Respiratory Flashcards
what do blood gases show?(14 things on gas, how paO2 should relate to FiO2, SpO2 vs paO2 for assessing O2 delivery and role of the paO2 inc why 8 is the target normally)
pH, pCO2, pO2
Bicarb, BE
Na, K, Ca, Cl (Ca is ionised, should be 1.15-1.3)
Glucose, lactate
Hb, metHb, carboxyHb
PaO2 should be approximately 10kPa less than the % inspired concentration FiO2 (so a patient on 40% oxygen would be expected to have a PaO2 of approximately 30kPa
in terms of pure oxygen delivery, SpO2 is most useful. In terms of oxygen titration PO2 becomes useful as if you think of the Oxygen Dissosciation curve a PO2 of 8 correlates with the steep part of the curve, and in an acute (non compensated by other factors offending the curve) ties in with the point where a further drop is going to cause a significant drop in SPO2 and hence oxygen delivery.
Hence why a PO2 of 8 is the traditional target in acute patients on ITU
4 sources of error in ABG
delay in processing: Potassium increases.
Phosphate increases. Total protein increases
LDH increases. Sodium decs. RBCs consume gluc, produce lact, acidosis devs
hypothermia: lower the temperature, the higher the gas solubility; higher the solubility, the lower the partial pressure; so, PaO2 drops by 5mmHg for every degree below 37°C and PaCO2 drops by 2mmHg for every degree below 37°C
blasts in the sample: Leukemic patients with extremely high white blood counts may exhibit the phenomenon of leukocyte larceny, in which white blood cells metabolize plasma oxygen in arterial blood gas samples (ABG) producing a spuriously low oxygen tension.
for every 4g/L decrease in serum albumin, the normal expected anion gap decreases by 1; very 10 g/L fall in albumin will increase the base excess by 2.5 mEq/L
O2 % from different cannulae x3 and masks x7 inc why min flow rate for simple mask, what paO2 should be based on FiO2 (target sats explanation, newBTS guide and 4 groups who may want higher than that + how to tell if possible retainer) (and what if on O2 for >24hrs)(absorption atelectasis paO2 FiO2 link) what rate can nebs run at?
nasal cannulae can run at 1/2/4 lpm (paeds only up to 2lpm) giving 24%, 28%, 36% O2
VT usually at 1 or 2 lpm for peep and can do FiO2 separately
Simple mask does 5-8lpm (less than 5 lets CO2 build up in mask)
Venturi:
Blue 2-4lpm 24%
White 4-6lpm 28%
Yellow 8-10lpm 35%
Red 10-12lpm 40%
Green 12-15lpm 60%
Non-rebreathe mask is 15lpm 85%
Target sats traditionally are 94-98%, 88-92% in CO2 retainers (COPD but also some neuromusc disease, bony abnorms etc); however BMJ best practice now is keep O2 <96% if giving supp O2 (ie stop once sats >96%), and if acute MI or stroke then don’t start if sats >90-92%; generally then most pt it is fine to aim 90-94%; this upper limit doesnt apply to pt with CO poisoning, sickle cell, cluster headaches, PTX all of whom might benefit grom greater sats; if you’re not sure if to do target sats 88-92% can get VBG/CBG/ABG and look at base excess and bicarb to see if theyre retaining
If on for over 24 hours O2 should be humidified
Also be aware of absorption atelectasis where slowly absorbed N2 replaced by O2 is FiO2 high enough -> absorbed, alveoli collapse
PaO2 should be approximately 10kPa less than the % inspired concentration FiO2 (so a patient on 40% oxygen would be expected to have a PaO2 of approximately 30kPa
nebs normally run at around 6-8lpm
what target sats for COPD/potential retainers?- explained by VQ effects and what sats are fine for more ppl
88-92% generally always, even if not currently retaining
worsening V/Q mismatch occurs by the hyperoxic uncoupling of V and Q by regional hypoxic vasoconstriction. There’s no way to know when or if this will occur, until your patient falls asleep with a sad blood gas (unless you have an art line in with gas monitoring).
Additionally, if you don’t have any acute ischemic pathology, and potentially even if you do, we’re increasingly learning that sats of about 90% are fine for pretty much everybody, especially for relatively brief durations
bleomycin target sats, another substance that is similar, reason for this inc exposure over what time frame
target of SpO2 85% to reduce potentiation of lung injury by oxygen, given that harm from hypoxaemia at this level has not be demonstrated in these settings
same if paraquat poisoning
reason being that supplemental oxygen therapy is considered to be a synergistic toxin with Bleomycin, particularly in the setting of general anaesthesia and hyperbaric oxygen therapy (HBOT). The dosage of oxygen which can result in toxicity has not been quantified. Even a modest increase in fraction of inspired oxygen can result in toxicity, and ILD like picture, and death
exposure to Bleomycin in the past six months is considered by some to be a significant risk factor
acid base disturbance causes for each subtype
resp acidosis (pco2 high), renal bicarbonate retained (high) to compensate within 2-5 days; common causes are ventilatory failure and COPD
resp alkalosis (pco2 low) oft due to mechanical ventilation, hypervent, living at high altitude, or type 1 resp failure
met acidosis oft lactate production due to shock or cardiac arrest, may also be DKA or due to chronic renal failure, loss of bicarb through gut, or via kidney in RTA; see hypervent to resp compensate unless resp centre depressed by eg drugs or head injury, or pt mechanically ventilated
met alkalosis - loss of acid eg from stomach with ng suction, or overzealous sodium bicarb treatment
respiratory failure definitions, causes, management (of low O2, high CO2)
type 1 - lung tissue damaged eg pneumonia, lung injury, pulm oedema, fibrosis
type 2 - ventilation insufficient eg COPD, GBS, resp depression, chest wall deformity
resp rate - most sensitive indicator of resp difficulty; pulse oximetry rough measure of oxygen carried in blood; blood gas analysis for more detailed knowledge of oxygen but also pH/pCO2
capnography can confirm intubation, and monitor end tital pCO2 (approximates to paCO2) to detect block of trach tube, or acute changes in cardioresp function
escalating management of: supplemental oxygen to correct sats (along with secretion control, treating any infections/oedema) by inc’g fiO2, then inc pO2 by inc’g pressure (CPAP); when ventilated want to inc mean pressure in system but cant inc peak insp pressure (pneumothorax risk), instead use CPAP to increase peep; finally inc insp:exp (IE) ratio, from the normal 1:2 to 1:1, maybe even 2:1 if extreme; called CPAP when pt breathing, PEEP when on ventilator
for controlling CO2 can blow it off by inc’g resp rate or tidal volume (product of which is minute volume/ventilation); resp rate can be restored in specific conditions by naloxone
otherwise TV or resp rate controlled by a ventilator (so ventilator often only way to remove excess CO2); TV dependent on deltaP which is pinsp-peep, so changing peep to maximise pO2 actually reduces TV and so CO2 clearance, however hypoxia kills so treat pO2, permissive hypercapnia eventually compensated by metabolic alkalosis; on BIPAP inc Pip to inc TV
volume vs pressure targeted ventilation
in pressure targeted ventilation, magnitude of each inflation is determined by the change in airway pressure (i.e. the difference between PIP and the baseline or positive end‐expiratory pressure (PEEP)). The VT for any inflation depends on both this pressure difference, which drives gas movement, and the lung compliance. Although VT is indirectly determined by the clinician when the PIP and PEEP are set, VT may not be consistent when the infant breathes, cries, splints, is apnoeic or when compliance and resistance change. For example, following administration of artificial surfactant, improved compliance may result in the delivery of increased VT if the PIP is not reduced
several studies have indicated that lung collapse and overdistension (or atelectasis and ‘volutrauma’) are the major instigators of inflammation in the preterm lung and thus higher rates of BPD rather than barotrauma hence utilising volume targeted ventilation
In general, volume control favours the control of ventilation, and pressure control favours the control of oxygenation.
Volume control:
Advantages:
Guaranteed tidal volumes produces a more stable minute volume
The minute volume remains stable over a range of changing pulmonary characteristics.
The initial flow rate is lower than in pressure-controlled modes, i.e. it avoids a high resistance-related early pressure peak
Disadvantages:
The mean airway pressure is lower with volume control ventilation
Recruitment may be poorer in lung units with poor compliance.
In the presence of a leak, the mean airway pressure may be unstable.
Insufficient flow may give rise to patient-ventilator dyssynchrony.
Pressure control:
Advantages:
Increased mean airway pressure
Increased duration of alveolar recruitment
Protective against barotrauma
Work of breathing and patient comfort may be improved
Disadvantages:
Tidal volume is variable and dependent on respiratory compliance
Uncontrolled volume may result in “volutrauma“ (overdistension)
A high early inspiratory flow may breach the pressure limit if airway resistance is high.
