Pancreatic Pathology Online

Pathology of Cystic Fibrosis

Dr Sampurna Roy MD

 

Syn: Mucoviscidosis.

Cystic fibrosis (CF) of the pancreas is the most widely accepted name of the most common fatal inherited single gene defect disease among Caucasians.

Its incidence among other races is thought to be significantly less, but mutations in the gene have been reported in most, if not all, major populations.

This autosomal recessive disorder is rarely noted in blacks and almost never in Orientals.

Many theories have been proposed to explain the increased viscosity of the mucus and the biochemical changes found in the sweat, but no unifying concept has emerged. 

Most of the research has concentrated on the biochemical analysis of the mucus and the role of hormones, minerals, and transport proteins that regulate various cellular secretory mechanisms.

Electrolyte disturbances are detectable in the sweat of affected individuals and serve as a test for early diagnosis.

The sodium and chloride content of sweat is two to three times normal, and levels of 60 mEq/liter are diagnostic.

Pilocarpine iontophoresis facilitates the collection of sweat and is the basic test for diagnosis of cystic fibrosis, with an accuracy of over 95%.

Cystic fibrosis is essentially an epithelial cell transport disorder caused by mutations of the cystic fibrosis transmembrane conductance regulator (CFTR) gene.

More than 1,000 mutations have been identified in the cystic fibrosis (CF) transmembrane regulator (CFTR) disease gene.

Because of defect of mucociliary action, thick mucus accumulates in the intestines and lungs that can hinder normal function of epithelial cells.

The genotype-phenotype relationships in CF are complex, and are affected by many factors, including pollution, smoking, bacterial infection, malnutrition, and certain therapeutic agents.

This is a common inherited fatal disease and as the life expectancy of affected individuals continues to increase with advances in disease management, this disease is no longer limited to the pediatric population.

Currently, 40% of patients with cystic fibrosis are adults.

In addition, patients may not present until adulthood and frequently have extrapulmonary symptoms.

Cystic fibrosis is a systemic disease that affects essentially all exocrine glands of the body and results in abnormal sweat electrolyte content  and hyperviscous secretions in  the pancreas, biliary tract, and bronchial tree.

Clinically, the condition presents even in utero.

Abdominal manifestations are common and affect multiple organ systems.

Pathologic changes in the pancreas and the salivary glands are found in practically all instances. 

The original name, cystic fibrosis of the pancreas, denotes the typical changes in that organ. 

Viscous mucus, which accounts for the synonymous term "mucoviscidosis" causes comparable changes in  salivary  and other mucus-secreting glands, and in organs containing mucus-secreting cells, such as the bronchi, biliary tree, epididymis, and intestine.

Diagram of a pancreas showing accentuation of lobules but general preservation of size and contour of organ.

Pancreas in cystic fibrosis showing dilated centrilobular ducts containing inspissated mucus. Acini are almost totally replaced by fibrous tissue that still reflects lobular pattern of the organ.

 

Excretory ducts of the pancreas are cystically dilated and plugged with inspissated mucus.

Acini are atrophic and are replaced by fibrous tissue. Pancreatic acini destroyed by stagnant pancreatic enzymes.

The islets of Langerhans are usually preserved, but they  may be compressed by the fibrous tissue.

About 33% of patients show some degree of endocrine pancreatic insufficiency.

Manifestations in the pancreas include acute pancreatitis, fatty replacement, calcifications, cysts, duct abnormalities, and carcinoma.

In the pancreas, acinar plugs of mucus have been reported as the earliest recognizable morphologic lesion in cystic fibrosis.

Fatty replacement of the pancreas is the most frequent pattern in older patients with cystic fibrosis.

This pattern correlates with pancreatic exocrine dysfunction.

Viscous contents of the gut (meconium) cause obstruction, which is associated with forceful peristaltic movements.

These blockage results in ileus or peritonitis, owing to the extravasation of intestinal contents (meconium peritonitis).

Gastrointestinal manifestations include gastroesophageal reflux, peptic ulceration of the gastric and duodenal mucosa, distal intestinal obstruction syndrome, intussusception, appendicitis, fibrosing colonopathy, pneumatosis intestinalis, rectal mucosal prolapse, malignancies, and pseudomembranous colitis.

In infancy and early childhood, nutritional deficiency is the major clinical problem.

Because the pancreatic ducts are obstructed, digestive enzymes do not reach the intestine.

Consequently, the patient shows the typical symptoms of   malabsorption, such as lipid intolerance, bulky fatty stools (steatorrhea), and deficiencies of the fat-soluble  vitamins (A, D, K).

Obstruction of the biliary tree is another contributory cause of malabsorption.

Hepatobiliary manifestations include fatty infiltration of the liver, gallbladder abnormalities, bile duct abnormalities, focal biliary fibrosis, and multinodular cirrhosis.

Bile ducts are obstructed, and 2% to 3% of older patients show signs of secondary biliary cirrhosis.

Mucous obstruction of the bronchopulmonary spaces, combined with superimposed infections, leads to recurrent  bronchitis, bronchiectasis, and bronchopneumonia.

Chronic infection and obstruction of air passages leads to recurrent and persistent pneumonia and pulmonary fibrosis.

The resulting pulmonary hypertension causes chronic cor pulmonale and right ventricular hypertrophy.

Cystic fibrosis is characterized by the elaboration of abnormal, thick, tenacious mucus resulting in obstructive disease in sites such as the lung and pancreas.

Children who survive infancy show stunned growth and suffer  predominantly from bronchopulmonary infections, which account for most of the morbidity.

Even with modern antibiotic therapy, the average life expectancy for girls is 12 years and for boys 16 years.

Epididymal obstruction in males causes sterility.

Staphylococcus aureus and a mucoid form of Pseudomonas aeruginosa are the most common pathogens.

Renal manifestations include nephrolithiasis, as well as secondary renal complications such as interstitial nephritis due to antibiotic therapy and amyloidosis.

 

Further reading:

Cystic fibrosis.

New horizons in the treatment of cystic fibrosis.

Cystic fibrosis: pathogenesis and future treatment strategies.

Cystic fibrosis: review of the decade.

Gene therapy for cystic fibrosis.

Estrogen and the cystic fibrosis gender gap.

Cystic fibrosis involving the cervix, mimicking a well-differentiated adenocarcinoma: a case report.

Plasma zinc in adults with cystic fibrosis: correlations with clinical outcomes.

Fungal infections and treatment in cystic fibrosis.

Intestinal complications of cystic fibrosis.

Moving forward: cystic fibrosis gene therapy.

 

 

 

 

Dr Sampurna Roy  MD

Consultant  Histopathologist (Kolkata - India)


 

 

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