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CYSTIC FIBROSIS
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01.07.08 (6 months ago)
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CYSTIC FIBROSIS
What is the mode of inheritance of CF?
Cystic fibrosis (CF) is an autosomal-recessive disease, CFTR gene found on chromosome 7. Both parents are usually heterozygous, and the affected child may be homozygous (two copies of the same
Autosomal dominant inheritance is NOT seen in:
a). myotonic dystrophy
b). Von Willebrands disease
c). hypertrophic cardiomyopathy
d). Hemophilia A and cystic fibrosi***
Which population is more affected by CF?
CF is most common in white children, common in North American Caucasians of European ancestry.
In this population, the frequency of the disease is 1 in 2500 live births.
The carrier rate is approximately 1 in 25 individuals
The most common and the most lethal autosomal recessive disease in Caucasians (MCCEE)
Which population is less common affected by CF?
CF is far less common inn Hispanics and blacks.
What is the most common type of mutation in CF
Over 800 different mutations identified but ∆F508 mutation is more common.
1. It is present in about 70% of North American whites, is the most common.
2. In Europe, the incidence of this mutation ranges from 40 to 80% in different population groups.
What is the pathophysiology of CF?
Cystic Fibrosis is caused by a defect in the CFRT (Cystic Fibrosis Transmembrane Conductance Regulator) protein, which leads to impaired chloride transport in tissues.
It causes cells to be impermeable to Cl which increases the reabsorption of Na. This leads to relative dehydration of airway secretions, resulting in impaired mucociliary transport and airway obstruction. There is increased salt content in sweat gland secretions, as well as thick, viscous secretions in the lungs, pancreas, reproductive tract and liver.
1. The pulmonary manifestations are a persistent, reproductive cough, which progresses to obstructive airway disease.
CF is the most common cause of bronchiectasis in young adults (MCCEE)
Death from CF is usually due to respiratory failure (MCCEE)
Excessively mucoid exocrine secretions are associated with CF (MCCEE).
2. A deficiency of pancreatic enzymes leads to fat and protein malabsorption. This causes bulky, greasy, foul-smelling stool. Fat malabsorption also leads to deficiency of fat-soluble vitamins (A, D, E & K), which presents as:
Dry skin (Vitamin A) Serum carotene concentration is abnormal
Epistaxis (Vitamin K).
Failure to thrive is the result of chronic malabsorption from pancreatic insufficiency.
What are the clinical features of CF?
1. Neonatal
Meconium ileus (failure to pass a stool in the first 24 hours of live with small bowel obstruction) is most common presentation in infant.
Dilated small bowel filled with a granular-appearing material or tiny bubbles in patients with CF suggest meconium ileus (MCCEE)
95% of patient with meconium ileus have CF (MCCEE)
Prolonged jaundice
Antenatal bowel perforation
2. Infancy
90% of patients with CF have exocrine pancreatic insufficiency (MCCEE)
Pancreatic insufficiency with seborrhea and FTT (despite voracious appetitive)
CF is the most common cause of significant steatorrhea in North American children (MCCEE).
CF is the most common cause of chronic pancreatitis in children (MCCEE)
3. Childhood
Anemia, hypoproteinemia, hyponatremia
Heat intolerance
Wheezing or chronic cough
Recurrent chest infections (S. aureus, P. aeruginosa, H.influenzae)
Hemoptysis
Nasal polyps (associated with milder disease)
Distal interstitial obstruction syndrome, rectal prolapse
Clubbing of fingers
4. Older patients
COPD
Infertility male patients with CF are sterile (absence or obstruction of the vas deferens) in approximately >95% (MCCEE)
What is the classic triad of CF?
1. COPD
2. Pancreatic enzyme deficiency
3. Abnormal high concentration of sweat electrolytes
What is the most common presentation of newborns with CF?
GI obstruction due to meconium ileus
Cystic fibrosis is LEAST likely to be associated with:
a digital clubbing
b abnormal xylose absorption
c glomerulonephritis***
d nasal polyps
e gallstones/biliary cirrhosis
Symptoms of cystic fibrosis at birth include:
a). pneumothorax
b). prolonged jaundice***
c). both
d). neither
Symptoms of cystic fibrosis at birth include:
a). nasal polyps
b). meconium ileus***
c). both
d). neither
Neonates with CF are least likely to have:
a). nasal polyps***
b). meconium ileus
c). prolonged jaundice
d). antenatal bowel perforation
Cystic fibrosis NOT is associated with:
a). nasal polyps and sinusitis
b). hemoptysis, pneumothorax and azoospermia
c). cor pulmonale and clubbing of the fingers
d). increased risk of lymphoma and other malignant lymphoma***
A 2-year-old boy has a sudden-onset nosebleed, which has now subsided. He is also suffering from a reproductive cough and diarrhea that refuse to go. His stools are greasy and foul-smelling. His appetite is normal. Although his diet consists mainly of milk. The childs weight is at the 25th percentile. Other findings are dry skin and dried blood at the nasal turbinate. What is the most likely cause of his failure to thrive?
a). lactose intolerance
b). Parental neglect
c). Chronic parasitic infection
d). Constitutional growth delay
e). Deficiency of pancreatic enzymes
f). Inadequate dietary intake
Correct answer: C
CF presents with failure to thrive, which occurs due to a fat and protein malabsorption from a pancreatic insufficiency.
