Chapter 15- The lung: ALI and ARDS Flashcards
What is ALI?
Acute lung injury (ALI) (also called noncardiogenic pulmonary edema) is characterized by the
abrupt onsetof significant hypoxemiaanddiffuse pulmonary infiltratesin theabsence of cardiac
failure
What is ARDS?
Acute respiratory distress syndrome (ARDS) refers to severe ALI
ARDS and ALI both
have:
inflammation-associated increase in pulmonary vascular permeability, and epithelial and
endothelial cell death.
What is the histologic manifestion of both ALI and ARDS?
The histologic manifestation of these diseases is
diffuse alveolar damage
(DAD).
Most cases of ALI are associated with an underlying etiology such as _____
sepsis.
What is Acute Interstitial Pneumonia ( AIP)
In the
absence of any etiologic association of ALI , such cases are called acute interstitial pneumonia (AIP).
ALI is a well-recognized complication of diverse conditions, including both direct injuries to the
lungs and systemic disorders ( Table 15-2 ). In many cases, a combination of predisposing
conditions is responsible (e.g., shock, oxygen therapy, and sepsis). Nonpulmonary organ
dysfunction may also be present in severe cases.
TABLE 15-2 – Conditions Associated with Development of Acute Respiratory Distress
Syndrome
-
INFECTION
- Sepsis [*]
- Diffuse pulmonary infections [*]
- Viral, Mycoplasma, and Pneumocystis pneumonia;
- miliary tuberculosis
- Gastric aspiration [*]
-
PHYSICAL/INJURY
- Mechanical trauma, including head
injuries [*] - Pulmonary contusions
- Near-drowning
- Fractures with fat embolism
- Burns
- Ionizing radiation
- Mechanical trauma, including head
-
INHALED IRRITANTS
- Oxygen toxicity
- Smoke
- Irritant gases
- chemical
-
CHEMICAL INJURY
- Heroin or methadone overdose
- Acetylsalicylic acid
- Barbiturate overdose
- Paraquat
-
HEMATOLOGIC CONDITIONS
- Multiple transfusions
- Disseminated intravascular
coagulation
- PANCREATITIS
- UREMIA
- CARDIOPULMONARY BYPASS
-
HYPERSENSITIVITY REACTIONS
- Organic solvents
- Drugs
More than 50% of cases of acute respiratory distress syndrome are associated with these four
conditions.
- Sepsis [*]
- Diffuse pulmonary infections [*]
- Viral, Mycoplasma, and Pneumocystis pneumonia; miliary tuberculosis
- Gastric aspiration [*]
- Mechanical trauma, including head
injuries [*]
What is the morphology of the ALI in acutae stage?
In the acute stage, the lungs are heavy, firm, red, and boggy.
They exhibit congestion, interstitial and intra-alveolar edema, inflammation, fibrin deposition, and diffuse
alveolar damage.
The alveolar walls become lined with waxy hyaline membranes ( Fig. 15- 3 ) that are morphologically similar to those seen in hyaline membrane disease of neonates (
Chapter 10 ).
Alveolar hyaline membranes consist of fibrin-rich edema fluid mixed with the cytoplasmic and lipid remnants of necrotic epithelial cells.
What is the morphology of ALI in organizing stage?
In the organizing stage, type II
- *pneumocytes undergo proliferation**, and there is a granulation tissue response in the alveolar
- *walls and in the alveolar spaces**.
In most cases the granulation tissue resolves, leaving
minimal functional impairment.
Sometimes, however, fibrotic thickening of the alveolar septa
ensues, caused by proliferation of interstitial cells and deposition of collagen.
Fatal cases
often have superimposed bronchopneumonia.
FIGURE 15-3 Diffuse alveolar damage (acute respiratory distress syndrome). Some of the alveoli are collapsed; others are distended, and many are lined by hyaline membranes
(arrows).
alveolar capillary membrane is formed by two separate barriers:
The alveolar capillary membrane is formed by two separate barriers:
- the microvascular endothelium and the
- alveolar epithelium.
What is the pathophysiology of ARDS?
