Liver cirrhosis

Introduction:

irst, I would like to apologize for my long lecture.

However, it contains just what the doctor said except for couple
of diagrams. I added a plenty of figures from the internet to
enrich what you read with proper imagination. My ultimate hope
that I would accomplish what I meant to.

Preface:

s what in

our minds, liver cirrhosis

is a serious disease. It is a
fatal progressive disease
unless treated.
Nonetheless, cirrhosis
needs pathological
diagnosis; having a liver
tissue by what is called:
"Liver biopsy". It is defined as a process composed of three
components that are:
1. Necro-inflammatory reaction.
2. Fibrosis.
3. Formation of regenerative nodules.
All mentioned components lead to loss of the lobular and the
vascular architecture of the liver lobules and consequently loss
of their function.
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ANATOMY:
Histology:
We know the histology of the
liver; a hexagonal shape. The
hexagonal structure contains a
central canal; vein. At the
meeting of each three lobules,
there is what is called: "Portal
tract". A portal tract contains:
1) A branch of hepatic artery, 2) A branch of portal vein, and 3)
A branch of bile duct. In between the portal tract and the central
vein, there are sheets of hepatocytes in addition to 1) Biliary
canaliculi and 2) Sinusoids penetrating those sheets. So, the
structure of the liver is very delicate in a way that is necessary
for its proper function. However, loss of this structural
architecture causes inability of functioning normally even with
healthy hepatocytes. Such pieces of information are important
for understanding the pathogenesis of liver cirrhosis concerning
the "Regenerating nodules" as they are a response to injury but
with a lack in the original architecture.

Gross Anatomy:
See the two blood sources of the
liver: Portal vein and the Hepatic
artery. Portal vein brings all
necessary nutrients to the liver
from gastrointestinal tract while
hepatic artery brings Oxygen from
lungs.
The portal vein is formed by the
union of the superior mesenteric
vein which comes from the small
intestine and the splenic vein
which brings blood from the spleen, stomach, and the lower part
of esophagus. Left gastric vein can empty in the portal vein and
can empty in splenic vein. Some other times, the inferior
mesenteric vein drains into splenic vein.
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See the nearby figure.

Blood of portal vein and
hepatic artery will enter the
mentioned sinusoids in the
liver, then mixed and get
drained by hepatic veins
which are systemic as they
empty immediately in the
inferior vena cava.
Actually, this is the reason
why the first organ to be
affected in congestive heart
failure is the liver. Stasis and congestion is transferred from the
heart to the IVC and to the hepatic veins. Consequently, what
we call "Cardiac hepatomegaly" results.

Etiology:

iver cirrhosis can result because of any of the causes

mentioned below but the order of these causes differs according

to the area where you work:
1. Hepatitis B & C. Hepatitis is the most common cause of
liver cirrhosis in our area. Dont forget that Hepatitis A
&E NEVER cause cirrhosis, not in any percentage, as
they cause acute inflammation. Hepatitis B is associated
with a higher percentage in causing cirrhosis than that with
C.
2. Alcohol is another cause. In areas like Scotland and
Ireland, it the commonest cause of liver cirrhosis.
3. Biliary disease either: 1) Primary biliary cirrhosis. Or 2)
Secondary biliary cirrhosis. We talked about them in the
lecture of liver's investigations as primary biliary cirrhosis
is an autoimmune disease while the secondary biliary
3

4.
5.

6.

7.

cirrhosis occurs due to obstruction in the biliary tract due

to a stricture, a stone or a tumor.
Autoimmune hepatitis may progress into cirrhosis.
Vascular causes. Many times, we find patients
complaining of right sided failure, CHF or pericardial
effusion then constrictive pericarditis. These patients may
develop congestive hepatomegaly with time, persistence
and uncontrollability of vascular causes. Over a year or
more, they will develop cirrhosis that is called "Cardiac
cirrhosis" that differs from other types where the insult is
mainly around the central veins. While patients who came
from the inferior vena cava or other venous diseases are
called to have veno occulusive disease; occlusion in the
central veins themselves like in Budd chiarry syndrome
which has occulosion in the hepatic veins .. The
vascular causes that are involved with cirrhosis are either
associated with the heart , occlusion in the hepatic veins
or occlusion in the central small veins.
Drugs: Drugs should be always suspected with a patient
having hepatic disease. Examples include: a)Toxins as
some herbs used for treatment for other illnesses may lead
to live cirrhosis. b) Substances used in committing suicide
like CCL4. c) Alcohol. d) Aphlatoxins. e) Benzene ..
Always ask cirrhotic
patients about drugs.
Hereditary and metabolic
causes like:

A) Hemochromatosis: It is a
disturbance in the metabolism
(absorptionVI) of iron resulting
in more iron deposited in organs.
This process needs time and
occurs in elderly aging more
than 40. It doesnt occur in
females as they menstruate.
Menstruation is going to act like
4

