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61 Cards in this Set
- Front
- Back
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What is the most common genetic mutation in CF patients?
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- deletion of PHE at base pair 508 on CFTR gene (F508) on chromosome 7
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Which portion of CFTR protein is defective with F508 mutation in CF?
- 12 transmembrane domain - NBD1 - NBD2 - regulatory domain |
Nucleoside binding domain 1 (NBD1)
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Which class of CFTR mutations?
- delta F508 mutation |
Class II: defective protein processing
- mutated sequence prevent the protein from trafficking to the correct cellular location. |
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Which class of CFTR mutations?
- nonsense, frameshift, splice-site mutations leading to premature termination of mRNA and complete absence of CFTR protein. |
Class I: defective protein production
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Which class of CFTR mutations?
- mutated sequence prevent the protein from trafficking to the correct cellular location. |
Class II: defective protein processing
- delta F508 |
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Which class of CFTR mutation is this?
- mutations led to diminished channel activity in response to ATP - many involves alterations of the NBD regions, and R domain. |
Class III: defective regulation
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Which class of CFTR mutation is this?
- the rate of chloride ion flow and the duration of channel opening are reduced - normal protein production and regulation |
Class IV: defective conduction
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In cystic fibrosis, what happens in the following locations?
- sweat glands - respiratory tract, GI tract, reproductive tract |
- sweat gland: salt secretion
- respiratory tract, GI tract, reproductive tract: water, salt absorption |
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What is the role of CFTR muation in increased infection in cystic fibrosis?
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promoting initial bacterial adhesion
- upregulating epithelial cell adhesion molecules for bacteria - decrease the production of innate host defense molecules, ie NO. |
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What kind of symptoms would you see if there is greater than 50% CFTR expression?
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none
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What kind of symptoms would you see if there is greater than 10% but less than 50% CFTR expression?
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- pancreatitis
- sinusitis - lung disease |
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What kind of symptoms would you see if there is 10% CFTR expression?
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CBAVD (congenital bilateral absence of vas deference)
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What kind of symptoms would you see if there is 5% CFTR expression?
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- sweat
- lung disease |
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What kind of symptoms would you see if there is 1% CFTR expression?
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pancreatic disease
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Name some common pathogens seen in CF.
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- H. influenza
- staph aureus - MRSA - pseudomonas species (aeruginosa, sternotrophomonas maltophilia, burkholderia cepaciae) - aspergilus fumigatus |
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What disease would you suspect when you see pseudomonas aeruginosa infection?
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- nosocomial infection
- CF |
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Where in the respiratory airway would you see bacterial infection in CF patients?
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lower airways
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What stage is this CF patient in?
- chronic bronchiectasis - clubbing |
more advanced stage
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The following are presentations of what disease?
- meconium ileus - hypochloremuc alkalosis (salt depletion) - bronchiectasis - pancreatitis - nasal polyps |
CF
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What is the gold standard test for CF?
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sweat chloride test
- quantitative pilocarpine (anticholinergic) iontophoresis - normally < 40mEq/L - borderline: 40-60 mEq/L - abnormal: > 60mEq/L |
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What test could be used for difficult diagnosis of CF?
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nasal potential difference
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What is the CF diagnostic criteria?
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- clinical phenotype and
- 2 positive sweat test or 2 CF mutations or abnormal nasal potential difference |
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What are some new born screening tools for CF?
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- IRT from heel blood spot: if elevated, sweat test
* all infants with maconium ileus should have a sweat test |
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Pathogenesis of pancreatic insufficiency in CF patients.
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- block of pancreatic duct
- prevention of pancreatic enzyme from entering the intestine - incomplete digestion of fats and proteins and fat-soluble vitamines |
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What are some nutritional interventions in CF?
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- pancreatic enzymes
- addition of high calorie foods and snacks - high calorie nutritional supplements - GI feeds |
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What is this disease associated with CF?
- concretions of eosinophilic material plugging the bile ducts - biliary proliferation - absence of marked bile stasis in the surrounding liver parenchyma |
biliary cirrhosis
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What are manifestations of liver diseases in CF patients?
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- focal biliary cirrhosis: elevated alkaline phosphatase, lobular hepatomegaly
- massive steatosis - obstructive jaundice in newborn - gallstones |
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What is the drug suggested by several obervational studies that arrest the progression of liver disease related to CF?
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ursodeoxtcholic acid
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What are some pulmonary management for CF patients?
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- evaluation of pulmonary status: spirometry
- airway clearance measures: chest physiotherapy(chest percussion and drainage), IPV, therapy vest, autogenic drainage - longterm preventative measures: inhaled antibiotics (tobramycin), anti-inflammation (ibuprofen, azithromycin), mucus thinning agent (pulmozyme), dornase sulfa - infection control measures - treatment for pulmonary exacerbation - treatment of pulmonary complications |
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What is the commonly used inhaled antibiotic for CF longterm therapy?
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- tobramycin
- aztreonam |
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What kinds of immunizations should CF patients receive?
