Cystic Fibrosis (CS) is a condition which results in the lungs and
digestive system being clogged with thick and sticky mucus. CS is a genetic defect
which is inherited from both parents.
Symptoms of CS include recurring chest infections and frequent coughing
due to CF exacerbation which occurs due to build-up of thick mucus in the airways.
And Difficulty putting on weight which is caused by thick secretions blocking
pancreatic ducts, which results in reduced number of digestive enzymes in the
People with CF can also develop other conditions, including diabetes, osteoporosis
and liver problems.
CF is caused by a faulty gene on chromosome 7 called the cystic fibrosis
transmembrane regulator (CFTR).The faulty CFTR gene is inherited from both
parents, this gene affects the movement of chloride ions in and out of the
cell, by disruption chloride channels on the cell membrane (NHS, 2016).
In this essay I will focus on how research to investigate the behaviour
of the healthy human body can help explain what happens in disease specifically
Cystic Fibrosis is an autosomal recessive disorder, which means two
copies of an abnormal gene must be present in order for the disease or trait to
develop. The gene in question is the CFTR
gene which codes for the CFTR protein. Cystic Fibrosis develops when a mutated
version of the CFTR gene is inherited
from both the mother and the farther. However an individual can be a carrier of
a single faulty CFTR gene without
developing Cystic Fibrosis. Being a carrier of the faulty CFTR gene means you are more likely to have children that have
Cystic Fibrosis, therefore it is important for parents to know the risk that
their children may have CF, despite themselves being healthy (Riordan,
The CFTR protein is a channel protein found on the cell membrane in the
lungs and pancreas, its purpose is to pump chloride ions into various
secretions outside the cell, such as mucus. Those chloride ions draw water into
the secretions, which dilutes and thins out the secretions. The most common
mutation of CFTR is the ?F508 mutation. This means that the 508th
amino acid in the CFTR gene which is
called Phenylalanine is deleted. The CFTR protein with the ?F508 mutation gets
misfolded and cannot travel from the endoplasmic reticulum to the cell
membrane. This results in a lack of chlorine ions in the bodily secretions such
as mucus, which intern results in thick mucus. (National Heart, Lung, and
Blood Institute, 2013).
Studying healthy cells shows
us what a CFTR protein is and what shape it is supposed to have. It also shows
us where it’s located and its function, all this information is very useful
when trying to understand what the defect is in people with cystic fibrosis. As
we compare a healthy cell to the cell of someone with CF we will immediately be
able to tell the differences in chloride concentration and the lack of CFTR
proteins on the cell membrane. We can also deduce the genetic cause of this
defect by comparing the genetic code of a healthy person to someone with CF.
In early childhood biggest
problem people suffering with CF face is pancreatic insufficiency. This happens
because thick secretions jam up the pancreatic duct not allowing digestive
enzymes to make it to the intestine. Without those enzymes proteins and lipids
cannot be properly digested and absorbed. Other time this leads to poor weight
Eventually the backed up
digestive enzymes in the pancreas degrade the cells that line the pancreatic
duct causing local inflammation, which can lead to acute pancreatitis and with
repeated episodes chronic pancreatitis. Which causes the development of cysts
and fibrosis. And also the destruction of pancreatic tissue can also compromise
the endocrine function of the pancreas causing insulin dependent diabetes.
Later in childhood people
with cystic fibrosis start to develop lung problems. Normally the ciliated
cells lining the airways of the lungs move mucus up the airway towards the
Pharynx this is called mucociliary action. This is important because the mucus
transports debris and bacteria. Thicker mucus is harder to transport for the
cilia, so the mucociliary action becomes defective. Which means that bacteria
is allowed to colonise in the lungs. And this increase in bacterial load causes
symptoms such as coughing, fever and decrease in lung function, this is called
CF exacerbation and is treated with antibiotics. It can be even more serious if
the bacteria become antibiotic resistant (University of Rochester Medical Center,
Chronic bacterial infection
and inflammation can cause bronchiectasis which is permanent damage to the
airway wall, this leads to permanent dilation of the bronchi. If the
inflammation erodes into a blood vessel there can be hemoptysis or coughing up
of blood. Overtime the repeated CF exacerbations can lead to respiratory
failure, which is the leading cause of death with CF (National Heart,
Lung, and Blood Institute, 2013).
The problems that people
with CF face shows us how important every little function in the human body is.
It shows us that the smallest changes in the genotype and therefore the
phenotype of our bodies can result in massive issues and even death. It is
important to understand what these defects are in people with CF as it might be
possible to cure or treat the symptoms to prevent severe outcomes. Knowing
defects to look for can also help diagnose CF quicker.
For example some countries
have started screening for CF in newborns, which helps start treatment earlier.
The screen detects a pancreatic enzyme called immunoreactive trypsinogen (IRT)
which is released into the blood when there is pancreatic damage from CF. If
that test is positive then a sweat test is performed, if high levels of
chloride ions are detected in the sweat CF in confirmed.
The reason behind this is
unlike in the lungs and pancreas where chloride ions cannot leave the cell when
CFTR isn’t working, in the sweat glands chloride ions cannot enter the body.
Resulting in sweat with high chloride levels on the skin.
Aside from diagnosis knowing
what the differences are in a healthy body and one effected by CF is helpful in
treatment. As I have discussed the major issues are problems digesting lipids
and proteins due to blockages in the pancreas and pulmonary issues due to
mucus. (Riordan, 1989)
As a way to treat these
issues fat soluble vitamins, extra calories and replacement of pancreatic
enzymes can be supplemented to help nutrient and aid healthy weight gain. In
terms of pulmonary treatment, there’s chest physiotherapy, which loosens the
mucus in the airways through contact or inhalers.
There are also medications
such as N-acetylcysteine which breaks disulfide bonds in mucus glycoproteins,
and Dornase Alfa, which is a nuclease which cuts up nucleic acid in the mucus
to thin it out. (Riordan, 1989)
To conclude it is very
important to study the behavior of both the healthy and unhealthy human body.
One of the main reasons for this is so that we can compare the different
behaviors and determine what the problem is and what is causing the problem.
Finding this out is the first step in treating or even curing the problem. I
have also shown that this is also important for diagnoses and the development
of new screening methods.