ARDS or DAD

Arthur C. Aufderheide, M.D.

Med 6728. Respiratory System

November 2008

NORMAL ANATOMY

Branching system

Double arterial supply

Alveolar wall components

Pulmonary defense mechanisms

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)

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

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

ATELECTASIS: MECHANISMS

Obstructive: tumor, foreign body, secretions

Compressive: fluid, pus, tumor air

Contractive: scar

Patchy: surfactant loss

ATELECTASIS: MECHANISMS

Obstructive: tumor, foreign body, secretions

Compressive: fluid, pus, tumor, air

Contractive: scar

Patchy: surfactant loss

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

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

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)

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.

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

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

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.

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

ARDS: CLINICAL SYNDROMES (1)

Shock lung

Respirator lung

Post-traumatic pulmonary insufficiency

Traumatic wet lung

Post-perfusion pulmonary insufficiency

ARDS: CLINICAL SYNDROMES (2)

Progressive pulmonary consolidation

Congestive atelectasis

Adult hyaline membrane disease

Adult respiratory distress syndrome (1967)

Now: Diffuse Alveolar Damage (DAD)

ARDS (DAD): MECHANISMS (1)

Endothelial cell injury (most common mechanism)

Shock (trauma, sepsis) tumor necrosis factor,

oxygen free radicals

Pancreatitis proteases, lipases

Heroin, nitrofurantoin

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

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

ARDS (DAD): SYMPTOMS & SIGNS

Dyspnea

Rapidly developing diffuse pulmonary infiltrate

Rapid course (days)

Positive pressure, mechanical ventilation required

Mortality 50%; higher in sepsis

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.

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

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)

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)

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