What Is the Connection Between Cystic Fibrosis and Pseudomonas?

Cystic fibrosis (CF for short) is the most common somatic recessive genetic disease in Western whites. Due to a defect in the CFTR (cystic fibrosis transmembrane conductance regulator) gene on the long arms of the seventh pair of chromosomes, the patient caused abnormal function of the exocrine glands such as the respiratory tract, pancreas, gastrointestinal tract, and sweat glands.

Cystic fibrosis

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Cystic fibrosis (CF for short) is the most common somatic recessive genetic disease in Western whites. Due to a defect in the CFTR (cystic fibrosis transmembrane conductance regulator) gene on the long arms of the seventh pair of chromosomes, the patient caused respiratory tract, pancreas, gastrointestinal tract,

The incidence varies by race. In the United States, cause accounts for 5% of the total population. Among them, the incidence rate of white people of Nordic origin is 1 / 3,200, and the cause rate is about 1 / 20-25. Other races are lower. Hispanics are 1 / 9,200, African Americans are 1 / 15,000, and Asians are the rarest, about 1 / 31,000. CF is an autosomal recessive inheritance, with 3% of gene carriers in whites. Related genes are located on 250,000 base pairs of genomic DNA on chromosome 7q (long arm). It encodes a membrane-associated protein called cystic fibrosis Transmembrane regulatory element (CFTR). The most common genetic mutation, F508, results in the deletion of the phenylalanine residue at position 508 of the CFTR protein and occurs in about 70% of alleles; another 30% has 600 CFTR functions are not yet clear, but it is clearly part of the cAMP-regulated chloride channel and regulates the transport of chloride and sodium across cell membranes. Heterozygotes have no abnormal clinical symptoms, but there are epithelial cell membranes Mild abnormalities in transport. Patients with congenital bilateral vas deferens, or obstructive azoospermia due to other causes, increased chance of mutations in one or two CFTR genes, or an incomplete spot at a non-coding site of CFTR Mutation (5T). These patients generally have no evidence of respiratory or pancreatic disease, and sweat chloride concentrations are normal, marginal, or elevated.

Almost all patients' exocrine glands are affected, but their distribution and severity vary greatly. The affected glands can be divided into three types: the glands are blocked by a thick and solid eosinophilic substance in the lumen (such as Pancreas, small intestine gland, intrahepatic bile duct, gallbladder, submandibular gland); glands that are normal in histology but produce excessive secretions, such as tracheobronchial and duodenal glands; normal in histology but secrete excessive sodium and chloride ions Glands (sweat glands, parotid glands, small salivary glands). Duodenal secretions are thick and contain abnormal mucopolysaccharides. 98% of adult male patients have infertility due to poorly developed vas deferens or other forms of obstructive azoospermia ; Adult female patients due to thick cervical secretions and reduced fertility, but many women with cystic fibrosis can still conceive to childbirth, but the incidence of maternal complications is high. There is evidence that the lungs of the child at birth The tissue structure is normal. In the future, the lungs are damaged due to the thick viscous secretions that widely block the small airways. Obstruction and infection are secondary to bronchiolitis and mucopurulent emboli obstructing the airways. Bronchial changes More common than lung parenchyma. Emphysema is not prominent. As the lung disease progresses, the bronchial wall thickens, the airway is filled with purulent, sticky secretions, enlarged atelectasis area, and hilar lymphadenopathy Chronic hypoxemia leads to pulmonary hypertrophy, pulmonary hypertension, and right ventricular hypertrophy. Many lung damage may be caused by immune-mediated inflammatory reactions secondary to the release of proteases by neutrophils in the respiratory tract. Even in early birth The tracheal alveolar lavage fluid contains a large number of neutrophils; the concentration of free neutral elastase, DNA and cytokine 8 increased. In the early stage of the disease, the most common pathogenic bacteria isolated from the airway was Staphylococcus aureus, but As the disease progresses, the most isolated is Pseudomonas. The mucus-like variant of Pseudomonas is the only pathogen associated with cystic fibrosis. The colonization of Pseudomonas onion occurs in more than 7% of adult patients And it is often related to the rapid deterioration of lung function.

