Cystic Fibrosis Flashcards
KNOW What are the major pathogens in cystic fibrosis
KNOW the major pathogens are pseudomonas and staph
CF Etiology
Most common genetic disease in Canada
Treatable but not curable
Caucasians are most often affected
Most cases of cystic fibrosis will be confirmed before age 1
The median life expectancy is 31 years
But some people will live beyond 50 years of age
Death will usually be cause by pulmonary complications
CF and Genetics
Cystic fibrosis is a genetic disease that is caused by mutations in a pair of genes that are located on chromosome 7
Normally, every cell in the body has 46 chromosomes with 23 pairs (½ inherited from father and ½ inherited from mother)
More than 700 different cystic fibrosis mutations have been identified on chromosome 7
The most common mutation is ΔF508
These mutated genes will be responsible for the production of a protein known as cystic fibrosis transmembrane regulator (CFTR)
CFTR is the reason for thick secretions, which can clog ducts and glands
What does mutations to the function of CFTR do
- The absence, abnormal production, or function of the CFTR leads to abnormal electrolyte and water movement in and out of epithelial cells, including those lining the:
- Bronchial airways
- Intestines
- Pancreas
- Gall stones
- Liver ducts
- Sweat glands
- Vas deferens-Can affect fertility in both males and females, but primarily in males and uncommon to see in females
- The abnormality in CFTR results in thick mucus accumulates and blocks
- Bronchial airways
- Passageways of pancreas etc.
- This condition inhibits the digestion of protein and fat
- The inhibition of digestion leads to a deficiency of vitamins: — A, D, E, K
- Diarrhea, malnutrition, and weight loss also are common
- Meconium ileus develops in some infants
- Meconium ileus: bowel obstruction that often leads to perforation (meconium peritonitis)
If both parents carry the cystic fibrosis gene, what is the possibility of their child have CF
If both parents carry the cystic fibrosis gene, the possibility of their children having cystic fibrosis follows the standard Mendelian pattern
25 % chance of having disease if both parents are carriers of recessive gene (25% no disease, 50% carrier)
1 in 25 carry CF gene
Anatomical Alterations
- Excessive mucus production and accumulation of thick, tenacious mucus in the trachea-bronchial tree
Thick secretions are the hallmark of this disease
Partial or total bronchial obstruction (mucus plugging)
Atelectasis
Hyperinflation of alveoli
Gastro-Intestinal Complications of CF
- Failure to thrive
- Foul spelling greasy stool
- Voracious appetite
- Milk and formula intolerance
- Rectal prolapse
- Meconium ileua
- Meconium peritonitis
- Bowel Perforation
- Distal intestinal obstruction syndrome
- Pancreatic insufficiency
- Pancreatitis
HEPATOBILIARY
Hepatomegaly
Focal Biliary Cirrhosis
Prolonged Neonatal Jaundice
Cholelithiasis (Gall Stones)
NUTRITIONAL DEFICITS
Fat-Soluble vitamin deficiency (vitamins A, D, E, K)
Hypoproteinemia
Hypochloremia
Metabolic acidosis
INFERTILITY
Will be in males only
Obstructive azoospermia
Diagnosis of CFT
There needs to be a labatory finding confirmed as well as a confirmed componenet of family history or clinical manifestation
Labartory Findings
There needs to be a confirmed labartory finding from below as well as a clinical manifestation
-
Sweet Chloride Level
- >60 mEq/L in children
- Sweat chloride most common
-
Two CFTR mutations
- Elevated levels of serum trypsinogen Abnormal difference in voltage potential reflects CFT
- Abnormal differences in voltage potential across the nasal epithelium
Cardiopulmonary Clinical Manifestations
- The clinical manifestations results from the pathophysiologic mechanisms caused/activated by
- Atelectasis
- Bronchospasm
- Excessive Bronchial Secretions
- The major anatomic alterations of the lungs associated with cystic fibrosis
- It is like patients have pneumonia all the time
- There are a lot of preventative measures in regards to infection and atelectasis
Clinical Bedside Data
- Increased RR, HR, CO, BP
- Use of accessory muscles of inspiration and expiration