Lactose intolerance causes abdominal cramping, bloating and diarrhea after the intake of lactose-containing products; however, a productive cough is not a symptom.
How CF is diagnosed?
1. Sweat Chloride Test x 2 (>60 mEq/L)
2. Genetic study useful where sweat chloride test is equivocal
3. Pancreatic dysfunction determined by 3-day fecal fat collection
What result from the sweat test is considered positive for CF?
>60 mEq/L
In which diseases/conditions Sweat Chloride Test becomes False +Ve tests
1. Malnutrition
2. Adrenal insufficiency
3. Anorexia nervosa
4. Hypothyroidism
5. Nephrotic DI
6. Nephrotic syndrome
In which diseases/conditions Sweat Chloride Test becomes False -Ve tests
1. Peripheral edema, Cloxacillin, glycogen storage disease
2. Hypothyroidism
3. Atopic dermatitis
4. Klinefelter syndrome
5. Hypogammaglobulinemia
4. Pancreatic dysfunction determined by 3-day fecal fat collection
5. Genetic useful where sweat chloride test is equivocal
Sweat test in cystic fibrosis is positive when:
a sodium and chloride concentrations are both low
b sodium and chloride concentrations are both igh***
c sodium is low and chloride concentration is high
d sodium is high and chloride concentration is low
Neonatal diagnosis of cystic fibrosis is made by heel-prick spacement demonstration of low levels of immunoreactive:
a lipase
b trypsin***
c glucagon
d vasopressin
e somatostatin
Which of the following is normal in CF?
a). Sweat test
b). D-xylose test***
c). Serum carotene concentration
d). Qualititive measurement of fetal fat
A 6-year-old girl presents to you with a history of significant seborrhea and failure to thrive. As a neonate she had prolonged jaundice and an unusual number of respiratory tract infections. The child had a poor appetite and general malaise. On examination, she looks little underweight and has a runny nose. Auscultation reveals mild wheezing and diminished air entry in both lungs. Clubbing is visible on the both hands. You decide to make a diagnosis by obtaining:
a). Blood culture
b). Sputum cultures
c). CT abdomen
d). Sweat test
e). Liver function tests
Correct answer: D
In child with cystic fibrosis the sweat chloride test must be done. The sweat test must be repeated twice to avoid any false positives or negatives.
Genetic studies should also be done when the sweat test is equivocal and prenatal screening should be offered to high-risk families.
The treatment is:
1. A high caloric diet
2. Pancreatic enzyme replacements
3. Fat soluble vitamins
The current median survival is 30 years.
What is the treatment of CF?
1. Nutritional Counseling
High caloric diet
Pancreatic replacements
Fat soluble vitamin supplements
2. Management of chest disease
Physiotherapy, postural drainage
Exercise
Bronchodilators
Aerosolized DNAse
Antibiotics depends on sputum C&S (e.g. Cephalosporin, Cloxacillin, Ciprofloxacin, inhaled Tobramycin)
Lung transplantation
3. Genetic counseling is available
A 6-month old infant has large, foul-smelling stools and is not gaining weight. Chloride levels as 68 mmol/L. appropriate nutritional recommendations include:
a). Supplementation with water-soluble vitamins
b). Pancreatic enzyme replacement
c). High-fat diet
d). Low-protein diet
e). Low-carbohydrate diet
Correct answer: B
The goal in treatment of patients with CF is to supply enough calories to maintain normal growth.
Extra calories are needed
1. To replace those lost as a result of gastrointestinal losses,
2. To offset the catabolic and anorectic effects of respiratory infection
3. For catch-up growth.
Deficiency of pancreatic function
1. Almost 90% of patients have poor digestion of fat and protein as a result of the deficiency of pancreatic function, which may be partially corrected by oral pancreatic enzyme replacement; protein and fat losses are reduced, and patients are usually able to tolerate a reasonably normal diet.
2. The high caloric density of fat is useful in meeting the patients caloric needs. Supplementation with fat-soluble vitamins (A, D, E & K) is necessary.
