Cystic Fibrosis Flashcards
What is the pathophysiology of cystic fibrosis?
Autosomal recessive mutation of CFTR gene on Chromosome 7 (usually 3bp deletion at 508 position)
Dysfunction in CFTR protein leads to defective chloride channels in epithelia of most bodily lumens (disrupts sodium and water balance) = decreased chloride secretion, increased sodium absorption, increased secretion viscosity
Affects GI, lungs, liver, reproductive system, bones and joints, and sweat glands
How does cystic fibrosis clinically present and how is it diagnosed?
Presentation: failure to thrive, recurrent pneumonia, uncontrolled asthma, nasal polyps, chronic sinusitis, meconium ileus, salty skin (abnormally high NaCl in sweat, and with excess sweating can lead to salt depletion)
Diagnosed majority before 2 years old:
Need 1+ characteristic signs/symptoms, CF in sibling, positive newborn screening (measures pancreatic enzyme precursor)
AND
CTFR abnormality evidence (elevated sweat chloride test x2 or known CFTR mutation)
*Sweat test = find concentration of chloride in sweat sample (positive if above 60 mmol/L)
*CFTR mutation found with chromosomal analysis
What are the problems that cystic fibrosis causes in the GI tract?
Pancreas clogged/insufficient (can diagnose with 72hr fecal fat collection) =
- Deficient digestive enzyme secretion leading to maldigestion (malnutrition and steatorrhea), fat-soluble vitamin deficiency, insulin deficiency
- Intestinal obstructions (meconium ileus or distal intestinal obstruction syndrome)
- Reflux
How are the GI problems caused by cystic fibrosis chronically managed?
Treat pancreatic enzyme deficiency (enzymes unavailable to small intestine) = pancreatic enzyme replacement i.e. Creon, Zenpep and Pancreaze to replace lipase, protease, and amylase
- Take enzyme replacement with meals or half dose with snacks
- ADR of enzyme replacement = nausea, diarrhea/constipation, cramps, greasy stool, farts… fibrosing colonopathy at high dose
- Manufacturing issue: bad enteric coating and acid resistance denatures enzymes, also possible poor outcome when switch between brand and generic enzymes (but FDA fixed this)
Treat malnutrition = high-calorie diet, nutritional supplement, fat-soluble vitamin replacement, extra salt
Treat Diabetes (increase risk with age, onset usually teens to adulthood) = use insulin and keep blood glucose 80-120 before meals, similar features of DM I and II
Treat GI Obstruction (distal intestinal obstruction syndrome with signs of vomiting, distention and pain) = electrolyte lavage solutions until stool passes and symptoms resolve
Treat GERD (trigger might be due to coughing and hyperinflation) = antacids, H2 blockers, proton-pump inhibitors
How does cystic fibrosis cause liver disease and how is this managed?
Causes chronic inflammatory infiltration, bile duct proliferation, biliary fibrosis
Diagnostics: Increased GGT can reflect liver damage even if other liver enzymes are normal
Treat with Ursodeoxycholate (to decrease liver inflammation and bile duct proliferation)
How does cystic fibrosis affect the lungs and what is the general goal of therapy?
Accumulation of viscous mucus in small airways = obstruction, inflammation, infection
Also may have also have chronic rhinitis, sinusitis, and nasal polyps
Main Goal = decrease long-term rate of lung function decline i.e. airway clearance techniques (ACT), anti-inflammatory agent, chronic antibiotics, mucolytics, bronchodilators
Specifically what are the techniques and drugs used for chronic pulmonary therapy for cystic fibrosis?
ACT = at least do BID to improve ventilation and reduce secretion accumulation (pre-treatment bronchodilator optional)
i.e. chest/back percussion with vigorous coughing, flutter valve, exercise, mechanical vest
Anti-inflammatory = best with NSAIDs i.e. Ibuprofen to decrease decline of FEV1… or Azithromycin to slow FEV1 decline and pulmonary exacerbations especially in patients with Pseudomonas
(using oral corticosteroids has undesirable side effects)
Mucolytics i.e. Pulmozyme to decrease sputum viscosity (AE include hoarseness, pharyngitis, and voice alteration)… or Mucomyst which is not really used (irritating and causes bronchoconstriction)
OR
instead can use nebulized hypertonic saline to draw water into airway to increase ability to cough out mucus (but may increase cough or lead to bronchospasm)
Bronchodilators i.e. inhaled B2-agonist with ICS (also useful if patient has asthma)
Chronic antibiotics = to prolong time between acute exacerbations, 28 days on and 28 days off i.e. TOBI (nebulized Tobramycin, against P. aeruginosa colonization)… or Cayston (nebulized Aztreonam against P. aeruginosa colonization
Immunization recommendations by CDC, also indicated for flu vaccine and S. pneumoniae (candidate to receive at younger age than 65, even though recommendation is above 65 for general population)
What are the major pathogens involved in lung disease due to cystic fibrosis? Is age a factor?
S. aureus = major usually under 1 year old
H. influenzae = major usually by age 3
Pseudomonas aeruginosa = major usually by age 5, colonized
Other pathogens include Bukholderia cepacia and Stenotrophomonas maltophilia
What is the effect of cystic fibrosis in males versus females?
Both have delayed puberty onset
99% males have congenital absence of vas deferens
Females may have less than normal fertility
What is the mechanism with which cystic fibrosis affects bones and joints?
Low bone mineral density from vitamin deficiency, decreased osteoblast with increased osteoclast activity (manage with calcium and vitamin D supplementation)
Arthritis possibly due to immune complexes formed from chronic pulmonary infection (manage with SHORT courses of NSAIDs or steroidal anti-inflammatory agents)
What are signs/symptoms of potential acute pulmonary exacerbation? How is this treated?
Signs/Symptoms = INCREASED cough frequency/duration, chest congestion, sputum production
DECREASED exercise tolerance, PFT, weight, oxygen saturation
Using accessory muscles to breathe and may/may not have fever
Main goal is to improve signs/symptoms (if culprit is P. aeruginosa, it is unlikely to be eradicated)
Also increase nutrition and ACT (airway clearance)
Treatment: Antibiotics oral or IV primarily to cover S. aureus, H.influenzae, and P aeruginosa (based on sensitivities)
i.e. Aminoglycoside with Antipseudomonal PCN (dose towards upper end range since CF patients have increased volume distribution and clearance)
What are some advanced treatment options for cystic fibrosis?
Lung transplant available after 10 years (only 50% 5-year survival after transplant)
There may be gene therapy in the future i.e. CFTR modulation to correct protein function or new VX-770 drug, both of which aim to CURE by addressing cause rather than just managing symptoms
What is the reason most patients with cystic fibrosis die?
Majority still die from respiratory failure (overall survival has improved over time though from symptomatic treatment)
Cystic fibrosis patient usually must be on a LOT of medications, typical regimen i.e.
Albuterol, Pulmozyme, Hypertonic Saline, ACT, Azythromycin
ADEK daily fat-soluble vitamin and multivitamin
Ursodeoxycholic acid (reduce liver inflammation and bile duct proliferation)
Ranitidine (reduce gastric acid)
Creon with meals
