ards or dad arthur c. aufderheide, m.d. med 6728. respiratory system november 2008
TRANSCRIPT
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ARDS or DAD
Arthur C. Aufderheide, M.D.
Med 6728. Respiratory System
November 2008
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NORMAL ANATOMY
Branching system
Double arterial supply
Alveolar wall components
Pulmonary defense mechanisms
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LUNG DEFENSE MECHANISMS
Nose (warms air; traps particulates)
Nasopharynx (warms, humidifies air)
Tonsils (IgG)
Epiglottis (prevents aspiration)
Trachea – bronchi (cilia – 1 cm/min)
Alveoli (macrophages)
Alveolar wall (lymphatics)
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CONGENITAL ANOMALIES
Bronchogenic cysts:
bronchial elements in lining
Bronchopulmonary sequestration:
systemic blood supply
independent bronchi
extralobular & intralobular
don’t connect with normal bronchi
secretion by bronchi cysts; pneumonia
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CONGENITAL ANOMALIES
Bronchogenic cysts:
bronchial elements in lining
Bronchopulmonary sequestration:
systemic blood supply
independent bronchi
extralobular & intralobular
don’t connect with normal bronchi
secretion by bronchi cysts; pneumonia
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ATELECTASIS: MECHANISMS
Obstructive: tumor, foreign body, secretions
Compressive: fluid, pus, tumor air
Contractive: scar
Patchy: surfactant loss
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ATELECTASIS: MECHANISMS
Obstructive: tumor, foreign body, secretions
Compressive: fluid, pus, tumor, air
Contractive: scar
Patchy: surfactant loss
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PULMONARY INFARCTION (1)
Source: leg veins (stasis; local injury; air travel) mural thrombi RA & RV
Effect: small emboli = none; huge = sudden death;
intermediate = infarct heart failure increases the probability of infarction multiple, recurrent showers of emboli can produce
pulmonary hypertension
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PULMONARY INFARCTION (2)
Sx: sudden dyspnea pleural pain 24 hr = hemoptysis
Gross: early = pale infarct; later = hemorrhagic bronchial arteries provide collateral circulation
Dx: clinical, perfusion scan; recently CT scan. Rx: anticoagulation
sometimes with thrombolytic Rx or surgical embolectomy
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PULMONARY HYPERTENSION (1)
Causes: Secondary: LV failure, emphysema, pneumoconiosis,
drugs (fen-phen; ergot); recurrent pulmonary thromboembolism, congenital heart disease (left to right shunt)
Chronic hemolysis (e.g., sickle cell) pulmonary hypertension via scavenging of NO by hemoglobin and upregulating endothelin 1 (vasoconstrictor)
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PULMONARY HYPERTENSION (2)
Causes: Primary: idiopathic (vasospastic: endothelin?)
Children and young women
In familial form, mutations in bone morphogenetic protein receptor 2 (BMPR2) — a member of the family of transforming growth factor beta (TGF-)—signalling pathway, blocks K outflow channel and permits Ca inflow,causing pulmonary arterial smooth muscle cell hypertrophy.
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PULMONARY HYPERTENSION (3)
Signs and symptoms:
Pulmonary artery b.p. > 35 mmHg
Loud pulmonary valve closure
Tricuspid insufficiency murmur
ECG = right ventricular hypertrophy
X-ray = pulmonary artery Right ventricular failure without left ventricular failure
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PULMONARY HYPERTENSION (4)
Pathology: Arteriopathic
intimal thickening medial hypertrophy plexiform lesion (arteriolar medial necrosis
with thrombosis & canalization) atherosclerosis of pulmonary artery if
pressure >60 mmHg Veno-occlusive
intimal fibrosis
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PULMONARY HYPERTENSION (5)
Rx: Bosentan = antagonist of receptor for the vasoconstrictor endothelin-1; prostacyclin (pulmonary vasodilator). Also in lung, NO effect is mediated by cyclic guanosine monophosphate (cGMP) . This is normally rapidly metabolized by phosphodiesterase (PDase). Sildenafil citrate can inhibit PDase,thus permitting cGMP ro rise in the cell and so increase the vasodilator effect of NO.
Result: Too soon to know with the new ones; in past progressively fatal.
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PULMONARY HYPERTENSION (6)
High altitude pulmonary edema: Young men: rapid ascent above 2500 meters S&S: cough, orthopnea, rales, frothy pink sputum Pathophysiology: pulmonary hypertension
(hypoxia-induced).Patent foramen ovale worse. Defective sodium ion channel clearance of fluid
from alveoli. Capillary pressure Rx: O2, nifedipine (vasodilator), nitric oxide, rapid
descent
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ARDS: CLINICAL SYNDROMES (1)
Shock lung
Respirator lung
Post-traumatic pulmonary insufficiency
Traumatic wet lung
Post-perfusion pulmonary insufficiency
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ARDS: CLINICAL SYNDROMES (2)
Progressive pulmonary consolidation
Congestive atelectasis
Adult hyaline membrane disease
Adult respiratory distress syndrome (1967)
Now: Diffuse Alveolar Damage (DAD)
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ARDS (DAD): MECHANISMS (1)
Endothelial cell injury (most common mechanism)
Shock (trauma, sepsis) tumor necrosis factor,
oxygen free radicals
Pancreatitis proteases, lipases
Heroin, nitrofurantoin
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ARDS (DAD): MECHANISMS (2)
Direct alveolar lining cell injury:
Toxic gases inhaled (sulfur dioxide, nitrogen
dioxide) or exhaled (carbon tetrachloride)
Viral respiratory infective agents
BUT: Alveolar cell + capillary = unit
Damage one and both suffer
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ARDS (DAD): LUNG’S RESPONSE
Alveolar damage: lining cells slough
Loss of alveolar lining cells type II result in surfactant
loss producing atelectasis
Endothelial damage: capillaries leak extrusion of
proteinaceous fluid into the alveoli (“hyaline membranes”)
Worst: capillary thrombosis
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ARDS (DAD): SYMPTOMS & SIGNS
Dyspnea
Rapidly developing diffuse pulmonary infiltrate
Rapid course (days)
Positive pressure, mechanical ventilation required
Mortality 50%; higher in sepsis
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ARDS (DAD): PATHOLOGY (1)
Early (exudative) stage
Edema–interstitial and intra-alveolar
Endothelial cells enlarged (injured);leak
protein (hyaline membranes)
Alveolar cells :slough;covered by the hyaline
membranes.
Capillaries: fibrin thrombi
Interstitium: inflamm. cells in 2-3 days.
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ARDS (DAD): PATHOLOGY (2)
Intermediate (proliferative) early healing stage:
Alveolar cells hyperplasia:
type II (make surfactant)
these eventually become type I (reparative &
protective effects)
Bronchial epithelium: squamous metaplasia
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ARDS (DAD): PATHOLOGY (3)
Late stage (repair):
Inflammation (lymphocytes) in the interstitium
Fibrosis in both the alveoli and interstitium
Alveolar macrophages engage in phagocytosis of
hyaline membranes (membranes disappearing)
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ARDS (DAD): MECHANISMS (3)
Proinflammatory agents (interleukin-8, tumor
necrosis factor) recruit neutrophils to lung
neutrophils release tissue-damaging substances
(proteases, platelet activating factor, oxidants)
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ARDS (DAD): PROGNOSIS
Mortality: 50%
Survivors:
Surprisingly good function in many
Severe cases develop diffuse pulmonary fibrosis &
pulmonary hypertension
Prognostic markers: extremes of pO2 decrease & fibrosis