***A patient having hemochromatosis with

porphyria cutana tarda and hepatoma.***

venesection till a female menopauses when she develops

hemochromatosis.
B)Wilson disease : Disturbance in the metabolism of the copper
leading to deposition of copper in the liver. In contrast to
hemochromatosis, the defect is in the excretion of copper not
the absorption. Wilson's patients develop manifestations early
in life in ages around 10, 15 years ..
C) Alpha 1 antitrypsin deficiency: Develops in middle aged
patients. A characteristic feature of this disease is the
accompanying emphysema. Dont forget this combination.
8. Non-Alcoholic SteatoHepatitis " Non-alcoholic fatty liver
disease " or as its abbreviation ( NASH ); deposition of fat
in liver cells.
We used to think that fat in the body is benign and is just a manner of storage. But now, it
is proved that it is a sort of inflammation in all tissues including the liver and blood
vessels Atherosclerosis which is proved to be an inflammatory process with increased
incidence in central obesity (Apple shaped body) not whose body is all over obese.

Photomicrograph on right shows transformation of fatty liver into a cirrhotic liver, on left
shows histology of nonalcoholic steatohepatitis in 62-year-old woman. Mallory's hyaline
bodies (pink filamentous structures, black arrowhead) are cytoplasmic inclusions in
hepatocytes consisting of abnormal keratin, hyaline, and other proteins. They are usually
found in hepatocytes that are ballooned (black arrow) and are morphologic hallmarks of
alcoholic and nonalcoholic steatohepatitis. Mallory's bodies are not cause but rather
consequence of cellular injury. Usually hepatocytes with Mallory's bodies do not contain
large fat vacuoles, although microvesicular fat may be seen. In this frame, other
hepatocytes are present, containing macrovesicular fat globules (white arrow), which
occupy almost all cytoplasm, displacing nucleus (white arrowhead) to periphery. (H and E,
x 400) (Courtesy of Romil Saxena, Department of Pathology, Indiana Universtiy School of
Medicine) .Extra info
5

Fatty liver leads to an inflammatory condition and a release of

cytotoxins and cytokines. Such an inflammatory reaction in the
liver leads to liver cirrhosis, Hepato Cellular Carcinoma, liver
failure and death.
9. Cryptogenic liver cirrhosis: unexplained liver cirrhosis
according to the reliable current science.

Features of liver cirrhosis:

s we said, liver cirrhosis is a continuous progressive

process that proceeds until all hepatocytes become destroyed

and functionless. Despite the presence of healthy tissues in a
cirrhotic liver but there is a loss of their architecture leading to a
loss of function.
We can divide cirrhotic symptoms according to what caused
them into two main categories
1- Portal HTN; due to disturbance in the architecture of the
liver preventing blood to go up.
2- Liver cell dysfunction; due to the individual failure of the
liver cells. We know that a hepatocyte is required to do
many jobs that some are synthetic, others are catabolic,
and others are excretory..
Renal cells have a much easier job and most of their functions
are excretory except for vitamin D and erythropoietin. We can
compensate for their loss whereas functions of hepatocytes can
be not. That is the logical reason behind not having artificial
liver or liver dialysis.

Pathogenesis: Composed of two parts:

Portal hypertension:

Illustrations:
Portal pressure should be around 5-6 mmHg. Portal
hypertension is defined as an elevation of portal vein pressure to
more than 10 mmHg due to anatomic or functional obstruction
to blood flow in the portal venous system. Portal hypertension
6

occurs when there is fibrosis in the liver preventing the flow of

the blood through the liver. Portal vein becomes congested and
enlarges due to stasis and the blood pressure elevates in all areas
that are supplying the portal vein and they enlarge, dilate and
get congested. So, splenic vein will be congested and the spleen
as well; spleenomegaly. In addition, the gastric veins will be
congested and problems follow parts they drain. Superior
mesenteric and inferior veins will have milder manifetations
because they have anastomosis with other veins.

Classification:
Portal hypertension is classified into:
A.Pre-sinusoidal portal hypertension: Due to causes
that are present before liver's entrance (Portal vein).
An example is portal vein thrombosis with a normal
healthy liver.
B. Sinusoidal: Due to causes that are present inside the
liver (Sinusoids) such as cirrhosis. Another name for
this type is: "Sinusoidal cirrhosis".
C. Post-sinusoidal: Due to causes that are present after
leaving the liver (Hepatic vein). Examples include:
Budd chiari syndrome, veno-oclussive disease.

Note: The most important thing to know that a cirrhotic

liver, as the one above, leads to portal HTN through
elevation of BP in the sinusoids.

