alveoli
- Hypoventilation
a) Airway obstruction
b) Depressed respiratory drive - central, medications
c) depressed respiratory strength
- Reduced FIO2 - high altitude - Decreased diffusion capacity
- Decreased surface area - Emphysema, ARDS, pneumonia
- reduced permeability - fluid, fibrosis - Decreased V/Q
- Pneumonia
- Shunt
- Dead space - Decreased mixed venous oxygen content
- Increased o2 consumption or decreased cardiac output
What does the barometric pressure vary by with altitude
Barometric pressure 200mmHg at 10 000 m (paO2 42)
Barometric pressure is 580mHg and PaO2 of 60 at 2700m
What happens to saturated vapour pressure with altitude
Stable as the upper respiratory tract continues humidification and therefore remains at 47mmHg reducing the space for O2
What happens to respiratory status with altitude
MV increases (hypoxic respiratory drive) moderated in part by response to hypocapnoea
Decreased PCO2
Cardiovascular consequences of altitude
Tachycardia and increased cardiac output – sympathetic drive over the first few days
Mild BP increase as PVR decreases
Neurological effects of increased altitude
Decreased cognitive funtion
Delirium
Renal and electrolyte consequences of altitude
Diuresis
Decreased serum bicarbonate
Chronic respiratory adaption to Altitude
- Minute volume remains the same
* Tidal volume may gradually increase due to thoracic remodelling
* Decreased PaCO2
* Increased pulmonary artery pressure and vascular density - allows for improved pulmonary perfusion
* Total pulmonary diffusing capacity increases - increased alveolar surface area, increased pulmonary blood volume
* Oxygen carrying capacity - increased 2,3 DPG in erythrocytes shifting O2 curve to the right facilitating release of O2 to the tissues
Cardiovascular chronic changes to altitude
HR remains elevates
Increased BP from SVR
Increased blood viscocity
SV return to normal
Acid base in chronic altitude
Bicarbonate decreases due to chronic hypocapnoea
Haematological changes in chronic altitude exposure
- Haematocrit increases over days/weeks, largely due to haemopoiesis and haemoconcentration
* Plasma volume reduces - high altitude diuresis due to BNP, renin, aldosterone and decreased vasopressin
Stimulus for cough comes from 2 potential sources
Chemical and biological stimuli
Mechanical stimuli
What chemical and biological stimuli can trigger cough?
Acids
Biological pathogens
Mediators associated with inflammation
What mechanical stimuli can trigger cough?
Aspiration of liquids
Solids - secretions
What is the purpose of cough 3
◦ Protective function
‣ Defense against foreign material in the airway
◦ Pathological consequences
‣ Damage to the mucosa with persistent or unproductve cough
◦ Diagnostic purpose
‣ Evidence of intact medullary function
What 3 types of receptors are implicated in cough
Rapidly adapting receptors
- Responding to dynamic lung inflation - bronchospasm, lung collapse and sporadically active during the respiratory cycle
Slowly adapting stretch receptors
- Responsive to mechanical forces
- Particiapte in the Hering Breuer reflex (increased HR to lung stretch)
C fibres - nociceptors
Afferent nerve supply for the cough reflex
Bronchial mucosa - vagus - the pulmonary, pharyngeal, superior larungeeal branches
Diaphragm 0 cardiac and oeosphageal branches of the vagus
Where is the central integrated control of the cough reflex
Caudal 2/3 of the NTS
Efferent pathway of the cough reflex?
◦ To the diaphragm: via the phrenic nerve
◦ To the abdominal muscles: via the spinal motor nerves
◦ To the larynx: via the laryngeal branches of the vagus, from the nucleus ambiguus
4 Phases of the cough
◦ Sensory phase: afferent fibres conduct mechanoreceptor and chemoeceptor stimuli to the central interator in the medulla, and a cough reflex is triggered
◦ Inspiratory phase: glottis opens and a deep breath is inhaled
◦ Compressive phase: glottis closes and expiratory muscles forcibly contract; the intrathoracic pressure may transiently rise to over 100 cm H2O.
