ARDS pathophysio

1. Understanding The Pathologic
And Pathophysiologic Changes
That Cause ARDS.

3.  Multiple organ failure syndrome with shock is the most common cause
of death in patients with ARDS ( attributable mortality: 45%)

4.  Have we made any difference to survival ?
 Have we understood the disease or shall we
call it the final common effect of various
diseases?
Lets revisit the basic science

5. Alveolar-capillary membrane failure

9. Instigation
 Endothelial injury: increased permeability of
alveolar - capillary barrier
 Epithelial injury : alveolar flood, loss of
surfactant, barrier vs. infection
 Pro-inflammatory mechanisms

10. Direct insult
 Common
• Aspiration pneumonia
• Pneumonia
 Less common
• Inhalation injury
• Pulmonary contusions
• Fat emboli
• Near drowning
• Reperfusion injury
Indirect insult
 Common
• Sepsis
• Severe trauma
• Shock
 Less common
• Acute pancreatitis
• Cardiopulmonary bypass
• Transfusion-related TRALI
• Disseminated intravascular
coagulation
• Burns
• Head injury
• Drug overdose

15.  Leucocytes and soluble
mediators
 Coagulation and platelets
 Surfactant
 Ventilator induced lung injury
 Late phase : dysregulated and
maladaptive repair.

16.  Primary lung insult is
associated with cascade of
events.
 The corner stone of such
cascade is inflammatory
cells mainly neutrophils.
 Recruitment of neutrophils
and activation of
macrophages leads to
release of both pro-
inflammatory and anti-
inflammatory cytokines

17. NETS
Neutrophils
Extracellular
Traps

18. PRR
Pattern Recognition
Receptors.
iNKT
Invariant
Natural Killer T

19. Lung injury
Interleukin 1β, TNF α
Activate alveolar epithelial,
Endothelial cells and lung
fibroblasts
IL 8 and MIP 1 release
Activation and
Chemotaxis of neutrophils
and macrophages
Leucocyte
Adhesion molecule
ACM failure
Endothelial
damage
Epithelial
damage
Cytokine release

21.  Massive literature
 Mediators involved but extent of cause/effect
unknown

22.  Leucocytes and soluble mediators
 Coagulation and platelets
 Surfactant
 Ventilator induced lung injury
 Late phase : dysregulated and maladaptive
repair.

23.  Histological Land mark of ALI and ARDS.
• Intra-alveolar Hyaline Membrane
• Microvascular Thrombi
• Deposition of Fibrin in the lung due to
imbalance in the production and degradation.
• In uninjured lung fibrinolytic state is
maintained through action of urokinase
plasminogen activator which converts
plasminogen to plasmin which is fibrinolytic.

24.  Leucocytes and soluble mediators
 Coagulation and platelets
 Surfactant
 Ventilator induced lung injury
 Late phase : dysregulated and maladaptive
repair.

25.  Produced by type II alveolar epithelial cells
 Composed of lipoprotein complex
 Function :
Biophysical - decrease surface tension at air/liquid
interface
Immunologic – innate host defense

26.  Surfactant production and composition
altered in ARDS: low lecithin-
sphingomyelin ratio
 Components of edema fluid may
inactivate surfactant

28.  Leucocytes and soluble mediators
 Coagulation and platelets
 Surfactant
 Ventilator induced lung injury
 Late phase : dysregulated and maladaptive
repair.

32. Lung injury from:
• Overdistension /shear - physical
injury
• Mechanotransduction - “biotrauma”
• Repetitive opening/closing
• Shear at open/collapsed lung
interface
Systemic inflammation:
• Systemic release of cytokines,
endotoxin, and proteases.
“atelectrauma”
“volutrauma/barotrauma”

33. Gas Extravasation
Barotrauma

34. “Stretch”
“Shear”
Airway Trauma

36. Lung inflammation “biotrauma”
• Lung overinflation or overstretching produces regional and
systemic inflammatory response
• Factors converting the shear stress applied to an injured lung into
regional and systemic inflammation are still incompletely
elucidated but could include:
- Repetitive opening and collapse of lung units
- Surfactant alterations
- Loss of alveolo-capillary barrier function
- Bacterial translocation
- Over inflation of lung regions
Rouby JJ, et al. Anesthesiology. 2004.
Dreyfuss D, et al. Am J Respir Crit Care Med. 2003.

38. Positive pressure ventilation may injure the lung
via several different mechanisms
VILI
Alveolar distension
“VOLUTRAUMA”
Repeated closing and opening
of collapsed alveolar units
“ATELECTRAUMA”
Oxygen toxicity
Lung inflammation
“BIOTRAUMA”

39. VILI can predispose to ALI/ARDS, while
ALI/ARDS patients are more prone to
effects of VILI

40.  Leucocytes and soluble mediators
 Coagulation and platelets
 Surfactant
 Ventilator induced lung injury
 Late phase : dysregulated and maladaptive
repair.

41. The pathological features of ARDS are
typically described as passing through three
overlapping phases:
• exudative,
• proliferative
• fibrotic phase

44. Formation of hyaline membrane

45. Proliferation of
type 2 pneumocytes
Thickening of alveolar wall
with loose Organizing connective
tissue

46. Severe fibrosis with vascular structures engulfing –
Leading to severe pulmonary hypertension

47. ARDS is the ultimate culminating point irrespective of
the pathophysiologic mechanisms