Consequences:
Portal hypertension can lead to:
7

1. Esophageal varices.
2. Splenomegaly and hypersplenism;
when a spleen enlarges, it will be
aggressive against all types of blood
components. So, instead of removing
old blood cells specifically, it will
destroy all RBCs, WBCs and platelets
however their state is. Consequently,
increment in the destruction of blood
components leading to anemia, thrombocytopenia,
and leucopenia. Please remember that the word
"Hypersplenism" names a hyperfunctioning spleen.
3. Ascites.
Ascitis
4. Hepatic encephalopathy.
Liver cell failure:

Manifestations:
As a hepatocyte is required to do multiple functions, its failure is
represented by many manifestations including:
1. Fatigue.
2. Low grade fever.
3. Fetor hepaticus (A mouth smell that is like toffah kharban
or a mouth with mouse-like-smell): It is caused by
absorption of toxins through intestines that
used to be excreted when the liver was intact.
As a result, toxins go through the circulation
and lungs are whom responsible for their
clearance producing that filthy breath.
4. Loss of muscle mass and subcutaneous fat:
Their limbs are cachexic while their abdomen
is distended.
5. Jaundice; increased accumulations of bilirubin.
6. Coagulopathy: A defect, decrement, in coagulation occurs
because the liver is the one which is responsible for the
synthesis of coagulation factors (Except for factor 8).
Thus, there will be bleeding represented by appearance of

ecchymosis, spots and hematoma all around the body.

Actually, cirrhotic patients can bleed easily from any site.
7. Low albumin: Albumin is exclusively
synthesized in the liver. When the liver gets
extensive chronic disease,
hypoalbuminemia develops.
Hypoalbuminemia's consequences are: a)
Lower limb edema. B) Defective healing;
Lower Limb Edema
albumin is required for the healing process.
8. Cardiovascular changes:
A) All patients with liver cirrhosis have warm extremities due
to their hyperdynamic state. This means that the pulse is
large in volume and collapsing in nature. Hyperdynamicity
and its consequences are due to AV shunts. In an AV shunt,
instead of completing into arterioles and venioles, an artery
will anastomose with a vein in an indirect shunt bypassing the
normal course a vasculature should follow.
B) Cardiac dysfunction due to cirrhosis: Please always
remember that cardiac failure results in liver cirrhosis and
liver cirrhosis causes cardiac problems.
9. Skin changes: Palmar erythema, spider nevi and
leukonychia.

A refilling spider
nevus

Leukonychia; white nail

Palmar Erythema

10.
Endocrine changes: In
males: infertility, decreased
potency, feminization
(Gynectomastia) and
testicular atrophy develop.
While in females: We find
Gynectomastia
infertility and amenorrhea.
11. Bone changes: They will have osteoporosis and
fractures.
12. Pulmonary changes:
Infections, pleural effusion, what is
called "Adult respiratory distress
syndrome", pulmonary
hypertension, impaired CO
diffusion, cyanosis.. And we may
put them on a ventilator. Liver
failure can mimic respiratory failure
as well.
13. Metabolic changes: impaired glucose tolerance,
hypoglycemia.
14. Ascites.
15. Hepatic encephalopathy.
(The last two manifestations; Ascitis and HE, were mentioned
in portal hypertension as well. So to get ascitis or HE, you need
both portal hypertension and liver cell dysfunction)
ALWAYS REMEMBER....

Liver can affect any part of the body

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Investigations in liver cirrhosis:

1. Biopsy is the gold standard for
diagnosis of liver cirrhosis. The
Diagnosis of cirrhosis is mainly
pathological as we said before.
There are things that prevent
biopsy to be done, an example is
Coagulopathy. As you know,
liver is a very vascular organ and
bleeding can result. So, we dont
do it always, however, if we want to
see the liver and we can't biopsy it
up, we get it while doing TIPs (Trans
jugular intrahepatic portal shunt).
Biopsy is the diagnostic test for
cirrhosis but usually when you see
features of portal hypertension and
liver cell dysfunction, you almost
properly are dealing with liver
cirrhosis.
2. Lab abnormalities:
Blood tests: Mild to moderate rise in AST and ALT
and you may sometimes find them normal.
Bilirubin and alkaline phosphatase may be mildly
elevated.
Low albumin.
Prolonged PT.
3. Non invasive measures to
evaluate for cirrhosis:
Laboratory tests:
APRI, Fibrotest (Dr
didnt talk about it).
Fibroscan: To assess
the stiffness, rigidity
or elasticity of liver
tissue by a special instrument. The more the level
11

of cirrhosis, the less the elasticity and the more

the stiff and rigid the liver is.

