2. dr. ravindra k. Sharma
Pediatric specialist
Fujairah hospital UAE
3. 1838
Carl Von Rokitansky’s
autopsy of infant with
Meconium peritonitis
1905
1938
Austrian Karl Landsteiner Cystic fibrosis disease
describes Meconium ileus identified by American
Dorothy H. Andersen
3
4. Fibrosis
Cystic
Know the clinical features of cystic
fibrosis.
Know how CF is inherited.
Be familiar with criteria to diagnose
CF.
Become aware of the myriad of
treatments used in CF.
5. Fibrosis
Cystic
A multisystem disease
Autosomal recessive inheritance
Cause: mutations in the cystic fibrosis
transmembrane conductance
regulator (CFTR) gene
chromosome 7
codes for a c-AMP regulated chloride
channel
6.
Very salty-tasting skin
Appetite, but poor
growth & weight gain
Coughing, wheezing ,at
times with phelgum &
shortness of breath
Lung infections, e.g.
pneumonia/bronchitis
greasy, bulky stools or
difficulty in bowel
movements
6
8. Fibrosis
Cystic
Most common ―life-shortening‖ recessive disease in
Caucasians
1:3,200 in the northern Europian US
1:15,000 population in blacks
1 :10,500 Native Americans
1 :9,200 Hispanics
1 :31,000 Asian Americans
1 :90,000 Asians
(Ref : emedicine medscape)
1,000 new cases diagnosed / year.
More than 70% diagnosed by age two.
More than 45% of CF population is 18 Y or older.
predicted median age of survival is more than 36.9 years.M>F
10.
The CFTR gene is located on
the long arm of chromosome 7.
There are 1604 mutations in
CFTR listed on the CFTR
mutation database
The most common mutation is
Δ F508---70% CF alleles in
caucasians.
11.
Defects in (CFTR), - encodes for a protein
that functions as chloride channel &
regulated by (cAMP).
Abnormalities of cAMP-regulates chloride
transport
Defective CFTR - decreased secretion of
chloride and increased re-absorption of
sodium and water
Reduced height of epithelial lining fluid
Decreased hydration of mucus - that is
stickier to bacteria
Result in viscid secretions
12.
13.
Class I
Defective protein production
Defects in processing
Class II
Class III
CFTR reaches cell surface
but regulation is defective
(channel not activated)
Class IV
ΔF508
CFTR in membrane with
defective conduction
Class V
Decreased synthesis of CFTR
Class VI
Accelerated turnover from cell
surface
18. Presentation of Disease in lung
Mucous in the airways cannot be easily cleared from
the lungs.
19.
Benign lesions in nasal
airway(5-20 yrs)
If large - associated with
nasal
obstruction, drainage, heada
ches, snoring
associated with chronic
inflammation
need surgical intervention
High recurrence rate
21. Fibrosis
Cystic
Focal inspissation of bile
Obstructs biliary ductules
Second leading cause of death in CF
Prevalence 9-37%
Spectrum of disease
increased liver enzymes
biliary cirrhosis
portal hypertension
GB stones
22. Fibrosis
Pancreatic insufficiency
―cystic fibrosis of the pancreas‖---mucus
plugging of glandular ducts
Chloride impermeability affects HCO3- secretion
and fluid secretion in pancreatic ducts
Cystic
Pancreatic enzymes stay in ducts and are activated
intraductally
Autolysis of pancreas
Inflammation, calcification, plugging of ducts, fibrosis
Malabsorption
Failure to thrive
Fat soluble vitamin deficiency(ADEK)
24. Fibrosis
Cystic
Women
Lower fertility rate than non-CF women
Viscid mucoid cervical secretions of low
volume in women with CF
Pregnancy and CF:
Goss et al, 2003---no significant difference
in survival in women who became
pregnant with CF compared to women
who did not become pregnant (after
adjusting for disease severity)
Fertility is mildly impaired
25. Fibrosis
Dr. Paul di Sant’ Agnese
1949 NYC heat wave----noted CF infants to
have a higher rate of heat prostration than
non-CF
Showed that sodium and chloride
concentration in CF patients’ sweat was 5
times higher than in non-CF
Became basis for sweat chloride test(1953)
Cystic
27. Fibrosis
Cystic
One or more clinical features of CF
OR
A history of CF in a sibling
OR
A positive newborn screening test
Plus
Laboratory evidence for CFTR dysfunction:
Two elevated sweat chloride concentrations
obtained on separated days
OR
Identification of two CF mutations
OR
An abnormal nasal potential difference
measurement
28.
First described by
Gibson and Cooke,1950
Chemical that stimulates
sweating placed under
electrode pad; saline
under other electrode pad
on arm
Mild electric current is
passed between
electrodes
Sweat collected(75100gm)
31. Fibrosis
Cystic
DNA testing- 30–80 of CFTR mutations.
This identifies ≥90% who carry 2 CF
mutations
increased potential differences across
nasal epithelium with reference to
forearm
loss of potential difference with topical
amiloride application is more in CF
33. Fibrosis
Cystic
American College of Obstetricians and
Gynecologists recommended offering
prenatal screening for CF
Carrier testing of 23 most common
mutations
Sensitivity of prenatal screening for CF
among the white population <78%
lower than that for newborn screening
sensitivity of prenatal testing in racial and
ethnic minority populations is lower
35. Fibrosis
Cystic
Goal: early diagnosis may be
associated with better nutritional
outcome
Immunoreactive trypsinogen usually first
followed by either sweat or DNA testing
46.
ACTs loosen thick, sticky lung mucus
move mucus from small to large airways to be coughed or huffed
out.
Coughing is the most basic ACT.
Huffing is a type of cough. involves taking a breath in
and actively exhaling. It is more like ―huffing‖ onto a
mirror or window to steam it up
Chest Physio Therapy
Oscillating Positive Expiratory Pressure (Oscillating PEP)
an ACT where the person blows all the way out many
times through a device named
FlutterTM, AcapellaTM, CornetTM and Intrapulmonary
Percussive Ventilation (IPV). Breathing with devices
47.
High-frequency Chest Wall Oscillation
Positive Expiratory Pressure (PEP)
Active Cycle of Breathing Technique
(ACBT) It gets air behind
mucus, lowers airway spasm and clears
mucus.
48.
Thoracic expansion exercises – deep breaths in.
done
with
chest
clapping
or
vibrating, followed by breathing control.
Forced expiration technique – huffs of varied
lengths with breathing control.
Autogenic Drainage (AD) means ―self-drainage.‖
uses varied airflows to move mucus.
aims to reach very high airflows in different
lung parts. This moves mucus from small to
large airways.
50.
Gene therapy is the use of
normal DNA to "correct"
for the damaged genes
that cause disease.
In the case of CF, gene
therapy involves 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.
