Block 8 Week 3
Acute onset jaundice
Tutor : Prof DF Wittenberg MD FCP(SA) dwittenb@medic.up.ac.za
Objectives:
To be able to
 list the causes and discuss the investigation of patients presenting with
acute onset of jaundice
 know and discuss the epidemiology, aetiology, pathogenesis,
pathophysiology, clinical features, diagnosis, complications and detailed
management of patients suffering from acute hepatitis
Illustrative Case Report Case 5:
AM, a 5 year old girl, presents to the hospital with jaundice of recent onset.
According to the grandmother, she has not been well for some time, although there have
been no specific complaints.
About a week ago, she started to complain of abdominal pain and intermittent vomiting. She
had no diarrhoea.
From one day ago, she has developed a yellow discoloration of her eyes and skin.
Today, she has passed a stool which was tinged with red blood. She is now lethargic and
cannot walk in a straight line.
On clinical examination, she has a fever of 38.5’C and looks acutely ill. She is deeply
jaundiced. Generalised lymphadenopathy is present in neck, axillae and groins. She is
moderately dehydrated, and also has mild pedal oedema. Her pulse rate is 160/ minute and
the respiration rate is 60/minute.
On abdominal examination, she has generalized tenderness, maximal over the liver. The liver
is enlarged 6 cm in the midclavicular line, firm and tender. The upper border of the liver is
percussed in the normal position. There is shifting dullness, and the spleen is just palpable.
Apart from the tachypnoea, there are no abnormalities identified on auscultation of the lungs.
A presumptive diagnosis was made and treatment started, but the patient deteriorated over
the course of the next few days and died.
Introduction
Jaundice refers to a yellowish discoloration of the sclera and is seen with an
accumulation of bilirubin in the blood.
Task:
Where does bilirubin come from? Review the production and metabolism of
bilirubin
Hyperbilirubinaemia is of 2 types:
Unconjugated hyperbilirubinaemia suggests excess production of
bilirubin, as seen in haemolysis, or an inability of the liver cell to take up or to
conjugate the bilirubin. Examples of such a type of jaundice are seen in
o Malaria : massive destruction of red cells by parasites
o Septicaemia
o Haemolytic crises of congenital haemolytic anaemia
o Acquired forms of haemolytic anaemia eg auto-immune
o Congenital conditions eg Gilberts disease, Crigler-Najjar
syndrome
Conjugated hyperbilirubinaemia occurs when there is failure by the liver
to completely clear the bilirubin from the blood stream
o Liver cell dysfunction : Hepatic cell damage (hepatitis) or
necrosis
o Bile flow obstruction
Task: Review the causes of hepatitis (Coovadia & Wittenberg p 583)
Management of acute onset jaundice
This includes the following key aspects:
1. History
Previous health ? Acute infective hepatitis usually occurs in previously
healthy individuals. Toxic or drug induced hepatitis follows an identifiable
episode/drug administration, often given for a particular illness. Acute liver
failure and septicaemia is associated with shocklike states and progressive
disease.
2. Clinical examination
Clinical state ? In acute infective hepatitis, the jaundice occurs in a generally
well patient, with the exception of some liver tenderness. The seriously ill
patient with confusion or coma is likely to be in hepatic failure or may be
septicaemic.
Examination of the liver ? Patients with very big, firm or hard or irregular
livers generally have a pre-existing condition involving the liver (chronic liver
disease, cirrhosis, systemic disease involving the liver). The liver of acute
hepatitis is generally mildly enlarged and somewhat tender. A small or
shrinking liver is indicative of liver necrosis and acute failure.
3. Investigation
Urine: If a freshly passed sample of urine is shaken to produce surface froth,
this will be yellow in cases of true jaundice (versus disoloured sclerae). The
colour is dark, bilirubin is present once the serum level of bilirubin is high.
Urobilin is found particularly when there is excess bile pigment production
(haemolysis) and stercobilin is reabsorbed from the gut.
Serum bilirubin is elevated and the presence of conjugated bilirubin points to
involvement of the liver.
Elevation of the liver enzymes points to cell damage. Involvement of the
various types of cells is reflected in differing elevations of the different
enzymes. The degree of enzyme elevation is not related to the degree of
damage; indeed, the enzyme levels can rapidly drop in cases of severe
fulminating liver cell necrosis.
The following are tests of liver function:
 Tests of synthetic ability: Serum albumen, prothrombin index
 Tests of detoxification/conjugation : Serum ammonia, serum urea
 Tests of excretion/ bile production : serum bilirubin and
conjugated bilirubin
 Maintenance of fasting blood glucose
 Integrity of liver cells : enzyme levels
The above tests will be able to tell that liver damage is present and whether
liver failure has occurred, but not what is causing it.
It is not enough to know that the liver is involved, ie that hepatitis is present.
Tests of aetiology are also required. These depend on the assessment of the
whole case, but in general we will wish to know whether a patient has
infection with hepatitis A or B or something else.
Case analysis : AM
This 5 year old girl has been unwell “for some time” before the onset of abdominal symptoms and jaundice.
Abdominal pain, vomiting and jaundice within the last week points to a recent insult of the liver. The liver may be
tender in acute hepatitis because of the swelling that occurs due to inflammatory cell infiltration. However, in acute
hepatitis the liver is usually only slightly enlarged and not firm. This child’s liver is 6 cm enlarged, suggesting that
there is another cause for hepatomegaly than just an acute infective insult.
The patient has become confused and cannot walk in a straight line. This suggests the complication of hepatic
encephalopathy.
There has been bleeding into the gut. This is further support for the possibility of liver failure with an inability to
manufacture the vitamin K dependent clotting factors. She also has some oedema, which may point to
hypoalbuminaemia.
She has generalised lymphadenopathy. This is a finding which does not fit with hepatitis alone. She has to have a
more generalised problem which has caused “unwellness” for some time.
The patient’s problem is therefore :

