Cystic Fibrosis

Front 1

HPI for CF

Back 1

10 mo male reffered for multiple episodes of pneumonia and failure to thrive, persistant loose and greasy stools

Front 2

Dx lab tests

Back 2

sweat chloride greater than 106 mMol/L normal is less than 40

Genotype F508 del

3 day fecal fat absoprtion 62% coefficient of absorption normal is greater than 93%

serum carotene and vitamin E levels are low

Front 3

determining pancreativ insufficiency

Back 3

if fat isnt digested by lipase that is found in the pancreas

it will pass through the GI tract and can be measured in the stool, will not form micelles so fat soluble vitamins are not absorbed

Front 4

fecal elastase

Back 4

also a test for pancreatic infsufficency

one of the many enzymes produced by the pancreas, but it is not digested

Front 5

Cause of Cf

Back 5

abnormality in CFTR

clinical signs are caused by ibstruction in tissues with tubular epithelial structures

mucus in lungs, 85-90 have pancreatic insuff, hepatobiliary problems, bowel obstructions, male infertifity and relative female infertility

median age 37

Front 6

CF dx

Back 6

presence of one ore more phenotypic features

history of cf in a sibling

plus; positive sweat test done at an approved lab, presence of two CF causing mutations

Front 7

CFTR gene and protein

Back 7

located on chromosome 7, camp dependent channel that regulates other apical channels

over 1900 mutations have been reported but not allof them cause CF

genotype can influence the pancreatic phenotype but is a less consistent effec on lung and liver disease

Front 8

5 classes of CFTR mutaiton

Back 8

defective production

defective processing

defective regulation

defective conductance

reduced amts

F508del is a class II mutation with features of classs 3

Front 9

CFTR hypothesis

Back 9

in the airways and GI CFTR is a secretory channel and in the sweat glands it is absopative

Front 10

Cycle of disease

Back 10

obstruction, infection inflammation

Front 11

CFTR dysfunction leads to obstruction throughout the GI tract and causes clincial disease

Back 11

decreased bicarb secertion in pancreatic duct, leads to obstruction and autodigestion which overwhelms the trypsin inhibitor

decreased hydration of intestinal mucus,

decreased secetion in bile ductule and decreased bile flow, sludging in ductules, periportal fibrosis leadinf to cirrhosis, gallbladder can sludge leading to gallstones

Front 12

Duodenal bicarb secertion

Back 12

two mechanism;

electroneutral via a CFTR assisted Cl/HCO3 exchange

electrogenci secertion via CTFR conducutance

Front 13

Infant clinical

Back 13

positive newborn screen

respiratory symptoms

steatorrhea

meconium ileus

Front 14

Meconium ileus

Back 14

obstruction in the bowel of the first bowel movement which is even more so abnormally tarry and sticky

Front 15

Presentations seen in older children and adults

Back 15

recurrent pancreatitis

gallstones/liver disease

intussusception - telescoping of the intestine

Front 16

Odd of PS

Back 16

genetically related but the phenotype trumps the genotype

about 12% of Cf will remain pancreatic sufficient

Front 17

Pancreatic function

Back 17

pancreatic enzyme and bicarbonate secertion have different stimuli

secretin stimulates for bicarb and cck for enzyme ins the acinus

Front 18

Fluid and bicarb secertion in CF-PS

Back 18

abnormal levels

Front 19

Need bicarb for

Back 19

neutralize gastric acid, drive fluid secertion and allows mucin to unfold

Front 20

Ivacaftor

Back 20

mutation specific Cf drug

safe, improves lung function, decerases admission for pulm exacerbations

decrease sweat chloride improves qulirt of life and leads to weight gain

Front 21

Why do subjects gain weight

Back 21

increased fat absorption

cephalad caudad and crypt villus gradient of mRNA and protein

high expression in bicarb regulators

Front 22

Ivacaftor in GI bicarb

Back 22

lack of bicarb obstructs the pancreatic duct, pancreatic tissue becomes atretic but not the duct

lack of bicarb also causes a mucus plug in Brunner's gland, submucosa glands fill wiht mucos but are still present

Front 23

Measurement of duodenal bicarb

Back 23

used a biomarker of treatment effect

measures pH as well as motility

single use, radiofrequency detector worn outside the body

Front 24

Gastric neutralization in people with CF

Back 24

delayed in those with CF