Cystic fibrosis

It is fundamentally a disorder of epithelialtransport affecting fluid secretion in exocrineglands and the epithelial lining of therespiratory , gastrointestinal and reproductivesystem.

Probability of occurrence of cystic fibrosis= 1in 3200 live births (in USA).

Hence, cystic fibrosis is the most common diseasethat effect white population.

It is uncommon among Asians (1 in 31,000 livebirths ) and Africans (1 in 15,000 live births ).

CF causes the mucus to be thick and sticky. Themucus clogs the lungs, causing breathingproblems and making it easy for bacteria to grow.This can lead to problems such as repeated lunginfections and lung damage.

The thick mucous also lead to pancreaticinsufficiency.

The symptoms and severity of CF vary widely.

Some people have serious problems frombirth.

Others have a milder version of the diseasethat doesn't show up until they are teens oryoung adults.

Although there is no cure for CF, treatments haveimproved greatly in recent years.

Until the 1980s, most deaths from CF occurred inchildren and teenagers.

Today, with improved treatments, some peoplewho have CF are living into their forties, fifties, orolder.

Cystic Fibrosis is also known as mucoviscoidosis.

CF is an autosomal recessive disorder.

It is caused by the presence of mutations in bothcopies of the gene for the protein cystic fibrosistransmembrane conductance regulator (CFTR).

Those with a single working copy are carriers andotherwise mostly normal.

The primary defect in cystic fibrosis (CF) isabnormal function of an epithelial chloride channelprotein encoded by the CF transmembraneconductance regulator (CFTR) gene.

CFTR gene is located at chromosomal locus7q31.2.

The changes in mucus are considered secondary tothe disturbance in transport of chloride ions.

In a normal person’s epithelia transport of chlorideions occurs through transmembrane proteins, suchas CFTR, that form chloride channels.

Mutations in the CFTR gene render the epithelialmembranes relatively impermeable to chlorideions.

The impact of this disorder is tissue specific.

The major function of the CFTR gene in sweatglands duct is to reabsorb luminal chloride ionsand augment sodium reabsorption through theepithelial sodium channel (ENaC).

Therefore, in sweat ducts loss of CFTR results indecreased reabsorption of sodium chloride andproduction of hypertonic (salty) sweat.

In contrast with that in the sweat glands, CFTR inthe respiratory and intestinal epithelium forms oneof the most important avenues for active luminalsecretion of chloride.

Since the CFTR gene was cloned in 1989, morethan 1300 disease-causing mutations have beenidentified.

They can be classified as severe or milddepending on the clinical phenotype.

Severe mutations are associated withcomplete loss of CFTR protein function.

Mild mutations allow some residual function.

The most common severe CFTR mutation is adeletion of three nucleotides coding forphenylalanine at amino acid position 508(ΔF508).

This causes misfolding and total loss of theCFTR. Worldwide, ΔF508mutation is found inapproximately 70% of patients with CF.

Since CF is an autosomal recessive disease,affected persons harbor mutations on bothalleles.

Symptoms at birth:

Around 10% of babies with cystic fibrosis are bornwith a serious bowel obstruction, known asmeconium ileus. This can make them very ill intheir first few days of life.

All babies are born with meconium in their bowels( a thick, black substance normally passed out ofthe body a day or two after the birth) .

However, in some babies with cystic fibrosis,the meconium is too thick to be passedthrough the bowels and causes a blockage.

If a baby is born with meconium ileus, anoperation to remove the blockage willprobably be required.

A few babies will also have symptomsof jaundice (yellowing of the skin, eyes andmucus membrane), which can last for a longtime.

However, there are many other, morecommon, causes of jaundice.

It is common for people with cystic fibrosis toexperience persistent coughing as the body tries toremove the thick mucus from the lungs. Suddencoughing fits can occur, which sometimes lead tovomiting.

Inflammation in the lungs may cause wheezing,shortness of breath and breathing difficulties,particularly after exercise.

The danger is that a person with cystic fibrosiswho has such an infection can pass it on toanother person with cystic fibrosis through closepersonal contact or by coughing near them. Thisis known as cross-infection.

As more and more people with cystic fibrosisbecome infected with these bacteria, the bacteriamay become resistant to antibiotic treatment,which is why cross-infection is such a problem.

Cystic fibrosis can cause mucus to block theducts in the pancreas. The pancreas producesessential food-digesting enzymes.

When it is blocked, not enough of theenzymes reach the intestines to help breakdown food, which can cause a number oftroublesome symptoms.

Large, smelly stools

Malnutrition

Diabetes

Ears, nose and sinuses

People with cystic fibrosis can be proneto sinusitis which may need to be treated withnasal sprays or antibiotics.

Some older children and adults develop nasal polyps, which are fleshy swellings that grow from the lining of the nose or sinuses. If they become troublesome, they may need to be treated with steroid nose drops or surgically removed.

Some older children with cystic fibrosisdevelop a form of arthritis(swelling and painof the joints), usually in one or two largejoints such as the knee. In most cases,symptoms improve with time and treatment.

Older children and adults may also be proneto thin bones, for many reasons, includingrepeated infection, poor growth or weight,lack of physical activity and lack of vitaminsand minerals due to digestive problems.

This can cause joint pain and bones mayfracture (break) more easily. Some people needto take drugs called bisphosphonates to helpmaintain their bone density.

Infertility

Liver:

In some people with cystic fibrosis, the tinybile ducts in the liver can become blocked bymucus. This can be serious as the diseaseprogresses, and in some cases it may benecessary to have a liver transplant.

Incontinence:

People with cystic fibrosis, especially females, aremore likely to have urinary incontinence (loss ofbladder control) as urine can leak out of thebladder during coughing fits.

This can often be treated with pelvic floorexercises.

A. Newborn screening and diagnosisB. Testing of older children and adults

CFTR is involved in production ofsweat, digestive fluids, and mucus.

When not functional usually thin secretionsbecome thick. The condition is diagnosed bya sweat test and genetic testing.

Screening of infants at birth take place in someareas of the world.

Testing of older children and adults

Imaging tests. Damage to your lungs or intestines can be monitored with X-rays, CT scans and MRI.

Lung function tests. These tests measure the size of your lungs, how much air you can breathe in and out, how fast you can breathe in and out, and how well your lungs deliver oxygen to your blood.

Sputum culture. Your spit (sputum) is analyzed for bacteria.

Organ function tests. Blood tests can measure the health of your pancreas and liver. Children with cystic fibrosis should be regularly tested for diabetes after age 10.

There is no cure for cystic fibrosis, but treatment can ease symptoms and reduce complications. Close monitoring and early, aggressive intervention is recommended.

The goals of treatment include:o Preventing and controlling lung infections

o Loosening and removing mucus from the lungs

o Preventing and treating intestinal blockage

o Providing adequate nutrition

Medications◦ Antibiotics to treat and prevent lung infections◦ Mucus-thinning drugs to help you cough up the

mucus, which improves lung function◦ Bronchodilators to help keep your airways open by

relaxing the muscles around your bronchial tubes◦ Oral pancreatic enzymes to help your digestive tract

absorb nutrients

Chest physical therapy◦ Inflatable vest, a device worn around the chest that

vibrates at high frequency◦ Breathing devices, usually a tube or mask through

which you exhale while performing breathing exercises

Surgical and other procedures

o Endoscopy and lavage. Mucus may be suctioned from obstructed airways through an endoscope.

o Bowel surgery. If a blockage develops in bowel, may need surgery to remove it. Intussusception, where a section of bowel has folded in on itself, also may require surgical repair.