cystic fibrosis

Cystic fibrosis

a serious genetic disease caused by a recessive allele which affects the production of mucus by the epithelial cells

defective gene inherited by people with cystic fibrosis

CFTR (cystic fibrosis transmembrane conductance regulator) on chromosome 7

Inheritance of cystic fibrosis

Cystic fibrosis is caused by a recessive allele, which means many carry the mutation without knowing it. These carriers are phenotypically normal and usually have no idea they are carrying the cystic fibrosis mutation
When two carriers have a child together, there is a 1 in 4 chance that any child of these parents will develop cystic fibrosis

How is cystic fibrosis caused?

It is caused by a defect in the CFTR (cystic fibrosis transmembrane regulator) which helps control the viscosity of mucus that lines the epithelial cells of the respiratory, reproductive and digestive system.
The CFTR acts as a channel to transport negatively charged chloride ions out of the epithelial cells and regulates the function of sodium ions.
The movement of chloride ions is blocked and an abnormally sticky mucus is produced outside the cell.
In people with cystic fibrosis, the CFTR protein does not work.

Regulation of water in the mucus in unaffected lungs

Na+ is actively pumped across the basal membrane into the tissue fluid and Cl- is pumped into the cell across the basal membrane.
Na+ ions diffuse through the sodium channels.
Cl- diffuses through the open CFTR channels into the mucus (secretion of Cl- ions).
They open CFTR channels which causes Na+ channels to close
Cl- diffuses across electrical gradient
|Elevated salt concentration in mucus draws water out of the cell by osmosis so mucus becomes more runny and less viscous.

Regulation of water in the mucus in affected lungs

CFTR channel is absent or non functional and is not able to regulate the sodium channels.
Na+ channel is permanently open and Na+ continue to enter the cells through the open Na+ channels
No Cl- secretion takes place.
Water is continually removed from the mucus by osmosis making the mucus more viscous and sticky.

Normal CFTR protein function in the airway

the balance of chloride secretion through CFTR protein channels and sodium reabsorption through epithelial sodium channels maintain a normal volume of airway surface liquid, allowing the cilia that line the airway to beat freely

CFTR protein defects in the airway

the absence or dysfunction of CFTR protein channels disrupts the chloride secretion and sodium is hyper absorbed due to the loss of CFTR protein regulation

Effects of cystic fibrosis on the respiratory system

Chloride ions accumulate in the cells so water moves out of the mucus and enters into the cells by osmosis.
Thicker mucus builds up in the airways and blocks the trachea/bronchi/bronchioles
Therefore less oxygen reaches the alveoli and the concentration gradient of gases is reduced in the alveoli

Effects of cystic fibrosis in the digestive system

The thick sticky bacteria block the pancreatic duct in the pancreas so enzymes do not reach the duodenum and as a result, food is not digested properly and nutrients from food are not absorbed properly as well. The digestive enzymes trapped in the pancreas may start to digest and damage the cells of the pancreas. If they affect the cells that make the hormone insulin, the person may also develop diabetes.
It is difficult for digested food to be absorbed in the blood. The gut secrets mucus to prevent the digestive enzymes damaging the delicate lining of the fut and to act as a lubricant but when the mucus is thick and sticky, it forms a barrier between the contents of the gut and lining of the intestine and clogs up the villi, reducing surface area absorption.
This puts people with cystic fibrosis at a severe risk of malnutrition

Effects of cystic fibrosis in the female reproductive system

Cervical secretions are too thick, blocking the cervix so that sperm cannot reach the oviducts. It also blocks the oviduct making fertilisation less likely.

Effects of cystic fibrosis in the male reproductive system

Almost all men have a low sperm count making them infertile.
They may lack the sperm duct which carries sperm out of the testes into the semen.
Even if the sperm duct was present, it may be partly or completely blocked by the thick sticky mucus so that a reduced sperm can leave the testes

Effects of cystic fibrosis in the sweat glands

The faulty CFTR protein means people with cystic fibrosis usually have sweat that is more concentrated and salty than normal. Normally, as the sweat passes along the duct of a sweat gland, salt (sodium chloride) is reabsorbed, largely as a result of the CFTR moving chloride ions into the cell.
Sodium ions follow along a concentration gradient and this reabsorption of sweat prevents too much salt loss in the sweat
Without functioning CFTR proteins, the chloride ions remain in the sweat and so do the sodium ions. This means the sweat is very salty.
The loss of sodium and chloride ions causes problems in the functioning of the nervous system and the heart