how many ml O2 in 100ml blood at diff sats (how many ml a 10% sats change is), hyperbaric O2 therapy, what paO2 and paCO2 should be, fundamental cause of normal and raised anion gap acidosis
100ml of blood binds 20.1ml of O2, as oxygen content of blood is 1.39 x hb conc x sats + dissolved (negligible); normal Hb conc is 15gHb per 100ml so fully saturated is 1.39 x 15
so sats of 90 contains 18.8ml, 80 is 16.6ml, 70 is 14.6ml etc (10% change is 2.1ml change)
dissolved oxygen is 0.003ml O2 per 100ml blood per mmHg paO2, so normally only 0.3mL O2 dissolved per 100ml so negligible
hyperbaric chamber for CO poisoning aims for 100-1000 paO2 which increases O2, up to max around 5ml per100ml blood aka 25% normal O2 delivery (plus some more as higher paO2 helps displace bound CO)
paO2 should be 10-13, paCO2 should be 4.7-6 - subtract 10 from fio2% to get predicted pao2
bicarb 22-28, BE -2-+2, anion gap10-18, lactate <2mmol/L
high base excess is metabolic alkalosis, low base excess is metabolic acidosis; raised anion gap is addition of acid eg DKA, normal anion gap is loss of bicarb eg diarrhoea, RTA
invasive ventilation (indications, 5 complications inc effect of raising PEEP)
used for ventilatory failure, or when resp failure can’t be managed through O2 and NIV: pt tiring, dec’g consciousness, can’t maintain own airway due to falling GCS etc
also postop in high risk patients, after head injury (acoid hypoxia/hypercarbia which raises cbf and so icp, after chest trauma, severe lhf, coma
tracheal intubation needed: risk of trauma to upper airway, tube in oesophagus, tube only in one main bronchus, blockage of tube with eg secretions or blood, or migration/leak of tube
need sedation (anaesthetic eg propofol), analgesia with opiate, sometimes muscle relaxants but minimising sedation is best
ventilator associated lung injury due to high pressures/TV (or normal in damaged lungs) can give pneumothorax/peritoneum/mediastinum, subcut emphysema; tension ptx possible and can be fatal: worsening hypoxia, hypercarbia, inc’g airway pressyre, hypotension, tachycardia, maybe rising cvp
up to 1/3 may get HAP
PEEP raises mean intrathoracic pressure, decreasing VR and so CO; expanding circulating volume or inotropic support may be needed as fall in CO can decreases O2 delivery despite improved paO2
if on ventilation for a while resp muscles get weak so can take a while to wean/be able to breathe for yourself
ecmo is the last resort if ventilation can’t work and is done in specialist centres like papworth
also PEEP can cause SIADH
mechanical ventilation (3 pros of NIV, what CPAP and eg BIPAP are good for, why sedation needed for invasive)
during surgery or resp failure to optimise gas exchange; uses positive pressure, which can have side effects even in healthy lungs; non invasive (masks or hoods) doesnt need sedation, doesnt impair mucociliary apparatus, can be done at home, but is still pos pressure so has risks; invasive (tracheostomy or tracheal/bronchial tubes)
CPAP: pos pressure during insp and exp, but pt must generate neg pressure to inflate lungs; least invasive, good for pulm oedema, lung collapse inc atelectasis (decs work of breathing
other noninvasive: good for hypercarbia (as improves minute ventilation unlike CPAP), resp muscle weakness, those in immunocompromised state (avoids risk from invasive)
invasive: anaesthesia needed as would stim laryngeal/pharyngeal reflexes; use min inflation pressure to avoid lung injury, ensure each tidal breath keeps lung open to prevent atelectasis; using lowest tidal volume likely to achieve this w/o causing harm
tracheostomy (4 acute indications, 6 chronic, mx of problems in emergency)
Indications for emergent tracheostomy include:
Acute upper airway obstruction with failed endotracheal intubation (foreign body, angioedema, infection, anaphylaxis, etc.)
Post-cricothyrotomy (if a cricothyrotomy has been placed it should be immediately formalized into a tracheostomy once an airway has been secured)
Penetrating laryngeal trauma
LeFort III fracture
Indications for elective tracheostomy include:
Prolonged ventilator dependence
Prophylactic tracheostomy prior to head and neck cancer treatment
Obstructive sleep apnea refractory to other treatments
Chronic aspiration
Neuromuscular disease
Subglottic stenosis
in emergency: high flow O2 to face and tracheo if breathing, if not then CPR
remove speaking cap and inner tube and suction, deflate the cuff, at every stage checking for improvement - if still none then remove tube, keep going with A-E if still breathing and CPR if not
BIPAP (indications, contrainds, initial settings and targets, interpreting repeat ABGs (inc how often to do), weaning pathway, if pt anxious)
indication (all needed): pH <7.35, pCO2 >6.5, able to maintain own airway; not if PTX - need a CXR before starting so you know no PTX; also not if fixed upper airway obstruction, GCS <8, pH <7.15 (all may need intubation); for COPD, neuromusc problems, OHS/OSA; if asthma/pneumonia then ITU review
start IPAP 15 EPAP 3, titrating IPAP up to 20-30 or as tolerated over next 10-30 mins; don’t go higher than 30/8; backup rate should be 16-20; IE ratio 1:2 in COPD, 1:1 in OHS/neuromusc
aim for sats 88-92% in all patients (pO2 7.3-10)
ABGs in 1 hr then 2 then 6 then every 24
repeat ABG after 1 hr: if pH/pCO2 improving then continue current settings, rpt ABG in 4-6 hours (sooner if pt deteriorates) then keep going until pH reset and pt stable (usually 24 hours), allowing breaks for eating, drinking, and meds/nebs but aim to spend as much time as possible on it in first 24 hrs
if on 1 hr ABG pH/pCO2 not responding or worsening then check mask fitting well, pt not aspirated or developed PTX, urgent sr r/v or ITU contact, inc IPAP by 2, rpt ABG in an hr, continue with new settings if improving and if not repeat process above or consider palliation if ward based ceiling of care
if on 1hr ABG pH/pCO2 improving but pO2 <7.3 inc FiO2 aiming for sats 88-92%, if non-COPD consider inc EPAP, pO2 should be 7.3-10kPa
weaning pathway: pH >7.34, sats >87%, sats stable, need hourly NEWS/obs while weaning; day 1 16 hours (all of night, 2hrs on 2 off during day), 12 hours next day (continuous o/n); so weaning time not settings
if while weaning sats drop, NEWS rises then rpt ABG immediately: if pH falling or PCO2 rising then back into BIPAP pathway, if thats okay but pO2 <7.3 then inc O2
if pt anxious: sedation can be used if closely monitoring them eg HDU/ICU setting, in which case IV morphine +/-BZD can help
BIPAP 4 complications and solutions
nasal bridge ulceration -> adjust mask fit, barrier dressing and regular breaks, topical steroids if rash and consider abx if looks infected
gastric distention: NG tube
mucosal congestion/sinus discomfort: topical steroids or decongestants
acute ptx: if new agitation, chest pain; needs intercostal drainage
home oxygen - 7 indications, when and how to assess, how long min to order for and how to titrate while setting up; equipment to order; 2 other forms of home O2
pulm HTN with rest paO2 <8
COPD, ILD, CF, CCF with rest paO2 <7.3 (or <8 if also pulm HTN, periph oedema, polycythemia); it can be used in neuromusc causes if hypoxaemia doesn’t improve with NIV
Patients with cancer or end-stage cardiorespiratory disease who are experiencing intractable breathlessness should be trialled on opioids and fan therapy in first instance; if intractable or have hypoxaemia (in eg severe ILD) then can give it
LTOT if at rest sats <92% (or <94% if periph oedema, polycythemia, pulm HTN); assess with an ABG at rest
should order for min 15hrs a day
if eligible titrate O2 up in 1lpm increments until sats >90% achieved, then confirm paO2 >8 with ABG
If the need is intermittent, then static cylinders may be considered. If it is considered, however, that the patients’ needs are going to increase to >4 hrs a day, then a static concentrator should be first choice; rate to request depends on rate given in hospital to get target paO2
besides LTOT there is AOT for LTOT pts outside the house and some pts who desaturate on exercise (not on LTOT but sats fall >4% to below 90% on exercise), needs a walk test on O2 and air; SBOT also for some indications eg cluster headache
airway adjuncts (when NPA, OPA contra’d), when jaw thrust better than chin lift; LMA indication, intubation indication
NPA: conscious or semiconscious (gag and cough intact); never if bleeding disorder eg low platelets as can be traumatic process and nosebleeds result, also not if basal skull fracture; lube up, insert; for eg pt w/ gag reflex but low or falling GCS
OPA: J shaped device, put in upside down and then twist, it will hold tongue and soft palate up so use if risk of these collapsing; dont use in conscious or semiconscious (gag/cough +ve) ppl as will make them vomit and maybe aspirate, thus test for these reflexes before deciding between NPA and OPA
suction can be done through either device to help clear airway, but pause after 10s to give O2 and avoid hypoxaemia; also clear mouth/nose of secretions first before inserting if you can; for OPA choose the right size, should reach from mouth to angle of jaw
if pt is not breathing but airway not at risk then you’ll want bag-mask ventilation: chin lift (unless neck injury, then jaw thrust), C clamp mask on to ensure tight seal, colleague ventilates 2 breaths per 30 compressions and check to see chest rising
supraglottic airway: aka laryngeal mask airway; use if indication for intubation but not qualified to do so, or during simple surgeries where muscle relaxants not needed; lube, have chin lift position, insert until reaches post pharynx, then pressure down and back until comes to sit on hypopharynx; inflate cuff if it has one (deflate cuff at start of process too!); attach ventilate, look for chest movements and auscultate to confirm in correct position; secure with tape; maybe attach capnography monitor for end tidal co2 to confirm placement; consider its use in cardiac arrest
indications for intubation: failing to ventilate, failing to oxygenate, failure to maintain airway patency; is there obstruction: (silence/complete or stridor/partial), is there risk of obstruction (inhalation of smoke, anaphylaxis, haematoma from trauma) if so reassess often and consult with seniors, if impending (eg clearly inhaled smoke or currently in anaphylaxis) then early intubation of what kind you can; is there risk of airway collapse ie falling GCS or GCS<8, if yes secure airway
when to do ABG vs VBG
pH correlates well between two (VBG v slightly (0.03) lower), pCO2 wide confidence interval (6mmHg higher but wide variability) in link so depends how closely you need to monitor this, pO2 doesnt correlate, bicarb correlates and closely approximates, lactate and lactate trend corresponds well, base deficits correlate well
so who needs an ABG rather than a VBG?
can be useful to get paO2 to work out A-a gradient if unsure of hypoxia cause
hypoxemic pts eg ARDS or T2RF should have ABG as VBG cant help with telling oxygenation (note: in terms of pure oxygen delivery, SpO2 is most useful. In terms of oxygen titration PO2 becomes useful as if you think of the Oxygen Dissosciation curve a PO2 of 8 correlates with the steep part of the curve, and in an acute (non compensated by other factors offending the curve) ties in with the point where a further drop is going to cause a significant drop in SPO2 and hence oxygen delivery.