- Pursed-lip breathing
- Increased anteroposterior chest diameter (barrel chest)
- Cyanosis
- Digital clubbing
- Peripheral edema and venous distention
- Distended neck veins
- Pitting edema
- Enlarged and tender liver
- Cough, sputum production, hemoptysis
Chest assessment findings
- Decreased or increased tactile and vocal fremitus
- Hyperresonant percussion note
- Diminished breath sounds
- Diminished heart sounds
- Crackles/rhonchi/wheezing
- Spontaneous pneumothorax
- Tactile and vocal fremitus
- Increased due to consolidation, secretions
- Decreased due to air trapping
Common Non-respiratory Clinical Manifestations
- Meconium ileus
- Meconium peritonitis
- Malnutrition and poor body development
- Deficiencies of vitamins A, D, E, and K
- Nasal polyps and sinusitis
- Infertility (males)
Sweat Chloride Test
Normal amount of sweat produced
Glands microscopically normal but secrete up to four times normal amount NaCl
Test used to measure electrolyte concentration of sweat
Stimulation of sweat production over forearm by applying sweat stimulating solution and placing electrode on it to induce current
~0.1 ml of sweat collected on absorbent gauze or filter paper (by squeezing it) and tested for chlorine concentration
Concentration > 60 mEq/L in children diagnostic of CF
Concentration > 80 mEq/L in adults diagnostic of CF
Blood Test
Complete blood count (CBC)
Elevated hemoglobin concentration and hematocrit
Increased white cells with superimposed infections
Radiologic Findings
Translucent (dark) lung fields
Depressed or flattened diaphragms
Right ventricular enlargement
Areas of atelectasis and fibrosis
Pneumothorax (spontaneous)
Abscess formation (occasionally)
Cor pulmonale
Air trapping
Constant infection
General Management
- Patient and family education
- PFTs
- Monitor FEV1
Respiratory Care Treatment Protocols
- Oxygen therapy protocol
- Home O2
- Bronchopulmonary hygiene therapy protocol
- Hyperinflation therapy protocol
- Aerosolized medication protocol
- Bronchodilators, mucolytics
- Mechanical ventilation protocol
- Mechanical vent only seen post-op, prep for transplant, end stage, or poorly
Treatment-Pharm to Mobilize Secretions
- Mucolytics, expectorants, aerosols, humidity to mobilize secretions
- Pulmozyme and amiloride
- Inhaled hypertonic saline also commonly used
- Used with small vol nebs
- Makes secretions less thick, easier to cough up
Treatment-Bronchoscopy
Either diagnostic or for bronch hygiene to suction
Treatment-Pharm
Bronchodilators, anti-inflammatory agents, xanthines
Antibotics
Oral quinolones, inhaled gentamicin or tobramycin
Treatment-Lifestyle
Diet changes-Pancreatic enzyme replacement, replacement of body salts, Vitamins A, D, K, E
Antibiotics
Treatment Mediated Gene Transfer
Mediated Gene transfer
Insert normal gene into cells of CF patient via virus
Reverse the electrolyte defect
RT are often involved
outpatients
Treatment- Transplants
Transplantation to increase life span
Liver and lung treansplants are commonly done
Bilateral lung transplants
Living lung transplant
Treatment-Chest Physical Therapy
- Postural drainage
- Cough assist techniques
- Airway oscillators
- A device which will transmit vibrations through the airways through intermittent positive expiratory pressure
- There are also MIE machines which provide and negative pressure to move secretions
- Important for these pts
- Help expectorate sputum
- Percussions and vibrations to get secretions moving
Prognosis of Cystic Fibrosis
Eventually overwhelmed by pulmonary secretions, infections and resulting patho-physiological changes in lung.
Require supplemental oxygen
Ventilation due to respiratory failure
Life expectancy 25 – 30 years
Lung transplant will increase life span 10 – 20 years
What is CF
It is a hereditary disease characterized by lung congestion and infection along with malabsorption of nutrients by the pancreas.
A multifaceted disease caused by genetically defective chloride ions in the apical surface of the epithelial lining resulting in impaired chloride-flow across membranes through the cystic fibrosis conductance regulator (CFTR) channel.