3. With severe disease, feeding by nasogastric tube, percutaneous enterostomy, or IV nutrition can be necessary.
An 18-year-old female with cystic fibrosis is admitted with fever and increased sputum production. She returned home a week ago from a camp for cystic fibrosis patients and their families.
Which antibiotic should be started whilst sputum cultures are awaited?
a. vancomycin
b. aztreonam
c. clarithromycin
d. Ceftazidime***
e. tobramycin
Ceftazidime
Now 90% of children suffering from cystic fibrosis (CF) survive into their teens and the median survival age is now 40years. The major hazard facing CF patients is infection with Burkholderia cepacia previously known as pseudomonas cepacia. The DOC is 3rd generation cephalosporin Ceftazidime
Transmission is from person to person and multiple drug resistant is common. It has been found that groups set up to support patients with CF can be a common place for transmission to occur and patients known to be colonized with the organism need to be excluded from these groups. Likewise colonized patients must be segregated during in patient stays from other CF patients.
A cystic fibrosis patient has severe shortness of breath, cough and fever 39.40C (1030F). The patient is excessively using accessory muscles. Lung auscultation reveals lower lobe crackles and expiratory wheezing. Pulse oximetry shows SaO2 of 85% that improves to 92% after the oxygen. Which of the following antibiotics or their combination is the best choice for this patient?
a). IV ceftazidime and gentamicin
b). IV Vancomycin and gentamicin
c). IV imipenem/cilastatin
d). IV Clindamycin
e). Oral ciprofloxacin
Correct answer: A
Acute severe exacerbation in patients with cystic fibrosis is usually due to Pseudomonas aeruginosa and is treated with IV antibiotics, usually a combination of two drugs active against Pseudomonas aeruginosa, which is Ceftazidime (or penicillin derivatives like Ticarcillin) and an aminoglycoside (Amikacin or Gentamicin).
The other drugs that are effective against pseudomonas are cefepime and imipenem/cilastatin combination
Oral ciprofloxacin covers Pseudomonas aeruginosa, but is not appropriate for severe exacerbations when IV antibiotics are usually employed.
The new generation fluoroquinolones, such as levofloxacin and Gatifloxacin, do not have a good coverage against pseudomonas.
You are seeing an 8-year-old Caucasian boy, who was diagnosed with cystic fibrosis for the first time, as he has recently entered your insurance group. His other past medical history is significant for appendectomy at age 18-months. He has a history of severe, allergic reaction to eggs and ibuprofen. His family history is significant for cystic fibrosis. Which of the following statement is most accurate about this patient?
a). He should be given influenza vaccine only
b). He should receive Pneumococcal vaccine
c). He should receive both influenza and Pneumococcal vaccine
d). Do not give influenza but consider Pneumococcal vaccine
Correct answer: d)
Routine influenza vaccine is recommended in all patients with cystic fibrosis; but Pneumococcal vaccine is not routinely indicated because patients with cystic fibrosis only rarely become infected with streptococcal pneumoniae. However, since it is readily advisable and safe, many physicians considerer giving this vaccine to these patients.
Influenza vaccine and yellow fever vaccine can cause severe allergic reactions in patients with severe egg allergy. A test dose skin testing is recommended before administrating this vaccine in patients with egg allergy.
An egg allergy is also a relatively contraindication to MMR vaccine. However, recent studies have shown that allergic reaction against MMR are more due to gelatin content of the vaccine rather than the egg, and thus m many physicians recommend MMR vaccine even in patients with an egg allergy.
What are the complications of CF?
1. Respiratory failure
2. Pneumothorax (poor prognostic sin)
3. Cor pulmonale (late)
4. Pancreatic fibrosis with DM
5. Gallstones
6. Cirrhosis with portal hypertension
7. Infertility
8. Early death (current median survival is 30 years)
What is the prognosis of CF?
The outcome of patients with CF is highly variable. Some will die in infancy from complications of meconium ileus, whereas others will live beyond the age of 50.
Average age30 years
CF PANCREASE
Chronic cough and wheezing
Failure to thrive
Pancreatic insufficiency (symptoms of malabsorption like seborrhea)
Alkalosis and hypotonic dehydration
Neonatal intestinal obstruction (meconium ileus/Nasal polyps)
Clubbing of fingers/Chest radiograph with characteristic changes
Rectal prolapse
Electrolyte elevation in sweat, salty skin
Absence or congenital atresia of vas deferens
Sputum with Staph or Pseudomonas (mucoid)
A 7-year old girl had a persistent postnasal drip even during the summer months. She gets repeated episodes of a runny nose. The girl also snores and is unable to smell her favorite food. In the winters, he gets repeated URTI, which lasts for two-to-three weeks at a time. The child had all her immunizations. On examination, the girl is a little under weight for her age and has a runny nose. The nasal drainage is colorless and stringy. Nasal inspection reveals bilateral nasal polyps and auscultation reveals coarse rales in the chest. The condition that you would like to rule out in this child is:
a). Leukemia
b). Cystic fibrosis
c). Foreign body aspiration
d). Nasal septal deviation
e). Allergic rhinitis
Correct answer: B
In a young patient with recurrent URTI and bilateral nasal polyps, one has to rule out cystic fibrosis.
