Roughly 1 in 25 people carry the recessive CFTR allele. There are many different mutations that can lead to cystic fibrosis.
FF - Normal Ff - Carrier ff - Sufferer
The average life expectancy is mid 30`s though it`s increasing all the time as new drugs and therapies are introduced.
Usually have a thin layer of mucus produced by goblet cells to help keep dust, debris and microorganisms. The mucus is removed by epithelial cells which are coated with hair like cilia, these move the mucus to either be coughed out or swallowed.
The CFTR Protein
In normal people - too little water in the mucus-
- Chloride ions are transported through the tissue fluid into the epithelial cells. - Creates a concentration gradient where there are higher Cl ions inside the cell. -CFTR channels open and Cl diffuses out through the channel into the mucus - blocks the sodium channels allowing it to build up and create an electrical gradient between mucus and tissue fluid - Sodium ions move down gradient into mucus. This movement draws water out of cells into mucus.
In a CF Sufferer, the CFTR channel is missing or not working -
Means the sodium channel is continuously open and Cl cant travel into mucus - Na continues to be absorbed by the epithelial cells - raisied Na levels draw Cl and water out of mucus making it more viscous.
As the mucus is thicker and stickier than normal, it cant be moved as easily meaning microorganisms get trapped and as the epithelial cells use more oxygen in CF sufferers, it creates anaerobic conditions causing illness as pathogens get trapped. White blood cells try to fight infection but get trapped, die and release DNa as they break down making mucus even stickier and causing damage to lungs. Mucus in bronchioles block narrow airways preventing ventilation of alveoli which reduces the number of alveoli providing gas exchange. often means air is allowed in but not out leading to over inflation of the lungs damaging the elasticity.
In the small intestine, exocrine glands (protrude outwards) secrete enzymes from the live and pancreas. However, in CF, the pancreatic duct can become blocked by a collection of mucus. This means lss enzymes in the small intestins, decreasing effeiceny of digestion. Food is not fully digested so not all the nutrients are absrobed. High amounts of energy are lost - MALABSORBTION SYNDROME. The protease, carbohydrase and lipase trapped in the pancreas can start to cause damage, if it damages insulin production, it can cause diabetes.
Mucus can cause CF sufferers to become infertile.
Female - Mucus can block the cervix entrance preventing sperm from reaching the egg.
Male - The sperm duct may be absent or blocked meaning preventing sperm being released.
This can mean probems concieving. For the female sufferer, she can concieve using IVF, for a male sufferer, sperm can be extracted by a needle to be used.
Testing for CF
Amniocentesis - A needle is inserted into the amniotic fluid to collect cells that have fallen off the placenta and foetus. This can be carried out at 15 - 17 weeks though it does carry a risk of miscarriage of 0.5 - 1%
Chorionic Villus Sampling - A small sample of placental tissue is removed and this can be carried out at 8 - 12 weeks though it does carry a higher risk of miscarriage at 1 - 2% however as it can be done earlier this can be preferrable as, if they wish to abort should it be unhealthy, it`s generally easier the earlier on it is carried out.
However, as there are many different types of mutations that lead to CF, they only test the most common meaning there can be a miss diagnosis.
Bronchodilators - Inhaled using a nebuliser to relax airway muscels.
Antibiotics - Used to help fight off frequent chest infections.
DNAase Enzymes - Break down the DNA released by the white blood cells so the mucus is easier to clear.
Steroids - To help reduce inflammation of the lungs.
Digestive Enzyme Supplements - Helps with digestion.
Pysiotherapy - Rhythmic tapping of the chest cavity helps to clear the mucus (twice a day).
Heart and Lung Transplant - If they become too damaged, may need a transplant.
Treatments - Gene Therapy
Normal gene allels are inserted into target cells.The normal form of the gene is transcribed and translated producing a functioning protein in the cells.
Using Viruses - the DNA section that allows it to replicate is reoved and replaced with the normal allele along with a promoter sequence that initiates transcription and translation of the gene. the viral DNA remains independant in the nucleus of the cell. Can cause symptoms similar to flu.
Using Liposomes - A copy of the normal allele is inserted into a plasmid of DNA. The plasmids are combined with Liposomes (phospholipid bilayers). The positive head groups combine with DNA to form a liposome-DNA complex. This is breathed in using a nebuliser.
So far Cl has been corrected but not Na problems. Cells from the airway lining are coninuously shed, only a temporary fix but lung function has been reduced to within 25% of normal. so far only lasts up to 15 days.
DNA Replication - Transcription
DNA is a chain of nucleotides. A mononucleotide is 3 molecules linked by a condensation reaction between deoxyribose (5-carbon sugar), a phosphate group and an organc base containing nitrogen. This base includes Adenine, Thymine, Guanine and Cytosine.
Transcription - DNA unwinds and hydrogen bonds break. Free nucleotides line up alongside DNA template strand determining bases on RNA. RNA leaves nucleus through nucleur envelope pore.
DNA Replication - Translation
Translation - Takes place in ribosomes. tRNA carrying an amino acid with 3 bases (anticodon) pair with bases on mRNA codon and join by a peptide bond.
- compact, ball shape structure.
- includes enzymes, membrane protiens, receptors and storage protiens.
- long and thin.
- have structural roles such as cologen.
- always composed of many polypeptide chains.
- 3D shape is lost if the hydrogen bonds break.
- polypeptide chain folds into a random coil.
- protien losses its function.
- temps above about 50 or very low PH.