pediatrics
Cystic Fibrosis
Pathophysiology of Cystic Fibrosis
Nearly all exocrine glands are affected in varying distribution and degree of severity. Glands may Become obstructed by viscid mucus in the lumen (pancreas, intestinal glands, intrahepatic bile ducts, gallbladder, and submaxillary glands) Appear histologically abnormal and produce excessive secretions (tracheobronchial and Brunner glands) Appear histologically normal but secrete excessive sodium and chloride (sweat, parotid, and small salivary glands) Although the lungs are generally histologically normal at birth, most patients develop signs of pulmonary disease beginning in infancy or early childhood. Mucus plugging and chronic bacterial infection, accompanied by a pronounced inflammatory response, damage the airways, ultimately leading to Bronchiectasis and respiratory insufficiency. The course is characterized by episodic exacerbations with infection and progressive decline in pulmonary function. Pulmonary damage is probably initiated by diffuse obstruction in the small airways by abnormally thick mucus secretions. Bronchiolitis and mucopurulent plugging of the airways occur secondary to obstruction and infection. Chronic inflammation secondary to the release of proteases and proinflammatory cytokines by cells in the airways also contributes to lung injury. Airway changes are more common than parenchymal changes, and emphysema is not prominent. About 50% of patients have bronchial hyperreactivity that may respond to bronchodilators. In patients with advanced pulmonary disease, chronic hypoxemia results in muscular hypertrophy of the pulmonary arteries, Pulmonary Hypertension , and right ventricular hypertrophy. The lungs of most patients are colonized by pathogenic bacteria. Early in the course, Staphylococcal Infections is the most common pathogen, but as the disease progresses, ( Staphylococcal Infections ) in the respiratory tract is now about 25%; patients who are chronically infected with MRSA have more rapid decline in pulmonary function and lower survival rates than those who are not. Colonization withBurkholderia cepaciacomplex occurs in about 2 to 3% of patients and may be associated with more rapid pulmonary deterioration. Nontuberculous Mycobacterial Infections , including , and Aspergillosis species. Overview of Anaerobic Bacteria and common The pancreas, intestines, and hepatobiliary system are frequently affected. Exocrine pancreatic function is compromised in 85 to 95% of patients. An exception is a subset of patients who have certain CFTR variants with residual function, in whom pancreatic function is preserved. Patients with pancreatic insufficiency have malabsorption of fats, fat-soluble vitamins, and protein. Duodenal fluid is abnormally viscid and shows absence or diminution of enzyme activity and decreased bicarbonate concentration; stool trypsin and chymotrypsin are absent or diminished. Endocrine pancreatic dysfunction is less common, but impaired glucose tolerance or diabetes mellitus is present in about 2% of children, 20% of adolescents, and up to 50% of adults. Bile duct involvement with bile stasis and biliary plugging leads to asymptomatic Hepatic Fibrosis in 30% of patients. About 3 to 4% of patients progress to irreversible multinodular biliary cirrhosis with varices and Abnormally viscid intestinal secretions can cause Meconium Ileus in neonates and sometimes Other gastrointestinal (GI) problems include Intussusception , volvulus, Infertility occurs in 98% of adult men secondary to maldevelopment of the vas deferens or to other forms of obstructive azoospermia. In women, fertility is somewhat decreased secondary to viscid cervical secretions, although many women have carried pregnancies to term. Pregnancy outcome for both the mother and neonate is related to the mother's health. Other complications include Sinusitis , osteopenia/ 