Clinical picture:
An idea:

s cirrhosis is a silent process, its patients dont come to

us unless they are in their terminal stages. The history of liver

cirrhosis starts with acute hepatitis, acute liver injury, then may
be converted into chronic liver disease and chronic liver disease
may progress into liver cirrhosis.
Please notify that not all acute liver insults are followed by
chronic ones. VI
Classification of liver cirrhosis: Liver Cirrhosis has two
stages:
1. Compensated cirrhosis; liver's functions are just sufficient
to make symptoms silent. This stage is what makes
patients come late in the second stage when manifestations
appear.
2. Decompensated cirrhosis; if the deterioration completes
and usually ends fatally..Terminal stage.

Clinical pictures associated with patients having Liver

cirrhosis:
1. Liver cirrhosis without Hepato-Cellular-Carcinoma; may
compensated or decompensated.
2. Liver cirrhosis with Hepato-Cellular-Carcinoma; any
cirrhotic patient may develop hepatocellular carcinoma
(HCC) which is a long story that leads to death apart from
liver cirrhosis.

Compensated Liver Cirrhosis:

A patient with compensated liver cirrhosis has no symptoms. In
rare cases, he might develop just fatigue. If you test him, you
may find abnormalities but not always. Nevertheless, you may
find signs of chronic liver diseases in the compensated stage
like: Spider nevi, palmar erythema, nail changes, gynectomastia,
12

testicular atrophy and hepatospleenomegaly. It is rare to find a

patient coming to you complaining of white nails or red spots
and so on .

Decompensated liver cirrhosis:

If a patient has one of the four criteria below, it would mean the
end of this pt as he is in the decompensated stage which is
usually a pre-terminal condition. The criteria are:
1. Jaundice: Bilirubin above 3 mg/dl.
2. Bleeding esophageal varices; esophageal varices are
asymptomatic but their bleeding is one of the worst types
of bleeding ever.
3. Ascitis.
4. Hepatic encephalopathy.

Notification:
There is an extremely important point: Most of patients with
chronic liver disease would have had their acute liver disease
MILD that passed unfelt or sub clinically. So, those patients
may deny any complaint of hepatitis. In addition, as all stages
are silent, conversion into decompensated stage is sudden and
leads to death or to HCC that leads to death as well.

Chronic liver disease

Compensated Cirrhosis

Hepatocellular Carcinoma
Decompensated cirrhosis

Death

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Now, we are going to discuss the four manifestations

of Decompensated liver cirrhosis each under a
headline...

Jaundice:
It is discussed in its own lecture.

Esophageal varices:
Overview:Esophageal varices is one of the worst complications
that can occur due to liver cirrhosis. It develops due to
prevention of blood from going to the systemic circulation
resulting in portal hypertension. As a result, the
blood is going to try to find an exit other than
liver to pass into the systemic circulation. By
searching upon the nearby veins, it increases
the pressure in collaterals (anastomotic
channels between portal and systemic). The
usual location of those collaterals is present in
lower esophagus and occasionally in gastric
fundus. These collaterals are adapted to a
Early varices
certain amount of blood that is less than the
new one. This will lead to congestion and
toturtousity of those blood vessels. These BV
are not healthy and may rupture at any time
leading to a massive severe bleeding which is
the worst type of acute upper gastrointestinal
bleeding.

Treatment:
We have many options including:
1. Resuscitation and blood transfusion as
needed (The most important) and it is usually needed.
2. Use of somatostatin, octreotide or
Moderate varices
glypressin to decrease the portal
pressure and it resultants; bleeding.

14

3. Variceal band ligation ( See the figure below to the left): A

way to stop bleeding that is better than
Sclerotherapy(described below). A band is made of rubber
and put through the endoscope to
suck the varice. Once you fire the
band, tie the vein from its end. In two
to three days, it heals with some
erosions then erosions disappear as
well. It is the best technique to stop
bleeding. We should do regular
endoscopy sessions to patients with
liver cirrhosis in order to detect any
Advanced varicesabove
varices before they rupture.
Large esophageal varices
with red spots on their
surface - indicating a high
risk of bleeding.below

4. Sclerotherapy injection: An example of a sclerosing agent

is Ethanolamine oleate which is a type of alcohol that
will mimic fibrosis in that area.

