Cystic Fibrosis

1. Cystic Fibrosis
Smriti Sharma

2. Commonest life limiting autosomal recessive
disorder in Caucasians.
The basic defect in Cystic fibrosis is a mutation in
the gene for chloride conductance channel i.e.
Cystic fibrosis transmembrane conductance
regulator (CFTR).
The failure of the chloride conductance by
epithelial lining leads to dehydration of secretions
that are too viscid and difficult to clear.

3. Cystic fibrosis is a multi-system disorder of the
exocrine glands, leading to increased production
of thick mucus in bronchioles, small intestines
and pancreatic and bile ducts.
It affects the glands which secrete body fluids,
causing damage to major organs including the
lungs, pancreas & liver & the digestive &
reproductive systems
It affects the entire body, causing progressive
disability & may lead to early death

4. CF causes obstructs of small passageways of these
organs:
Lungs (bronchioles): atelectasis (lung collapse) &
Emphysema (Overinflation of the alveoli)
Pancreatic ducts become clogged, impairing
digestion and absorption
Small intestine: absence of pancreatic enzymes
unable to absorb fats and protein

5. The fundamental problem in CF is a defective
protein called the cystic fibrosis transmembrane
conductance regulator (CFTR).
The gene for CFTR is located in the long arm of
chromosome 7.
Till now more than 1400 mutations in gene have
been recognized.
Commonest mutation is Delta F508, is a deletion
of three nucleotides that results in a loss of
amino acid phenylalanine at the 508th position of
the protein.

6. Less common in other ethnic groups.
Incidence: 1 in 2500 live births
Carrier rate: 1 in 25
Average life expectancy: mid 30s
Life expectancy in new borns: 4o years

7. Inheritance
CF develop when a person inherits the genetic
fault which causes CF from both parents.
Ways in which our bodies develop determined by
pairs of genes: One from mother One from
father
CF occurs in children who have inherited 2
abnormal copies of a specific gene, 1 from each
parent.

8. A parent who is a CF carrier but doesn’t have CF
has 1 normal copy of this gene and 1 abnormal
copy.
The normal dominates so the parent shows no
sign of CF.
Carriers pass on either their normal or in some
cases their abnormal copy of the CF gene to
their child.
Child receiving a normal copy from 1 parent and
an abnormal copy from the other CF carrier.
Child receiving abnormal gene from both parents
develop CF.

10. Pathophysiology
CFTR is a chloride channel found in the
membrane of cells.
Defect (mutation) in CFTR results in abnormal
ion transport across the epithelial cells affecting
the absorptive and secretive characteristics of
epithelial cells.
In the airways this leads to reduction in the
airway surface liquid layer and consequent
impaired ciliary function and retention of
mucopurelent secretions.
Chronic endobronchial infection with specific
organisms such as Pseudomonas aeruginosa

11. In the intestine, thick viscid meconium is
produced leading to meconium ileus
The pancreatic duct also gets blocked by thick
secretions leading to pancreatic enzyme
deficiency and malabsorption.
Abnormal function of the sweat gland results in
excessive concentrations of sodium and chloride
in the sweat.

12. Role of CFTR protein
CFTR protein transports chloride ions across
epithelial cells in lungs & intestinal tract
Since water follows ions by osmosis thus
prevents water depletion& viscous mucus (thick
& sluggish mucus )
CFTR protein helps to produce mucus which is a
complex mixture of salts, water, sugars &
proteins that cleanses, lubricates & protects
many passageways in the body, including lung
and pancreas

13. Normal Functioning of CF
gene
CF gene codes for
chloride channel in
apical membrane
of epithelial cells in
conducting airways
Channel is controlled
by cyclicadenosine
monophosphate(cA
MP) & indirectly by
beta adrenoreceptor
stimulation

14. Controls quantity &
solute content of
airway – lining fluid
Normal channels
inhibit adjacent
epithelial sodium
channels