What happens in cystic fibrosis?
Mucus clogs the lungs leading to chronic respiratory infections and mucus obstructs the ducts of the pancreas preventing digestive enzymes from reaching the intestines.
What system is cystic fibrosis a dysfunction of?
The exocrine system.
What causes the thick secretions in cystic fibrosis?
The disruption of the chloride transport causes the thick secretions in cystic fibrosis. Sodium is absorbed in the airways, pancreas, and bile ducts.
What would the x-ray look like for patients with cystic fibrosis?
Translucencies, enlarged heart, and a flattened diaphragm.
How is cystic fibrosis diagnosed?
Sweat chloride test is performed to screen for cystic fibrosis.
What two infections do we mainly see present in cystic fibrosis?
Staphylococcus Aureus and Pseudomonas.
. What common respiratory issues does a cystic fibrosis patient have?
Atelectasis, bronchial hyperreactive, asthma, hemoptysis, pneumothorax, pulmonary hypertension, respiratory failure, sleep breathing problems and symptomatic rhinosinusitis.
Aside from respiratory issues, what other clinical condition does a cystic fibrosis patient have?
Anemia, appendicitis and cystic fibrosis-related diabetes (CFRD) due to the scarring of the pancreas. Studies show that 75% of adult suffering from cystic fibrosis has a gallbladder disease, gastroesophageal reflux disease (GERD), malnutrition, growth failure, infertility, pancreatitis and meconium ileus.
How many positive results should one have to be diagnosed as suffering from cystic fibrosis?
Two positive results.
What are the common signs and symptoms of cystic fibrosis?
Salty sweat, residue on skin and/or clothes, abdominal distention and cramping, fatty stools and malnutrition even with ravenous appetite (FTT). Pulmonary indications include advanced chronic obstructive pulmonary disease (COPD), hypercapnia and severe hypoxemia when the disease is very advanced.
How can you manage patients with cystic fibrosis?
Most patients suffering from cystic fibrosis are treated with pulmozyme, sympathomimetics, percussion and postural drainage (P&PD).
In addition, positive expiratory pressure (PEP), flutter, vest therapy, hypertonic saline and xanthines must also be considered an important option in managing this disease.
Another way to bronchial dilate is to take steroids and ibuprofen that reduces fifty percent of forced expiratory volume in the first second (FEV1).
What is the prognosis for cystic fibrosis patients?
The disease has no cure but can be managed. According to a study conducted in 2017, the life expectancy of a person suffering from this condition is 37.5 years compared to 32 years in 2000 and 36.5 years in 2009. This shows that treatment and management for this disease continue to develop effectively.
What deficiencies does cystic fibrosis involve?
Nutritional deficiencies.
What is the typical arterial blood gas (ABG)’s for a patient with cystic fibrosis?
A mixed of respiratory acidosis and metabolic alkalosis is the typical ABG of cystic fibrosis.
What kind of disease is cystic fibrosis?
It is an inherited obstructive disease.
Where can you find the defective gene for cystic fibrosis?
It is found on Chromosome 7.
What is the major pathologic structure associated with cystic fibrosis?
The major pathologic structure of this disease is hyperinflation, thick tenacious mucus and airways obstruction leading to atelectasis.
What common indication of a person with cystic fibrosis?
They present as malnourished, with excessive secretions, and suffering from meconium ileus (bowel obstruction).
What are the chances that a child will be a carrier of cystic fibrosis gene if both mother and father are carriers?
There is a 50% chance that the child will be a carrier.
What condition do patients with cystic fibrosis have on their fingers and toes?
Clubbing of the fingers and toes are present on patients with cystic fibrosis.
Clubbing is the result of chronically low oxygen levels
What is the median age of survival of the people with cystic fibrosis?
37 years.
What test is used to diagnose cystic fibrosis?
An elevated sweat chloride test is performed to diagnose cystic fibrosis.
What are the four commonly used therapies in the management of cystic fibrosis?
Oral enzymes and vitamins, Antibiotics, Postural drainage, Expectorants.
What medications are used to treat cystic fibrosis?