In ARDS the integrity of alveolar capillary membrane is formed by two separate barriers: the microvascular
endothelium and the alveolar epithelium, this barrier is compromised by either endothelial or epithelial injury or, more commonly, both
Markers of endothelial
injury and activation such as____-can be detected at high
levels in the serum of patients with ARDS.
endothelin and von Willebrand factor
What is the evidence of epithelial injury in the alveolar membrane?
Evidence of epithelial injury in the form of swelling,
- *vacuolization, bleb formation, and frank necrosis is also noted early in the course of acute lung
injury. **
What is the acute consequence of damage of alveolar capillary membrane?
The acute consequences of damage to the alveolar capillary membrane include:
- increased vascular permeability and alveolar flooding,
- loss of diffusion capacity, and
- widespread surfactant abnormalities caused by damage to type II pneumocytes.
- Endothelial injury also triggers the formation of microthrombi that add the insult of ischemic injury
What is the characterisitc of ALI / ARDS?
Hyaline membranes so characteristic of ALI/ARDS result from inspissation of protein rich
edema fluid that entraps debris of dead alveolar epithelial cells.
FIGURE 15-4 The normal alveolus (left side) compared with the injured alveolus in the early
phase of acute lung injury and acute respiratory distress syndrome.
Pro-inflammatory
cytokines such as interleukin 8 (IL-8), interleukin 1 (IL-1), and tumor necrosis factor (TNF)
(released by macrophages), cause neutrophils to adhere to pulmonary capillaries and extravasate into the alveolar space, where they undergo activation.
Activated neutrophils release a variety of factors, such as leukotrienes, oxidants, proteases, and platelet-activating factor (PAF), which contribute to local tissue damage, accumulation of edema fluid in the
airspaces, surfactant inactivation, and hyaline membrane formation.
Macrophage migration
inhibitory factor (MIF) released into the local milieu sustains the ongoing pro-inflammatory
response.
Subsequently, the release of macrophage-derived fibrogenic cytokines such as
transforming growth factor β (TGF-β)andplatelet-derived growth factor (PDGF) stimulate
fibroblast growth and collagen deposition associated with the healing phase of injury.
Although the cellular and molecular basis of acute lung injury and ARDS remains an area of
active investigation,it appears that inARDS, lung injury is caused by an :
imbalance of proinflammatory
and anti-inflammatory mediators
The most proximate signals leading to
uncontrolled activation of the acute inflammatory response are not yet understood.
However,
__________, a transcription factor whose activation itself is tightly regulated under
normal conditions, has emerged as a likely candidate shifting the balance in favor of a proinflammatory
state.
nuclear factor κB (NF-κB)
What happens as early as 30 min after acute insult in the lungs?
- As early as 30 minutes after an acute insult, there is increased synthesis of
interleukin-8 (IL-8), a potent neutrophil chemotactic and activating agent, by pulmonary
macrophages.
- Release of this and similar compounds, such as IL-1 and tumor necrosis factor
- *(TNF),** leads to endothelial activation, and pulmonary microvascular sequestration and
- *activation of neutrophils.**
______ are thought to have an important role in the pathogenesis
of ARDS.
Neutrophils
Histologic examination of lungs early in the disease process shows increased
numbers of neutrophilswithin the vascular space, the interstitium, and the alveoli.
How
neutrophils are sequestered in the lung in ALI is not entirely clear.
There are two possible
mechanisms.
- Firstly, neutrophils that are activated by cytokines like IL-8 and TNF upregulate the expression of adhesion molecules that allow them to bind to their ligands on activated endothelial cells.
- Secondly, activated neutrophils become “stiff” and less deformable and thus get trapped in the narrow capillary beds of the lung.
Activated neutrophils release a variety of
products (e.g., oxidants, proteases, platelet-activating factor, and leukotrienes) that cause damage to the alveolar epithelium and fuel the inflammatory cascade.
Combined assault on the
endothelium and epithelium perpetuate vascular leakiness and loss of surfactant that render
the alveolar unit unable to expand.
It should be noted that the destructive forces unleashed by neutrophils can be counteracted by an array of endogenous antiproteases, antioxidants, and
anti-inflammatory cytokines (e.g., IL-10) that are upregulated by pro-inflammatory cytokines.