15

5. Drugs to lower portal pressure: B-blockers, nitrates,

carvidolol.
6. TIPS ( Transhepatic
Intrajugular Portosystimic
Shunt ): A technique that
provides an exit for the
portal circulation into the
systemic through routes
other than collaterals. By this
technique, we put a stent in
the liver between the
systemic circulation and the
portal circulation. ( Hepatic
veins drain into IVC and, thus, is the representative of the
systemic circulation). All the work will be through
branches not the major veins. Radiologists are who
perform this technique. This technique is useful in
treatment of esophageal varices. For futher understanding, see
the figure about the procedure in page 28.
7. Surgical shunt operations: these are done when other
manipulations fail . What we do here is bringing a
branch of the portal vein and transplant it in the systemic
circulation directly (We mean here the IVC not hepatic
veins). The 1st patient who was manipulated in this way
had his portal vein cut and anastomosed to the IVC; endto-side procedure. That patient died the day after the
procedure. Death was the result of shifting toxins into
systemic circulation bypassing the liver and leading to
hepatic encephalopathy manifested by comma which is
mostly followed by death. Then, doctors decided to pass
half the blood to the IVC by side-to-side junction. The
patient died two or three weeks later. Then, they thought
that opening a passage away will compensate even if after
a while. So, they did a shunt between splenic vein and the
renal vein of the systemic circulation. It is a long way but
the best one as not all the blood will be shunted. This shunt
is called "Splenorenal shunt" It is better than portacaval
16

shunt (Both end-to-side or side-to-side). TIPs is a type of

shunt which is not a surgical one but a
Nonselective
portosystemic shunts
either immediately or
eventually divert all
portal blood flow from
the liver into the
systemic venous
circulation. Shown are
the four main variants:
(a) end-to-side
portacaval shunt, (b)
side-to-side portacaval
shunt, (c) interposition
shunt (portacaval [1],
mesocaval [2], and
mesorenal [3]), and (d)
conventional
(proximal) splenorenal
shunt.

radiological one and is

not to shunt blood but to decrease the portal pressure a little bit.

Ascitis:
Definition:
It is an accumulation of fluids in the
peritoneal cavity of the abdomen
distending it forwards. It can be
unfelt if occurred in obese patients
but if the patient is thin, the abdomen
starts soon to increase in size.

Etiology:

In cirrhosis, ascitis results from 2 main pathogenic

mechanisms:
1. The main mechanism is sinusoidal hypertension
which sends signals to the kidney to conserve the
17


1.
2.
3.
4.

sodium and fluids. This leads to exudation of fluids

in the peritoneal cavity and the resulting ascitis.
2. Sodium retention secondary to systemic and
splanchnic vasodilatation.
Other causes for ascitis:
Hypoalbuminemia whether by nephrotic syndrome,
malnutrition.
Lymphatic exudation.
Cardiac dysfunction CHF.
May result from a tumor or an inflammation (peritonitis)
in the peritoneal cavity.

Stages:
Stages of ascitis are:
1. Preascites stage; during which signals are transferred from
liver to kidneys due to splanchnic vasodilatation and AV
shunts. So, kidney is going to understand the situation as
having decrement in the body fluids and pressure and will
try to preserve normal pressure values by increasing the
levels of aldosterone to conserve more sodium and fluids.
2. Diuretic responsive ascitis: The stage where diuretics can
relieve the ascetic fluids.
3. Refractory ascitis: When diuretics become ineffective and
abdominal distention persists unless we take the fluids out.
4. Hyponatremia: A very dangerous stage due to the
communication between the liver and the kidney with
relative (not absolute) decrement in the sodium levels with
its sequences.
5. Hepatorenal syndrome: The final fatal condition in which
the kidney strikes (Stops working) despite its normal
healthy structure and blood supply.

Treatment:
1.
2.
3.
4.

Sodium restriction and bed rest. Initially

Spironolactone we need to give it with
Loop diuretics.
Albumin infusion to correct hypoalbuminemia.

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5. Large volume paracentesis

When diuretics fail Removal of
fluids from the abdomen is called
"Paracentesis".. See the nearby
figure
6. TIPS It is also beneficial in case
of ascitis. It decreases the portal
Related to point 6: TIPs is used in
pressure, then the sinusoidal pressure ascitis and esophageal varices but
and so decreasing the pathogenicity
the problem of a TIPs is like the
problem of any shunt may lead
of ascitis.
to hepatic encephalopathy.
7. Peritoneovenous shunts by opening a
hose or a stent between the peritoneal cavity that has the
fluids and the SVC in order to shift the fluids from the
cavity back to the system.
8. Liver transplantation is the only beneficial and long-term
treatment we can achieve.

Hyponatremia (comes with ascitis):

The basic idea:
This hyponatremia is a dilutional not an absolute one. In Ascitis,
portal hypertention leads to systemic and splanchnic
vasodilatation. Kidney reabsorbs a lot of both Na and water in
respose to the false alarm of hypotension. However, the
percentage of water is much much more due to such a retention.
Actually this dilutional hyponatremia is mainly attributable to
impaired free water excretion through the non-osmotic release
of VASOPRESSIN. This will lead to more absorption of fluids
in order to compensate for the low circulatory volume that
occurs.

Notifications:
1. Hyponatremia occurs in patients having cirrhosis and
ascites.
2. It is usually asymptomatic because it develops slowly.
3. It may lead to hepatic encephalopathy, increased mortality
in pre and post transplantation.

