Acute Respiratory Distress Syndrome (ARDS) is an acute lung injury syndrome characterized by hypoxemia, bilateral pulmonary infiltrates, and respiratory failure. It has a complex pathophysiology involving direct or indirect lung injury leading to increased permeability, protein-rich fluid accumulation in the lungs, and impaired gas exchange. ARDS progresses through exudative, proliferative, and fibrotic phases. Diagnosis is based on timing of onset, radiographic findings, and hypoxemia as defined by the Berlin criteria. Treatment involves supportive care, ventilator management to avoid further lung injury, and treating underlying causes.

1. Acute Respiratory Distress
Syndrome (ARDS): Part 1
PRESENTED BY : Dr. Manasvi
Kalra

2. WHAT IS ARDS?
 It is a clinical syndrome of severe dyspnea of rapid
onset, hypoxemia, and diffuse pulmonary infiltrates
leading to respiratory failure.
 A common condition with a complex pathophysiology
caused by many underlying medical and surgical
disorders.

3. Epidemiology
 Incidence of ARDS varies widely
Annual incidence: 60/100,000
Approximately, 10% of ICU patients meet criteria for
ARDS
However, there is very little data regarding incidence of
ARDS in India.
 Morbidity / Mortality
26-44%, most (80%) deaths attributed to non-pulmonary

4. Definition
 ARDS  syndrome with multiple risk factors that trigger
acute onset of respiratory insufficiency
 Until recently, most accepted definition of ARDS for use
at bedside or to conduct clinical trials
American-European Consensus Conference (AECC)
definition published in 1994

5. AECC Definition
 ARDS was defined as:
 Acute onset of respiratory failure, bilateral infiltrates on
chest radiograph,
 Hypoxemia (PaO2/FiO2 ratio ≤200 mmHg,) and
 No evidence of left atrial hypertension or a pulmonary
capillary pressure <18 mmHg (if measured) to rule out
cardiogenic edema.
 In addition, Acute Lung Injury (ALI),  less severe form
of acute respiratory failure, different from ARDS 
(hypoxemia,  PaO2/FiO2 ≤300 mmHg)

6. AECC Definition  Drawbacks
elatively low specificity
eliability of the chest radiographic criteria of ARDS 
oderate with substantial interobserver variability
ypoxemia criterion (PaO2/FiO2 <200 mmHg)  may
e affected by pts ventilator settings
Wedge pressure can be difficult to interpret and if a
atient with ARDS develops a high wedge pressure

7. Development of New Definition
European Society of Intensive Care
Medicine with endorsement from
American Thoracic Society and the
Society of Critical Care Medicine
Convened an international expert panel to
revise the ARDS definition panel met in
2011 in Berlin,
New definition was coined the Berlin
definition

8. ARDS Berlin definition

9. ARDS Berlin definition :
Advantages
 In Berlin definition  there is no use of term Acute Lung
Injury (ALI) (committee felt  term ALI was used
inappropriately in many contexts and hence was not
helpful )
 ARDS was classified as mild, moderate and severe
according to the value of PaO2/FiO2 ratio
 PaO2/FiO2 ratio value is considered only with a CPAP or
PEEP value of at least 5 cmH2O
 Timing of acute onset of respiratory failure to make
diagnosis clearly defined in berlin definition

11. GENETICS
More than 40 different genes associated with the
development or outcome of ARDS have been identified,
which include : ACE, SOD 3, MYLK, SFTPB, TNF, VEGF.
Amongst these, a gene with a strong association with
ARDS is ACE.
 This association came to prominence during the SARS
pandemic, when the ACE2 Protein, which contributes to
regulation of pulmonary vascular permeability , was
identified as the receptor for the novel corona virus that
caused SARS.

12. Factors influencing risk of ARDS
INCREASED RISK OF ARDS WITH :
Chronic alcohol abuse
Cigarette smoking
Hypoproteinemia
Advanced age
Hypertransfusion of blood products

13. Interestingly , Diabetes Mellitus and pre
hospitalization antiplatelet therapy have been
found to decrease the risk of ARDS in
research studies.
Role of obesity as a risk factor has been
found to be doubtful.

14. Common Causes of ARDS

15. PATHOPHYSIOLOGY OF
ARDS

16. NORMAL
ALVEOLUS

17. Pathophysiology
1. Direct or indirect
injury to the alveolus
causes alveolar
macrophages to
release pro-
inflammatory
cytokines

18. Pathophysiology
2. Cytokines attract
neutrophils into the
alveolus and
interstitum, where
they damage the
alveolar-capillary
membrane (ACM).

19. Pathophysiology
3. ACM integrity is
lost, interstitial and
alveolus fills with
proteinaceous fluid,
surfactant can no
longer support
alveolus
.

