In this lecture, we are going to talk about cystic fibrosis.
So when we think of
it may be important to
step a little bit back
and look at some of the epidemiologic
facts about the disease.
We need to remember that 4% of Caucasian
people in the United States carry this gene.
It’s incredibly highly prevalent.
It’s less common, but absolutely
occurs in all ethnic groups.
I have myself seen cases where a
child was of a different ethnicity
and there was a delay in the diagnosis
because there was a presumption that
because this child wasn’t Caucasian
that he might not
have the illness.
The disease is autosomal recessive,
so while the gene is in 4%, far
fewer actually have the illness.
Fifty percent of the cases are
diagnosed before six months of age
so many of these children
are diagnosed in infancy,
some are diagnosed a little bit
later on in early childhood,
but most is diagnosed by the age
of five, virtually all of it,
before the age of two.
So let’s look a little bit
at the genetics of the
disease and then specifically
at the CFTR gene.
The primary issue in cystic
fibrosis is a genetic defect
in the cystic fibrosis transmembrane
conductance regulator protein or CFTR.
This protein is found in all exocrine
tissues and many epithelial tissues
including lung, liver, the
GI tract, and the skin.
So a mutation in this gene, and there are
many different mutations that can occur,
results in abnormal secretion
of chloride in these tissues.
This can affect the lungs
of a patient, the pancreas,
the liver, the intestine,
and the reproductive tract.
We’re going to talk about all of these.
So let’s focus first on pulmonary disease
in patients with cystic fibrosis.
So the idea here is that because these
patients have very thick airway secretions
as a result of a defect in
that chloride transport,
these patients are at
increased risk for infection.
They’re more prone to unusual organisms
like Pseudomonas aeruginosa,
whereas, regular people, who
get a bacterial pneumonia,
are more likely to have
something like Strep pneumo.
These recurrent infections
of unusual organisms
result in chronic
inflammation of the lung.
That in turn will destroy
the parenchyma of the lung
and will result in
This gradual degradation of pulmonary
mechanics and pulmonary function
is the hallmark of this disease.
Airways frequently will be colonized.
Certainly, Staph aureus and increasingly
MRSA is colonizing in these airways
or things like
But again, because of the
thickness of the secretions,
these patients can have
unusual organisms like
or Burkholderia cepacia.
Cepacia in particular has a
high degree of resistance
and may be a negative
predictor of mortality.
These patients with Burkholderia
cepacia may be in big trouble.
Those bugs will grow as a biofilm
along the surface of the airway
and can be very difficult if
not impossible to eradicate.
The damage from these infections
results in lots of different things,
such as spontaneous,
pulmonary hemorrhage, respiratory
distress, and eventually death.
Pancreatic disease in these
patients is also very troubling.
Remember, these duct secretions are
very thick in the pancreas, as well.
This results to an acute
or a chronic pancreatitis.
The pancreatitis results in an inadequate
release of lipase and other important enzymes
that are responsible for
degradation and digestion of food.
So these patients can
have fat malabsorption,
they can have poor absorption of fat
soluble vitamins A, D, E, and K.
As a result of their
difficulty with absorbing fat,
they often have
poor weight gain.
They can also develop an endocrine
disorder in their pancreas
because of the damage and can
get CF-related diabetes,
which is a lot like
type 1 diabetes.
The intestinal disease in these
children is very bad as well.
These patients develop thickened
This rather disgusting substance
you see on the slide is meconium
and we sometimes see a delay in the
passage in meconium in newborns
that looks like that,
and a delay in the passage of that
meconium is highly concerning
for an underlying diagnosis
of cystic fibrosis.
Older children can have a
complete or partial small
bowel obstruction from
the thickened stools.
Infants can get a
which is where the meconium doesn’t pass at
all and there’s actually an obstruction.
In patients with chronic constipation,
they can develop rectal prolapse,
where the rectal vault actually
extrudes out past the rectum
and there’s an inversion of
the colon outside the body
that has to be pushed
back in again.
Patients with very severe distal
obstruction can develop DIOS
or distal intestinal
where they actually are
completely incapable of
passing stools because of
this distal obstruction.
And remember, any infant who hasn’t
passed a stool within 48 hours
is at increased risk of
having cystic fibrosis.
Patients with cystic fibrosis
may also develop liver disease.
In patients like this, and you
can see here in this picture
some fibroblasts and some
these patients may develop
a focal biliary cirrhosis,
which causes an
underlying liver failure.
Thick biliary secretions
slow down the flow of bile
and cause a backup, especially
around the biliary tree.
This also can result in gallstones
and gallstone formation
and patients may require
They may get bile duct dilatation
as a result of these gallstones,
which in turn can increase
liver enzymes through backflow
and congestion resulting in hepatomegaly
and increased liver enzymes.
Ten percent of cystic fibrosis patients
die ultimately of liver disease
rather than pulmonary disease.
There are many other problems that can
occur in patients with cystic fibrosis,
and during the course of this lecture,
I unfortunately can only
touch upon a few of them.
In males, infertility
is almost ubiquitous.
Males usually have a problem with an absence
or an inadequacy of the vas deferens,
which results in inability to conduct the
sperm effectively outside of the male penis.
In females, they may also have infertility,
but usually have normal fertility
and pregnancy outcomes are
actually usually excellent
and they are excellent with
Remember, what’s key in these
patients is the GI disease
and the malabsorption as a result
of pancreatic insufficiency.
It is incredibly important for a pregnant
woman to gain appropriate weight
so that the fetus inside can
grow and develop effectively.
Patients with cystic fibrosis who are
pregnant need extra special care
to track weight gain and
make sure that’s going well.
Patients with cystic fibrosis
are at increased risk
for fractures because of
poor bone mineralization.
Remember that vitamin D is one
of the fat soluble vitamins;
D, E, A, K,
and vitamin D at low levels will
cause poor bone mineralization
and put them at
risk for fractures.
Another issue can be renal stones.
Renal stones happen because
patients with fat malabsorption
will hold on to fat inside
the lumen of the gut.
That fat will now saponify with calcium.
That calcium is usually binding oxalate and
now oxalate can be absorbed and extruded in the
renal system, and these patients may get
oxalate stones. Fat saponifies calcium leading
oxalate to be reabsorbed in increased amounts.
The nephrolithiasis in cystic fibrosis is mostly
due to hyperoxaluria. Patients with cystic
fibrosis also can get venous thrombosis in the
kidney as well.