Hence why a PO2 of 8 is the traditional target in acute patients on ITU; eg a PaO2 of <8 kPa on 15L well require consideration of escalation (eg NIV/I+V) versus a PaO2 of >11kPa - even though both may have same spo2 on a sats probe. Tells you where they are on the oxygen-haemoglobin dissociation curv)
if worried about metabolic acid-base status then VBG will give you pH, bicarb, lactate and can screen for hypercarbia (but in neuro trauma or post cardiac arrest where really important to follow and manage pCO2 go with ABG) - if <6kPa then not hypercapnic - you worry about this in metabolic acidosis as tiring so may need ventilation to maintain pH), if >6 then ABG to know true value and guide vent decisions
finally if in shock do ABG as 1) pulse oximeter less useful for O2 status, need to check SaO2, and 2) pH and pCO2 no longer correlate
PE vs anxiety blood gases and doses for cardiac membrane stabilisiation, anaphylaxis
PE vs anxiety blood gases: both will hyperventilate and so blow off CO2 giving resp alkalosis, but in anxiety pO2 will be v high and in PE
not
give 30ml of ca gluconate 10% for cardiac membrane stabilisation; adr anaphylasis is 500mcg (0.5ml 1:1000)
body pH buffering systems (inc pH equation)
static systems inc protein, haemoglobin, hydrogenphosphate - quickly depleted; dynamic system bases on bicarbonate, acid reacts to make sodium salt, CO2, water - H/H equation 6.1 + log([HCO3]/0.03*pCO2) 0.03 is solubility constant to make it a conc based on Henry’s law, lungs keep pCO2 constant (some compensation) so non-volatile acids deplete bicarbonate, kidneys replace
generation of a pressure gradient in the lungs
flow = pressure/resistance; thoracic cage has natural outwards elastic recoil and lungs an inwards elastic recoil (seen in pneumothorax) held together by interactive forces within 10 micron thick pleural fluid, which also serves as a lubricant; Pip generated of -5cmH20 relative to atmos and helps make respiration more efficient, Pip is more negative at apex of lungs due to gravity/posture pulling lungs down; diaphragm lowers by ~1cm, external intercostals contract, thoracic cage volume increases and (by boyle’s law), pressure falls giving a distending transmural pressure on lungs so they expand and (by Boyle’s law) pressure falls giving a pressure differential to drive flow; expiration passive in eupnea but muscles can be recruited under which circumstances Pip may exceed atmos pressure, muscles may be recruited in inspiration to facilitate greater Pip decrease too; transmural pressures come from pressure inside minus outside; at end of expiration muscles relax, no air flow, alveolar pressure = 0 and Pip -5 so tp pressure is 5 (always positive, keeps lungs inflated, Pip falls to -8 to raise tp and drop alveolar pressure (very small differential) and alveolar pressure >0 during expiration; effusion reduces all volumes of lungs (but not as much as effusion volume as chest also expands); transpulmonary pressure (with static compliance) determines lung volume, alveolar pressure determines flow, so sustained negative shift in Pip initially causes transient negative Pa for flow, energy then used to maintain new, larger lung volume
spirometry and lung volumes
inverted bell immersed in water to form a seal, attached by pendulum to drum rotating at constant speed and when bell rises pen deflects downwards; TV is vol of air in a breath ~500ml, multiplied by frequency of breaths to give minute ventilation, volume of air entering is ~1% greater than leaving due to more O2 consumed than CO2 produced; IRV is extra vol could inhale after normal, depends on muscle strength, lung compliance, flexibility of skeleton and joints, posture (if recumbent, more difficult for diaphragm to move abdo contents) and ERV same but for expiration; RV (residual volume) is air left after ERV which has advantages as collapsed airway takes unusually high pressure to reinflate so helps maximise energy expenditure and blood flow can continue in inflated lung so gas exchange can too, a low residual volume would thus give oscillation of blood gas content, never reaches zero (even in pneumothorax/atelectasis) as proximal airways collapse first; TLC is sum of those volumes and is max air that can fill lungs, FRC is ERV + RV, amount of air left after normal expiration, inspiratory capacity is max air that can be inspired, TV + IRV, VC is maximal achievable TV (IRV+TV+ERV)
dead space, minute ventilation, and alveolar ventilation (inc physiological dead space 2x causes)
~350ml gets to alveoli due to dead space (which aloows for warming, humidifying etc), alevoli with no bloodflow are also dead space or ventilation exceeding perfusion; combine to make physiological dead space which should be equal to anatomic in healthy individual (weight in pounds = anatomic roughly); deep slow breaths more effective than shallow quick ones; expired minute volume is TVxbreath frequency, represents minute ventilation but not quite as western diet means less CO2 made than O2 consumed; Va is (TV-TD)xf; can assume expired CO2 produced in body, no gas exchange in DV so Veco2 = Va x Faco2, Veco2 found from spirometry and Faco2 from sampling last part of exhaled gas, Veco2 usually at STPD and Va at BTPS plus Faco2 usually expressed as partial pressure so Va = Veco2/PAco2 x k (conversion factor): Va and PAco2 have inverse relationship and alveolar gas equilibrates with arterial blood so PA=Pa so effects of hypo/hyperventilation; if PAco2 too high then ventilation inadequate as Veco2 varies only in exercise, fever, hyperthyroidism and Va increases to match the increase to maintain Paco2; respiratory exchange ratio and inspired O2 not zero so not exact relationship between Va and PAo2, R would be 1 if we only had carbs in diet but fats/proteins mean less CO2 made than O2 used so R<1 and PAo2 = Pio2 - PAco2x(Fio2 + ((1-Fio2)/R))), should be 100mmHg; PAn2 increases as R<1, also as Po2 decreases more than Pco2 increases in capillary beds, total pressure in venous blood less than atmospheric
lung surfactant and surface tension
70dynes per cm for air/water interface at 37 degrees c; arises due to non-compensated pull between liquid molecules whose interactions are stronger than the gas can provide; inflation/deflation of lungs in air and saline show saline far more compliant and less hysteresis, and surface tension deduced to account for 2/3 to 3/4 of elastic recoil of lungs; surface tension discovered as oedema foam has air bubbles which are very stable; type ii pneumocytes secrete phospholipid rich surfactant, (90% lipids, 50% of which are DPPC, proteins 10%, half plasma proteins and half contribute to inate immunity by promoting phagocytosis, help improve surfactant rate of disribution with congenital absence leading to acute respiratory distress syndrome) principle component dipalmitoyl phosphatidyl choline (DPPC) with production dependent on precursors (glucose, palmitate, choline) supplied by pulmonary circulation; turnover rate high has each lung expansion has surfactant renewal; surface balance used to study effect of surfactant, test material in saline with adjustable surface area, adding detergent reduces surface tension independent of surface area, lung washings reduce it dependent on surface area and at low surface area the surface tension falls to very low values
surfactant role and ARDS
surfactant reduces surface tension to increase compliance and decrease the work of breathing, also allows alveoli of different sizes to co-exist as LaPlace’s law p = 2D(surface tension)/R so smaller alveoli should collapse into larger ones (atelectasis) as larger pressure developed in smaller ones, but surfactant reduces surface tension more in smaller alveoli (also they’re tethered together to keep each other open); DPPC is amphipathic and intermolecular forces oppose attractive forces between surface water dependent on surfactant per unit area (reduction greatest when film compressed); at low lung volumes some DPPC squeezed out of surface layer so upon expansion amount per area is less requiring new surfactant or redistribution of old film, thus hysteresis; in quiet breathing surface area can remain ~constant which impairs surfactant distribution, deep sighs or yawns increase the volume to help spread new surfactant, abdo/thoracic surgery patients may find it painful to breathe deeply leading to poor surfactant distribution and possibly atelectasis; foetal lung surfactant production matures at 85-90% gestation period, premature babies often have insufficient surfactant production leading to infant respiratory distress syndrome (laboured breathing as a result of increased compliance), developing atelectasis and pulmonary oedema; surfactant helps keep alveoli dry, inwards collapsing force from surface tension would lower interstitial pressure to draw fluid from capillaries giving oedema, surfactant reduces this; rapidly expanding alveoli expand faster than surfactant reaches surface so surface tension increases, may double in inspiration, to help slow expansion of some alveoli to match slower ones (and reverse for expiration with faster than surfactant can leave surface, tension halving and collapse slowing)
ARDS (def, causes -inc most common cause - management)
resp distress, new bilat patchy or homogeneous pulm infiltrates, no cardiogenic cause for this oedema (pulm art pressure <18)
common causes inc pneumonia, aspiration, sepsis, shock; rarer inc fat or amniotic fluid embolism, reperfusion after lung transplant or pulm embolectomy, inhalational injury inc near drowning, acute panc, TRALI, eclampsia, burns, vasculitis, altitude, heroin/barbiturate overdose
sepsis is commonst predisposing factor, 20-40% severe sepsis pts will dev ARDS
mechanical ventilation cornerstone of management, limit oedema with diuretics and fluid restriction, pt adopt prone position; surfactant replacement in neonatal resp distress
4 ARDS criteria, 8 causes, 4dd, 4 ix, and management
ARDS: Berlin Definition, which broadly consists of 4 key points:
Acute onset within 7 days
PaO2:FiO2 ratio <300 (with PEEP or CPAP >5cmH2O)
Bilateral infiltrates on CXR
Alveolar oedema not explained by fluid overload or cardiogenic causes
The degree of ARDS severity can be further defined, based on degree of hypoxemia via the PaO2:FiO2 ratio
direct causes: pneumonia, smoke inhalation, fat embolus, aspiration (not just asp pneum); indirect inc polytrauma, sepsis, major burns, acute panc
dyspnoea, usually in the presence of a related risk factor or underlying cause.
This then rapidly leads to hypoxia and tachypneoa, often with inspiratory crackles on auscultation
Multiple conditions present in a similar manner to ARDS, therefore ensuring the Berlin criteria are met for the diagnosis to be made is key.
