1. Cystic Fibrosis Done by : Layan Talib Marwa Adil Marwa Abdulsatar
supervised by : dr.RABAB

2. 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.

5. 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

7. 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.

8. 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.

10. Pathophysiology
Lung
Mucus adheres to airway surface, leads to decreased mucus clearing
Predisposition to Staph and Pseudomonas infections

11. 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.

12. 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.

13. Pathophysiology Gastrointestinal Sweat Biliary tree
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

14. Symptoms Gastrointestinal (GI) symptoms : 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.

15. Respiratory symptoms Cough Recurrent wheezing Recurrent pneumonia
Atypical asthma
Dyspnea on exertion
Chest pain
Genitourinary symptoms :
Undescended testicles or hydrocele
Delayed secondary sexual development
Amenorrhea

16. 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

17. 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)

18. Findings related to the GI tract include the following:
Abdominal distention
Hepatosplenomegaly (fatty liver and portal hypertension)
Rectal prolapse
Dry skin (vitamin A deficiency)
Cheilosis (vitamin B complex deficiency)
Examination of other systems may reveal the following:
Scoliosis
Kyphosis
Swelling of submandibular gland or parotid gland
Aquagenic wrinkling of the palms (AWP)

19. Complications Nasal polyps Chronic and persistent sinusitis lung
Bronchiectasis
Atelectasis
Pneumothorax
Allergic bronchopulmonary aspergillosis (ABPA)
End-stage lung disease

20. GIT:
Gastroesophageal reflux
Pancreatitis
Cystic fibrosis–related diabetes mellitus
Meconium ileus
Distal intestinal obstruction syndrome
Rectal prolapse
Vitamin deficiency (especially fat-soluble vitamins)

21. Fatty liver
Focal biliary cirrhosis
Portal hypertension
Liver failure
Cholecystitis and cholelithiasis
Rickets
Osteoporosis

22. Diagnosis Requirements for a CF diagnosis include 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

23. Diagnostic Tests Sweat Test Genetic Analysis
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
“The standard diagnostic test for cystic fibrosis is a sweat test, which measures the amount of sodium or chloride in a person’s sweat” (Mayo Clinic, 2007, Para 3). The procedure involves placing a small amount of a sweat producing chemical to the arm or leg. An electrode stimulates a weak and painless impulse, which causes a tingling sensation. Sweat is collected after a few minutes and analyzed by lab. To ensure that a false-positive or false-negative result has not happened two separate tests are taken on the same day. If the individual has an unusually high level of salt on the test that is indicative of CF. The sweat test is not useful in newborns as babies do not produce enough sweat to confirm the diagnosis. Physicians will wait until the newborn is a few months old to perform test.
If the newborn has the signs and symptoms of CF physicians may recommend doing a genetic analysis to confirm diagnosis. Other tests can also be done to assess the extent and severity of disease process. Test done will include measuring lungs, pancreas and liver. An inherited disease, the physician may recommend that immediate family members and first cousins be checked for CF even if no signs and symptoms are shown.

25. 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).

26. 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

27. 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.

28. 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

29. 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

31. Viscous meconium in the terminal ileum may cause intestinal obstruction.

32. 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

33. Treatment Antibiotics Nebulized, inhaled, oral, or intravenous
Mucus-thinning drugs(Mucolytics)
Thins secretions
Easier to cough up
Bronchodilators
Relaxes smooth muscles in the airways
Treatment for CF is aimed at relieving the symptoms and complications of the disease process. “The main goal is to prevent infections, reduce the amount and thickness of secretions in the lungs, improve airflow, and maintain adequate calories and nutrition” (Mayo Clinic, 2007). In order to accomplish these objectives treatments for patients with CF may include:
Antibiotics – New antibiotics fight bacteria more effectively in airway passages. To do this aerosolized antibiotics may be used. Long-term antibiotic use is associated with drug-resistant bacteria.
Mucus-thinning drugs – When WBCs attack bacteria in airway passages DNA is released by cells making the mucus in airways even thicker. An aerosolized drug, such as Pulmozyme, fragments DNA making the mucus thinner and easier to cough up.
Bronchodilators, such as albuterol, are used to relax the smooth muscles in the airways.

34. Bronchial airway drainage Postural drainage
Oral enzymes and better nutrition
High calorie diet
Special vitamins & pancreatic enzymes
Lung transplant
Pain relievers
Ibuprofen .

35. 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.

36. 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.

37. THANK YOU