HEPATOBILIARY SYSTEM WORKSHOP
Case 1
A 38 year-old man was referred to hospital for investigation of a 6 month history of
increasing tiredness, weakness, loss of weight and upper abdominal discomfort. He had
vague digestive symptoms, which included anorexia and gaseous abdominal distension.
The patient gave a history of excess alcohol intake for 20 years. He had also injected
heroin from the ages of 18 to 22 years, but not since. His G.P. had prescribed antidepressants in the past two months.
On examination his sclerae were a pale yellow and he had facial spider naevi and palmer
erythema. The liver and spleen were palpable, the former felt very firm but not tender.
He was noted to have testicular atrophy but no gynecomastia.
His blood count was normal apart from slightly reduced platelets. Liver blood tests
revealed:
bilirubin 60 μmol/l (N. 0-17)
AST 120 iu/l (N. 7 – 40)
ALT 200 iu/l (N. 7-35)
Alk. phosphatase250 iu/l (N. 30 – 100)
gamma glutamyl transpeptidase 300 iu/l (N. 10 – 55)
Total protein 25g/l (N. 60 – 80)
albumin 28g/l (N. 35 – 50)
HCV antibody was positive
PCR negative
HBV markers were negative
Ferritin and alpha-1-antitrypsin levels were normal
Question 1
What is the basic underlying condition in this patient?
Answer:
Question 2
What is the significance of
a)
The hepatomegaly
b)
The splenomegaly?
Answer:
Question 3
What are the possible aetiological factors suggested by the clinical history?
Answer:
Question 4
What is the most likely cause of the thrombocytopenia?
Answer:
Question 5
What does the
a)
raised transaminases and γGT
b)
raised alkaline phosphatase
c)
low serum albumin indicate?
Answer:
Question 6
Explain the HCV serology
Answer:
Question 7
Why are serum ferritin and alpha-1-antitrypsin (AAT) of importance in this case?
Answer:
Question 8
What investigations would you suggest should be done at this stage?
Answer:
Contrary to medical advice the patient continued to consume large quantities of alcohol.
After a particularly heavy bout of drinking, he was admitted to hospital in a confused
state. He had been taking paracetemol for muscle cramps and was severely constipated.
On examination he had foetor hepaticus, a flapping tremor (asterixsis) and hyper-reflexia.
The abdomen was distended and tense due to marked ascites. Abdominal paracentesis
was done to relieve the tension. There was peripheral oedema of the lower limbs. He
was jaundiced and had scattered petechial haemorrhages on the skin. Liver blood tests
were markedly raised. Bilirubin was now 250 μmol/l. Prothrombin time (PT) and
activated partial prothrombin time (APTT) were prolonged. Despite supportive therapy,
he developed deepening jaundice and coma and renal failure and a low-grade fever.
Question 9
What does the confusion, deepening to coma, flapping tremor and hyper-reflexia
indicate?
Answer:
Quest 10
What may have precipitated this?
Answer:
Question 11
What does the prolonged PT and APTT indicate?
Answer:
Question 12
The ascites was tapped and an aliquot sent to the laboratory for analysis. What do you
expect ascitic fluid to show?
Answer:
Question 13
The low grade fever suggests infection. Where might this be located?
Answer:
Question 14
An autopsy was conducted. What do you expect were the findings in the following
organs:
peritoneal cavity
liver
spleen
oesophagus
kidneys
Answer:
Case 1
Answer 1
Chronic liver failure. Although his symptoms are non-specific, the jaundice, skin
changes and endocrine changes (testicular atrophy) are pointers to this.
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Case 1
Answer 2
a)
b)
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continuing liver damage and inflammation.
suggestive of portal hypertension and therefore of cirrhosis.
Case 1
Answer 3
Alcohol is the most likely. Viral hepatitis as a co-factor is possible in view of the history
of IVDU. Drugs can cause chronic liver disease but in this case the timescale indicates
that the liver disease pre-dated the anti-depressant therapy. Furthermore anti-depressants,
when they do cause liver disease, cause a hepatitis or cholestatic hepatitis.
