Transcript Cystic Fibrosis

Cystic Fibrosis
Done by : Layan Talib
Marwa Adil
Marwa Abdulsatar
supervised by : dr.RABAB
Cystic fibrosis (CF)
• is a disease of exocrine gland function that
involves multiple organ systems but chiefly
results in chronic respiratory infections,
pancreatic enzyme insufficiency, and
associated complications in untreated
patients. Pulmonary involvement occurs in
90% of patients surviving the neonatal period.
End-stage lung disease is the principal cause
of death.
Epidemiology
• Cystic fibrosis is an autosomal-recessive
disease.
• Each offspring of 2 heterozygote parents has a
25% chance of developing cystic fibrosis.
• Compared with males, females with cystic
fibrosis have greater deterioration of
pulmonary function with increasing age and
younger mean age at death.
• Median age at diagnosis is 6-8 months
Pathophysiology
• Cystic fibrosis is caused by defects in the cystic
fibrosis gene,(Gene located on 7th
chromosome)
• which codes for a protein transmembrane
conductance regulator (CFTR) that functions
as a chloride channel and is regulated by cyclic
adenosine monophosphate (cAMP).
Mutations in the CFTR gene result in
abnormalities of cAMP-regulated chloride
transport across epithelial cells on mucosal
surfaces.
• Defective CFTR results in
• decreased secretion of chloride and
• increased reabsorption of sodium and water
across epithelial cells.
• The resultant reduced height of epithelial
lining fluid and decreased hydration of mucus
results in mucus that is stickier to bacteria,
which promotes infection and inflammation.
Pathophysiology
• Lung
– Mucus adheres to airway surface, leads to
decreased mucus clearing
– Predisposition to Staph and Pseudomonas
infections
Pathophysiology
• Gastrointestinal
– Pancreas
• Absence of CFTR limits function of chloride-bicarbonate
exchanger to secrete bicarbonate
• Reduced bicarbonate secretion affects the digestion so
that neither endogenous nor exogenous pancreatic
enzymes can work at their optimal pH
• reduced water content of secretions, precipitation of
proteins, and plugging of ductules and acini, prevent
the pancreatic enzymes from reaching the gut.
Autodigestion of the pancreas occasionally leads to
pancreatitis.
– Intestine
• The pancreatic insufficiency decreases the
absorption of intestinal contents.
• Mechanical problems associated with inflammation,
scarring, and strictures may predispose the patient
to sludging of intestinal contents, leading to
intestinal obstruction by fecal impaction or to
intussusception. Adhesions may form, leading to
complete obstruction.
Pathophysiology
• Gastrointestinal
– Biliary tree
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Retention of biliary secretion
Focal biliary cirrhosis
Bile duct proliferation
Chronic cholecystitis, cholelithiasis
• Sweat
– Normal volume of sweat
– Inability to reabsorb NaCl from sweat as it passes
through sweat duct
Symptoms
• Gastrointestinal (GI) symptoms :
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Meconium ileus
Abdominal distention
Intestinal obstruction
Increased frequency of stools which suggests malabsorption .
Failure to thrive (despite adequate appetite)
Flatulence or foul-smelling flatus, steatorrhea ( pancreatic
insufficiency have fat-soluble vitamin deficiency and
malabsorption of fats)
• Recurrent abdominal pain
• Jaundice
• GI bleeding as a result of hepatobiliary involvement.