Meconium-induced intestinal obstruction caused by sticky meconium may be the earliest sign (see Section 261 Gastrointestinal Defects) and occurs in 15% to 20% of neonates affected. It is often accompanied by bowel torsion, bowel perforation or Closure, with few exceptions, and other features of cystic fibrosis always follow. Cystic fibrosis can also be associated with delayed neonatal meconium excretion and meconium obstruction syndrome (a temporary terminal intestinal obstruction, caused by One or more concentrated meconium emboli is caused in the anus or colon).

In infants without meconium-induced intestinal obstruction, the onset of the disease is often signaled by a slow recovery of weight after birth and insufficient weight gain within 4 to 6 weeks after birth.

Infants with cystic fibrosis due to protein malabsorption, even if fed with soy protein formula or breast milk, the child will still develop hypoproteinemia secondary to edema and anemia.

Pulmonary involvement in 50% of patients, often with chronic cough and wheezing, associated with recurrent or chronic lung infections. Cough is the most disturbing symptom, often accompanied by sputum, nausea, vomiting, and disturbed sleep With the development of the disease, the auxiliary respiratory muscles participate in breathing exercises to produce inspiratory intercostal depressions, barrel chests, clubbing fingers (toes) and cyanosis. Injuries to the upper respiratory tract include nasal polyps and chronic recurrent sinusitis. Adolescence Patients may have stunted growth, delayed pubertal development, and decreased endurance of activity. Pulmonary complications in adolescent and adult patients include pneumothorax, hemoptysis, and right heart failure caused by pulmonary hypertension.

85% ~ 90% of the clinically affected children have pancreatic insufficiency, which usually appears early in life and then gradually worsens. Clinical manifestations include frequent stools, stench, oily stools, and swollen abdomen. Although the appetite is normal or vigorous, the growth and development are poor. Good, subcutaneous tissue and muscle tissue reduced. Rectal shedding occurred in 20% of untreated infants and toddlers. Clinical symptoms of fat-soluble vitamin deficiency can also be seen clinically.

Excessive sweating during hot days and fever can cause hypotonic dehydration and circulatory failure. In dry climates, babies can show chronic metabolic alkalosis, salt crystals and salty taste on the skin are obvious signs of cystic fibrosis .

10% of adult patients develop insulin-dependent diabetes mellitus, 4% to 5% of adolescent and adult patients develop nodular biliary cirrhosis with varicose veins and portal hypertension. Chronic and / or recurrent abdominal pain and intussusception, Peptic ulcers, abscesses around the appendix, pancreatitis, gastroesophageal reflux, esophagitis, gallbladder disease, or partial bowel obstruction caused by abnormally thick stools are related.

Inflammatory complications include vasculitis and arthritis.

The lungs and digestive tract are the main affected organs. Viscous secretions block the bronchi and secondary infections are the main pathological basis of the respiratory system. At the time of birth, the patient found no pathological changes in the airways, bronchial gland hypertrophy and goblet cells degeneration in the early stages of onset. Later, the mucous glands of the bronchus secreted viscous secretions, which inhibited the mucous epithelium cilia and blocked mucus drainage. Bronchial obstruction causes atelectasis and secondary infections; repeated attacks produce extensive bronchitis, pneumonia, bronchiectasis, bronchiectasis, lung abscesses, and gradually cause extensive fibrosis and obstructive emphysema in the lungs. On the basis of the above pathology, obstructive and restrictive mixed respiratory damage is caused, which is manifested by insufficient pulmonary ventilation, uneven distribution of inhaled gas, imbalance of ventilation and blood flow, and diffuse dysfunction, and symptoms of hypoxia and carbon dioxide retention, and finally lead to Respiratory failure; at the same time, pulmonary circulation resistance increases, causing pulmonary hypertension and pulmonary heart disease. Nasal polyps and chronic sinusitis are also common complications. The viscous secretions blocked the pancreatic exocrine ducts, and the pancreatic ducts expanded and the acinus expanded to form cysts in the early stage, followed by extensive fibrosis with cell infiltration and atrophy, which caused diabetes. The outer pancreatic duct is blocked, and the secretion of pancreatic enzymes including trypsin, lipase, and amylase is insufficient or lacking, leading to digestion, especially fat malabsorption.