Nasal septal deviation may be developmental or traumatic. Individual may be asymptomatic or may present with
1. Unilateral nasal obstruction
2. Facial pain
3. Anosmia or may be
For asymptomatic individuals, no treatment is required. Nasal septal deviation does not lead to recurrent URTI.
Allergic rhinitis is characterized by an IgE mediated hypersensitivity to foreign allergens.
It may be acute or chronic and can be confused with recurrent cold. It may present with itchy eyes and tearing, swollen mucosa, headaches and nasal obstruction, if the age of onset in second decade of life. Diagnosis is by allergy testing and findings of eosinophilia in the nasal discharge.
Grams stain of the sputum of an 8-year old patient with cystic fibrosis shows gram negative rods. Which of the following organism is the most likely cause of pneumonia in this patient?
a). Legionella
b). Pseudomonas
c). Staphylococcus aureus
d). Streptococcus pneumonia
e). Klebsiella
Correct answer: B
Three most common organisms that cause pneumonia in patients with cystic fibrosis are:
1. Pseudomonas aeruginosa
2. Staphylococcus aureus
3. Haemophilus
Haemophilus & Pseudomonas are gram negative rods
Although Legionella and Klebsiella are gram negative rods they are not common organisms that cause pneumonia in cystic fibrosis patients.
CF & alpha1-anntitrypsin deficiency should be considered in the diagnostic evaluation of any child with obstructive jaundice.
Other causes of obstructive jaundice include:
1. ABO incompatibility
2. Choledochal cyst
3. Rh incompatibility
4. Gilbert disease
5. Crigler-Najjar syndrome
A 3-month-old child has been diagnosed by sweat chloride testing to have cystic fibrosis. The appropriate next step is?
a). Have all siblings assessed for cystic fibrosis with sweat chloride testing
b). Determine parental carrier state with DNA analysis for carrier state
c). Determine siblings carrier state with DNA analysis
d). Determine the couples carrier state by sweat chloride testing
e). Determine siblings carrier state with sweat chloride testing
Correct answer: C
Pancreatic insufficiency is present:
1. in 99% of patients who are homozygous for ∆F508
2. in 72% who are compound homozygous for ∆F508
3. in only 32% who do not carry the ∆F508 mutation.
DNA analysis for carrier testing is now recommended
1. for relatives of CF patients and
2. for reproductive parents of carrier.
Its role in mass population screening is controversial.
DNA testing is of value for postmortem investigations as well as in sick premature infants and other patients when sweat collection is unsuccessful.
The sweat test is diagnostic in virtually all cases of classic CF and is equally useful in all ethnic groups, but it is not useful in detecting heterozygote
A 25-year-old primigravida woman comes to the physician for her first prenatal visit. Her last menstrual period was 7 weeks ago. She has had some nausea and vomiting but otherwise has no complaints. Past medical and surgical history are unremarkable. Her family history is significant for cystic fibrosis with an affected aunt. Her husband has an affected cousin. Physical examination is unremarkable. Given her family history, she is concerned about the risks of having a child with cystic fibrosis. She inquires about cystic fibrosis screening. Which of the following is the appropriate response?
A. Screening is available
B. Screening is inappropriate in her case
C. Screening is mandatory
D. Screening is not available
E. Screening is unnecessary: she has a 1 in 4 chance of having an affected child
The correct answer is A
Kartageners syndrome is NOT characterized by:
a). polycystic kidney disease***
b). dextrocardia (sinus inversus)
c). nasal polyps and chronic sinusitis
d). bronchiectasis and infertility (nonmotile sperm)
Which of the following does NOT cause diarrhea?
a). hypercalcemia***
b). cystic fibrosis
c). metabolic alkalosis
d). milk protein sensitivity
DNA analysis from amniocentesis can NOT detect
a). cystic fibrosis
b). thalassemia
c). Tay Sachs disease***
d). sickle cell anemia
Risk factor for pancreatic cancer (90% duct cell adenocarcinoma) include all of the following, EXCEPT?
a). cystic fibrosis
b). diabetes mellitus***
c). Gardners syndrome
d). high fat and low fiber diet
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