Cystic Fibrosis Flashcards
How does CF occur?
How would someone inherit CF?
How does a mutation in CFTR gene lead to CF?
Mutation in the CFTR gene - a single gene which codes for the cystic fibrosis transmembrane regulator protein
In the UK the most common mutation responsible for around 70% CF cases is F508del
CF is an autosomal recessive disorder – to have CF a child needs to inherit 2 x CF genes.
People who inherit one CF gene are known as carriers.
- birth rate of CF is ~1/2500 newborns
- carrier rate is ~1/20 caucasians
The CFTR protein allows the passage of chloride ions through epithelial cells, notably in the lungs, intestines, pancreatic ducts and vas deferens.
Dysfunctional CFTR channel results in altered electrolyte/fluid composition of secretions (mucus) resulting in thick, sticky mucus.
Describe some clinical features of CF
Gastrointestinal:
- Pancreatitis
- Pancreatic insufficiency
- Maldigestion and malabsorption
- Cirrhosis
- Meconium ileus
Respiratory:
- Pneumonia
- Sinus disease
- Bronchitis
Reproductive:
- Male infertility due to atresia of vas deferens
Musculoskeletal:
CF related osteoporosis
How can respiratory issues in CF lead to malnutrition?
- Acute infection increase energy demands
- Repeated coughing can cause vomiting
- Large meals worsen breathlessness
- Patients prioritise breathing over eating
- Inflamed bronchi may bleed and lead to IDA.
- Chronic sinus disease may lead to impaired taste and smell
How can gastrointestinal issues in CF lead to malnutrition?
Pancreatic insufficiency (PI) is the main gastrointestinal clinical feature of CF (others include pancreatitis, meconium ileus, distal intestinal obstruction syndrome, fibrosing colonopathy, GERD/GORD).
All CF patients experience some degree of pancreatic dysfunction:
PI - pancreatic insufficient - the majority of patients - need PERT with all meals.
PS - pancreatic sufficient - retain exocrine pancreatic function - can digest by themselves
PI results from pancreatic damage and occurs when >95% capacity is impaired
PI causes maldigestion and malabsorption of macronutrients, particularly protein, fat and fat sol vitamins.
Additionally, the products of intestinal fat digestion (glycerol and fatty acids) are not absorbed properly in the intestine due to reduced bile acid secretion.
Fat malabsorption causes steatorrhoea, greasy stools that won’t flush.
Protein malabsorption causes offensive stools.
How is pancreatic insufficiency (PI) treated?
What is a complication of PERT dosing?
PI is treated with oral pancreatic enzyme replacement therapy (PERT) which must be taken with meals (otherwise enzymes will attack the GI system).
PERT treatment ensures that fat is digested in the intestine, though absorption of free fatty acids may still be impaired.
Dose of PERT is individualised to each patient however sometimes it is calculated based on fat content of meal.
Shouldn’t exceed 2500 LU per kg BW per meal or 10000 LU per kg BW per day.
Maximum dose of PERT is 10,000 lipase units/kg/day - if maximum dose is reached but GI symptoms persist then investigation is needed as increasing PERT further can cause fibrosing colonopathy.
Precise dosage is impossible due to several dietary and physiological factors
- gastric emptying pattern
- differences in absorption of fat & protein
- PERT is an unstable product - gradually degrades itself
What are the main nutritional complications in CF?
- Malnutrition (maldigestion and malabsorption) caused by PI
- Cystic fibrosis related diabetes
- Cystic fibrosis related osteoporosis
How is malnutrition defined in CF?
How does malnutrition occur in patients with CF?
Children - malnutrition = weight to height value <90%
In adults, malnutrition = BMI <20kg/m2.
Combination of increased energy demands and increased energy losses = resulting in negative energy balance.
Most people with CF can maintain positive energy balance, however those who cannot are susceptible to malnutrition.
Factors contributing to impaired intake in CF:
- Poor appetite
- Coughing and vomiting
- Gastrointestinal disturbances
- Medication side effects
- Impaired taste/smell
- Social peer pressure e.g., diet foods
Factors contributing to increased energy demands in CF:
- Intrinsic increased metabolic demand (higher BMR)
- Periods of infection and recovery from infection
- Advancing pulmonary disease
Factors contributing to increased energy loss in CF:
- Malabsorption (even with maximised PERT)
- Energy lost in urine as a result of uncontrolled CFRD
- Loss of energy and protein in sputum (up to 274 kcal/day lost)
(whilst energy expenditure increases in some patients, some will compensate for this by reducing level of PA)
Describe CFRD and explain how it occurs in patients with CF
- incidence/prevalence of CRFD
- dietary and medical management of CFRD
What are the main differences between CFRD and DM (type 1 & type 2)
CFRD is distinct from T1D and T2D.
Primarily caused by insulin deficiency caused by atrophy of insulin producing cells.