Other differentials to consider include Congestive Heart Failure, Interstitial Lung Disease, Diffuse Alveolar Haemorrhage, and Drug-Induced Lung Injury.
ABG, routine bloods (and inc amylase/CRP), CXR, echo to exclude cardio cause
(i) supportive treatment with ventilation (ii) focused treatment of the underlying cause. It is highly likely that patients with ARDS will require early intubation and ITU admission for respiratory and circulatory support.
Patients who remain severely hypoxic despite conventional therapy, Extra-Corporeal Membrane Oxygenation (ECMO) can be considered
*Proning patients has also been shown to improve oxygenation and CO2 clearance, therefore can be used in conjunction to the other ventilation measures
SIRS and sepsis criteria (+severe sepsis, septic shock)
SIRS if 2 or more of temp >38/<36, HR >90, RR >20, WBC >12,000 or <4000
sepsis if SIRS + source of infection
severe sepsis if lactic acidosis or SBP either <90 or dropped 40 or more from normal
septic shock if severe sepsis w hypotension despite adequate fluid resus
respiratory failure causes/pathophys (inc gradient for type 1, why hypercap doesn’t occur, 4 causes of diffusion defect, 2 causes of VQ mismatch and 3 of shunt; 20 causes for t2rf)
t1rf can be split based on A-a gradient (alveolar pO2 - arterial pO2), and all causes of t1rf can progress to t2rf if sufficiently severe
normal gradient if FiO2 down
gradient decreased if:
Diffusion defect: Structural changes to the alveolar component of the alveolar-capillary interface, such as decreased surface area or increased thickness, may result in diffusion defects across the membrane. Hypercapnia does not occur, as carbon dioxide more soluble than oxygen; seen in emphysema, ILD, ARDS, CHF
V/Q mismatch: PE, COPD
r->l shunt: physiological when V/Q ratio reaches zero (no vent, still perfusion); AVM, complete atelectasis, severe pneumonia or oedema
t2rf either manifested by “won’t breathe” due to a central drive issue or “can’t breathe” as a result of a peripheral neuromuscular defect, resistive loading (narrow airway) or restrictive defect or dead space volume >50% that leads to hypoventilation and hypercapnia
note CO2 more soluble than O2 so less lung needed for its effective removal, hence why the t1rf aetiologies don’t cause t2rf initally
alcohol, benzos, opioids, encephalitis, stroke, tumour, head/cord injury
GBS, myasthenia gravis, organophosphate, SCI/transverse myselitis, ALS, tetanus/botulism
flail chest, kyphoscoliosis, OHS, effusions
muscular dystrophy, diaphragm paralysis/rupture
hypovent with dead space >50% eg PE, bronchitis/COPD, bronchiectasis
obesity hypoventilation syndrome OHS (what it is, 2 things that dec and one that incs to raise work of breathing, what happens in eucapnic obese individuals (and how does their fat distribution differ?), what ix needed, 2 mx
Obesity hypoventilation syndrome is a respiratory consequence of morbid obesity that is characterized by alveolar hypoventilation during sleep and wakefulness
In morbid obesity, central fat accumulation imposes a significant load on the respiratory system, with overall effect of marked decrease in lung volumes, in lung and chest wall compliance and increased airway resistance, in all contributing to a higher work of breathing
Individuals with OHS have greater degree of central obesity reflected by larger neck circumferences and higher waist: hip ratios than those with eucapnic obesity or OSA
Eucapnic obese individuals have a higher rate of oxygen consumption and CO2 production at baseline. This is generally compensated by increased respiratory drive to increase minute ventilation and maintain alveolar ventilation
individuals with OHS fail to compensate their respiratory drive in response to the added load created by excess weight, thus permitting a gradual increase in PCO2
OHS is a diagnosis of exclusion that requires evaluation for other potential causes of hypoventilation and hypercapnia such as obstructive or restrictive lung diseases, neuromuscular disease, severe restrictive chest wall disorders, metabolic causes like hypothyroidism and congenital hypoventilation syndromes
treatments inc weight loss and CPAP/BIPAP
why pneumonectomy doesnt need O2 but pneumonia/white out does?
V/Q mismatch. If we assume that there’s no gas exchange with an area of pneumonia, there is still blood flowing round it (possibly more due to inflammation). Whether that blood comes from the pulmonary artery/ right heart, or the bronchials, it all drains into the left atrium. There it mixes with, and dilutes all the blood that’s passed through the lungs and is oxygenated.
So, if the blood passing through the right lung has sats of 100%, and the blood passing through the pneumonia enters the LA with sats of 75% (as if venous), the blood pumped out of the left heart will have sats somewhere between the two, probably in the 80’s if it’s a big pneumonia (interestingly supplemental oxygen might be limited in potential to improve this)
On the other hand a pneumonectomy has no blood flowing through it because the PA stump has been tied off. Therefore there’s no blood draining from it into the LA and no shunt
O2 transport in blood (hb structure and what part binds how much O2, what types A and F are, 1g binds how much so how many g in 100ml blood, equation for total amount, normal sats in arterial and venous blood, how paO2 relates to saturation% and why we evolved this way + utility of steep fall below this number, effect of right shift of curve inc 4 things that shift curve and what is Bohr effect, role of 2,3DPG inc 3 situations more made; how HbF shifts curve and importance of this; how pulse oximetry works)
bound to Hb, 2a/2b subunits with porphyrin moity that binds 4O2, adult is type A and foetal type F; pH, pCO2, temp and diphosphoglycerate influence Hb affinity for O2; 1g binds 1.39 ml, 15g per 100ml; PaO2 is amount not bound, but total amount is what keeps us alive and is (1.39x[Hb]x%sat)+(0.003xpO2)
97.5% saturated in arterial blood, 75% in mixed venous blood; sigmoidal shape so Hb largely saturated at pp >8kPa (loading plateau), so fluctuations in barometric pressure have little effect on blood O2 content, and remains same over large range of ventilation rates so can regulate Paco2 without effecting O2 supply; marked fall in saturation <8kPa facilitates unloading
modest right shift of curve will result in release of O2, this is how temp, pCO2, pH and DPG work; Bohr effect is exercising muscle is warm with high pCO2 and low pH (lactic acid, extra pCO2 to bicarb/proton) so facilitates greater O2 release; RBCs have high levels of 2,3DPG due to DPG mutase acting on glycolysis intermediate 1,3BPG, 2,3DPG has higher affinity for type A Hb, displacing bound O2 to shift curve to right (RBCs make more 2,3-DPG in chronic aneamia, altitude acclimatisation, heart failure)
type F less sensitive and curve shifts to left - important as pO2 in blood to foetus is 4kPa which type a would be 55% saturated at and type f is 75%
%saturation measured by pulse oximetry based on changing red/IR light absorption, allowing pulsatile component (arterial blood) to be measured
CO2 transport in blood (3 forms, how is most carried, role of haldane effect, importance of non bicarb bases, where is most dissolved CO2 processed, how this flux helps trigger haldane effect and role of reverse haldane)
3 forms: dissolved, bicarbonate, carbamino compounds; 25x more soluble than O2 so dissolved CO2 represents 5-10% of total; most is bicarbonate (90%) due to carbonic acid dissociation, fast in RBCs where CA is and slow in plasma; proteins reversibly bind to amino groups so 5% bound to plasma proteins and those in RBCs, however the R-NHCOOH will dissociate and cause a pH change unless buffered
Haldane effect is amount CO2 carried depends on pO2 and Hb%sat as deoxy Hb weaker acid so binds more protons at physiological pH (to His residues) helping maintain gradient for bicarbonate production, also forms more carbamino compounds, so deoxy blood carries more CO2 - and in lungs O2 binds so protons released and less CO2 made into bicarb, meaning more free to be breathed out
CO2 down conc gradient from tissue into plasma, some forms carbamino compounds, some converted to bicarbonate, both release protons which are buffered by proteins, thus non bicarbonate bases important in minimising pH change driven by CO2 flux; most dissolved CO2 enters RBCs where rapidly hydrated and degraded by CA, buffered by imidazole groups on Hb which have pKa near 7 making them good buffers; bicarbonate leaves RBC down conc grad with charge movement compensated by Cl (Cl-HCO3 exchanger) so Hamburger’s phenomenon/chloride shift where RBCs accumulate Cl and this increased anion content causes RBCs to swell, their membranes are permeable so exchange rapid in capillary beds; pH fall or pCO2 generate proton) inc shifts Hb curve to right so oxy to deoxy so Haldane effect; reverse Haldane in lungs with high pO2 favouring CO2 exit
VQ matching
matching airflow to bloodflow: Va 4l per min and Q 5l per min (whole CO) so overall ratio 0.8 but there is regional variation; Va higher at base due to effect of gravity on Pip/compliance and perfusion better at base due to effect of gravity on Pa, so both increase down lung but bloodflow proportionately greater at base and Va at apex: Q shows 5-fold difference from apex to base, Va 2-fold so Va/Q varies from 0.7 at botom to 3 at top; ratio doesn’t change much in lower 2/3 of lung, dramatic change in upper 1/3 due to change in Q
ratio important as can have marked effect on gas exchange; increased ratio means inc Pao2 and dec Pco2, actual pulmonary venous concs mix of all ratios based on relative contribution; regional ratios can influence disease eg TB at apex as overventilation relative to Q provides high O2 environment;
hypoxic vasoconstriction causes diversion of blood to better ventilated parts of the lung. However, in most physiological states the haemoglobin in these well ventilated alveolar capillaries will already be saturated. This means that red cells will be unable to bind additional oxygen to increase the pO2. As a result, the pO2 level of the blood remains low, which acts as a stimulus to cause hyperventilation. However, as the rest of the lung can still remove CO2, hypercapnia does not occur. In cases of severely limited ventilation, hypercapnia may develop
