CF Flashcards
IRT
Cf with meconim ileus mau show normal IRT
Imunreactive trepsenogen
Pathophysiology
v General considerations
The CFTR gene encodes the CFTR protein, which is an important component of the ATP-gated chloride channel in cell membranes.
Mutated CFTR gene → misfolded protein → retention for degradation of the defective protein in the rough endoplasmic reticulum (rER) → absence of ATP-gated chloride channel on the cell surface of epithelial cells throughout the body (e.g., intestinal and respiratory epithelia, sweat glands, exocrine pancreas, exocrine glands of reproductive organs)
Pathophysiology
v In sweat glands
The chloride channel is responsible for transporting Cl- from the lumen into the cell (reabsorption).
In CF: this normal reabsorption does not occur which leave sweat reach in Cl and Na > become hypertonic, and when mom kiss the baby will be salty in taste ( Mom skin test “ ) Be careful loss of Na and Cl in sweat can cause electrolytes abnormality
Defective ATP-gated chloride channel → inability to reabsorb Cl- from the lumen of the sweat glands → reduced reabsorption of Na+ and H2O → excessive loss of salt and elevated levels of NaCl in sweat
Pathophysiology
In all other exocrine glands (e.g., in the GI tract or lungs)
In the other secretions of the body , Normally Cl is secreted while sodium and water is reabsorbed The chloride channel is responsible for transporting Cl- from the cell into the lumen (secretion). In CF: chloride channel not work so Cl trapped inside the cell and sodium channel become
hyper-active so more sodium reabsorbed and water follow » secretion become Thick Defective ATP-gated chloride channel → inability to transport intracellular Cl- across the cell membrane → reduced secretion of Cl- and H2O → accumulation of intracellular Cl- → ↑ Na+ reabsorption (via ENaC) → ↑ H2O reabsorption → formation of hyperviscous mucus → accumulation of secretions and blockage of small passages of affected organs → chronic inflammation and remodeling → organ damage ↑ Na+ reabsorption → transepithelial potential difference between interstitial fluid and the epithelial surface increases (i.e., negative charge increases; e.g., from normal -13 mv to abnormal -25 mv)
that can present with protein and fat malabsorption
that can present with protein and fat malabsorption (FTT, hypoalbuminemia, steatorrhea), liver disease (cholestatic jaundice), or chronic respiratory infection • In Pancreas thick secretion will obstruct the duct leaving the food in duodenum without helping of pancreatic enzyme which important in fat protein digestion >> fat , protein malabsorption
usually presentation depend on the age
usually presentation depend on the age ( there are exceptions always ) • neonate ( delayed passing of meconium ) • younger : Gi defect manifestation esp related to pancreas • older : respiratory defect manifestation
The respiratory epithelium of patients with CF exhibits
The respiratory epithelium of patients with CF exhibits
o marked impermeability to chloride and an excessive reabsorption of sodium.
o This leads to thicker airway secretions,
o resulting in airway obstruction and impaired mucociliary transport.
o This, in turn, leads to endobronchial colonization with bacteria,
especially Staphylococcus aureus (less than 5 y) and Pseudomonas aeruginosa (more than 5 y) o Chronic bronchial infection results in persistent or recurrent cough
that is often productive of sputum, especially in older children. o Chronic airway infection leads to airway obstruction and bronchiectasis and, eventually, to
pulmonary insufficiency and premature death. o The median age of survival is currently >40 years. o Digital clubbing is common in patients with CF, even in those without significant lung disease. o Chronic sinusitis and nasal polyposis (bilaterally) are common.
Pulmonary infections with P. aeruginosa and some strains of Burkholderia cepacia are difficult to treat and may be associated with accelerated clinical deterioration.
CFTR mutations by molecular class
Class1 / decrease num / no functional pr prdued
Class2 / :::::/ abesnt or deminished pr processing
Class3 / decrease function/ devictive gatind
Class 4/ dec function / dec conductance
Class5 / dec n / anbormal splicing canonical = complete or non canonical = partial
Class6 /dec n /dec cell surface stability
CF respi infla
↖️nut > NE Mac > TNF@ O2- IL8 I1b
CYSTIC FIBROSIS PULMONARY INFECTION • Methicillinresistant Staphylococcus aureus
• CYSTIC FIBROSIS PULMONARY INFECTION • Methicillinresistant Staphylococcus aureus • (MRSA) is associated with steeper lung
function decline and increased mortality in
patients with CF
CYSTIC FIBROSIS PULMONARY INFECTION • Burkholderia cepacia complex
Burkholderia cepacia complex • Catalase producing, lactose non fermenting gram-
negative bacteria composed of many different
species • Accelerate lung function decline in patients with CF • There is large variability in the course of the disease
CYSTIC FIBROSIS PULMONARY INFECTION • Achromobacter xylosoxidans
• is evolving and poses significant clinical
challenges • Usually present in sinuses • Aminoglycoside resistant
CYSTIC FIBROSIS PULMONARY INFECTION • Aspergillus fumigatus
CYSTIC FIBROSIS PULMONARY INFECTION • Aspergillus fumigatus
$$$ cental broncheacresis
CFTR potentate
Trikafta= elexa teza iva caf tor
Anti infection in CF
Amikacin Azithromycin Az treo nam Inhaled tobra mycine Tobramycin inhaled powder