Short-acting beta-agonists, hypertonic saline, Vest/flutter/etc, Pulmozyme (not to be mixed) TOBI (always given last).
Lung infections with Pseudomonas aeruginosa are most often treated with this antibiotic. What is the name of this antibiotic?
Tobramycin (TOBI)
A cystic fibrosis patient in generally good condition may be a candidate for what surgical procedure?
Lung Transplant
What is the percussion note of the cystic fibrosis patient?
Hyper-resonant percussion note.
What are typical breath sounds of cystic fibrosis patient?
Rales (crackles)
Vocal and tactile fremitus is related to trapped air. Trapped air causes tactile and vocal fremitus to be?
Decreased
What is a common non-respiratory clinical manifestation of cystic fibrosis?
Sinusitis.
What supplementary vitamins does cystic fibrosis patient must have?
A, E, D, and K.
The Respiratory Therapist may aerosolize and administer drugs that helps thin secretions. What are the two drug options that can be used?
DNAse or Pulmozyme.
What protein is responsible for cystic fibrosis?
Cystic Fibrosis transmembrane conductance regulator protein
What are the side effects of oral corticosteroids, a steroid used among children with persistent severe asthma?
Glucose intolerance should be monitored as it may lead to overt cystic fibrosis-related diabetes. Growth failure and hypertension are other side effects of this.
What are the two linked clinical manifestations of cystic fibrosis?
Meconium Ileus and distal intestinal obstructive syndrome.
What lung and upper respiratory tract diseases are associated with cystic fibrosis?
A person suffering from cystic fibrosis will show persistent bacterial infection that occurs from failure of lung defense mechanisms.
They will also experience intense inflammation.
Airway destruction specifically bronchiectasis and bronchiolectasis will also be present. They will also suffer from mucus plugged airways, goblet cell hyperplasia and their cilia function will be disrupted.
What gene is responsible for the cystic fibrosis transmembrane conductance regulator (CFTR) protein (channel)?
Cystic fibrosis transmembrane conductance regulator (CFTR) gene.
What is the most common amino acid that is deleted from the channel protein in cystic fibrosis?
Phenylalanine changes the structure of the CFTR (cystic fibrosis transmembrane conductance regulator) protein (channel) in a way that it can no longer transport chloride.
What is the result of impaired Cl (chloride) – flow due to the defective chloride ions and their ability to flow across membranes?
Disordered secretion and reabsorption resulting in higher than normal chloride levels in sweat and thicker than normal mucus in respiratory tract, gastrointestinal tract, pancreatic ducts, bile ducts and reproductive tract.
What cellular mechanism takes place within the sweat glands of cystic fibrosis patients?
There is an inhibited chloride reabsorption that results in inhibited sodium reabsorption which makes sweat saltier than normal.
Why does a patient with cystic fibrosis have saltier sweat?
Sweat is usually mostly water, as chloride and sodium ions are normally reabsorbed. Human haveno water pumps, therefore water is released from the body as it follows the chloride and sodium ions, entering the duct of the sweat gland, making sweat start out as an isotonic saline solution. The CFTR (cystic fibrosis transmembrane conductance regulator) channel is involved in the reabsorption of those chloride ions, causing the sodium ions to follow and be reabsorbed as well. However, in an individual with cystic fibrosis, the CFTR channel no longer works properly. It inhibits the chloride and sodium ions from being reabsorbed, and therefore causing them to be released in sweat that makes it saltier.
What is the typical body osmolarity?
Around 300 mosm/L = 150 mmol/L
How would you explain the “low-volume” model as a result of cystic fibrosis?
In the “low-volume” model, the chloride channel is involved in chloride outflow into the mucus that somewhat traps the sodium and water, retaining its fluidity. Normally, a significant amount of chloride remains in the mucus, causing sodium and water to remain in the mucus. In the cystic fibrosis patient, there are not enough chloride outflows into the mucus. This results in less negative charge that is capable of keeping the sodium and water in the mucus, thus, causing the mucus to thicken and lose its fluidity.
What two organs are greatly affected by the thickened mucus in cystic fibrosis patients?
Lungs and pancreas.