15. CF gene defect
One of many CF gene
defects cause absence
or defective function of
chloride channel
leading to chloride
secretion & loss of
inhibition of sodium
channels and
an excessive sodium
reabsorption and
dehydration of airway

16. CF occurs when there is mutation in CFTR gene.
Protein created by this gene is anchored to the
outer membrane of cells in sweat glands, lungs,
pancreas &other affected organs.
Protein spans this membrane and acts as a
channel connecting the inner part of the cell
(cytoplasm) to the surrounding fluid

17. Sodium Reabsorption
Sodium channel primarily responsible for controlling
movement of chloride from outside to inside cells
When CFTR stops working, chloride is trapped
outside the cell
Since chloride is negatively charged, positively
charged ions cannot cross cell
Sodium is most common ion in extracellular space
and combination of sodium + chloride =salt which is
lost in amounts in sweat of individuals with CF

18. Dehydration of airway
liningCFTR protein cannot allow chloride ions out of mucus
producing cells.
Less chloride ions leaving, less water leaves
Mucus thick & sticky
No longer move freely through passageways Clogged
mucus in lungs plug airways preventing good
air exchange & ultimately leading to emphysema
DEHYDRATION OF AIRWAY LINING

19. CF is caused by a mutation in the gene cystic
fibrosis transmembrane conductance regulator
(CFTR). The most common mutation, ΔF508, is a
deletion (Δ signifying deletion) of three
nucleotides that results in a loss of the amino
acid phenylalanine (F) at the 508th position on
the protein. This mutation accounts for two-thirds
(66–70%[17]) of CF cases worldwide and 90% of
cases in the United States; however, there are
over 1500 other mutations that can produce CF.

20. Clinical Features
Newborn:
In the newborn the period is marked by
 Poor weight gain
 Intestinal blockage
 Accompanied by thick feces

21. Infancy
Respiratory:
 Cough (most common initial pulmonary
manifestation)
 Recurrent chest infections
 Thick mucous
 Difficulty in breathing
 Bronchiectasis
 Eventually pulmonary insufficiency and death
 Digital clubbing
 Chronic sinusitis

22. Gastrointestinal:
 Persistent diarrhea
 Bulky, foul smelling and greasy stools
 Maldigestion with secondary malabsorptions
 Steatorrhea
 Nutrient malabsorption (vitamin A, D, E and K)
 Intestinal obstruction resulting from meconium
ileus
 Malnutrition
 Poor growth

23. Young child
 Frequent respiratory infections
 Fever
 Cough
 Difficulty in breathing
 Abdominal pain and discomfort
 Fast respiration
 Flaring of nostrils
 Poor appetite

24. Older child and adolescent:
Respiratory:
 Allergic bronchopulmonary aspergillosis
 Pneumothorax or recurrent haemoptysis

25. Endocrine:
 Relative Insulin deficiency
 Hyperglycemia and CF related diabetes
 Cirrhosis and portal hypertension
Gastrointestinal:
 Distal intestinal obstruction (DIOS, meconium
ileus
 Malabsorption
 Maldigestion
 steatorrhea

26. Reproductive:
 Dysfunctional due to inspissation of mucus in
reproductive tract
 Sterility in males (atrophy or absence of vas
deferens)
 Secondary amenorrhea due to chronic illness or
marked body weight loss.

27. CF also can cause other medical problems such as;
 Sinusitis
 Nasal polyps
 Digital clubbing
 Pneumothorax
 Coughing up blood
 Enlargement of right side of heart (cor pulmonale)
 Rectal prolapse
 Liver, gallbladder and pancreatic problems
 Delayed puberty

28. Diagnosis
Essential diagnostic test is sweat test
Concentration of chloride in sweat is evaluated
Normal children: 10-40mmol/L
Confirmation of CF: > 60mmol/L on two or more
occassions

29. The most common test for children and young
adults is the electrolyte sweat test.
This test measures the amount of electrolytes
(sodium [salt], potassium and chloride) in a
person's sweat. This is done by applying a
chemical (called pilocarpine- used to stimulate
sweat production) to the forearm and using a
mild electric current to cause the area to sweat.
It analyzes sodium and chloride content in sweat
and if this results to higher than normal amounts
of sodium and chloride CF is present.
It is done after 3-4 weeks after birth. Patient often
report that infants taste salty when kissed.

