Cystic Fibrosis B&B

Question 1

explain the pathophysiology of cystic fibrosis

Answer 1

AR mutation in CFTR transmembrane ATP ion transporter - pumps Cl- out of epithelial cells against concentration gradient

this draws out Na/H2O, hydrating mucosal surfaces (lungs, GI, tract) - mutation therefore causes mucus to be thick/sticky

also has sweat gland function - removes NaCl from sweat to make it more hypotonic

Question 2

explain why cystic fibrosis patients have a high concentration of NaCl in their sweat (“sweat test”)?

Answer 2

CFTR: ATP ion transporter, pumps Cl- out of epithelial cells against its gradient (draws out Na/H2O to hydrate mucosal surfaces)

CFTR also has sweat gland function - removes NaCl from sweat to make sweat more hypotonic

Question 3

what is the most common mutation known to cause cystic fibrosis? what is the consequence of this mutation?

Answer 3

delta F508: deletion of 3 DNA bases causes deletion in phenylalanine

results in abnormal protein folding, preventing CFTR trafficking to cell membrane

Question 4

what are the typical symptoms of cystic fibrosis and why do these occur?

Answer 4

mutation in CFTR ion transporter prevents Cl- (and water which follows) from leaving cell —> thick/sticky mucus

—> recurrent pulm infections (Pseudomonas, S. Aureus), chronic bronchitis, bronchiectasis
—> impaired bile/pancreatic secretion, malabsorption of fats/ fat-soluble vitamins (DAKE), steatorrhea (“foul smelling/greasy stool”)

Question 5

how do patients with cystic fibrosis typically present when they are first diagnosed (in most cases)?

Answer 5

usually diagnosed <2yo with respiratory disease or failure to thrive or meconium ileus (bowel obstruction)

Question 6

you’re on pediatric rounds when you encounter an infant presenting with respiratory disease and meconium ileus - what should you be thinking?

Answer 6

cystic fibrosis - thick/sticky mucus is causing respiratory illness and bowel obstruction (meconium ileus)

meconium = first stool of newborn, very thick/sticky, made more thick/sticky with CF —> obstruction, abdominal distention, vomiting, failure to pass

Question 7

does cystic fibrosis follow an obstructive or restrictive pattern?

Answer 7

obstructive - hyperinflation of lungs on CXR

thick/sticky mucus makes it difficult to expel air, bronchiectasis develops (permanent dilation of airways)

Question 8

describe how pulmonary remodeling occurs in cystic fibrosis?

Answer 8

thick/sticky mucus increases risk of infection

neutrophils are recruited, which release proteases that cause pulmonary remolding —> bronchiectasis develops (permanent dilation)

Question 9

what is the major pathogen associated with cystic fibrosis? (found in sputum samples)

Answer 9

pseudomonas aeruginosa

Question 10

why does pancreatic insufficiency occur in cystic fibrosis patients?

Answer 10

thick/sticky mucus blocks secretion of pancreatic enzymes and bile —> fat malabsorption, steatorrhea (“foul smelling, greasy” stools), deficiency of fat-soluble vitamins (DAKE)

—> CF-related diabetes

Question 11

for which vitamins are cystic fibrosis patients at risk of deficiency, and what is the effect of deficiency in each of these vitamins?

Answer 11

fat-soluble vitamins:
D —> rickets
A —> night blindness
K —> coagulopathy
E —> ataxia, hemolysis

Question 12

how does biliary disease present in patients with cystic fibrosis?

Answer 12

thick/sticky mucus causes bile duct obstruction

—> pale/clay-colored stool, elevated LFTs, hepatomegaly, cirrhosis, gallstones

Question 13

Pt. is a 32yo M presenting to a new GP for the first time. PMH includes intermittent respiratory distress that was diagnosed at age 10 as asthma. PMH also includes infertility and Vit. K and E deficiency, for which the patient takes supplements. On PE, you note clubbing. Assuming the original diagnosis of asthma is wrong (hint: it’s wrong), what could this be?

Answer 13

cystic fibrosis

most males with CF have diagnosis of infertility (absent vas deferens)

CF also causes deficiency of fat soluble vitamins (DAKE)

clubbing can also be a symptom of CF

Question 14

emphysema + clubbing =

Answer 14

most likely lung cancer

(just remember this for step1)

Question 15

most males with cystic fibrosis are infertile - why?

Answer 15

mutation in CFTR gene causes there to be absence of vas deferens —> spermatogenesis occurs but sperm are not transported

(can have children with assisted techniques)

Question 16

how are newborns screened for cystic fibrosis?

Answer 16

measure blood levels of immunoreactive trypsinogen (high IRT = positive)

follow positive blood test with sweat test (measure concentration of Cl- in sweat)

*if sweat test is negative but symptoms highly suggestive, can measure nasal transepithelial potential difference (more negative in CF, due to abnormal Na+ processing)