ALSO
CF = increased production of cytokines = damage to insulin producing beta cells = impaired insulin release = IGT = CFRD
Incidence of CFRD is increasing as survival rates and life expectancy in CF increases.
~50% of CF patients 30+ years have some degree of IGT
Dietary management of CFRD differs from that of T1D T2D:
- High energy intake with no calorie restriction
- High fat intake as macrovascular disease not a concern
- Protein restriction not advised due to risk of malnutrition
- Flexible meal plans to allow for periods of infection
- Intake of sugar may need to be reduced and replaced with complex carbs and protein if blood sugar levels is uncontrolled.
Medical management of CFRD is centred around insulin therapy - short acting insulin given to allow for flexibility.
Differences between CFRD & T1D/T2D:
- in CFRD insulin production is severely decreased but not absent
- insulin sensitivity is somewhat decreased (unlike T2D)
- microvascular and macrovascular complications unlikely
- cause of death pulmonary disease (not CVD/nephropathy)
Describe how osteoporosis can occur in patients with CF
- how is it managed?
Mean BMD is often one or more SD below the expected range.
Possible contributory factors include:
- Malnutrition
- Reduced PA level
- Gonadal dysfunction (less sex hormones)
- Vitamin D & Vitamin K deficiency (fat sol vitamins)
Compliance with PERT reduces risk of osteoporosis as PERT maximises absorption of fat sol vitamins (D&K).
Vit D & K supplementation is recommended as serum levels are low in CF patients.
What are some nutritional complications associated with lung transplantation in CF and how are these managed?
Patients needing bilateral lung transplant often have poor nutritional status/malnutrition.
Lung transplant recipients are at increased risk of CFRD due to use of immunosuppressants.
Management of malnutrition:
Acceptable nutritional status can be achieved by artificial feeding both before and after surgery
- improves the outcomes of surgery.
- Post transplant blood glucose levels need close monitoring
What are the aims of nutritional management in CF?
- To achieve ideal weight for height at all ages.
- Achieve and maintain optimal growth in children
- Maximise the immune system
- Modify nutritional advice in light of related conditions e.g., CFRD
How are energy requirements of CF patients calculated?
Many CF patients have raised BMR however TEE may not be increased due to decreased levels of PA.
Energy requirements depend on TEE which can vary among CF patients depending on genotype.
Calculations for energy requirements:
Mild CF disease (no acute illness) = REE x 1.5
Moderate CF lung disease (infection or recent weight loss) = REE x 1.75
Malabsorption, severe wasting, acute illness = REE x 2.0
Describe body composition changes in patients with CF compared to non-CF patients.
- Deficits in total body mass
- Deficits in lean body mass
- Deficits in fat mass
- Generally weigh less than age/sex-matched controls.
Reliability of electronic anthropometry measures is poor due to altered body water content in CF patients.
What is the general dietary advice given to patients with CF?
Describe the role of nutrition support in CF patients.
Oral intake:
- high energy and high protein intake with no fat restriction
- frequent and regular meals/snacks with PERT
- If dietary regime is inadequate, high-energy nutritional support is needed either orally or enteral tube feeding (feed containing high protein advised)
- Short term ONS have shown to produce weight gain and facilitate recovery from infection.
Enteral feeding:
- Overnight enteral feeding should be considered if weight falls below 85% ideal weight for height or BMI falls below 19kg/m2.
- EN feed usually given overnight to allow patient full mobility during day to eat and drink orally.
- Short term - NG tube & longer term - PEG
- Feed types:
Whole-protein polymeric feeds + PERT
Or semi-elemental formula + small dose PERT
Or fully elemental formula
Vitamin and mineral supplementation
Why is vitamin and mineral supplementation necessary in CF patients?
Vitamin:
Recommended that CF patients take a multivitamin as multiple vit deficiencies can be anticipated.
Fat sol vit deficiency (A, D, E & K) is common due to fat malabsorption caused by PI.
PERT generally decreases risk of vit deficiency, however, patients may be at high risk of deficiency if:
Diagnosed with CF late
Had previous bowel resection
Poor compliance with PERT
Liver disease
Serum vitamin levels should be checked in both PS & PI patients as deficiency may be an indicator of PS turning into PI.
Mineral:
Iron, zinc and selenium are the common mineral deficiencies in CF.
Iron deficiency can affect up to a third of CF patients caused by:
Poor intake
Chronic infection
Oesophagal bleeding
PERT can interfere iron absorption
However, supplementation should only be given if evidence of iron deficiency as iron is an essential substrate for the growth of major CF pathogen
Zinc deficiency can be caused by:
Diarrhoea
Intestinal mucosal abnormalities
Malnutrition
Short bowel syndrome
- PERT can increase zinc absorption.
Zinc status deteriorates as lung disease worsens - related to fatty acid status.
Serum zinc not a good indicator of total body zinc.