shunting in lungs (causing hypoxia, type 1 resp failure)
right to left as in septal defect or in bronchial circulation with admixture as some bronchial venous blood enters pulmonary veins; all individuals thus have some right to left shunt 0f ~1-2% CO; alveolar shunt where blood passes alveoli without gas exchange due to poor diffusion eg oedema, pneumonia or atelectasis, or underventilation (at base of lung); effect of venous admixture is to lower Pao2 to 12kPa, 20% of this is from anatomic shunting and 80% due to low vent/perf ratios at base of lung
why not to over-oxygenate CO2 retainers
often said it’s bc hypoxia relied on by these pts to drive ventilation but this not the case in acute decompensations - experis show high drive even when oxer-oxygenated (until slip into coma driven by acidosis)
instead it is mix of increased VQ mismatch as higher alveolar pO2 relieves hypoxic vasoconstriction in the less well ventilated parts of the lungs, effectively increasing dead space + the haldane effect with more oxyhaemoglobin so less CO2 bound to Hb
respiratory control centres
poorly defined collections of neurons with numerous components; dorsal respiratory group associated with inspiration (in medulla) projects to motor neurons innervating inspiratory muscles; ventral respiratory group has inspiratory and expiratory functions; inspiratory cells make repeating bursts of APs that propagate to diaphragm in absence of afferent input, give basic periodicity, pneumotaxic centre can terminate through inhibitory impulses; thus central pattern generator is neural network in DRG/VRG that are bilaterally paired with cross communication to ensure symmetric movements; we know pneumotaxic inhibits as stimulating it activates inspiration and normal rhythm can exist without it; apneustic centre excites medulla groups to prolong inspiration giving regular inspiratory phase; voluntary control possible (singing, talking) but involuntary can take over
resp physiology tied to some clinical examples
swallow a bead and occlude a bronchus: no ventilation, so ventilation perfusion ratio zero and hypoxic constriction redirects bloodflow; airplane loses cabin pressure so lower Pio2 so lower PAo2 giving hypoxia, so breathing mask; restrictive disease minimises elastic work at cost of higher flows/more work against resistance through small, fast breaths; obstructive have long slow breaths to minimise flow/work against resistance, purses lips to hold airways open and breathes at higher lung volumes; bradycardia may accompany hypercapnia/hypoxia
alterations in lung compliance, info on disease, and elastic properties of chest wall
loss of compliance stiffens lungs so more work for normal Va, due to fibrosis or scarring of alveoli (eg filtering mechanisms overwhelmed by carbon (black lung), silicon (silicosis - glass workers), asbestos (asbestosis), cellulose (brown lung - textile workers) - a restrictive lung disease with FEV1 and FVC reduced but FEV1 may reduce less so FEV1/FVC ratio (prop of vital capacity person can expire in one second) normal or even increased in contrast with obstructive pulmonary diseases; increased compliance may occur in eg emphysema (an obstructive pulmonary disease) due to damage to alveoli causing difficulty exhaling as elastic recoil decreased and more work done to exhale; changing compliance may change FRC; chest wall has own pressure-volume curve which interacts with that of the lungs to give total effect; at 0 transmural pressure lungs at less than residual volume and chest wall at 75% of vital capacity, at FRC transmural pressure across chest wall is negative to resist outwards recoil, oposing pressures equal at FRC, total pressure thus zero as total always sum of transmural pressure across each of lungs and chest wall, altering pressure volume curve for lungs or chest wall thus alters system and thus influence FRC, hence altered compliance affecting FRC (decrease together/increase together)
surface tension, secretion/make-up of surfactant and its experimental effect
70dynes per cm for air/water interface at 37 degrees c; arises due to non-compensated pull between liquid molecules whose interactions are stronger than the gas can provide; inflation/deflation of lungs in air and saline show saline far more compliant and less hysteresis, and surface tension deduced to account for 2/3 to 3/4 of elastic recoil of lungs; surface tension discovered as oedema foam has air bubbles which are very stable; type ii pneumocytes secrete phospholipid rich surfactant, (90% lipids, 50% of which are DPPC, proteins 10%, half plasma proteins and half contribute to inate immunity by promoting phagocytosis, help improve surfactant rate of disribution with congenital absence leading to acute respiratory distress syndrome) principle component dipalmitoyl phosphatidyl choline (DPPC) with production dependent on precursors (glucose, palmitate, choline) supplied by pulmonary circulation; turnover rate high has each lung expansion has surfactant renewal; surface balance used to study effect of surfactant, test material in saline with adjustable surface area, adding detergent reduces surface tension independent of surface area, lung washings reduce it dependent on surface area and at low surface area the surface tension falls to very low values
role of surfactant, inc. IRDS, post-surgery, hysteresis
surfactant reduces surface tension to increase compliance and decrease the work of breathing, also allows alveoli of different sizes to co-exist as LaPlace’s law p = 2D(surface tension)/R so smaller alveoli should collapse into larger ones (atelectasis) as larger pressure developed in smaller ones, but surfactant reduces surface tension more in smaller alveoli (also they’re tethered together to keep each other open)
DPPC is amphipathic and intermolecular forces oppose attractive forces between surface water dependent on surfactant per unit area (reduction greatest when film compressed); at low lung volumes some DPPC squeezed out of surface layer so upon expansion amount per area is less requiring new surfactant or redistribution of old film, thus hysteresis; in quiet breathing surface area can remain ~constant which impairs surfactant distribution, deep sighs or yawns increase the volume to help spread new surfactant, abdo/thoracic surgery patients may find it painful to breathe deeply leading to poor surfactant distribution and possibly atelectasis
foetal lung surfactant production matures at 85-90% gestation period, premature babies often have insufficient surfactant production leading to infant respiratory distress syndrome (laboured breathing as a result of increased compliance), developing atelectasis and pulmonary oedema; surfactant helps keep alveoli dry, inwards collapsing force from surface tension would lower interstitial pressure to draw fluid from capillaries giving oedema, surfactant reduces this; rapidly expanding alveoli expand faster than surfactant reaches surface so surface tension increases, may double in inspiration, to help slow expansion of some alveoli to match slower ones (and reverse for expiration with faster than surfactant can leave surface, tension halving and collapse slowing)
airflow - inc Re, types, resistance (inc why obstructive disease hard to diagnose early, and how turbulent flow affects work of breathing)
turbulent in large airways at high flow rates as in exercise, laminar (and silent) in small airways, though changing calibre and irregular surfaces means most flow is transitional; poiseuille’s law, halving radius causes 16-fold increase in resistance and doubling length only doubles resistance, and viscosity not density influences resistance; however largest resistance/pressure drop is up to 7th generation as large number of small airways arranged in parallel and thus hard to diagnose obstructive pulmonary disease early as change in R tends to start in small airways which make little contribution to total R; reynolds number , flow laminar if <2000, turbulent if >3000 but only really for long straight tubes, with bifurcations in bronchial tree establishing eddies leading to transitional flow; laminar flow prop to pressure and turbulent to sqrt pressure so less laminar flow, more work to generate the same flow
factors affecting airway resistance - 2 static(3 things that influence second) and 1 dynamic, Pip in forced expiration and how PA compares (why), what is EPP and implication for airway structure, effect of elastic recoil vs Pip on flow rate (inc why smaller longs have lower max flow rate) and EPP, 2 ways COPD pt try to compensate for these factors
lung volume - as lungs expand radial traction causes airway radius to increase so R drops, and alveoli are dilated helping to pull open the bronchioles
bronchial smooth muscle can contract or relax to change airway diameter, symp makes it relax and decreases mucous secretion and parasymp contract and increase mucous secretion, beta2 agonists thus used as asthma treatment to dilate airways; increased Pco2 can induce airway dilatation and decreased airway constriction
dynamic - flow-volume curves show flow quickly rises to peak then declines over most of expiration with expiratory flow rate limited by increased resistance due to airway compression by intrathoracic pressure
during forced expiration Pip can reach +30cmH2O and PA even greater (due to elastic recoil as well as Pip), PA drops towards mouth but Pip remains same and at equal pressure point they are equal, beyond this point airway could collapse hence cartilage
increasing Pip also increases PA so doesn’t affect max expiratory flow rate, the difference which can affect it is thus elastic recoil and decreased elastic recoil is main reason why smaller lungs have smaller max flow rate; less elastic recoil in emphysema so EPP shifts distally which can cause airway collapse, stopping flow until pressure rises and airway opens giving wheezing, patients compensate by breathing at higher lung volume where compliance less (so more elastic recoil) and pursing lips so greater pressure drop there
describe gravitational effects on lung blood flow