Treatment:
1. Fluid restriction to less than 1L/day to compensate for the
percentage.
19

2. Plasma expansion with IV Albumin infusion.

3. Vasopressin receptor antagonists. New edition of drugs.

Hepatorenal syndrome (HRS):

An idea:
HRA is a fatal condition that
requires a patient to be cirrhotic
and ascitic. The problem in such a
complication is the development
of renal failure despite normality
of structure (An evidence on that
is the fitness of that failed kidney
if removed for cadavaric
transplantation). It develops in
patients having refractory ascitis.
It can be explained by the
decrement in renal perfusion
which elicits an increment in urea
and creatinine in blood.

Classifications; types:
There are 2 Types of hepatorenal
syndrome:
Type 1: Rising serum creatinine to more than 2.5 mg/dl
within 2 weeks. Fatal condition This means that this
patient will die in 2-3 weeks.Within one month.
Type 2: Slowly rising creatinine: more than 1.5 mg/dl in
more than 2 week (Over 1-2 months)This patient has a
better prognosis but not that lot. He will die within 6
months.

Notifications:

When a patient has renal failure after hepatic cirrhosis, it

means that the patient is going to die soon. So, check
creatinine and classify it according to the levels. Dont
forget to check for urea levels as well.
Sodium in urine will be less than 10 mmol/L.
Ascitis and hyponatremia are usually present.
20

 Carries a very poor prognosis.

Treatment:
Surgical: In these pts, the only thing is liver
transplantation and you should compete transplantation
before the kidney fails functionally or structurally. Be
aware to save the situation especially before structural
damage in order not to do a combined hepatorenal
transplantation.
Conservative: Preparing the liver before transplantation:
1. Discontinue diuretics and expand the intravascular
volume with IV albumin and antibiotics.
2. Factors known to precipitate renal failure in cirrhosis
(infection, fluid or blood loss, hypotension) need to
be investigated, and if present, should be treated.
3. Vasoconstrictors and albumin infusion may be
helpful.

Spontaneous (Primary) Bacterial Peritonitis (SBP):

An idea:

There is another type of

peritonitis that is "Secondary
peritonitis" which occurs
when there is perforated
viscous. This infection in the
peritoneal cavity will be
associated with multiorganisms.

It is another complication that develops in

patients with ascitis and may end fatally.
SBP is the most common bacterial infection
in hospitalized cirrhotic patients. There will
be a bacterial invasion through a process called
"Translocation" from intestine. Remember. It is from the
intestine not from the blood stream. This inflammation is
usually monomicrobial.
SBP should be suspected if there is:
1. Fever (may be absent as well): There may be fever with or
without infection along with abdominal pain, tenderness
and leukocytosis.
2. Unexplained encephalopathy (hepatoencephalopathy),
jaundice or worsening renal manifestations.

Diagnosis:

21

Diagnosis of SBP should be established by paracentesis of the

ascetic patient; polymorphonuclear cell count will be > 250
cells/mm3.
Treatment: Should be initiated before obtaining bacteriological
culture results and we use:
1. The third-generation cephalosporins (cefotaxime,
ceftriaxone) are the agents of choice.
Or we do it as a prophylactic therapy .
2. Daily norfloxacin, ciprofloxacin or DS Co-trimoxazole are
effective in preventing SBP recurrence because SBP will
shorten the age of the patient.

Hepatic encephalopathy (HE):

An idea:
It is the worst complication of liver
Normally, ammonia is absorbed
cirrhosis. It is a Neuropsychiatric
from intestines where there are
bacteria acting on ingested proteins
syndrome in patients with advanced
to produce it before being
liver disease. A liver is responsible for
detoxification of substances coming into absorbed. Then, it accumulates in
the circulation in large amounts.
it. The main toxin we are talking about
When goes to the liver, it is
is ammonia. Ammonia accumulates in
converted into urea which is easy
the circulation, of cirrhotic patients, and to be cleared by the kidneys. When
bypasses the liver through
the liver is diseased, it will not
produce urea.
portosystemic shunts to the areas of
esophageal varices and others.
However, the detoxified ammonia goes to the brain making this
syndrome and this is the main mechanism of developing hepatic
encephalopathy.

Features:
1. Deterioration in the level of
consciousness.
2. Behavioral and psychiatric changes.
3. Lack of concentration.
4. Sleep disturbances; a patient with HE
will sleep during day and awake during
night.
5. Flapping tremors (See the nearby
22

figure); characteristic but not specific. To elicit this

tremor, ask the patient to extend his hands and
hyperextend his wrists and they will move spontaneously
this way..

