Cystic fibrosis (mechanism of disease)

This is a mechanism of disease flowchart for cystic fibrosis, covering the etiology, pathophysiology, and manifestations.

ADDITIONAL TAGS:
Risk factors / SDOH
Cell / tissue damage
Ion channel physio
Cystic fibrosis
Medicine / iatrogenic
Infectious / microbial
Biochem / molecular bio
Immunology / inflammation
Signs / symptoms
Tests / imaging / labs
Diet / nutrition
Genetics / hereditary
Blockage of flow
Pathophysiology
Etiology
Manifestations
Mutation ΔF508 in CFTR gene on long arm of chromosome 7
Absence of phenylalanine (F) in position 508 of the CFTR protein
Misfolded protein
Defective protein is retained in the rough endoplasmic reticulum
Protein degradation
Absence of ATP-gated chloride channel on the cell surface of epithelial cells throughout the body
Recessive disease:
children of parent(s) who are heterozygous carriers (if both parents affected → 25% chance in child)
Cannot reabsorb Cl- from the lumen of the sweat glands
↓ reabsorption of Na+ and H2O
↑ NaCl loss in sweat
In sweat glands:
Cannot transport intracellular Cl- across the cell membrane into lumen
In gastrointestinal, respiratory, or urogenital tracts:
↓ secretion of Cl- and H2O →
↑ intracellular Cl-
↑ Na+ reabsorption (via ENaC)
↑ H2O reabsorption by osmosis
Hyperviscous mucus and secretions accumulate and block small passages in…
Salty sweat, salty baby
+/- electrolyte wasting
Sweat chloride testing with Cl 60 mmol/L
GI tract
Failure to thrive
Malabsorption
Meconium ileus
No meconium or stool for first 1-2 days of life
Abdominal distension
Bilious vomiting
Pancreas
Weight loss
Pancreatitis
Steatorrhea
Hypoproteinemia
Fat-soluble vit deficiency (DEAK)
Liver and bile duct
Cholecystolithiasis → cholestasis
Dark urine
Jaundice
Pale stools
Pruritus
Cholangitis → cirrhosis
Portal hypertension
Esophageal varices
Nasal sinuses
Chronic sinusitis
Congestion
Nasal discharge
Lungs / bronchioles
Recurrent pulmonary infxns → bronchiectasis
Hemoptysis
Chronic cough
Dyspnea
Wheezing
Barrel chest
Hypoxia → digital clubbing
Urinary tract
Dysuria
Frequent UTIs
Nephrolithiasis
Flank pain
Cloudy urine
Hematuria
Genitalia
Azoospermia
Absent/obstructed vas deferens
Viscous cervical mucus
Infertility
Amenorrhea