Underlying disease causing generalised lymphadenopathy and hepatomegaly

Progressive liver failure
Investigations:
Chest XRay : Brochopneumonia changes with reticulonodular pattern
Urine : Bilirubin 3+
Serum Biochemistry:
S-Albumen 16 g/l (N 39 – 50)
INR 4.1 ( N 1)
PTT 110 seconds (N 26 – 36 secs)
S-Bilirubin 211 umol/l
Conj Bilirubin 183 umol/l
Enzymes :
ALP 111 (N 96 – 297)
S-GGT 77 (N 0 – 34)
S-ALT 288 (N6 – 32)
S-AST 390 (N9 – 34)
S-LD 983 (N 10 – 295)
S – NH3 83 ( N 21 - 50)
P-Glucose 1.9 (N 3.9 – 5.8)
Virus serology :
Hep A negative
Hep B negative
The above tests confirmed liver cell damage and functional liver failure and that this was not due to an acute virus
hepatitis. Despite treatment, she died a few days later.
At autopsy, she was found to have miliary tuberculosis with superimposed centrilobular hepatic necrosis.
Task:
Study the approach to acute onset jaundice (C&W 579 – 580) and acute
hepatitis (C&W p 582 – 588)
Objectives:
To be able to
 list the causes and discuss the investigation of patients presenting with
hepatomegaly and/or hepatosplenomegaly
 list the causes and discuss the principles of investigation and
management of patients suffering from chronic liver disease and portal
hypertension
Illustrative Case Report Case 2, page 60 : O.N.
ON, a 9 year old girl, has a complaint of gradually progressive abdominal distension. This
has been present for at least 2 years. It is now so bad that she has difficulty lying down on a
flat bed, and becomes short of breath with exertion. She cannot play with her friends
anymore.
She has had a few episodes of epistaxis, and her stools have also been seen to be tinged
with bright blood.
There is no history of any disease. She has not been jaundiced. Her urine and stools are
apparently normal.
On examination, she is a thin girl with gross abdominal distension. She is not jaundiced. She
is fully conscious and cooperative. There are no signs of hepatic decompensation. There is no
lymphadenopathy. She has moderate pedal oedema. Some veins are visible on her
abdomen; these are evident between the upper abdomen and lower chest and the flow
seems to be from abdomen to chest.
Abdominal examination reveals a very large firm liver. This is firm in consistency. The spleen
is not palpable, but there is a large amount of ascites making palpation difficult. Apart from
the discomfort of tense abdominal distension, there is no pain, tenderness or rebound on
abdominal examination. There are no haemorrhoids on rectal examination.
Her heart and lungs are normal on examination. There is no pulsus paradoxus and her blood
pressure is normal.
Blood tests show a normal serum albumen and normal liver function tests. The enzymes are
normal.
Introduction
In order to be able to decide that a patient has hepatomegaly, one needs to
know the range of normal sizes at different ages.
The liver’s position in the abdomen is dependent on its relationships with the
diaphragm and the lung above it.
A paralysed diaphragm on the right hand side means that the liver is not
splinted downwards by the contraction of the diaphragm and therefore moves
higher into the chest. In such a case, the liver may not be well felt even
though it could be significantly enlarged. This can also happen if there is
collapse of a segment of the right lung, again pulling the diaphragm higher up
into the chest than normal.
A lung which is overfilled with air (air trapping) tends to push the diaphragm
down, therefore pushing the liver further into the abdomen than normal. In
such a case the lower margin of the liver may be palpated much further down
than expected, giving the impression of liver enlargement. This happens in
cases of asthma, bronchiolitis, air trapping with mucus plugging or foreign
body.
It follows therefore that the determination of the upper border of the liver is
an essential part of the examination of the liver size. This is done by
percussion of the chest downward from resonant to dull in the midclavicular
line opposite the 9th costal cartilage.
The bottom margin is then similarly identified by palpation or percussion, and
the distance between the two points is the perpendicular width of the liver,
the Liver Span.
This varies by age :
 5 cm at 1 week
 6 - 7 cm at 8 years
It is normal to be able to palpate the lower edge of the liver in children. In
the first 6 months of life, the liver may be palpated up to 3,5 cm below the rib
margin, thereafter 2 cm is usual. However, the span is much the better
assessment of true liver size.
Causes of hepatomegaly
It is useful to consider the normal liver architecture, list the causes of
enlargement or hyperplasia for each cell type or structure, and then list
abnormal cells or structures which might be involved:

Hepatocytes : Infiltration or storage with
Fat - Fatty change
Malnutrition, metabolic, toxic diseases
- lipid storage
Mucopolysaccharides
Glycogen – Glycogen storage disease
Amyloid protein - Amyloidosis
Mineral - Copper, Iron
Hepatocyte invasion with virus – CMV, EBV, Hep B and A
Abnormal hepatocyte proliferation - cirrhosis

Blood cells :

Reticulo-endothelial cells :
Congestion and damming up of blood
Congestive cardiac failure
veno-occlusive disease
constrictive pericarditis
Abnormal accumulations
Extramedullary haemopoiesis
Generalised RES hyperplasia
HIV, Auto-immunity
Inflammatory cell infiltration
Hepatitis
Fibrosis and cirrhosis
Granulomata
Malignant infiltration
Leukaemia

Abnormal cells/conditions:
Metastases
Abscesses
Cysts
Causes of hepatosplenomegaly
In general, these can be seen in one of the following categories:
1)
The same pathogenetic process happening in liver and spleen at
the same time: Look for a generalised disorder
Reticulo-endothelial hyperplasia
Infiltration with the same type of cells
Leukaemia
Gaucher/Niemann-Pick etc
Inflammatory cells and granulomata eg TB
2)
Disease of the liver with splenomegaly secondary to portal
Hypertension: look for evidence of liver disease/dysfunction
Cirrhosis and chronic liver disease
Hepatic fibrosis and portal hypertension
3)
Portal hypertension without significant liver disease
Hepatic or Portal vein obstruction
Look for evidence of portal hypertension
4)
Disease involving predominantly spleen
Removal of damaged red cells
Malaria
Haemolytic anaemia
Look for evidence of haemolysis
Case analysis :
This girl has the following problems:
Gross liver enlargement
Gross ascites
History of bleeding
The bleeding could be caused by either liver dysfunction with diminished clotting factor
synthesis, or alternatively portal hypertension with bleeding varices. In view of the normal
results on albumen and liver function tests, the second explanation is more likely. A
paracentesis of the abdomen would be expected to yield a transudate without inflammatory
cells and with a low protein content. In that case, the ascites is not due to peritonitis, but is
due to increased hydrostatic oncotic pressure secondary to portal hypertension.
The patient has a very big liver with normal liver function tests and enzyme values. This
rules out hepatitis. A big liver with associated ascites on the basis of increased hydrostatic
pressure is found in obstruction to venous return from the liver (Veno-occlusive disease, Budd
Chiari syndrome of hepatic vein obstruction, inferior vena cava obstruction or constrictive
pericarditis). She does not have the clinical signs of constrictive pericarditis. A clinical
diagnosis of veno-occlusive disease is made.
A radiological contrast study of the inferior vena cava demonstrated complete obstruction of
the hepatic vein. No venous drainage from the liver caused massive congestive hepatomegaly
and portal hypertension.
Task Study the approach to hepatomegaly, chronic liver disease and portal
hypertension (C & W p 581 – 592)