The small bile ducts in the liver are blocked by mucus, causing multilobular cirrhosis, portal hypertension, and liver damage, and may be accompanied by hypersplenism. Biliary obstruction can cause jaundice. Bile deficiency has adverse effects on fat digestion, absorption of fat-soluble vitamins, digestion of pancreatic and intestinal fluids, and intestinal motility. Mucus can exfoliate the intestinal epithelium and damage the structure. Meconium obstruction at the end of the ileum in newborns is a common early manifestation. The content of sodium chloride in sweat glands was significantly increased. Fibrosis of the vas deferens obstructs fertility. Female fertility decline.

Cystic fibrosis (CF) is a genetic disease that invades multiple organs. Mainly manifested as dysfunction of exocrine glands, hyperplasia of mucus glands, viscous secretions, and increased sodium chloride content in sweat. Clinically, there are a series of symptoms caused by viscous secretions in the glands of the lungs, airways, pancreas, intestines, biliary tract, vas deferens, cervix, etc., with respiratory damage being the most prominent.

The respiratory system is mainly manifested by repeated bronchial infections and airway obstruction symptoms. Symptoms can appear within a few days after birth. There may be mild cough in the early stage, accompanied by pneumonia, coughing after atelectasis, sticky sputum is not easy to cough, and shortness of breath. If the patient coughs up a lot of purulent sputum or is accompanied by hemoptysis, it may indicate bronchiectasis and lung abscess. On physical examination, clubbing fingers (toes) are common. Lung infections are mostly caused by S. aureus, Pseudomonas aeruginosa, or other Gram-negative bacteria. After extensive fibrosis and emphysema occur in the lungs, there are wheezing, shortness of breath after activity, and often accompanied by spontaneous pneumothorax or mediastinal emphysema. When symptoms of hypoxia and carbon dioxide retention occur, shortness of breath worsens, cyanosis, and finally causes respiratory failure and pulmonary heart disease.

About 10% of newborns have intestinal obstruction and rectal prolapse due to increased mucus secretion and viscosity, and protein digestion due to lack of pancreatic enzymes. Insufficient secretion of the pancreas results in dyspepsia such as abdominal distension, abdominal bulge, discharge of a large amount of foamy stench, and even fatty diarrhea and azotorrhea. Vitamin deficiency, especially vitamin A deficiency, can cause dry eye disease. Although the sick child has a strong appetite and an adequate diet, he still suffers from malnutrition and stunted growth. Biliary obstruction can occur with jaundice, and concurrent liver cirrhosis can occur with portal hypertension and hypersplenism. If a baby sweats too much, he loses a lot of electrolytes and water, which can easily lead to collapse.

Different stages of disease can be seen on the X-ray as a ring-shaped, small piece of fuzzy inflammation that deepens or scatters the bronchial texture of the two lungs. It can also show signs of limited atrophy (atelectasis), bronchiectasis, lung abscess, and pulmonary heart disease.

Increased sodium chloride content in sweat is characteristic of this disease. Normal children's sweat contains 30-40 mmol / L of chloride and 60 mmol / L of sodium. The content of chloride in the sweat of sick children can be as high as 105 125mmol / L, and the sodium content is 120mmol / L. If the content of chloride in sweat is higher than 60mmol / L (more than 70mmol / L in adults) and sodium is higher than 80mmol / L, and adrenal insufficiency can be ruled out, it has important diagnostic significance. 0.2% pilocarpine nitrate electrophoretic penetration method can be used to stimulate skin sweating to determine electrolytes. However, the content of sodium chloride in the sweat of normal adults can exceed the above range, and it is not suitable to perform a sweat test. Duodenal fluid can be taken for examination. If the viscosity is increased, and various trypsin, especially trypsin, is reduced or lacking, that is Diagnose based on. Others, such as rectal mucosal biopsy, see that the glandular duct is full of mucus and expands to form a mucus layer; jejunal mucosal biopsy shows that intestinal mucosal villi are disappeared; 5-hydroxyindoleaceticacid in urine is increased, etc., are also useful for diagnosis.