◦ Expulsive phase: the glottis opens and rapid airflow begins; the bronchial tissues oscillate due to the rapid turbulent flow, which loosens the secretions.
What is viscocity?
Used to indicate a fluid’s internal resistance to flow. Also thought of as a measure of the friction of a fluid.
What is density
(ρ): relates the mass of a substance to its volume such that ρ = kg/m3
What is Reynolds number?
preidcts the likelihood of turbulent flow
Re = 2rvp / n
i.e. radius x velocity x density/viscicity
How is density related to laminar flow
Density is related to Reynolds number, not resistance precisely
Increasing density increases the Reynolds number and favours turbulent flow
How is viscocity related to flow
It is both related directly to the resistance of laminar flow
And it decreases the Reynolds number increasing the likelihood of laminar flow
What is the equation for resistance in turubulent flow?
= pl/pi x r^5
i.e. density x length / pi x radius ^5
Therefore radius becomes even more important, and viscocity is not a factor
Non respiratory functions of the lung
Filtering
- Particle filtering
- Filtering clots in the circulation
Blood
- reservoir
- modulates the clotting cascade
Immunological
Metabolism
- Surfactant
- Protein
- Removal of proteases e.g. alpha 1 antitrypsin
- Carbohydrate metabolism
- Metabolism of NA and vasoactive substances
Organ of speech
Acid base balance
Heat regulation in upper respiratory tract
Route of administration for drugs
How does particle filtering work in the airways
◦ Particle filtering
‣ 5-10 micrometre deposited in upper airway (impaction) - hit the walls
‣ 2-6 micromtres - lower respiratory tract
‣ 0.5-2 micrometres in alveoli - deposition
‣ 0.2-0.5 micromtres wash in and out of alveoli without interacting with walls
‣ <0.2 micrometres deposit into the walls
What immunological role does the lung have?
Physical defence systems
- Sneezing, coughing
- Mucociliary elevator
Cellular defence systems
‣ Alveolar macrophages
‣ Lung neutrophils
‣ Mast cells in the lung and bronchi
◦ Immunologic defence mechanisms
‣ Lymphatic system of the lung and antigen presentation site with lymphoid tissue in the lung
‣ Immunoglobulin in mucus and cell surfaces - IgA
‣ Direct antibacterial action of surfactant (Wu et al, 2003)
What role does the lung have in medications
◦ Route of drug administration (eg. nebulised steroids and bronchodilators)
‣ Droplets <5micromtres if absorption required and ideally - high lipid solubility, small size, and inhalation technique matters dependent on site desired.
◦ Route of drug elimination (eg. volatile anaesthetics, paraldehyde)
‣ Ammonia, alcohol, acetone
How does the lung function with respect to blood (3)
◦ Modulator of the clotting cascade: the lungs contain thromboplastin (procoagulant converting prothrombin to thrombin), heparin (from lung mast cells) and tissue plasminogen activator (fibrinolytic product)
◦ Filter for the bloodstream: particles larger than an RBC are trapped (~8 μm size barrier), which includes clots, tumour cells and other emboli - fat and amniotic fluid can pass through to systemic circulation
◦ Reservoir of blood: the lungs contain about 10% of the circulating blood volume
‣ 200-300ml/metre squared
‣ 20-25% in pulmonary capirllaries, and this may increase to 50% (250mls) with heavy exercise
What is the lung involved in from a metabolism perspective
◦ Modulation of body temperature: heat loss can occur by respiration
◦ Metabolism (eg. conversion of of angiotensin-I, and degradation of neutrophil elastase by α1-antitrypsin)
‣ Inactivation of neutrophil proteases
‣ Activation of deadly toxins - chlorine gsa to HCl
‣ Activation of circulating hormones e.g. angiotensin activation by ACE
‣ Noradrenaline, serotonin, PGE 1 and 2, adenosine and bradykinin metabolism
◦ Metabolised and released - arachadonic acid metabolites —> leukotrienees and prostaglandins
◦ Secreted - Ig, especially IgA in bronchial mucous
Describe the characteristics of CO2 as a drug pharmaceutically
◦ Colourless gas, pungent smell in high concentration
◦ Non flammable
◦ Specific gravity 1.98