Classification: ( Not important except for type C)

What we see usually is the C type:
Type A: Associated with ACUTE liver failure.
Type B: Associated with (Bypass) portosystemic shunts
without cirrhosis.
Type C: Caused by Cirrhosis and it has 3 stages:
1. Minimal stage hepatic enceohalopathy; subclinical HE.
This stage is not apparent but with a special test. This is
dangerous as patients with this type drive with us every
day and they could be cabs, truck drivers so you should
identify them as early as possible.
2. Persistent HE.
3. Episodic (Recurrent) HE: Usually these patients can be
dealt with and attacks can be preventd.

Illustrations on episodic HE:

HE is usually is the end result of liver cell failure and with time
will end in comma and dies. Nonetheless, sometimes the pt will
enter in between the life and the death, in the other world as the dr
said, and with treatment they recover. This is called "Attacks of
hepatic encephalopathy" and the condition is called "Episodic
hepatoencephalopathy" that is usually precipitated by many
conditions like renal failure, high protein ingestion, GI bleeding,
surgical hemorrhages, hypokalemia, constipation, drugs (as
diazepam, sedatives and narcotics..), infections all of them
are precipitating factors that should be identified to be treated
because if not, pt will have a HE attack and will die following a
comma.

Treatment of HE:
1. Identify and treat the underlying cause.
2. Lactulose; a laxative and the main line of treatment of HE.
(The reason is clarified below).
3. Antibiotics: Neomycin (not available in KAUH),
metronidazole (hepatotoxic if used in more than a week),
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rifaximin These are specific to the bacteria of the GUT

Give antibiotics just for one week not more as most of
the bacteria develop resistance.
4. All of these patients should be considered as candidates for
liver transplantation. As transplantation is the definitive
treatment.
5. Drugs that metabolize ammonia:
To hippuric acid: sodium benzoate.
To glutamine: L-aspartate, L-ornithine (LOLA).
6. Extracorporeal albumin dialysis.
An illustrative diagram on HE is present in page 29

About lactulose.
An idea:
Lactulose is associated with lactose that is present in milk and
called milk sugar. Many people can digest lactose except for
some who has lactase defeciency. Lactulose, like the lactose, is
a disaccharide but is composed of galactose and fructose (While
lactose is composed of galactose and glucose).

Advantages:
1. There is no human being who can digest lactulose so it is
not absoped as it is not digested. We cant absorb
disaccharides unless digested into monosaccharide.
Lactose can be digested by lactase into galactose and
glucose. For lactulose, there is no enzyme to digest it into
galactose and fructose.
2. It acts in the GI as a laxative and washes all the
continents... It is an osmotic laxative.
3. Certain bacteria has lactulase and acts on lactulose but
coverts it into fatty acids instead of galactose and fructose.
It produces gases and water as well.
4. Due to the point above, no.3, fatty acids will lower pH of
the colon.
5. Suppression of ammonia-producing- bacteria as acidic
medium is not favorable for them.
6. Decrement in the absorption of ammonia due to increased
acids by converting it into ammonium salts instead of
being free ammonia . Salts are not absorbed.
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7. Fatty acids may stimulate more diarrhea in the colon

washing proteins and mucosa as well as bacteria.
8. Encouragement of growth of lactobacillus species the
enemy of ammonia-producing-bacteria.
Important notes:
We dont give lactulose in acute stage only but also after
recovery of the patient from HEs comma and we maintain
all patients of HE on lactulose.
Give lactulose anyway you can.. Through mouth if
patient is awake, by Nasogastric tube if uncoscious or
rectally through enema if you couldnt put NG tube.
Treatment by lactulose if the first line but after
identification of the precipitating factors.
Advice your HE patient not to ingest a lot of proteins but
enough proteins that are necessary for their metabolism. If
these patients have hypoalbuminemia, we cant prevent
them from protien ingestion.

Hepato Cellular Carcinoma:

his disease ends fatally.

Risk factors:
Cirrhotic patients are at increased risk
for HCC especially:
1. Hepatitis B (Hep B is the most important anyone with a
marker of Hep B is more liable to develop HCC even if
there is no cirrhosis ) and Hepatitis C (doesnt cause HCC
unless if there is cirrhosis ).
2. Alcoholic cirrhosis.
3. Genetic hemochromatosis.
4. Primary biliary cirrhosis.

Notes:
Screening is for any patient with cirrhosis is essential to
detect early appearance of HCC by:

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1. serum alpha-fetoprotein (AFP) testing; raised in pt

with HCC.
2. ultrasonography; space occupying lesion.
Screening is to be done at intervals of 6 or 12 months.
There is treatment for HCC at certain stage but in
advanced stage there is no treatment.

Liver transplantation:
An idea:

ransplantation is the ultimate treatment of liver

cirrhosis especially if you cant find the cause or you cant arrest
the disease progression. If we can find the cause or can stop it,
we can regress the process of cirrhosis. The development of
decompensation (ascites, variceal hemorrhage, HE) in patients
with cirrhosis is associated with a median survival of only 1.5
years. So, liver transplantation should be considered in these
patients.