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Case 1
Answer 4
Hypersplenism, that is increased destruction of platelets in the enlarged spleen.
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Case 1
Answer 5
a) continuing liver cell damage, the γGT indicating peri-venular (zone 3) damage.
b) an element of obstruction, this is a feature of liver blood tests in alcoholic liver
disease.
c) failing synthetic function of the liver.
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Case 1
Answer 6
The patient has had infection with HCV in the past and developed antibodies thereto.
The negative PCR excludes circulating viral particles. There is an increased prevalence
of HCV infection in alcoholic patients. Continuing chronic infection accelerates
progression to cirrhosis. The patient, however, appears to have cleared the virus.
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Case 1
Answer 7
A raised serum ferritin would point to the possibility of haemochromatosis with
implications, not only for the patient, but for his family. It can, however, be raised in
extensive hepatocyte necrosis through release of stored ferritin. A low AAT would
indicate AAT deficiency as a possible co-aetiological factor in the liver disease.
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Case 1
Answer 8
Imaging (US, CT) of the abdomen: an abnormal liver pattern can be seen with fatty
change and cirrhosis.
OGD to look for oesophageal varices, evidence of portal hypertension and a potential
source of gastrointestinal haemorrhage.
Liver biopsy to determine the presence or absence of cirrhosis, indicate the aetiology if
possible and identify the presence of any other liver disease.
Liver biopsy is required in alcoholic liver disease to distinguish between fatty change,
alcoholic hepatitis and cirrhosis. All three may co-exist in the same biopsy however.
This patient’s biopsy showed micronodular cirrhosis with fatty change and alcoholic
hepatitis. There was a mild siderosis in Kupffer cells and hepatocytes, sometimes seen in
alcoholic liver disease. The degree of chronic inflammation did not suggest a
concomitant HCV and stains for HBsAg, copper-associated protein and AAT globules
were negative
Here are seen the lipid vacuoles within hepatocytes. The lipid accumulates
when lipoprotein transport is disrupted and/or when fatty acids accumulate.
Alcohol, the most common cause, is a hepatotoxin that interferes with
mitochondrial and microsomal function in hepatocytes, leading to an
accumulation of lipid.
Mallory's hyaline is seen here, but there are also neutrophils, necrosis of
hepatocytes, collagen deposition, and fatty change. These findings are typical for
acute alcoholic hepatitis. Such inflammation can occur in a person with a history of
alcoholism who goes on a drinking "binge" and consumes large quantities of alcohol
over a short time.
At high magnification can be seen globular red hyaline material within
hepatocytes. This is Mallory's hyaline, also known as "alcoholic" hyaline because it
is most often seen in conjunction with chronic alcoholism. The globules are
aggregates of intermediate filaments in the cytoplasm resulting from hepatocyte
injury.
Micronodular cirrhosis is seen along with moderate fatty change. Note the
regenerative nodule surrounded by fibrous connective tissue extending
between portal regions.
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Case 1
Answer 9
Hepatic encephalopathy. This disorder of cerebral neurotransmission is due to liver
failure and porto-systemic shunting of blood. Nitrogenous compounds from the bacterial
breakdown of protein in the colon have been incriminated. This is the basis for
attempting to reduce gut bacteria and for advising a low protein diet.
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Case 1
Answer 10
The recent increase in alcohol intake worsening the fatty change and alcoholic hepatitis.
Constipation caused by the paracetamol would be another precipitating factor.
Paracetamol itself is toxic to the liver, especially in the presence of alcohol intake. Other
factors which can precipitate hepatic encephalopathy include gastro-intestinal
haemorrhage, increased protein intake in the diet, infection, hypokalaemia and drugs such
as sedatives, anti-depressants and hypnotics.
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Case 1
Answer 11
The onset of a coagulopathy with risk of bleeding. The prolonged PT (N. 12 – 15 sec)
indicates deficiency of factors II, V and VII.