◦ Critical temperature 31 degrees and critical pressure 73 atmospheres ◦ Melting point -55.6 degrees
◦ boiling point -78 degrees - sublimates
◦ In aqueous solution acts as a Lewis acid - slowly spontaneously hydrating to produce carbonic acid
◦ More soluble with reducing temperatures
◦ Base concentration 0.03% in room air
Effects on respiratory function of CO2
- Depressed airway reflexes
- Respiratory drive with mild hypercapnoea
- Respiratory function - bronchodilation, right shift of oxyhaemoglobin dissocaition curve
How does CO2 affect the cardiac system
◦ Sympathetic overactivity, thus:
‣ Hypertension
‣ Tachycardia
‣ Serum catecholamine excess - however catecholamine sensitivity is reduced by the acidosis
‣ Increase in cardiac output despite direct CO2 cardiodepressant effect
‣ Coronary artery vasodilator
◦ Prolonged QT interval and arrhtyhmias
◦ Vasodilation generally
◦ Myocardial depressant - although balanced with sympathetic effects often warm, flushed, sweaty, tachycardic with bounding pulse
* Vasoactive effects:
◦ Systemic arterial vasodilation - relaxes smooth muscle - however net effect of CO2 is still increase in BP
◦ Pulmonary arterial vasoconstriction - hypocapnoea reverses the positive effects of pulmonary hypoxic vasoconstriction
CNS effects of high CO2
◦ Progressively increasing sedation - disorientation, confusion –> obtunded
◦ Increased intracranial pressure - due to increases in cerebral blood flow doubles with CO2 of 8-11kPa PaCo2 - periarteriolar pH leads to a change in nitric oxide synthase activity –> intracellular cGMP production –> change in IC calcium
‣ 1-2ml/100g/min increase in blood flow for every 1mmHg change in PCO2
* 4% increase in cerebral blood flow per 1mmHg rise
‣ This mechanism becomes lost in damaged brain - which results in areas of undamaged brain vasodilating and stealing the blood supply fromt eh damaged area (which is what the damaged area usually does anyway); in hypocapnoea the reverse happens and undamaged vessels contrsict diverting blood into vasoplegic vessels
How does increasing CO2 affect cerebral blood flow
‣ 1-2ml/100g/min increase in blood flow for every 1mmHg change in PCO2
* 4% increase in cerebral blood flow per 1mmHg rise
‣ This mechanism becomes lost in damaged brain - which results in areas of undamaged brain vasodilating and stealing the blood supply fromt eh damaged area (which is what the damaged area usually does anyway); in hypocapnoea the reverse happens and undamaged vessels contrsict diverting blood into vasoplegic vessels
Saturated vapour pressure
Pressure exerted by a vapour at equilibrium with a liquid of the same substance i.e. rate of evaporation = rate of condensation
voltaile gas has a high vapour pressure i.e. tendancy to be a gas
In general saturated vapour pressure is influenced by temperature and pressure
Critical temperature
- Critical temperature is the temperature above which it is not possible to liquefy a given gas by increasing its pressure
◦ A substance is a gas when it is above its criticial temperature, and a vapour when it remains in gaseous phase below its critical temperrature
If a graph was drawn with nitrous oxide at 40 degrees it is above its critical temperature and therefore no additional pressure would force it to become a liquid. (36.5)
Critical pressure
- Critical pressure is the minimum pressure which would suffice to liquefy a substance at its critical temperature - above the critical pressure increasing temperature will not cause a fluid to vapourise
If a graph was drawn with nitrous oxide at 40 degrees it is above its critical temperature and therefore no additional pressure would force it to become a liquid. (36.5)
Absolute humidiity
Relative humidiity
Draw a diagram demonstrating V/Q ratio to height of the lung
How is V/Q related to PaO2 and PaCO2 - depict graphically
What effect does V/Q have on PaCO2
◦ This change has minimal effect on CO2 because the relationship of CO2 clearance to V/Q ratio is more flat and linear. Ventilatory responses to increasing CO2 are able to compensate for reduced V/Q in part due to the increased diffusion capacity of CO2 (24x oxygen)