Assessments for liver transplantation:

In order to assess the priority of patients for liver transplantation
from cadavers, we have 2 scoring systems that are:
The Child, Tutcotte, Plough (CTP) score which is based
on 5 parameters:
1. Encephalopathy.
2. Ascites.
3. Bilirubin.
4. Albumin.
5. prothrombin time.
The MELD score: Depends on 3 objective variables:
1. Creatinine.
2. Prothrombin time international normalized ratio.
3. Bilirubin.
There are two types of liver transplantations either:
1. From a dead person and called cadavaric transplant
or graft.
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2. From a Living donor: The Right lobe of liver (half of

his liver) from the donor transplanted in the patient
(recipient).
Luckily, the transplantation is greatly successful with 5year-survival of more than 80% which is a good
percentage.
References:
For scientific material:
Doctors sonic lecture.
Doctors slides.
For figures:
Doctors slides.
The following web-links:
http://altered-states.net/barry/update200/
http://radiographics.rsna.org/content/28/2/359/F3.expansion
http://1aim.net/fourm/showthread.php?p=125780
http://www.ajronline.org/cgi/content-nw/full/190/4/993/FIG3
http://dermis.multimedica.de/dermisroot/en/35559/image.htm
http://www.gihealth.com/newsletter/previous/022.html
http://www.plasticsurgery4u.com/gynecomastia_gallery/teenage_gyno_gallery.htm
http://www.nucleusinc.com

http://web.uct.ac.za/depts/liver/page%20patient%20having%20a%20biopsy.htm
http://www.hivandhepatitis.com/hep_c/hepc_news_liver_biopsy.html
http://www.union.org/gicentre/fibroscan_e.htm
http://www.gastrohep.com/images/image.asp?id=570
http://www.medscape.com/viewarticle/463473_4
http://gastro.dom.uab.edu/cirrhosis/treatment.html
http://www.heart-intl.net/HEART/011507/PortalHypertension.htm
http://www.endo-mds.com/Pages/Paracentesis.html
http://homes.jcu.edu.au/path/Pathology%20Database/Term2/Hepatobiliarypancreas/G
I%20-%20Liver/image_39.html
http://legacy.owensboro.kctcs.edu/gcaplan/anat2/notes/Notes8%20Digestive%20Anat
omy%20II.htm
The best link I found through all over the web sites is this one of Johns Hopkins
medicine.illustrations on Liver cirrhosis for further understanding esp for
sclerotherapy. I couldnt you with its figures because of copy right
http://www.hopkinsgi.org/GDL_Disease.aspx?CurrentUDV=31&GDL_Disease_ID=9ED2FD7351A1-49E1-B77A-D4B753B384AD&GDL_DC_ID=9AA60584-3607-4D15-A459-BD3F67A3A4A7

27

Depicted is the procedure for performing TIPS. (a) A needle is

passed under radiologic guidance from a hepatic vein into a
major portal venous branch, and a guide wire is advanced
through this needle. (b) A balloon is passed over the guide wire,
creating a tract in the hepatic parenchyma. (c) An expandable
stent is placed though this tract. (d) The effective result is a
nonselective portosystemic shunt.

AN EXTRA
28

Staining for nitrotyrosine in the cerebral cortex of a portacaval-shunted rat receiving

an ammonia infusion. The upper right-hand picture shows glial fibrillary acidic protein
(GFAP) positive astrocytes in the cerebral cortex. The upper left-hand picture shows
nitrotyrosine staining in astrocytes; the lower right-hand picture reveals the overlap of
GFAP and nitrotyrosine staining in cortical astrocytes. Methods: Ammonia (55
mol/kg/min) was infused through the femoral vein for 3 hours. At the end of the
infusion, the brain was fixed by the perfusion-fixation method. After blocking with 1%
bovine serum albumin (BSA) and 5% goat serum, cerebral cortex sections were
incubated overnight in rabbit antinitrotyrosine antibody (Upstate Group
[Charlottesville, VA], 1:75) at 4C followed by incubation in Alexa Fluor 488 antirabbit
secondary antibody (Molecular Probes [Eugene, OR], 1:400) for 1 hour at 25C.
Following nitrotyrosine staining, astrocytes labeling was revealed with an overnight
incubation in mouse anti-GFAP antibody (Chemicon International [Temecula, CA],
1:1000) at 4C followed by incubation in Alexa Fluor 568 anti-mouse secondary
antibody (Molecular Probes, 1:400) for 1 hour at 25C. The fluorescent-stained slides
were scanned using a LSM 510 confocal microscope.

Ahmad Monther Nazzal

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