blood is 1/2 weight of lungs, heart in middle so pulmonary arterial pressure at top 11mmHg less than in middle which is llmmHg less than at base; lung has 3 zones based on PA, Pa, Pv: zone 1 PA>Pa>Pv, capillaries collapsed with no bloodflow, doesnt exist in healthy people as Pa should overcome PA unless Pa falls in haemorrhage or PA increased in forced ventilation; zone 2 Pa>PA>Pv, PA supercedes Pv and bloodflow is difference between Pa and PA, initially venous end of capillary occluded by PA, Pa forces capillary open and flow resumes, cycle repeats; zone 3 Pa>Pv>PA so flow determined by normal arteriovenous pressure difference; zone 4 may exist in low lung volumes where Pip can partially collapse vessels due to reduced radial tethering, only at base; exercise increases pulmonary arterial pressure so moves boundaries of each zone upwards, improving perfusion
describe how lung volume/pressure and regional hypoxia affects blood flow/pressure
pressure difference on alveoli/extra-alveolar vessels mediates resistance: pulmonary arts/veins influenced by Pip and capillaries by alveolar volume with tissue network around vessels stopping Pip having an effect; high volume means big alveolus, small capillary, large arteries/veins and vice versa around low volumes; resistance smallest around FRC and increases in reductions to RV and increases to TLC; regional hypoxia causes localised vasoconstriction to divert blood away from area with little change in pulmonary arterial pressure, general hypoxia causes general vasoconstriction (in CF or emphysema, or at altitude) increasing vascular resistance and pressure leading to pulmonary hypertension and oedema; signalling for this unclear with low Po2 possibly acting on smooth muscle of pulmonary vasculature
factors that govern control of ventilation - central (inc why no tachypnoea in chronic retainers)(inc why csf more sensitive to change than plasma)
pH and Pa(gas) are stimuli, and overventilating a patient can stop breathing due to fall in Paco2; bilateral chemoreceptors in medulla at level of cranial nerve roots 8-11 and very superficial, with additional areas in root of cranial nerve XII; integrator of all these signals central but distinct from DRG-VRG, direct local application of acidic/high pCO2 saline increases ventilation, anesthetics and cold solutions decrease; sensors bathed in ECF of brain, composition influenced by CSF and metabolism, with CSF most important, and blood brain barrier regulating entry into CSF as shown by radioactive dye injection
BBB impermeable to proton/bicarbonate but CO2 gets in, if bicarbonate supplied and pCO2 increased to maintain pH then no change in ventilation so sensors respond to pH; CO2 lowers the CSF pH and its delivery is facilitated by vasodilation of cerebral vessels in respone to inc Paco2, CSF also has greater change as no protein so reduced buffering capacity; Paco2 may be elevated without inc ventilation in patients with chronic lung disease as bicarbonate actively transported into CSF if pH displaced for long period to buffer and restore to normal levels in CSF
factors that govern control of ventilation - peripheral (inc what paO2 level and why)
aortic/carotid bodies with type 1 glomus cells , decreased pH/Pao2 inhibits a K channel to depolarise the cell, calcium enters and NT released signalling to medulla to increase ventilation; 20-40% of response to hypercapnia is due to peripheral receptors so central more dominant, peripheral sole response to hypoxaemia; Pao2 below 8kPa gives marked ventilation increase, any increase before this would do little as Hb still 90% saturated; in absence of carotid bodies severe hypoxia can depress CNS activity and reduce ventilation; gases interact with Pao2 below 13kPa stimulating response if Paco2 raised, combined effects greater than sum of individuals
stretch receptors in airway smooth muscle discharge in dilation to prolong expiration time, hering-breuer inflation reflex from these receptors along vagus to inhibit DRG-VRG and apneustic centre to prevent overinflation of lungs - animals may use it to control rate/depth of breathing, not humans unless large TV, also projects to cardiac vagal motor neurons to give tachycardia sinus arrhythmia; irritant receptors between airway epithelial cells detect irritants and inflammation to initiate coughing, gasping, prolonged inspiration; unmyelinated C fibre endings (pulmonary if near alveoli, affected by pulmonary circulation, bronchial if affected by bronchial circulation), pulmonary also called j (juxtapulmonary) receptors (though usually call them pulmonary c fibres) stimulated by large inflation, injury (PE/pneumonia), chemical agents, oedema, and cause rapid shallow breathing in eg left heart failure -> responsible in part for tachypnoea and the feeling of dyspnoea
nitrogen washout test (purpose of test, how it’s done inc what value suggests right to left shunt, why you want to be careful, 3 non cardioresp causes of cyanosis in kids, and specific value that causes cyanosis inc sats value in normal person and how Hb value effects, one reason for peripheral but not central cyanosis)
to distinguish between cardiac and resp causes of cyanosis in baby
abg taken, breath 100% O2 for 10-15 mins, another ABG taken; PaO2 less than 20kPa suggests r->l shunt ie cardiac cause like tof, if >25-50kPa suggests this unlikely, consider lung pathology, l->r shunt causing pulmonary oedema, or mixing of pulm and systemic circulations
danger if dependent on l->r mixing through pda if duct dependent (eg pulm stenosis) as O2 may stimulate duct to close, so PGE1 should be available during the procedure
finally dont forget non cardioresp causes of cyanosis inc central resp depression (inc fits), polycythaemia, and methaemoglobinaemia (well baby who is cyanosed, normal hyperoxic test, blood looks brownish even after breathing O2)
cyanosis appears when when the level of deoxygenated hemoglobin in the arteries is above 5 g/dL (typically sats of 85%) - > thus cyanosis is rare in anemia and common in polycythemia, but tissue may still be hypoxic; peripheral cyanosis without central may be due to reduced skin bloodflow sec to vasoconstriction (if eg cold)
obstructive and restrictive lung volumes, and interpreting spirometry algorithm if >0.7 2 further steps and if <0.7 2 steps
obstructive: air trapping giving increased residual volume, FRC and TLC; vital capacity is decreased
restrictive: vital capacity, FRC, residual volume, TLC, and ERV all decreased
so FEV1/FVC, if >0.7 look at FVC and TLC, if these low its restrictive, then TLCO low means fibrosis and normal means neuro/obesity/bone etc; if FVC and TLC normal then normal lung mechanics, if TLCO low means vasc problem like HTN or oedema
if FEV1/FVC <0.7 look at FVC, if small then mixed picture, if normal look at TLCO which is low in emphysema and normal in asthma/chronic bronchitis/bronchiectasis
adjusting ventilator settings in context of abnormal blood gases (aka adjusting paO2/CO2. inc how to raise both)
inc pO2 by inc’g fiO2 then PIP, then inspiratory time, then PEEP (risk of ptx and reduced CV function so careful with PIP and PEEP)
dec pCO2 by inc rate, inc PIP
to raise both inc PEEP; another way to raise pCO2 is to extubate, or if ventilation still necessary increase dead space by using longer endotrach tube
5 reasons for acute resp acidosis in pt on ventilator
dislodged endotrach tube (listen to lungs, look for chest movement)
blocked tube (ditto)
ventilator failure (inspect it)
ptx (transilluminate +/- CXR)
intraventricular h+ (cranial uss)
Non lung origin hypercapnia ddx x5, resp alkalosis ddx x3
hypercap: eg OSA, central resp depression, resp neuromusc disease eg GBS, thoracic wall disorders (eg scoliosis), obesity
alkalosis: hypervent syndrome, often anxiety but also consider PE, resp stimulant ingestion, and early stages of salicylate overdose
things that increase (3) or decrease (6) TLCO
decrease: infiltration/fibrosis, PE, pulm HTN, VQ mismatch (pneumonia, pulm oedema), anaemia
increase: polycythaemia, exercise (higher in athletic individuals), pulmonary haemorrhage, may be inc’d in asthma but oft normal
O2 dissociation curve shifters (8 right, 6 left)
right shift, ie makes Hb release O2 better but take it up worse: increased pCO2/dec’d pH (Bohr effect), inc’d temp, chronic hypoxia, anaemia, inc’d RBC 2,3DPG (production of this increased in chronic hypoxia eg altitude or chronic lung disease), HbS, polycythemia
left shift: dec’d pCO2, inc’d pH, dec’d temp, metHb, carboxy Hb, HbF
lung development (and tof types)
derivatives of gut tube with signals from mesoderm dictating characteristics: liver mesenchyme makes lung buds develop into hepatic cells, bronchial mesenchyme into bronchial buds, stomach mesenchyme into gastric glands etc; 2 tracheo-oesophageal ridges start to separate oesophagus from lung bud as respiratory divericulum, lung bud then bifurcates into two branches to form paired bronchi and lungs; the ridges fuse to divide oesophagus from trachea/lungs and laryngo-tracheal endoderm lines airways
barium swallow can diagnose tracheoesophageal fistula or oesophageal atresia affects 1 in 5000 births due to failure of two componanets to separate; causes severe choking in neonatal baby as fluids eg milk may be aspirated into lungs; gastric contents may enter respiratory system; polyhydramnios (excess amniotic fluid and distension of uterus) frequent complaint as foetus cannot swallow amniotic fluid; 90% of cases proximal oesophagus blind ending, distal part comes off trachea, 4% proximal and distal blind ending, 4% both parts connect into oesophagus and fused, 1% each with proximal part connected and distal blind ending or both parts connecting separately; repaired surgically by closing off fistula and connecting parts of oesophagus
FGF10 secreted by mesenchyme guides bronchial branch outgrowth and induces new gene expression in cells at end of bronchial branches; negative feedback with Shh inhibiting Fgf10 expression locally, arresting outgrowth to promote next round of branching; replacing piece of tracheal mesoderm with bronchial causes ectopic lobe of lung to arise directly from trachea