20. Pathogenesis
Aspiration, trauma or sepsis can lead to insult or injury to
alveolar epithelium & capillary endothelium
Injury  generally detected in both endothelium &
epithelium at time of diagnosis
Leads to leakage of plasma proteins through interstitial
compartment & into alveolar space
Many of these plasma proteins in turn activate procoagulant &
proinflammatory pathways that lead to fibrinous & purulent
exudates

21. Pathogenesis (Contd)
 In response to direct lung injury or a systemic insult such
as endotoxin,  in pulmonary or circulatory pro-
inflammatory cytokines occurs
 Activated neutrophils secrete cytokines, such as tumor
necrosis factor-alpha and interleukins  inflammatory
response
 Neutrophils also produce oxygen radicals & proteases
that can injure capillary endothelium & alveolar
epithelium.

22. Pathogenesis (Contd)
 Some patients achieve complete resolution of lung
injury before progressing into fibroproliferative stage,
whereas others progress directly to develop fibrosis
 The extent of fibrosis may be determined by :
 Severity of initial injury,
 Ongoing orrepetitious lung injury,
 Toxic oxygen effects, and
 Vventilator-associated lung injury.
Piantadosi CA, Schwartz DA. The acute respiratory distress syndrome. Ann Intern Med 2004;141:460-

23. Pathogenesis (Contd)
 Epithelial & endothelial damage, in turn  leads to 
permeability
 Leads to subsequent influx of protein-rich fluid into
alveolar space
 In addition to these structural changes, there is evidence
of impaired fibrinolysis in ARDS that leads to capillary
thrombosis and microinfarction.

24. Clinical Course and
Pathophysiology
The natural history of ARDS is marked by three phases –
 EXUDATIVE
 PROLIFERATIVE
 FIBROTIC
Each phase have characteristic clinical and
pathological features.

25. Exudative phase ( 0-7 days )
In this phase, alveolar capillary endothelial cells and type 1
pneumocytes ( alveolar epithelial cells ) are injured, and tight
alveolar barrier is damaged giving away the entry to fluid and
macromolecules.
The protein rich fluid accumulates in the interstitial and
alveolar spaces.
Pro – inflammatory cytokines are increased in this acute
phase, leading to recruitment of leukocytes( especially
neutrophils) into pulmomary interstitium and alveoli .

26. There is plasma protein aggregation in air spaces with
cellular debris and dysfunctional pulmonary surfactant to
form hyaline membrane whorls .
Collapse of large sections of dependant lung can
contribute to decreased lung compliance.

27. EXUDATIVE PHASE

28. Chest x ray
finding in
exudative stage
of ARDS

29. CT Chest findings in
exudative stage of
ARDS

30. PROLIFERATIVE STAGE

31. FIBROTIC STAGE
FIBROTIC PHASE

32. Time course of evaluation of
ARDS

34. Pathophysiology
Consequences of lung injury include:
• Impaired gas exchange
• Decreased compliance
• Increased pulmonary arterial pressure

35. Pathophysiology
Impaired Gas Exchange
 V/Q mismatch
 Related to filling of alveoli
 Shunting causes hypoxemia
 Increased dead space
 Related to capillary dead space and V/Q mismatch
 Impairs carbon dioxide elimination
 Results in high minute ventilation

36. CONCEPT OF TWO
COMPARTMENT MODEL OF LUNG

37. Basis of explanation of hypoxia
When large portions of the lung are non-ventilated due to
alveolar collapse or flooding, the blood flow to these units
is effectively shunted through the lungs without being
resaturated.
Thus, despite a high concentration of supplemental oxygen
and high alveolar Po2 in ventilated lung unit ( “ referred to
as a baby lung “) , these blood flows mix in accord with
their o2 contents, that is, the resultant left atrium receives
blood which has weighted mean oxygen content of both
shunted and non shunted blood.

38. Pathophysiology
 Decreased Compliance
 Hallmark of ARDS
 Consequence of stiffness of poorly or non-aerated lung
 Fluid filled lung becomes stiff/boggy
 Requires increased pressure to deliver Vt

39. Pathophysiology
  Pulmonary Arterial Pressure
 Occurs in up to 25% of ARDS patients
 Results from hypoxic vasoconstriction
 Positive airway pressure causing vascular compression
 Can result in right ventricular failure.

40. Role of RAS
In addition to classical views of ARDS including role of
cellular & humoral mediators :
 Role of Renin-Angiotensin System (RAS) has been
highlighted
 RAS thought to contribute to pathophysiology of ARDS
  vascular permeability
Angiotensin-converting enzyme (ACE)  key
enzyme of RAS that converts inactive angiotensin I
to vasoactive & aldosterone-stimulating peptide
angiotensin II

41. Role of RAS
 ACE also metabolizes kinins along with many other
biologically active peptides
 ACE  found in varying levels on surface of lung
epithelial & endothelial cells
 Angiotensin II induces :
 Apoptosis of lung epithelial & endothelial cells and is a
potent fibrogenic factor
 Based on these biological properties of ACE  there
is considerable interest in its potential involvement in
ARDS

42. Physiology of ventilator induced
lung injury

43. Physiology of ventilator induced
lung injury
Volutrauma : delivering too much pressure leads to
overdistention of alveoli . Because the compliance of the
ARDS lung is heterogenous, the same airway pressure
may cause underdistention of a more affected lung region
with low compliance and overdistention of a less affected
region.
Atlectrauma : allowing alveoli to collapse completely
during each breath cycle with too little airway pressure

44. Biotrauma :
The physical force and trauma of ventilation leads
to release of mediators that sustain inflammation
and translocation of proinflammatory products and
bacteria through already permeable barriers,
causing systemic damage.

