Lecture 3: Cystic Fibrosis Flashcards
CF is an autosomal recessive disease. What does this mean?
A. Only mom carries the mutation
B. Only dad carries the mutation
C. Mom and dad both carry the mutation
D. Neither mom nor dad carries the mutation
CF is Progressive, life-shortening, genetic
disorder, Autosomal recessive.. originally from Europe/ whites (most common in white as well but effects all race!). orginally thought to be ped disease but can happen in all ages!
.
C! both mom and dad have to have that mutation but they do not have to have the disease..for each preg? 25%!
CF Pathophysiology
- Mutation of the cystic fibrosis transmembrane
conductance regulator (CFTR) gene causes CFTR protein to dysfunction - Regulates chloride, sodium, bicarbonate transport across the cell membrane… dysfunction? mucus becomes thick and sticky
- Over 2000 mutations: Different mutations result in different levels of CFTR function! not everyone will look the same! There are difference variance based on different gene mutation
– F508del: Most common mutation… Protein misfolded, doesn’t reach cell surface
Diagnosis of CF
- Newborn screening
– Immunoreactive trypsinogen - produced by pancreas
- Sweat test
– Sample of sweat is collected, and concentration of
chloride is determined
– Positive test is ≥ 60 mmol/L in children and adults - Chromosomal analysis
Involved Organ Systems of CF… (general)
- Gastrointestinal system
- Hepatic system
- Pulmonary system
- Reproductive system
- Musculoskeletal system
.
Involve of organs is related to where the CFTR gen is located!
Possible Patient Signs and Symptoms for CF
- Poor growth or weight gain (due to the GI involvement! lack of nutrition absorbed)
- Meconium ileus
- Frequent, greasy, bulky stools or difficulty in bowel
movements (due to not absorbing food well) - Frequent lung infections
- Wheezing or shortness of breath
- Persistent coughing, at times with sputum
- Chronic sinusitis
- Very salty-tasting skin (due to CFTR reg of salt!)
- Male infertility
- Nasal polyps
Pharmacological Therapy (2 main class)
- Chronic therapy
- Acute exacerbation therapy
Gastrointestinal System: Goals of therapy
– Control pancreatic insufficiency by providing adequate enzyme supplementation (cant absorb food and fat soluble vit!)
– Optimize growth and nutritional status
– Promote healthy bowel habits
– Maintain normal vitamin levels
Gastrointestinal Tract Manifestations
- Insufficient secretion of pancreatic enzymes
- Fat-soluble vitamin malabsorption
- Insulin deficiency
- Intestinal obstruction
– Meconium ileus
– Distal intestinal obstruction syndrome (DIOS)
Pancreatic Insufficiency: Maldigestion of nutrients (symp)? - a Gastrointestinal Tract Manifestation
- Symptoms: steatorrhea (greasy stool), frequent loose stools, flatulence, cramping, bloating, poor weight gain, sometimes constipation
- Below age-related norms for both weight and height
- Result of pancreatic enzymes deficiency
Pancreatic Insufficiency: Treatment?
Pancreatic enzyme replacement therapy (PERT)!
.
– Creon®, Zenpep®, Pancreaze®, Ultresa™,Pertzye®, Viokace™
……. ALL Contain lipase, protease, amylase!
.
– Enzyme brands are not interchangeable
– Delayed release capsules: Containing enteric-coated microspheres or minitablets
– Products are porcine (pig) derived
.
- Delayed release capsule administration: Do not crush or chew contents, Capsules may be opened and added to small amount of room temperature, acidic food like applesauce. Consume immediately, follow with water, juice, formula, breast milk
- Regular release tablet administrations: Swallow tablets whole with sufficient liquid
Pancreatic Insufficiency: Treatment dosing
Dosing (no need to calc for exam! )
– Based on total body weight or fat ingested
– Dosed on lipase units
* 500-2,500 units/kg/meal
* 10,000 units/kg/day
* 4,000 units/gram of dietary fat/day
* Take with every meal and snack
Pancreatic Insufficiency: Treatment Adverse events and monitoring
– Mucusal irritation
– Fibrosing colonopathy and colonic strictures reported at high doses (>6,000 lipase units/kg/meal): Diarrhea, Constipation, Abdominal pain
.
Monitoring parameters
– Stool fat content
– Abdominal symptoms
– Nutritional intake
– Growth
Another issue in CF (Gastrointestinal Tract Manifestations): Fat Soluble Vitamins and Nutritional Intake and Insulin Deficiency
1.) Fat soluble vitamin replacement
– A, D, E, K
– Doses higher compared to people without CF
.
2.) Energy intakes can be greater than standard for general population
– BMI >50-85% for age (need to take extra calories! healthy fat! )
– May require nutritional supplementation (Enteral feedings)
* Promotes healthy pulmonary function
.
3.) Cystic fibrosis-related diabetes
– Prevalence increases with age
– Associated with worse lung function, poorer nutritional status and increased pulmonary infections
– Distinct from type 1 and type 2 diabetes
– Treatment: Insulin
Another issue in CF: DIOS (intestine is obstructed): symp and therapy?- a Gastrointestinal Tract Manifestation
- Symptoms
– Cramping abdominal pain, poor appetite, abdominal distention
. - Therapy
– Electrolyte lavage solutions - Endpoint is passage of stool, symptom resolution
Another issue in CF: Hepatic System/ Hepatic Manifestations. symp and tx?
- Bile duct obstruction can lead to cirrhosis, portal hypertension
. - Ursodeoxycholic acid
– Controversial
– Thought to reduce liver injury
– 15-20 mg/kg/day; divided BID