lungs mature progressively with glandular period (week 5-16) with brnaching to form bronchi, no respiration, foetus can’t survive; some respiration possible towards end of canalicular period where respiratory bronchioles developing, foetuses born towards end of this period (weeks 22-25) may survive if given intensive care; terminal sac week 26-birth with capillaries and primary alveoli developing; alveolar priod from week 36 until 8-12 years old where new alveoli continue to mature postnatally, ~1/6th of your adult alveoli number when born
carbon monoxide poisoning (commonest source and 4 others, how much more avid for Hb is CO and 3x consequences of its binding, what is normal value, what percent is found in smokers, than for each percent decile what sx do you get 1:1:7:4:2), 9sx of chronic exposure over time, 2 main ix, 3 mx, range for one pack a day smoker (percentage)
Exposure is most commonly from suicide attempts using car exhaust, and accidental exposures from incomplete combustion in charcoal burners, faulty heaters, fires, and industrial accidents
Carbon monoxide has ~210 times the affinity for haemoglobin than oxygen, giving tissue hypoxia and also triggers endothelial oxidative injury, lipid peroxidation and an inflammatory cascade
Normal COHb 0.5%
<10% (nil, commonly found in smokers)
10 – 20% (nil or vague nondescript symptoms)
30 – 40% (headache, tachycardia, confusion, weakness, nausea, vomiting, collapse)
50 – 60% (coma, convulsions, Cheyne-Stokes breathing, arrhythmias, ECG changes)
70 – 80% (circulatory and ventilatory failure, cardiac arrest, death)
chronic exposure often lower dose for longer time which incs risk of neurological sequelae: can include headache, personality changes, poor concentration, dementia, psychosis, Parkinsonism, ataxia, peripheral neuropathy and hearing loss
get ABG (HbCO and lactate up, paO2 normal), ECG
give NRBM O2, hyperbaric O2 if acidotic or significant sx; treat coexistent cyanide toxicity if suspected (e.g. house fire)
If you are a one-pack-a-day smoker, your carboxyhemoglobin is about 6%, but could be as high as 10%
tracheo-oesophageal fistula repair complications
anastomotic leaks, strictures at site of anastomosis (may need balloon dilatation), GORD, rec cough, bronchitis, pneumonia
note in most cases surgical strictures are due to scarring
foetal circulation and lungs - 2 shunts that achieve pulmonary bypass, 2 differences from adults in ventricle contraction, how total CO compares, role of ductus venosus, lungs at birth and last few weeks before, when foetal breathing movements detectable and 2 things this important for
2 shunts, foramen ovale and ductus arteriosus, achieve pulmonary bypass
right and left heart beat in parallel instead of in series, as they do in the adult; right ventricular output higher than left due to the shunts
total CO is 4x higher than it is in adult,
ductus venosus bypasses liver from umbilical vein to IVC
lungs: entirely fluid filled but ready to carry out gas exchange at birth with alveolar dev in last few weeks of birth and continuing postnatally + late in dev surfactant production
can insert artificial surfactant into lungs, or give mum high dose of synthetic glucocorticoids 24hrs before premature delivery to stimulate lung maturation
from around 10 weeks gestation can detect foetal breathing movements and this provides important mechanostimulation for alevoli dev/surfactant release
neonatal resp physiology (fetal breathing, lung liquid, surfactant, first breath)
fetal breathing movements start at week 10, peak 2-3 weeks before delivery to strengthen resp muscles with absent movements stopping proper lung growth/maturation, happens during REM for 1-4hrs a day
fetal lungs secrete Cl rich lung liquid at 330-450ml per day and is 1/3 to 1/2 daily amniotic fluid turn over; at birth LL secretion stops (shortly before delivery catecholamines inhib Cl pump), circulating adr to beta receptors opens lung epithelium Na channels and LL absorbed, mechanisms for absorption also under control of TH and cortisol; latter inc betar and Na pump expression, also makes PMNT up so more NA to adr, and upreg of enzymes doing T4 to T3
30% ll reabsorbed in labour via mouth (ie pressure pushes out of mouth) due to raised intrathoracic pressure during vaginal delivery and over next 12 hours rest lymph to blood to kidneys, diuresis for ~12 hours; c-section prevents some hormone changes and squeezing out of fluid, too much fluid causes transient tachypnea of newborn
surfactant mainly DPPC, appears in amniotic fluid after 28 weeks (moved ut by breathing movement with cortisol inducing its production and betaR required for its release; reduce surface tension to increase compliance
lungs filled with fluid, pO2/pH fall immediately after birth and pCO2 rises then O2 quickly rises as fetus breathes; for first breath baby grunts against closed glottis to establish FRC by creating high trans-pulmonary pressure with light sound not needed to trigger (blind + death babies still breathe) but generalised arousal due to inc sensory input, cold (c fibres), tying/cutting umbilical cord cause hypoxia and hypercapnia in newborn, activating reticular formation where nuclei controlling resp are
transient tachypnoea of newborn (what it is, cause, imaging appearance, mx, how long to resolve)
the commonest cause of respiratory distress in the newborn period. It is caused by delayed resorption of fluid in the lungs
It is more common following caesarean section; thought due to the lung fluid not being ‘squeezed out’ during the passage through the birth canal but actually more about lack of stress hormones causing lung liquid resorption
Chest x-ray may show hyperinflation of the lungs and fluid in the horizontal fissure.
Management
observation, supportive care
supplementary oxygen may be required to maintain oxygen saturations
Transient tachypnoea of the newborn usually settles within 1-2 days
hyperoxia (4 risks and general PaO2 limit)
a risk of oxygen therapy, generally paO2 raised above 11-13kPA, 16kPa as a maximum; may make infarcts in MI or stroke worse, injure lungs, or cause retinopathy, or suppress breathing in chronically hypercapnic pts
so titrate the O2 being received to avoid hyperoxia; reserve 15L/min non-rebreathe mask for emergency situations
ARDS and TSS (toxic shock syndrome 4 sx, 2 bacti cause, 6 sx may dev but less characteristic)
ARDS is pulm oedema not explained by cardiac or fluid overload reasons but inc’d perm of pulm caps; causes inc sepsis, pancreatitis,
trauma, pneumonia, aspiration
toxic shock syndrome: fever, sunburn like rash, skin peeling, and low blood pressure/shock; due to staph aureus/strep pyogenes; may also
see some of d&v, myalgia, AKI, liver inflam, confusion, thrombocytopenia
resp distress in the newborn
rr >60/min, nasal flaring, intercostal recession, expiratory grunt, cyanosis, poor feeding
if mum is diabetic: transient tachypnoea of newborn due to caesarean sec to macrosomia, resp distress syndrome also more common, as is persistent fetal circulation and polcythemia induced stiffnes of lungs
congenital diaphragmatic hernia, esp if mum had no antenatal care; caused by failure to close of foramen of Bochdalek and leads to hypoplastic lungs, worsens when air enters intestine esp if eg bag and mask ventilation; may see scaphoid abdo, reduced breath sounds/chest movement, displaced heart sounds; delayed presentation can give epsodes of breathlessness after feeding and intermittent obstruction (pain/vomiting) intubate, NG tube to deflate intestines, pulm vasodilators for HTN, resus with fluids etc, then refer for surgical correction
general diffs: resp distress syndrome (within 4 hrs of birth, esp if premie, asphyxia, hypotherm, acidosis), sepsis/pneumonia (more likely if PROM, maternal pyrexia, culture pos vaginal swabs, neonate may be floppy and acidotic), meconium aspiration syndrome (esp postmature), PTX (vent history, traumatic delivery, spont in 1% of deliveries) phrenic nerve palsy after traumatic birth, congenital heart disease, pulmonary h+
baby developes resp distress +/- cyanosis shortly after birth, intubated and ventilated but doesnt seem to need it, extubated and resp distress again; sx may improve when crying; consider choanal atresia (problem as babies nasal breathers); intubate or magill airway until surgery can be done; sometimes clearing the nares with eg saline can work wonders to calm resp distress if problem is more mucous blocking the choana
child choking during feeds, vomiting/regurg of feeds, reluctance to feed or crying after, rec aspiration/chest (or ear) infection, or in premies apnoeic episodes/bradys/desats (even in absence of above other sx); growth normal or poor, intercurrent CXRs normal
consider GORD and tracheo-oesophageal fistula (contrast barium swallow)
DVTs - 5x symps, where to measure for swelling (and how much counts), how to use well’s score, when to repeat neg uss, mx (inc preg) and how long for, what to check for if first w/o clear cause, 2 things to test for when reached end of mx time
DVTs are almost always unilateral. Bilateral DVT is rare and bilateral symptoms are more likely due to an alternative diagnosis such
as chronic venous insufficiency or heart failure. DVTs can present with:
Calf or leg swelling
Dilated superficial veins
Tenderness to the calf (particularly over the site of the deep veins)
Oedema
Colour changes to the leg
To examine for leg swelling, measure the circumference of the calf 10cm below the tibial tuberosity. More than 3cm difference between
calves is significant.
consider that they may have a PE
well’s score: 2+ do uss, <2 do d dimer if pos then uss; repeat negative ultrasound scans after 6-8 days if a positive D-dimer and the
Wells score suggest a DVT is likely
treatment dose apixaban or rivaroxaban
then doac, warf, or lmwh (pregnancy); note you need to do age adjusted d-dimer as d dimer levels are higher in older people, so conventional threshold for negativity too low ie more false positives
3 months if there is a reversible cause (then review)
Beyond 3 months if the cause is unclear, there is recurrent VTE, or there is an irreversible underlying cause such as thrombophilia (often
6 months in practice)
3-6 months in active cancer (then review)
When patients have their first VTE without a clear cause, the NICE guidelines from 2020 recommend reviewing the medical history, baseline
blood results and physical examination for evidence of cancer.