30. Immunoreactive
Trypsinogen Test (IRT)
In newborn babies who cannot produce
enough sweat for a sweat test,an IRT may be
done.
An IRT is a blood test that involves drawing
blood a couple of days after birth and
evaluating the presence of the protein
trypsinogen.
If the test is positive, it should be confirmed
by amutation analysis (i.e., genetic testing).
The combination of an IRT and mutation
analysis is sensitive 90% to 100% of the time.

31. Nasal Potential Difference
(NPD) Measurement
As Na+ (sodium) and Cl- ions move across the
membranes of the cells lining the airway, they
generate what is called an electric potential difference
In the nasal passages, this electrocpotential
difference is known as the nasal potential difference
(NPD), and it can be easily measured with a surface
electrode.
Because Na+and Cl- transport is abnormal in CF
patients, NPD measurements are very different in CF
patients than in people who do not have CF.
This test is especially helpful when the sweat
electrolyte test and/or the genetic tests are
inconclusive. However, the success of the test is
highly dependent on the skill of the technician, and
should be done in aspecial center.

32. Genetic Testing
A genetic test, also known as a genotype test or
mutation analysis, is designed to analyze DNA
for the presence of one of the several hundred
mutations that can cause CF.
The test involves collecting a sample of the
patient's blood. The test cannot detect all of the
mutations that can cause CF, however, so its
sensitivity is only about80% to 85%.
Genetic testing cannot be used to predict the
severity of symptoms. There is no way to know,
based on a person's genotype whether CF will
be fatal or mild

33. Generally, a genetic test is done if a patient's
sweat test is negativeand there is still high
suspicion that the patient has CF

34. Pulmonary Function Tests
Pulmonary function tests may be done to
assess the patient's respiratory dysfunction
and whether the patient is healthy enough to
receive a lung transplant, if necessary
72 hour stool collection
o Analyzes fat and enzyme content
Chest x-ray
o To reveal atelectasis and obstructive emphysema

35. Management
Effective management requires a multi-
disciplinary team approach, including
paediatricians, physiotherapists, dieticians,
specialist nurses.
All patients with CF should be reviewed annually
in a specialist centre.

36. Respiratory Management
The principle components of care includes
 Airway clearance
 Antibiotics
 Anti-inflammatory agents

37. Airway Clearance:
1. Physiotherapy
2. Nasal toilet
3. Exercise
4. Postural drainage
5. Percussion/ Chest clapping

38. Antibiotics:
o Continuous prophylactic oral antibiotics
(flucloxacillin) with additional oral antibiotics for
any increase in respiratory symptoms or decline
in lung functions.
o If signs and symptoms persists: prompt and
vigorous intravenous therapy for 14 days
o Daily nebulised antipseudomonal antibiotics for
chronic Pseudomonas infection.
o Macrolide antibiotics (azithromycin) : decreases
respiratory exacerbations.

39. o More severe CF : regular intravenous antibiotic
therapy.

40.  Anti-inflammatory agents:
A. Nasal Corticoids
These agents decrease mucosal edema and
promote mucus clearance.
• Fluticasone furoate (Veramyst)
• Mometasone furoate monohydrate (Nasonex)

41. B. Systemic corticoids
• Prednisolone
• Prednisone
• Dexamethasone

42. C. Decongestants
Are helpful in improving the nasal airway and
shrinking down swollen tissues
• Pseudonephrine hydrochloride (Sudafed, Actifed)

43. Surgical Management
o Nasal polypectomy to relieve obstruction is the
most common surgical procedure in CF to have
symptomatic relief
o Gallstones are common, ands symptomatic
disease may require elective cholecystectomy in
as many as 5% of CF adults.
o Lobectomy is occasionally indicated formassive
hemoptysis that is refractory to bronchial artery
embolization.
o Partial lung resection has been advocated for
apparently localized disease and recurrent
severe exacerbations.