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- influenza
- pneumococcus - RSV (palimizumab) |
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What is a typical drug for this infection in CF?
- s. aureus |
cefazolin
nafcilin |
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What is a typical drug for this infection in CF?
- MRSA |
vancomycin
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What is a typical drug for this infection in CF?
- p. aeruginosa |
beta-lactam(ceftazidime, or piperacillin...) + aminoglycoside (tobramycin or amikacin)
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When can home IV antibiotic therapy be applied to CF patients?
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If patient is responding in hospital setting for a few days and family is capable and willing.
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When is lung transplant indicated in CF patient?
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- if FEV1<30% predicted
- increase functional impairment - major life threatening complications (recurrent massive hemoptysis) |
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What does this kid have? Symptoms in the first hour after birth.
- tachypnea - grunting - flaring - retractions - hypoxia - cyanosis |
respiratory distress
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What is the difference between respiratory distress and RDS?
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respiratory distress:
- tachypnea, grunting, flaring, retractions, hypoxemia, cyanosis that arise from a number of underlying causes RDS - respiratory distress associated with prematurity and surfactant deficiency or abnormality. - also called "hyaline membrane disease"(HMD) |
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What is hysteresis?
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a lag or delay in change of alveolar size after distending pressure stops.
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List some hormones that stimulate the development of surfactant production.
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- corticosteroids
- glucocorticoids - thyroxine: act synergistically with glucocorticoids |
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List some hormones that impedes the development of surfactant production.
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- insulin
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How is surfactant produced from typeII pneumocytes?
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- produced as lamellar bodies
- secreted by exocytosis |
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What are the components of surfactant?
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- phospholipids
- proteins: SP-B and SP-C (hydrophobic), SP-A (glycoprotein, inhibit surfactant production) and SP-D (glycoprotein, enhance phagocytosis of bacteria) - neutral lipids (major component): DPPC, phosphatidylcholine, phosphatidyglycerol |
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How do the lamellar bodies (surfactant) look under EM?
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tubular myelin
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Why is RDS also called hyaline membrane disease?
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absence of surfactant -> injury to alveolar ducts and alveoli -> necrotic tissue in terminal bronchioles and alveolar ducts -> debris incorporated into hyaline membranes lining the bronchioles
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What are some risk factors for RDS?
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- premature labor
- premature rupture of amniotic membrane - placental insufficiency - chorioamnionitis - C-section delivery - infant of diabetic mother - surfactant protein deficiency (genetic) |
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Pathophysiology of RDS.
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alveolar collapse -> instability of lung volume, decreased compliance -> V/Q mismatch, intrapulmonary shunt -> hypoxemia
surfactanct deficiency -> inflammation -> pulmonary edema, high airway resistance -> worsen lung function |
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Changes of the following in RDS.
- pulmonary function - resistance - dead space - alveolar ventilation |
- pulmonary function: decreased compliance and low FRC
- resistance: slightly increased, worsened by inflammation - dead space: increased - alveolar ventilation: decreased |
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What is a typical clinical finding in a RDS infant?
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intercostal and subxiphoid retractions: highly compliant rib cage drawn in during inspiration by high intrathoracic pressure
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What is this disease?
CXR - diffuse reticulogranular ground-glass apperance - low lung volume |
RDS
- feature results from atelectasis and edema |
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How to treat RDS?
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- exogenous surfactant: artificial, synthetic, animal derived
- antenatal corticosteroid administration - O2 supplement - mechanical ventilation: CPAP - diuretics |
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What are some exogenous surfactant approved for use in the U.S.?
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- exosurf (synthetic)
animal derived - curosurf - infasurf - survanta |
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What is BPD (bronchopulmonary displasia)?
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- lung damage from prolonged mechanical ventilation in premature infants with severe RDS
- O2 requirement at 28 days of postnatal age |
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premature lungs + O2 toxicity+ ventilator baro-trauma + inflammatory response = ?
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BPD
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BPD occurs frequently in what patient?
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birth weight < 1250 grams and
gestational age >30 weeks |
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What are the characteristic path finding in established BPD?
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disruption of lung development
- decreased septation - alveolar hypoplasia - fewer, larger alveoli in severe BPD,also see - fibrosis - bronchial smooth muscle hypertrophy, increased elastic tissue formation, thickening of interstitium. - interstitial edema |
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What are the characteristic path finding in BPD seen in infants proior to availability of surfactant therapy?
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- airway injury
- inflammation - parenchymal fibrosis |
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CXR finding of BPD at 1 month.
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- hyperinflation
- small lucencies, cystic changes - coarse densities - areas with some fibrotic changes |
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CXR finding of BPD at 2 month.
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- lucencies coalesce
- areas of hyperinflation mixed with areas of volume loss |
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CXR finding of BPD at 7 month.
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- lucencies shrink
- hyperinflation imporves - resolution of cysts |
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Treatment for BPD.
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- support good growth
- support ventilation and oxygen - bornchodilators - diuretics - systemic corticosteroids |
