Acute Lung Injury Flashcards
What is the Berlin Defintiion (2102) for ARDS with regards to:
Timing
Hypoxaemia
Origin of Oedema
Radiological abnormalities
Timing:
Acute onset within 1 week of known clinical insult
Hypoxaemia:
- MILD: 200 < PaO2/FiO2 ≤ 300 ; PEEP ≤ 5
- MODERATE: 100 < PaO2/FiO2 ≤ 200 ; PEEP 5-10
- SEVERE: PaO2/FiO2 ≤ 100 ; PEEP ≥ 10
Origin of Oedema:
Respiratory failure not explained by cardiac failure or fluid overload
Radiological Abnormalities:
Bilateral opacities - not explained by effusions, atelectasis or nodules
Name some pulmonary/direct insults that increase the risk of ARDS
Common:
- Pneumonia
- Aspiration pneumonitis
Uncommon:
- Inhalation Injury
- Fat Emboli
- Near Drowning
- Reperfusion Injury (Iatrogenic?)
Name some extrapulmonary/indirect insults that increase the risk of ARDS
Common:
- Sepsis
- Severe Trauma
Uncommon:
- Acute Pancreatitis
- Cardiopulmonary Bypass
- Transfusion-Related ALI (TRALI)
- DIC
- Burns
- Drug Overdose
What is the biggest single risk factor for ARDS and what comes second to it?
Sepsis Syndrome
Transfusions
Mortality of ARDS is 31% - 74%. The variability is due to the definition used and the fact that cause of death is usually _____. Early death is usually caused by the underlying illness or injury whilst late deaths are caused by _____ or multiorgan dysfunction.
Mortality of ARDS is 31% - 74%. The variability is due to the definition used and the fact that cause of death is usually non-respiratory. Early death is usually caused by the underlying illness or injury whilst late deaths are caused by sepsis or multiorgan dysfunction.
Describe the ‘sponge’ lung concept
Lung parenchyma affected by the pulmonary oedema.
Gravity pulls the fluid downwards so that there is gravity-dependent atelectasis
Patients with ARDS will almost certainly require mechanical ventilation for oxygenation. Describe how this can lead to Ventilator-Induced Lung Injury
VILI = Iatrogenic causes of lung injury due to:
- Volutrauma = Lung stretch
- Barotrauma = ↑pressure
- Atelectorauma = repeated collapse-recruitment of lung
Descirbe the ‘Baby’ lung concept and how this is releveant to current management
The baby lung refers to the small areas of lung which are aerated and that can ventilate
Ventilation pressures need to be carefully selected to avoid VILI in the aerated lungs -> lung protective ventilation (lung rest)
The ARDS Network’s landmark study showed what?
Low Tidal volumes led to reduced mortality (6ml/kg vs 12ml/kg)
Name the current treatment/supportive strategies for ARDS
- Mechanical Ventilation
- ↓Tidal Volume
- PEEP (lung recruitment)
- Prone Positioning
- ECMO
- Pharmacological
- Neuromuscular Blockade
- Sedatives
- Inhaled NO
- B2 agonists (↑AFC)
ECMO = Extracorporeal Membrane Oxygenation
How does ECMO work?
Catheter is inserted through the femoral vein into theinferior vena cava
Takes deoxygenated blood to an external oxygenator where gas exchange occurs
Oxygenated blood is pumped back into the heart through the internaljugular vein and superior vena cava.
Outline the role of the pulmonary epithelium in ARDS and explain how it achieves this
Regulate fluid across the alevolar-capillary membrane
- Tight Junctions
- Prevent fluid leakage in between cell spaces
- Tight junctions, adherens junctions, desmosomes
- Tight junctions linked to actin - active process to resist tension
- Sodium transport
- ENaC takes Na from alveolar space into alveolar epithelial cell
- Na/K ATPase transport the Na into the capillary
- H2O follows
Describe the role of neutrophils in ARDS
Insult to the lungs lead to CXCL8 release (neutrophil chemoattractant)
Neutrophil moves via diapedesis
It can produce elastase or MMP to break through the tight junctions between cells so that it can translocate to the parenchyma
Inhibition of these mediators do not have an effect on ARDS severity
B2 agonists were looked at in the BALTI study to enhance alveolar fluid clearance. What was the proposed mechanism and did this work?
B2 agonist increased vectorial transport of Na across the epithelium
Reduced fluid BUT no improvements in:
- Oxygenation
- Mortality or ventilator-free days
Broadly describe the resolution process in ARDS (3 phases)
- Early Phase
- Removal of signal
- ↓Oedema
- ↓Inflammatory mediators
- ↓Leukocyte recruitment
- Neutrophil death leads to resolution of inflammation
- Clearance Phase
- Apoptosis of recruited leukocytes
- Removal of cell debri
- Nautrophil uptake by macrophages leads to release of pro-resolving mediators (M2 phenotype?)
- Restoration of function
- Proliferation
- Bioenergetics
What can affect the resolution of inflammation in ARDS?
Secondary Insults (from VILI, Infection, aspiration)
The alveolar epithelial cells release mediators as they are stretched. These mediators do not cuase disease until there is decompartmentalisation. Explain this concept.
Insults to the lung leads to the spillage of mediators into the circulation
Can lead to multi-organ failure
Describe some feautres of the acute exudative phase of ARDS
- Alveolar Capillary Membrane dysfunction
- ↑permeability
- ↓AFC
- Epithelial Apoptosis
- ↑leakage past tight junctions
- Leukocyte Recruitment
- Inflammation
- Macrophage Activation
- Intraalveolar coagulation
Describe some limitations in modeling ARDS in animals
- Heterogeneous condition
- Species differences
- Metabolism
- Signalling
- Cellular Phenotypes
- Difficult modeling of co-morbidities
Describe the fibro-proliferative phase of ARDS
Pro-inflammatory mediators activate macrophages
ACM damage leads to fibroblast deposition of collagen
There is vascular remodelling to repair area -> Pulmonary HTN and RHF
Cellular Inflammation and cell infiltration
Long-term recovery involves lung inflammation resolution. What other outcome needs to be fixed?
Muscle mass
ARDS requires a lot of energy and disuse in ARDS leads to muscle metabolism