44. Lung transplantation
Lung transplantation has become an accepted
treatment for respiratory failure secondary to CF.
More than 1600 lung transplants have been performed
for CF around the world. The transplanted lungs remain
free of CF but are subject to secondary infection, acute
rejection, and chronic rejection(bronchiolitis obliterans
syndrome).
The 5-year survival is 48%—as good as that of lung
transplant recipients with other causes of lung disease.

45. Living lobar transplantation is an effective
alternative to conventional cadaveric lung
transplant.
The lobe donors must have sufficiently large
lungs that their lower lobe fills the recipient’s
hemithorax.
Survival appears to be similar to that following
conventional lung transplantation

46. Nutritional Management
Dietary status should be assesses regularly.
Pancreatic insufficiency treated with oral enteric
coated pancreatic replacement therapy taken
with all meals and snacks.
Dosage adjusted according to clinical response.
A high calorie diet, dietary intake recommended
at 150% of normal
Overnight feeding with gastrotomy
Fat soluble vitamin supplements

47. Teenagers and adults
Most children with CF now survives into adults
but complications increases as age increases.
Most common is Diabetes Mellitus due to
decreasing pancreatic endocrine function
1/3rd have evidence of liver disease with
hepatomegaly , abnormal liver function
Rarely the liver disease progresses to cirrhosis,
portal hypertension and ultimately liver failure

48. Increasing chest infections as well as other late
respiratory complications including
pneumothorax and life threatning hemoptysis.
Increase in transmission of virulent strains of
pseudomonas and Burkholderia cepacia causing
rapid decline in lung function.
Females have normal fertility and unless severe
lung disease, can tolerate pregnancy well. Males
are always infertile due to the absence of vas
deferens.

49. Screening
Screening allows early identification of CF and
thus early introduction of regular treatment.
Immunoreactive trypsinogen (IRT) is raised in CF
patients and can be measured in routine heel-
prick blood taken for biochemical screening of all
babies. The test is called Guthrie test.
Those samples with a raised IRT are then
screened for common CF gene mutations and
infants with two mutations have a sweat test to
confirm the diagnosis.

50. Nursing diagnoses 1: Ineffective airway clearance R/T
inability to clear mucus.
Interventions
 Provide moistened oxygen (30-40%) to correct hypoxia
and acidosis.–
 Use mucolytic agents and do not give cough
suppressants.
 Aerosol therapy 3-4 times a day.
 Postural drainage– Encourage activity–
 Provide respiratory hygiene– Frequent mouth washes
 Frequent observation of the child

51. Nursing diagnosis 2: Altered nutrition less than body
requirement R/T inability to digest fat.
Interventions
 Provide a high calorie, high protein, moderate fat diet.
 Supplement vit. ADE and K as water miscible forms
 Add extra salt in diet, especially during summer.
 Supplement with synthetic pancreatic enzymes before
each snack and meal.
 In small infants open the capsule and mix the contents to 1
tsp. of food or warm water and give. It should not be added
to bottle or formula.
 Make sure the room temperature is always below 720F to
prevent excessive perspiration

52. Nursing diagnosis 3: Risk for altered skin integrity
R/T acid stools
Interventions
 For infants change diapers immediately when the
stool is passed.
 After a bowel movement check the child’s rectum
for prolapse.
 If prolapse is present with a gloved lubricated
finger replace it gently back.
 After replacement tape the buttocks together to
maintain gentle pressure on the anus.

53. Nursing diagnosis 4: High risk for ineffective family
coping R/T chronic illness of a child.
Interventions
 Teach the home care
 Regular follow up visits
 Arrange for schooling or a home tutor
 Encourage all family members in giving care