There are many feasible treatments for the clinical manifestations and complications of cystic fibrosis. The main goals of treatment are to prevent infections, reduce the amount and viscosity of lung secretions, improve breathing, and maintain adequate nutrition. In order to achieve these goals, the treatment of cystic fibrosis includes: antibiotics: for lung infections in patients with cystic fibrosis, a new generation of antibiotics may be more effective, such as antibiotic sprays, which can deliver drugs directly to the airways to function . One of the biggest problems with long-term use of antibiotics is that the bacteria may develop resistance, which gradually makes the antibiotics ineffective. In addition, long-term use of antibiotics increases the risk of fungal infections in the mouth, throat, and respiratory tract. Mucus thinner: When white blood cells in your airway attack bacteria, the DNA in the cells is released, making the mucus in the airway more viscous. Alpha-chain enzyme spray is an enzyme that can degrade DNA, making the mucus thinner and easier to cough. Side effects of this medicine include the potential to irritate the airways and cause throat pain. Bronchodilators: Bronchodilators (such as salbutamol) can reach the site of action through an inhaler or spray to help maintain the opening of the bronchial tubes and clear the thick secretion fluid. Bronchial drainage: Patients with cystic fibrosis often need an artificial method to help clear mucus from the lungs. This can usually be assisted by patting the chest and back, that is, the patient chops on the edge of the bed with his head down, and then pats the back of the chest back and forth with his own hands or by others to help clear the secretion with the help of gravity. Patients can also use an electric tapping device to help tap, or use a high-frequency vibrating inflatable vest to help cough up secretions. Many adults and children with cystic fibrosis require bronchial drainage at least twice a day for 20-30 minutes each time. Older children and adults can learn to do this by themselves, using electronic aids such as inflatable vests or back-shots with high frequency vibration. Young children need help from parents or others. Oral digestive enzymes and strengthening nutrition: As cystic fibrosis prevents the pancreatic enzymes needed for digestion from reaching the digestive tract, hinders the digestion and absorption of food, and leads to malnutrition. Therefore, patients should supplement with high-energy nutrients and fat-soluble vitamins. And enteric-coated pancreatic enzymes, which can help you increase nutrition and even gain weight. Lung transplant: If you have serious breathing problems, life-threatening pulmonary complications, and antibiotics used to treat lung infections are failing, your doctor may recommend a lung transplant. Your suitability for this procedure depends on many factors, including your overall health, your specific lifestyle habits, and whether you have a donor organ that is right for you. Lung transplantation is a major surgery that can cause serious complications, especially postoperative infections. Analgesics: Ibuprofen may delay lung disease progression in some children with cystic fibrosis.

This disease affects multiple organs and exocrine glands, so the symptoms are quite variable and behave differently:

Intestinal tract is not resolved due to intestinal obstruction at birth (12%)

Intestinal obstruction

Loss of appetite

Slow growth

Flatulence, frequent abdominal pain or bloating

Gastrointestinal bleeding

Diarrhea, malabsorption

intussusception

Gastroesophageal reflux

bile duct

jaundice

Fatty liver (30-60%)

Pancreatic duct

Fat malabsorption

Deficiency of fat-soluble vitamins

Fatty stool

Adult patients may cause diabetes due to damaged pancreas (8-12%)

Respiratory tract

Recurrent respiratory infections

Chronic cough

Recurrent bronchitis or pneumonia

asthma

Sinusitis, nasal polyps

Sweat glands

The skin is salty due to sweat concentration

Males of the reproductive system may be infertile due to abnormal development of the vas deferens

Female secondary sexual dysplasia

other

Scoliosis