What happens in the lungs as a result of thickened mucus?
Bronchiectasis is a result of thickened mucus that stays in the bronchioles and physically pushes them open, distending them and causing them to widen. The result is permanent and eventually leads to fibrosis of these bronchioles. Pulmonary infections isalso a result of thickened mucus that remains in the lungs instead of moving up and out, causing a breeding ground for infectious bacteria like pseudomonas, staphylococcus, and haemophilusfamilies.
How does mucous affect cilia?
Flattens the cilia
How are lungs affected by cystic fibrosis?
Decreased chloride secretion from epithelial lining cells in the airway lumen cause thinning of liquid lining surface of the airway leading to impaired mucociliary clearance. This leads to chronic infections, bronchiectasis, bronchiolectasis, bronchial stenosis, fibrosis, and mucous plugging.
How is cystic fibrosis manifested in the lungs? How does it progress as the patient get older? What is the primary pathogen with cystic fibrosis?
Cystic fibrosis is manifested in lungs as acute exacerbations that include cough, dyspnea, decreased exercise tolerance, fatigue, and increased sputum production. This leads to accelerated permanent loss of lung function.
Pulmonary function is often preserved until adolescence. A steep decline can occur at this point. By late adolescence, most patients have a daily productive cough.
Airway infection with pseudomonas aeruginosa is the primary pathogen. Staphylococcus aureus and methicillin resistant Staph aureus are also common. Other lung pathogens include allergic bronchopulmonary mycoses, and nontuberculous mycobacterial infections.
How are sinuses affected by cystic fibrosis?
Nasal and sinus polyps
How is cystic fibrosis manifested in sinuses?
Pan-sinusitis and nasal polyposis
How is cystic fibrosis diagnosed?
If newborn screening is positive, a cystic fibrosis genetic panel is done followed by a sweat chloride test and a complete CFTR exon sequencing.
nasal electrical potential difference
What mucolytic agents are given for cystic fibrosis?
Dornase alfa (Pulmozyme) and hypertonic saline.
How does Pulmozyme work?
It breaks down extracellular DNA, decreased mucus viscosity and increased expectoration of mucus.
Which antibiotics are used to treat cystic fibrosis?
Tobramycin (TOBI), aztreonam (Cayston) and colistemethate (Colistin).
How is tobramycin taken?
300 mg BID for 28 days.
When are tobramycin levels checked?
Two and ten hours after infusion. Peak concentration is 20-30 mcg/mL.
What is the pathophysiology of cystic fibrosis?
Mutation in chloride transport leading to thick secretions from the exocrine glands and blockage of secretory ducts.
What are the clinical features of cystic fibrosis?
Severe lung disease, pancreatic insufficiency diabetes, azoospermia, chronic lung infections, usually presents in childhood as failure to thrive/malnutrition and chronic lung infections
What results of sweat chloride test indicate cystic fibrosis?
Increased concentrations of NaCl (sodium chloride) and K (potassium) in the sweat.
What will be the result of the PFT (pulmonary function test) in cystic fibrosis?
Decreased airways leading to airflow obstruction.
What can be observed in the chest x-ray of a person suffering from cystic fibrosis?
Hyperinflation and increased pulmonary markings.
What ABG results are seen in severe cystic fibrosis?
Hypoxemia and hypercapnia.
What methods are generally used to manage cystic fibrosis?
Chest physiotherapy for secretion drainage, pancreatic enzyme replacement, administration of salbutamol and ipratropium bromide, inhalation of hypertonic saline or DNAsa, and antibiotics for infectious exacerbations.
What is the gold standard management treatment for cystic fibrosis?
Lung Transplant
What are the characteristics of cystic fibrosis?
Chronic obstruction and infection of airways
Exocrine pancreatic insufficiency (maldigestion and small bowel obstruction) elevated sweat chloride concentrations
On physical examination there is a adolescent patient exhibiting malnourishment with poor body development, clubbing, hyperresonance, and a productive cough. The patient is also having foul smelling stools. These findings are suggestive of
- Acute bronchitis
- Cystic fibrosis
- Heart failure
- ARDS
Cystic fibrosis
