RESTRICTIVE LUNG DISEASES
Restrictive lung diseases are characterized by reduced lung volume, either because of an alteration in lung parenchyma or because of a disease of the pleura, chest wall, or neuromuscular apparatus.
In physiological terms, restrictive lung diseases are characterized by reduced total lung capacity (TLC), vital capacity, or resting lung volume. Accompanying characteristics are preserved airflow and normal airway resistance, which are measured as the functional residual capacity (FRC).
Parenchymal restrictive lung diseases
In this group of diseases, there is reduction in oxygen diffusion capacity, lung volume & lung compliance.
They are classified into (acute & chronic interstitial - infiltrative diseases).
Alveolitis (interstitial pneumonitis), occurs in almost all cases. It is characterized by accumulation of inflammatory cells & immune effector cells in the alveolar wall & interstitium.
With chronicity, the changes in the interstitium dominate the picture, so this group of diseases is known as interstitiun pneumonitis
Release of chemical mediators causes injury to the endothelial cells of the capillaries & flat epithelial cells of the alveoli. It also stimulates fibrosis
The final result is an end stage fibrotic lung known as “stiff lung”. The alveoli are replaced by cystic spaces separated by thick bands of connective tissue containing inflammatory cells known as “honey-comb lung”. In such case the function of alveolocapillary membrane is lost.
Patients of this group of disease have dyspnea, tachypnea & cyanosis without wheezing or any evidence of airway obstruction
Cause of dyspnea is the stiffness of the lung which in turn reduces the lung compliance & necessitates increased effort of breathing
Chest radiographs show diffuse infiltration by small nodules, irregular lines or “ground glass shadows” hence the term infiltrative lung diseases
Restrictive lung diseases may end in severe hypoxia & respiratory failure associated with pulmonary hypertension, corpulmonale & right sided heart failure.
Acute Restrictive lung diseases
Best example is : Adult respiratory distress syndrome (diffuse alveolar damage)
Direct lung injury:
Common causes: Severe lung infection (e.g., bacterial or viral pneumonia) & Inhalation of vomited stomach contents
Uncommon causes: Fat embolism (globule of fat that blocks an artery), Near drowning
Indirect lung injury: Serious infection in the blood or other tissues (called sepsis; accounts for more than 30% of cases), Severe chest trauma, Inhalation of smoke or other toxic fumes, Massive blood transfusion, Cardiopulmonary bypass surgery & Ingestion of certain drugs
The alveolar capillary membrane is formed by two separate barriers: the microvascular endothelium and the alveolar epithelium.
In ARDS the integrity of this barrier is compromised by either endothelial or epithelial injury, or, more commonly, both.
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 .
In ARDS, lung injury is caused by an imbalance of pro-inflammatory and anti-inflammatory mediators.
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.
Morphology: In the acute phase of ARDS the lungs are dark red, firm, airless, and heavy. With deposition of collagen they are diffusely gray & fibrotic.
There is capillary congestion, necrosis of alveolar epithelial cells, interstitial and intra-alveolar edema and hemorrhage, and (particularly with sepsis) collections of neutrophils in capillaries.
The most characteristic finding is the presence of hyaline membranes, particularly lining the distended alveolar ducts. Such membranes consist of fibrin-rich edema fluid admixed with remnants of necrotic epithelial cells.
In the organizing stage there is marked proliferation of type II pneumocytes in an attempt to regenerate the alveolar lining.
Resolution is unusual; more commonly there is organization of the fibrin exudates, with resultant intra-alveolar fibrosis. Marked thickening of the alveolar septa ensues, caused by proliferation of interstitial cells and deposition of collagen.
The end result of diffuse fibrosis of interstitial tissue interspersed with dilated & distorted air spaces (honey-comb lung)
Predictors of poor prognosis in ARDS include advanced age, underlying bacteremia (sepsis), and the development of multisystem (especially cardiac, renal, or hepatic) failure.
Diffuse interstitial fibrosis may occur and continue to compromise respiratory function. However, in most patients who survive the acute insult and are spared the chronic sequela, normal respiratory function returns within 6 to 12 months.
Chronic restrictive (interstitial) lung diseases
This group of diseases is divided into two categories: those with known etiology & others with unknown. the reaction in the interstitial tissue is associated with granulomas in some diseases
Chronic interstitial lung diseases those with known etiology
Occupational & environmental agents Iinorganic dust, fumes & gases)
Following acute respiratory distress syndrome
Drugs (chemotherapeutic agents, penicillin & anti arrhythmic)
Chronic interstitial lung diseases those with unknown etiology
Collagen vascular diseases (scleroderma, rheumatoid arthiritis, SLE, dermatomyositis & mixed connective tissue diseases
Idiopathic pulmonary fibrosis
Idiopathic pulmonary haemosiderosis
Idiopathic pulmonary fibrosis
Idiopathic pulmonary fibrosis (IPF), also known as cryptogenic fibrosing alveolitis, refers to a pulmonary disorder of unknown etiology
The inciting agent for recurrent alveolitis in IPF is unknown.
Males are affected more often than are females, and approximately two-thirds of patients are older than 60 years of age at presentation.
It should be stressed that similar pathologic findings in the lung may be noted with well-defined entities such as asbestosis, the collagen-vascular diseases, and a number of other conditions. Therefore, known causes must be ruled out before the appellation of "idiopathic" is used.
Grossly, the pleural surfaces of the lung have the appearance of cobblestones because of the retraction of scars along the interlobular septa. The cut surface shows fibrosis (firm, rubbery white areas), with lower lobe predominance and a distinctive distribution in the subpleural regions and along the interlobular septa. The pattern of fibrosis in IPF is referred to as usual interstitial pneumonia (UIP).
Histologically: hallmark of UIP is patchy interstitial fibrosis, which varies in intensity and with time. The earliest lesions contain exuberant fibroblastic proliferation and appear as fibroblastic foci. With time these areas become more collagenous and less cellular. The dense fibrosis causes collapse of alveolar walls and formation of cystic spaces lined by hyperplastic type II pneumocytes or bronchiolar epithelium (honeycomb fibrosis). The interstitial inflammation is usually patchy and consists of an alveolar septal infiltrate of mostly lymphocytes and occasional plasma cells, mast cells, and eosinophils. Secondary pulmonary hypertensive changes (intimal fibrosis and medial thickening of pulmonary arteries) are often present.
IPF usually presents insidiously, with the gradual onset of a nonproductive cough and progressive dyspnea.
Cyanosis, cor pulmonale, and peripheral edema may develop in the later stages of the disease.
Figure . General scheme for the pathogenesis of chronic restrictive lung disease