HOW DOES PBC AFFECT THE BILE DUCTS
Article from the Bare Facts Newsletter
produced by The PBC Foundation UK
The liver is a unique organ in the body, on
the one
hand, it appears to be very complex, performing literally hundred of
functions
related to making substances that the body needs such as (blood
proteins),
and breaking down unwanted substances so that the body can get rid of
them
(such as bilirubin, the chemical responsible for jaundice in liver
disease,
formed as a result of the re-processing of haemoglobin from red blood
cells).
On the other hand, the liver is very
simple, consisting
of millions of identical liver cells (hepatocytes), each of which
carries
out all the functions of the liver. Because one of the important
functions
of the liver is to clear toxic by products present in the blood, it has
a waste outflow system, the bile duct. This allows these unwanted
substances
to drain out into the bowel.
Blood, therefore, enters the liver (via
both an
artery-the hepaticartery, which supplies oxygen rich blood from
the
lungs via the leftside of the heart-and, uniquely in the case of the
liver,
a vein called the portal vein-which brings blood rich in absorbed food
products from the bowel) is treated by the hepatocytes and, now rich in
new proteins, etc made by
the hepatocytes, drains out and back to the
right
side of the heart via another vein, called the hepatic vein.
The unwanted products from the
blood are
meanwile "treated by the hepatocytes and expelled into a network
of tiny channels (bile canaliculi) which, like small streams at the
start
of a river system, join together to form progressively larger
bile
ducts (small rivers) which then go on to join together to eventually
form
the bile duct (a river) which drains into the bowel (an estuary).
In PBC..............
The smallest bile ducts (the streams in
my river
analogy) become damaged, narrowed and eventually blocked preventing the
normal flow of bile out of the liver. The damage to the bile duct
lining cells appears to be caused by the bodies own immune system
which,
for reasons that are at present unclear (although the subject of
much scientific research), attacks the cells as if they were infected
or
foreign to the body and ultimately destroys them. In the earliest
stages of PBC (when patients may have anti-mitochondrial antibodies
-AMA,
the characteristic blood antibody which is closely linked with
PBC
but normal liver blood tests) this damage to the bile duct cells
can be quite active. Later on in the disease, when there are few
bile ducts left, this immune attack may burn itself out.
Failure of bile to flow freely out
of the
liver appears to have a number of consequences. Firstly, bile
salts,
instead of being able to leave the liver in the bile, build up within
it.
Bile salts, although not part of the toxic waste being expelled from
the
body in bile (in fact, they are hitching a ride in the bile in order to
get to the bowel where they may help with the absorption of fat in the
diet), are toxic to the liver cells and may cause further secondary
damage
to them. This build-up of bile salts means that damage to the liver may
go on even if the immune system has stopped attacking the bile duct
cells,
and it is likely that this secondary damage plays a very significant
role
in the progression of PBC to Stage 4.
Secondly, the build-up of other toxins
in the
liver may lead to the typical symptoms of PBC, namely tiredness and
itching.
Thirdly, failure of bile salts to get into the bile and hence the
bowel may prevent the normal absorption of fat to the diet which may in
turncontribute to the weight loss, loose bowels and crampy abdominal
pain
seen in many patients.
Finally, failure to absorb fat soluble
vitamins
from the diet (if you can't absorb fat you can't absorb the vitamins
dissolved
in it) can contribute to, amongst other things bone disease
in PBC.
Many questions remain to be answered.
a.) Why does this whole process start,
and why does it pick the patients it does?
b.) Why does the disease progress in some patients
whilst the majority remain with stable mild disease
for many years?
c.) What is the precise link between the damage to
bile ducts and the symptoms of PBC?
All these questions are the subject of scientific
research currently being performed in the UK and
elsewhere in the world. In the next edition * of this
column, I hope to explain how our approach to the
treatment of PBC results from our understanding of
this disease process.
MedicalAdviser Dr David Jones Freeman Hospital
Newcastle UK
* The Bare Facts Newsletter UK
|