In patients with an unprovoked DVT or PE that are not going to continue anticoagulation (they have finished 3-6 months of treatment and are
due to stop), NICE recommends considering testing for:
Antiphospholipid syndrome (check antiphospholipid antibodies)
Hereditary thrombophilias (if first deg rel has also had dvt or PE)
pulmonary embolism
often from DVT of calf, femoral, or iliac veins (more likely the more proximal the vein); also sometimes from IVC, right side of heart, catheters in subclavian or jugular veins; may be silent, but be aware of oedema or tenderness in leg with erythema and pain on dorsiflexion; compression US to confirm/exclude
PE presents in various ways dependent on size:
acute massive usually in patient recovering from surgery who suddenly collapses with hypotension, cyanosis, tachypnoea, engorged neck veins
major and minor PE will have dyspnoea, hyperventilation and after infarction occurs also pleuritic pain and haemoptysis plus effusion and segmental collapse or consolidation on CXR; chronic small emboli may give pulmonary hypertension and progressive dyspnoea
also a single PE can present with a chronic cough, breathless, haemop episodes (1+) etc; additive calf oedema (ie one leg swells then the other) points to this rather than HF
do ecg to exclude MI but often normal or signs of right heart strain if PE
CXR often normal but may have some signs
d dimer good to exclude PE but dont confirm it as clot could be elsewhere
CTPA (CT pulmonary angiography) is definitive investigation, can also do V/Q scan with multiple areas of perfusion defects not matched on scans of ventilation defects as would be for eg carcinoma or effusion
first suspect: dyspnoea, resp rate >20/min, pleuritic pain, haemoptysis (sudden collapse); score +1 if COPD, pneumonia, pneumothorax unlikely; score +1 if major risk factor for venous thrombosis present (pregnant, travel, surgery, major illness, previous thrombosis, immobility); if 2 then start heparin anticoagulation immediately and do CTPA; if +1 then do d dimer, if positive move to LMWH and CTPA; if zero can still do d dimer but remember it is to exclude and not confirm PE, CTPA is gold standard; note you need to do age adjusted d-dimer as d dimer levels are higher in older people, so conventional threshold for negativity too low ie more false positives
note you start LMWH before definitive results come in, can reevaluate later; once confirmed can move to oral warfarin or rivaroxaban
thrombolytic therapy with alteplase reserved for patients with massive PE; give if signs point to that and exclude other things like pneumothorax etc, not if active H+, recent surgery, or trauma
high flow O2 for acute PE may also be good
note other things may embolise to lungs eg fat (fratcure of long bones), amniotic fluid (post partum), air (disconnected central line), tumour (if invades veins), infected vegetation (tricuspid endocarditis), foreign materials (from contaminated drugs by IVDU)
be aware that pregnancy plus CTPA has risk of later beast cancer, maybe first do US for DVT and a CXR, if that normal and US -ve then half dose VQ scan (gamma emiting albumin injected, impacts in caps so gamma camera can pick up perfusion; ventilation from radiolabelled xenon)
pathophys: Obstruction of the pulmonary arteries creates dead space ventilation as alveolar ventilation exceeds pulmonary capillary blood flow. This contributes to ventilation-perfusion mismatch, with vascular occlusion of the arteries increasing pulmonary vascular resistance. In addition, humoral mediators, such as serotonin and thromboxane, are released from activated platelets and may trigger vasoconstriction in unaffected areas of lung. As the pulmonary artery systolic pressure increases, right ventricular after load increases, leading to right ventricular failure. As the right ventricular failure progresses, impairment in left ventricular filling may develop
once diagnosed you can calculate a PESI score which is a risk assessment tool sued to decide whether to ambulate the pt or not looking at obs and past medical history; troponin is also a useful marker as it can help tell you the degree of heart strain
PE scoring (7 criteria) and pulm hypertension (5 groups, sx, ix)
well’s score: signs/symptoms of DVT 3 pts, PE most likely diagnosis 3 pts, HR >100 1.5pts immobilisation 3 days or surgery in last 4
weeks 1.5 pts, previous PE 1.5 pts, haemoptysis 1, malignancy 1; 4+ CTPA <4 d dimer
note you need to do age adjusted d-dimer as d dimer levels are higher in older people, so conventional threshold for negativity too low ie more false positives
causes of pulmonary hypertension can split into 5 groups:
Group 1 – Primary pulmonary hypertension (idiopathic or heritable) or connective tissue disease such as systemic lupus erythematous (SLE)
Group 2 – Left heart failure usually due to myocardial infarction or systemic hypertension
Group 3 – Chronic lung disease such as COPD, ILD
Group 4 – Pulmonary vascular disease such as (rec or chronic) pulmonary embolism, arteritis
Group 5 – Miscellaneous causes such as sarcoidosis, glycogen storage disease, sickle cell
pt may have sob, chest pain, tiredness and palpitations, signs of right heart failure
PH has right sided heart strain causing ECG changes such as:
Right ventricular hypertrophy seen as larger R waves on the right sided chest leads (V1-3) and S waves on the left sided chest leads (V4-6)
Right axis deviation
Right bundle branch block
CXR: Dilated pulmonary arteries
Right ventricular hypertrophy
raised NT-proBNP blood test result indicates right ventricular failure
Echo can be used to estimate pulmonary artery pressure, and pulm hypertension likely if >20mmHg; after this CT scan can look for more evidence but the echo is the diagnostic test
pulmonary hypertension - definition, CXR appearance, what ECG will show, 4 tests for subgrouping, another 3 important tests, then 10 ix for cause, gold standard test, 8mx steps
defined by a mean pulmonary arterial pressure (mPAP) >20 mmHg at rest
Radiographic signs of PH include a characteristic configuration of the cardiac silhouette due to right heart (right atrium [RA]/RV) and PA enlargement, sometimes with pruning of the peripheral vessels. In addition, signs of the underlying cause of PH, such as LHD or lung disease, may be found
ECG will show right heart strain
to subgroup need forced spirometry, body plethysmography, lung diffusion capacity for carbon monoxide (DLCO), and ABG
need an echo for heart and valve function, and to estimate PAP, and a CT scan may eb done to look for cause and further evaluate likelihood of PH, VQ scan can be used for chronic multiple PEs if suspect that
FBCs, U&Es, LFTs, iron studies, NT-pro BNP, HIV and hepatitis serology, autoimmune screen, look for antiphos syndrome if multiple PEs; liver US in case that is cause or portocaval shunt etc
gold standard ix is right heart catheterisation
exercise, diuretics/O2 as needed, vaccination against flu/pneumococcus, if vasoreactivity shown during right heart catheterisation start CCB then re-assess after 3-6mo and inc therapy if needed/start if no CCB with eg endothelin R antag + phosphodiesterase inhibitor
In patients who are at intermediate–low risk despite receiving ERA/PDE5i therapy, adding selexipag should be considered
In patients who are at intermediate–high or high risk while receiving oral therapies, the addition of i.v. epoprostenol or i.v./s.c. treprostinil and referral for LTx evaluation should be considered
Lung transplantation remains an important treatment option for patients with PAH refractory to optimized medical therapy
portopulmonary hypertension - what it is, pathophys, 2 ix, things not to use in mx, 5mx
one of the leading causes of pulm hypertension
exact pathophys unclear but hyperdynamic state -> raised CO -> inc shear stress on pulmonary vessels giving vasoconstriction and remodelling; portosystemic shunts allow not only iNOS activation but also vasoactive substances like VIP and secretin from the splanchnic circulation into systemic
initial echo then right heart cathetrisation will diagnose as part of pulm hypertension workup
CCB no as inc hepatic venous gradient and shunting, anticoag no as bleeding risk
supplemental O2 yes to prevent pulm vasoconstriction
ERAs, prostanoids, and PDE5i yes
if mild can have liver transplant, if severe then no due to risks -> can try to control medically then transplant
alveolar capillary dysplasia
rare, congenital diffuse lung disease characterized by abnormal blood vessels in the lungs that cause highly elevated pulmonary blood pressure and an inability to effectively oxygenate and remove carbon dioxide from the blood
typically presents in newborn babies within hours of birth as rapid and labored breathing, blue-colored lips or skin, quickly leading to respiratory failure and death
Most cases of ACD are caused by mutations affecting the gene FOXF1 or its nearby enhancer region; abnormal lung development is characterized by thickened alveolar interstitium, misplacement of pulmonary capillaries away from the alveolar surface, and fewer capillaries overall. This results in poor gas exchange and pulmonary hypertension
If an echocardiogram is performed, marked thickening of the right ventricle will be seen, resulting from highly elevated pulmonary blood pressure. ACD is generally resistant to treatment. Babies who have persistent symptoms that are poorly relieved by standard therapies for neonatal pulmonary hypertension is commonly observed in ACD
gold standard for ACD diagnosis is by examination of lung tissue under a microscope. The diagnosis is made if the pathologist sees the characteristic findings of ACD: misplaced pulmonary veins adjacent to pulmonary arteries, abnormal alveoli with thickened interstitia and abnormal capillary development. Due to the rapidly progressive course of ACD, this diagnosis is frequently made during autopsy. If ACD is suspected early, examination of tissue from lung biopsy results in the quickest diagnosis
Initial treatments attempt to improve low blood oxygenation and high pulmonary blood pressures. Because blood oxygen content is usually very low, babies with ACD are often intubated, sedated, and mechanically ventilated with pure oxygen. Pulmonary vasodilators like sildenafil or inhaled nitric oxide can be used to reduce pulmonary blood pressures; As symptoms worsen, ECMO can be used, but it also offers only brief improvement. There are no effective treatments for severe ACD
For infants with atypical ACD who initially had milder symptoms and present at months of life, there can be better response to therapy. There have been reports of infants with ACD surviving to 20 or 36 months without lung transplantation. Bilateral lung transplantation may be the definitive treatment
PERC criteria (8)
All criteria must be negative to rule out PE, done to reassure if you doubt it’s PE (but still <2% risk it might be); if you are suspicious of PE move straight to Well’s score
Crit: >/=50yo, HR >/=100, O2 sats </=94, previous DVT/PE, trauma or surg in past 4 weeks, haemoptysis, unilat leg swelling, oestrogen use (HRT, contraceptives)
Again, all of the above must be absent for crit to be met
pleural effusion (pleural fluid cycle, signs)
cap pressure in parietal pleura plus negative intrapleural pressure and oncotic forces result in fluid entering the pleural cavity, lower pressure of the pulmonary system supplying the visceral pleura favours movement of fluid from pleural space into veins and lymphatics so parietal filtrates and visceral absorbs
thus effusion from: raised cap pressure, dec’d plasma oncotic pressure, inc’d cap permeability, obstructed lymphatic drainage
patients typically present with dyspnoea, sometimes pleuritic pain, and features of associated diseases like heart failure or carcinoma
signs: dec’d expansion on side of effusion, stony dullness, diminished breath sounds, reducec vocal resonance/tactile fremitus, sometimes bronchial breathing
inquire about asbestos/TB exposure, smoking, signs of other disease (look for lymphadenopathy, heart failure, breast lumps), certain drugs eg dantrolene
pleural effusion investigations
CXR: dense white opacity with concave upper edge (usually, although can be less smooth due to consolidation of tissue); small effusions may just blunt costophrenic angle, so look to see if you can see it
if patient supine may only see the fluid as haziness
US can be used to guide test tube placement and CT to detect tumours hiding within the fluid and the underlying condition of the lungs and mediastinum
thoracocentesis is key: protein >30g/L and LDH >200 units/L suggest fluid is an exudate so investigate for pleural disease; bloodstained suggests malignancy, severe inflam, or pulmonary infarction; pus indicates empyema, milky suggests chylothorax, blood suggests haemothorax; low glucose content suggests infection or connective tissue disorder; high amylase content may mean associated pancreatitis or adenocarcinoma; neutrophils in acute infection and lymphocytes in chronic (esp TB, malignancy); can send to microbiology to identify pathogen
CT guided biopsy for areas of pleural thickening, to check for malignancy and TB
further investigations based on suspected cause