Respiratory symptoms
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Cough
Recurrent wheezing
Recurrent pneumonia
Atypical asthma
Dyspnea on exertion
Chest pain
Genitourinary symptoms :
• Undescended testicles or hydrocele
• Delayed secondary sexual development
• Amenorrhea
• Genitourinary
– Late onset puberty
• Due to chronic lung disease and inadequate nutrition
– >95% of male patients with CF have azospermia
due to obliteration of the vas deferens
– 20% of female patients with CF are infertile
– >90% of completed pregnancies produce viable
infants
Physical signs
• Findings related to the pulmonary system may include
the following:
• Tachypnea
• Respiratory distress with retractions
• Wheeze or crackles
• Cough (dry or productive of mucoid or purulent sputum)
• Increased anteroposterior diameter of chest
• Clubbing
• Cyanosis
• Hyperresonant chest upon percussion (crackles are heard
acutely in associated pneumonitis or bronchitis and
chronically with bronchiectasis)
• Findings related to the GI
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Abdominal distention
Hepatosplenomegaly (fatty liver and portal hypertension)
Rectal prolapse
Dry skin (vitamin A deficiency)
Cheilosis (vitamin B complex deficiency)
• Examination of other
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tract include the following:
systems may reveal the following:
Scoliosis
Kyphosis
Swelling of submandibular gland or parotid gland
Aquagenic wrinkling of the palms (AWP)
Complications
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Nasal polyps
Chronic and persistent sinusitis
lung
Bronchiectasis
Atelectasis
Pneumothorax
Allergic bronchopulmonary aspergillosis (ABPA)
End-stage lung disease
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GIT:
Gastroesophageal reflux
Pancreatitis
Cystic fibrosis–related diabetes mellitus
Meconium ileus
Distal intestinal obstruction syndrome
Rectal prolapse
Vitamin deficiency (especially fat-soluble
vitamins)
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Fatty liver
Focal biliary cirrhosis
Portal hypertension
Liver failure
Cholecystitis and cholelithiasis
• Rickets
• Osteoporosis
Diagnosis
• Requirements for a CF diagnosis include
1) Signs and symptoms
2) positive genetic testing or
positive sweat test findings
3) Positive family history (usually affected
sibling)
4) A positive newborn screening test
Diagnostic Tests
• Sweat Test
– Measures chloride in
person’s sweat
– Two samples
• Ensure false-positive does
not occur
– Not reliable on
newborns
– positive sweat chloride
test findings (>60 mEq/L)
• Genetic Analysis
– Newborn with signs and
symptoms may confirm
diagnosis with blood
test.
– Inherited disease
• Recommend checking
family members and
first cousins
Immunoreactive trypsinogen
• This is a protein produced by the pancrease
that is linked to CF.
• How is it used?
• Immunoreactive trypsinogen (IRT) is used as
part of a newborn screening program to
screen for an increased risk of cystic fibrosis
(CF).
• When is it ordered?
• This test is ordered as part of a newborn
screen for cystic fibrosis, in cases of
• meconium ileus,
• symptomatic young infants who are not
producing enough sweat to do a sweat
chloride test.
• children or adults present with symptoms
suggesting cystic fibrosis andpancreatic
dysfunction
• What does the test result mean?
• If an IRT level is elevated, an infant may
have cystic fibrosis; an infant or adult may
have abnormal pancreatic enzyme
production, pancreatitis, or pancreatic cancer;
• may be a false positive. Elevated levels need
to be followed with further testing.
• Is there anything else I should know?
• IRT testing is only useful for the potential
detection of cystic fibrosis. It will not
identify carriers of CF; their trypsinogen
production and function will not be affected.
• In those who do have CF, the degree of IRT
elevation does not reflect the severity of the
disease
Chest x-rays
• are insensitive to the early changes of cystic fibrosis,
Later changes include:
• bronchiectasis
• hyperinflation
• lobar collapse
• pulmonary arterial enlargement due to pulmonary
arterial hypertension is seen in patients with long
standing disease
Viscous meconium in the terminal ileum may cause
intestinal obstruction.
The primary goals of CF treatment
include the following:
• Maintaining lung function as near to normal
as possible by controlling respiratory infection
and clearing airways of mucus
• Administering nutritional therapy (ie, enzyme
supplements, multivitamin and mineral
supplements) to maintain adequate growth
• Managing complications
Treatment
– Antibiotics
• Nebulized, inhaled, oral, or
intravenous
– Mucus-thinning drugs(Mucolytics)
• Thins secretions
• Easier to cough up
– Bronchodilators
• Relaxes smooth muscles in the
airways
– Bronchial airway drainage
• Postural drainage
– Oral enzymes and better nutrition
• High calorie diet
• Special vitamins & pancreatic enzymes
– Lung transplant
– Pain relievers
• Ibuprofen
GENE THERAPY
• The only way to cure CF would be to use gene therapy
•(Gene therapy is the use of normal DNA to "correct" for the
damaged genes that cause disease)
•By inhaling a spray that delivers normal DNA to the lungs.
The goal is to replace the defective CF gene in the lungs to
cure CF or slow the progression of the disease.
•For patients with advanced stages of the disease, a
lung transplant operation may be necessary.
prognosis
• Although treating the symptoms does not cure
the disease, it can greatly improve the quality of
life for most patients and has, over the years,
increased the average life span of CF patients to
30 years.
• With current treatment strategies, 80% of
patients should reach adulthood. Nevertheless,
cystic fibrosis remains a life-limiting disease, and
a cure for the disease remains elusive.
•THANK YOU