The prolonged APTT (N. 30 – 40 sec) indicates deficiency of factors II, V, VIII, IX, X,
XI and XII.
This is due to failing synthetic function of the liver.
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Case 1
Answer 12
A straw coloured liquid with low (<25g/l) protein content (transudate) and a few scanty
mesothelial cells and lymphocytes. The pathogenesis of ascites is complex but is
basically due to salt and water retention by the kidneys, reduced oncotic pressure in the
circulation due to low serum albumin and localisation in the peritoneal cavity due to the
portal hypertension.
This is the reason for advising a low sodium diet and avoiding prescribing sodiumcontaining or sodium-retaining drugs.
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Case 1
Answer 13
Alcoholics are prone to infections due to the suppressive effects of alcohol on neutrophil
polymorphs and on the immune system. Pneumonia is a frequent occurrence. Cirrhotic
patients whatever the aetiology are also prone to infections and with the onset of ascites,
are very liable to spontaneous bacterial peritonitis. Clinically, the latter is heralded by the
onset of abdominal pain, rebound tenderness and pyrexia. The abdominal symptoms and
signs would be absent in this comatose patient. An ascitic tap would show a turbid fluid
with high protein content (exudates) and a high neutrophil polymorph count (>250/mm3 )
and a growth of enteric organisms, usually Escherichia coli.
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Case 1
Answer 14
Peritoneum – a yellow turbid fluid which grew E.coli on culture. This could be
spontaneous peritonitis or have been a complication of the paracentesis.
Liver -
2500 grams (Normal up to 1700gm) with micronodular cirrhosis and
yellow appearance due to fatty change. This together with on-going
alcoholic hepatitis explains the enlargement. A cirrhotic liver is usually
shrunken and hard. There was also cholestasis in the liver which is a
feature of the terminal stage of failure but could also have been partly due
to sepsis.
Spleen -
enlarged and congested due to portal hypertension
Oesophagus - oesophageal varices
Kidneys -
no pathological changes were seen microscopically. Hepatorenal
syndrome is due to reduced renal blood flow and not to intrinsic kidney
disease.
Brain -
the brain was slightly overweight due to oedema of the white matter. In
the grey matter Alzheimer type II astrocytes were seen with large nuclei
and nucleoli (they have nothing to do with Alzheimer’s disease). Both
these changes are seen in some patients with hepatic encephalopathy.
This is the external surface of a normal liver. The color is brown and the surface is
smooth. A normal liver is about 1200 to 1600 grams.
This is an example of a micronodular cirrhosis. The
regenerative nodules are quite small, averaging less than 3
mm in size. The most common cause for this is chronic
alcoholism. The process of cirrhosis develops over many
years.
Here is another example of micronodular cirrhosis. Note that the liver also
has a yellowish hue, indicating that fatty change (also caused by
alcoholism) is present.
Portal hypertension results from the abnormal blood flow pattern in liver created by
cirrhosis. The increased pressure is transmitted to collateral venous channels.
Sometimes these venous collaterals are dilated. Seen here is "caput medusae"
which consists of dilated veins seen on the abdomen of a patient with cirrhosis of
the liver.
One of the most common findings with portal hypertension is splenomegaly, as
seen here. The spleen is enlarged from the normal 300 grams or less to between
500 and 1000 gm. Another finding here is the irregular pale tan plaques of collagen
over the purple capsule known as "sugar icing" or "hyaline perisplenitis" which
follows the splenomegaly and/or multiple episodes of peritonitis that are a common
accompaniment to cirrhosis of the liver.
Here is another varix near the gastroesophageal junction that is dark red black
because it has been bleeding. (The esophagus has been turned inside out.) The
plexus of veins also involves some of the upper stomach, but it is generically called
the esophageal plexus of veins and, hence, bleeding here is termed esophageal
variceal bleeding. Endoscopic views of esophageal varices are shown below, with
dilated veins bulging into the lower esophageal lumen.
Below the squamous mucosa is an elongated, inflamed varix. Variceal
bleeding can be massive and difficult to control.
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