46. Physiological effects of Prone
Ventilation

47. Physiological effects of Prone
Ventilation
Improves gas exchange by :
1. Ameliorating the ventral dorsal transpulmonary pressure
difference
2. Reducing dorsal compression
3. Improving lung perfusion

48. Ventral- Dorsal transpulmonary
pressure ( Ptp)
The distending pressure across the lung is estimated by
transpulmonary pressure.
Defined as airway pressure(Paw ) and pleural pressure
(Ppl)difference. [ Ptp= Paw – Ppl]
 In a supine patient, the dorsal pleural pressure is greater
than ventral pleural pressure. Hence, Ventral Ptp is greater
than dorsal Ptp and there is greater expansion of ventral
alveoli than the dorsal alveoli ( leading to their collapse).
This difference is favourable reduced by prone positioning.

49. Reduction of dorsal compression
by prone ventilation
In prone position, the heart becomes dependant lying on
the sternum, potentially decreasing posterior and medial
lung compression.
In addition, the diaphragm is displaced caudally ,
decreasing the compression of posterior caudal lung
parenchyma.
These effects improve ventilation and oxygenation.

50. Imroved lung perfusion in prone
positioning
 Improved v/q mismatch as the previously dependant
alveoli begin to reopen in prone position.

51. CLINICAL PRESENTATION OF ARDS

52. CLINICAL PRESENTATION
The development of ARDS usually follows a rapid course
, occuring most often between 12 to 72 hours of the
predisposing event.
At its onset, patient usually becomes anxious, agitated,
and dyspneic .
Inflammatory changes in lung decrease lung compliance,
which in turn leads to increased work of breathing, small
tidal volumes, and tachypnea.

53. CLINICAL PRESENTATION
The hallmark of ARDS is hypoxemia resistant to oxygen
therapy because of the large right to left shunt .
Initially, patients may be able to compensate by
hyperventilating , thereby maintaining an acceptable
PaO2 with an acute respiratory alkalosis.
Typically, patients deteriorate over several hours,
requiring endotracheal intubation and mechanical
ventilation.

54. Differential Diagnosis Of ARDS

56. Differentials of ARDS

57. Differentials of ARDS

58. Diagnosis
A/c Berlin definition
 Within 1 week of a known clinical insult or new or
worsening respiratory symptoms
 Bilateral opacities — not fully explained by effusions,
lobar/lung collapse, or nodules on Chest X ray
 Edema d/t Respiratory failure not fully explained by
cardiac failure or fluid overload

59. Diagnostic evaluation
No lab findings are specific for ARDS other than the
diagnostic criteria.
Blood Gas Analysis :
o In early phase : hypoxemia and respiratory alkalosis
due to shunt or low ventilation – perfusion ratio.
o In the late phase : increased dead space ventilation and
work of breathing , reduced CO2 elimination : Respiratory
Acidosis

60. Diagnostic evaluation( contd)
Hematological abnormalities : such as anemia ,
leucocytosis/ leucopenia, thrombocytopenia due to
systemic inflammation and endothelial injury.
Acute phase reactants : increased ceruloplasmin,
decreased albumin.
Pro inflammatory cytokines : Increased TNF alpha and IL-
1 ,6,8
Imaging : in form of chest xray and CT scan.

61. Diagnostic evaluation( contd)
BAL : Testing is helpful in ruling out the differentials of
ARDS. Eg:
o High eosinophils(> 15-20%) : possibilities of
eosinophilic pneumonia.
o High erythrocytes and hemosiderin laden macrophages
: diffuse alveolar hemorrhage( seen in Goodpasture
syndrome, granulomatosis with polyangitis, SLE, APLA)
o High lymphocytes : hypersensitivity pneumonitis,
sarcoidosis , cryptogenic organizing pneumonia.

62. Lung biopsy :
o Routine lung biopsy is not recommended in patients with
ARDS.
o Should be reserved for highly selective group of patients
where alternative diagnosis are possible and would
significantly change management and prognosis.

63. INVESTIGATIONAL MODALITIES THAT MAY BE USED IN DIAGNOSIS OF
ARDS

64. PREDICTING ARDS
LUNG INJURY PREDICTION SCORE( LIPS)
Generated in a multicentre cohort, LIPS is aimed at
identifying those at highest risk of developing ARDS.
It includes 2 broad categories for scoring :
Pre disposing conditions: 9 included
Risk modifiers : 6 included.

65. References
Harrisons principles of internal medicine , 20th edition
Fishman’s textbook of pulmonary medicine , 6th edition
Robbins and cotran textbook of pathology , 19th edition
Uptodate