12.cystic fibrosis

Question 1

what is cystic fibrosis

Answer 1

autoimmune recessive mutation in CFTR (cystic fibrosis transmembrane regulator) gene
causing misfolding of CFTR protein
Causing chloride ion transport defect w/in cells
Primarily affecting exocrine gland. Increasing the viscosity of their secretion (hyper viscosity)

Question 2

which organs does cystic fibrosis affect

Answer 2

lung
bronchiectasis, atypical infec, chronic simisitus w/ nasal polyps

pancreas
-pancreatitis, exocrine pancreatic insufficiency. cystic fibrosis diabetes

Bile
-cholestasis, Cholelithiasis, biliary cirrhosis

liver
-hepatomegaly, cirrhosis

intestine
-constipation. Meconium ileus. distal obstruction. Rectal prolapse

genitourinarry
-delayed sex development
infertility in males d/2 obstructive azoospermia
Infertility less common in females

Question 3

respiratory sx of CF

Answer 3

Cough
 Recurrent wheezing
Recurrent pneumonia
atypical asthma
Dyspnea on exertion
Chest pain

Question 4

pathogen of lung disease

Answer 4

thick mucus traps atypical bac in biofilm
(reccurent pneum)

chronic inflammation and paranchymal destruction

permanent dilation of bronchi (bronchiectasis)

Question 5

Gastrointestinal (GI) symptoms

Answer 5

Meconium ileus
Malabsorption 
Vit A D E K A def sx (night blindness, rickets, neuropathy, coagulopathy) 
Abdominal distention
Intestinal obstruction
Increased frequency of stools/ DIARRHOEA 
Failure to thrive (despite appetite)
Flatulence or foul-smelling flatus, STEATORRHOEA
Recurrent abdominal pain
jaundice
GI bleeding
Elevated glucose

Question 6

pathogenesis of GI disease

Answer 6

thick mucus blocks pancreatic duct

back flow of lipase and proteases
(pancreatitis & malabsoprtion)

pancreatic damage imparairs insulin secretion
(CF DB)

thick bile secretion causing cholestasis and cholelithiasis,

bile backflow to liver (hepatomegaly & cirrhosis)

Rectal prolapse: Excessive straining because of chronic constipation/diarrhoea lead to weakening of the pelvic structures fixating the rectum.

Question 7

clinical signs of CF

Answer 7

nasal polyps

tachypnoea, resp distress, retractions, wheezing, cyanosis, clubbing

Muconeum ileus in abdominal distension, hepatomegaly, cheliosis

Pathological fractures

Frequent uti

Undescended testes,

Question 8

dg of cf

Answer 8

GOLD: sweat test

cftr genetic testing

cxr, axr,

barium enema

sputum microbiology

Question 9

which atypical bac are found in CF pneumonia

Answer 9

pseudomonas

burkholderia

Question 10

what criteria determine CF dg

Answer 10

positive genetotype/ sweat test

PLUS

1. COPD
2. Pancreatic insufficiency
3. positive fam history

Question 11

what determines a positive sweat test

Answer 11

A value higher than 60 mmol/L of chloride is consistent with CF

 A value of 40-60 mmol/L is considered borderline, and the test must be repeated

 In babies aged 3 months or younger, a value of 30-60 mEq/L is considered borderline and requires retesting

Question 12

how is CF managed

Answer 12

1. manage resp infec to maintain normal lung func
   - Hypertonic saline nebulization(decrease the viscosity secretions,preventing bacterial infection and allowing air to flow)

• Bronchodilator therapy (albuterol)
• Chest physiotherapy
• Chronic rhinosinusitis: intranasal glucocorticoids
• Mucolytics
• chronic respiratory insufficiency:Long-term oxygen inhalation therapy
• Treatment of last resort: lung transplantation

2. nutritional therapy
   Additional sodium chloride intake to compensate rinse loss in sweat
   High-energy diet to compensate for increased demand by accessory respiratory muscles
   Pancreatic enzyme supplements
   Oral supplementation of lipophilic vitamins A, D, K, and E
3. manage/ prevent complications

Question 13

rx of CF exacerbation

Answer 13

bronchodilator
postural drainage
flouroquinolone abiotics
mucolytics
fat sol vitamin supp
CS
insulin for db
inhaled hypertonic saline to reduce mucous thickness

Question 14

which complications rewuire surgical rx

Answer 14

lungs: plum emphysema causing
pneumothorax

gi
muconeum ileus
intusussecption
rectal prolapse

Question 15

General pathophys of cystic fibrosis

Answer 15

Mutated CFTR gene → misfolded protein → retained in RER & unable to reach the cell membrane → defective chloride channel → no transport of intracellular chloride ions across the membrane → exocrine glands produce hyperviscous secretions → accumulation of secretions and blockage of exocrine glands → chronic inflammation → organ damage
Elevated levels of NaCl in sweat → gold standard diagnostic tool

Question 16

Rx of pulmonary infection

Answer 16

Common pathogens in children
1)Staphylococcus aureus
2)Haemophilus influenzae
Rx w/ IV vancomycin

Common pathogens in adults 
1)Pseudomonas aeruginosa
2)Burkholderia cepacia
First line: inhaled tobramycin
Alternative: ciprofloxacin 

IV antibiotics in rx resistant : tobramycin, ceftazidime, or meropenem