Clinical notes

1. Jaundice is a marker of severity of liver disease, as well as a consequence of decompensation.

Yellow discoloration is not usually seen until the serum bilirubin is (twice the upper limit of
normal). although the earliest signs of jaundice can be detected in the periphery of the
conjunctivae. or in the buccal mucosa. Remember, there are other causes of jaundice in liver
disease, such as Zieve's syndrome (hemolysis and hyperlipidemia in alcohol misuse), or
biliary obstruction.
2. cachexia can be established by demonstrating muscle and fat loss. Wasting of the temporalis
muscle is an early sign of generalized muscle atrophy. A reduced triceps skin-fold thickness is
a marker of loss of fat stores. This can be demonstrated by palpating for redundant skin over
the triceps area between your thumb and forefingers.
3. anemia a is most reliably demonstrated by looking for conjunctival pallor. This is thought to
be more sensitive than looking for pallor of skin creases. nails, or other mucosal membranes.
If there is no evidence of anemia, it is an important negative to mention to the examiner. The
principal causes of anemia in chronic liver disease are blood loss from portal hypertensive
gastropathy. alcohol excess causing bone marrow suppression and poor nutrition.
4. Other gastrointestinal (GI) causes of clubbing include inflammatory bowel disease (IBD),
coeliac disease. Gl lymphoma and rare causes of malabsorption such as topical sprue and
Whipple's disease.
5. Leuconychia is a non-specific finding which is associated with hypoalbuminemia as well as
other condition such as heart failure. renal disease. Hodgkin's lymphoma (HL) and diabetes
mellitus
6. Palmar erythema reflects the vasodilated state of cirrhosis. Other causes of palmar erythema
include hypercapnia, rheumatoid arthritis. thyrotoxicosis, pregnancy. fever; and exercise.
7. Spider naevi are vascular lesion. with a central arteriole that supplies smaller surrounding
vessels. Generally. the number and size correlate with the severity of liver disease. although
they may occur in normal individuals and pregnancy. Spider naevi. palmar erythema.
gynaecomastia, and loss of body hair are thought to be the consequence of altered sex
hormone metabolism. and an increase IN the oestradiol:free testosterone ratio. Carefully
inspect the superior vena cava (SVC) distribution, and remember not to miss inspecting the
patient's back!
8. Petechiae and echymoses are a consequence of coagulopathy and thrombocytopenia.
9. Gynaecomastia and loss of body hair are also thought to be the consequence of altered sex
hormone metabolism (oestradiol:free testosterone ratio). In male patients. the gynaecomastia
may be evident. but it is best to examine and palpate the areolar regions in all male patients to
clearly demonstrate your understanding to the examiner. Gynaecomastia can be identified by
palpating glandular tissue beneath the nipple and areolar region-it is often a firm and mobile
disc of tissue.
10.Before proceeding to palpation and percussion, carefully inspect the abdomen. Many useful
CLinical signs can be identified in patients with chronic liver disease. In particular, note the
following:
 Scars suggesting paracentesis or liver biopsies
 Surgical scars. i.e. Chevron (roof top) modification incision or Mercedes-Benz
modification
 suggesting previous pancreatic, gastric, or hepatobiliary surgery
 Fullness of the flanks sugesting ascites
  Distended abdominal Wall veins (see below)
11.Caput medusae are a result of umbilical vein recannalization due to portal hypertension.This
leads to prominence of abdominal wall veins. The appearance is thought to resemble the head
(caput) of the Medusa. The direction of flow in abdominal wall vessels distinguishes portal
hypertension from inferior vena cava obstruction. In portal hypertension, the flow is AWAY
from the umbilicus.
12.The cirrhotic liver may be small or enlarged. In most cases, a cirrhotic liver is small and
shrunken, but in cases where it is due to alcohol or nonalcoholic fatty liver disease (NAFLD)
hepatomegaly may be present. Always comment on the liver edge. Tender hepatomegaly
suggests stretch of the liver capsule, by a process that has caused recent hepatic enlargement,
such as infective hepatitis, alcoholic hepatitis, or malignancy. A hard irregular liver edge
suggests malignancy. Cirrhosis due to alcohol or NAFLD may cause hepatomegaly due to fat
deposition.
13.Volume status must be assessed in all patients with ascites. This can be done at the end of the
examination. after sitting the patient forward to inspect the back and palpate cervical lymph
nodes. Cirrhosis is typically associated with systemic vasodilatation, hence the cardiac filling
pressure is low or normal However, congestive cardiac failure is a rare cause of hepatic
congestion and cirrhosis. These patients may have an elevated venous pressure and associated
tricuspid regurgitation.
14.The hepatic venous hum is a murmur that is audible in portal hypertension or hepatocellular
carcinoma. It results from collateral formation between the portal system and remnant of the
umbilical vein. It is best a appreciated over the epigastrium.
15.A hepatic bruit over the liver can be heard with alcoholic hepatitis or hepatic carcinoma
(primary or secondary). Other rare causes include hepatic arteriovenous malformations,
intestinal arteriovenous m1alformations, hepatic haemangioma. and TIPS (transjugular
intrahepatic portosystemic shunt).
16.The mechanism for oedema Is hypoalbuminaemia and stimulation of the rennin-angiotensin
system.
17.Asterixis is a frequent finding in hepatic encephalopathy.The flapping tremor is best elicited
1n outstretched, dorsiflexed hands. Flexion and extension movements of the fingers and wrists
are seen. with the flexion phase being more rapid than the extension phase, which returns the
fingers and wrists to the initial position. The spectrum of clinical features of hepatic
encephalopathy begins with disturbance in the diurnal sleep pattern (insomnia and
hypersomnia). which precedes overt neurological signs. Bradykinesia and asterixis
subsequently occur, preceding hyperreflexia, transient decerebrate posturing and coma.
Asterixis is not specific for hepatic encephalopathy. but may also occur in other toxic
encephalopathies such as uraemia or respiratory failure. Asterixis is almost alwaysbilateral;
unilateral asterixis suggests a structural neurological lesion.
18.Specific signs to suggest an underlying cause of liver disease are rare, but the candidate
should be prepared to mention them if the examiner asks about further examination findings.
 Alcohol: Dupuytren's contractures, parotid enlargement {see signs of alcohol
misuse below)
 Chronic hepatitis B and C infection: tattoos, signs of intravenous drug use.
Hepatitis C is also associated with porphyria cutanea tarda and type Ill
cryoglobulinaemia (palpable purpura and livedo reticularis).
  Primary biliary cirrhosis: hyperpigmentation, xanthelesma, tendon xanthomata,
excoriation marks
 Humochromacosis: bronze pigmentauon. Arthropathy, finger skin brick because
glucose tedting)
 Congestive cardiac failure ~raised venous pressure , third heart sounds
 Wilsons disease ,kayser flesher ring only seen by slit lamp exam
 Alfa 1 antitrypsin deficiency (lower zone emphesema)
 Budd-Chiary syndrome_ loss of hepatojegular reflexe (due to Inferior ava
Involvement
What ore the causes of cirrhosis?
1. Alcohol
2. VIral
 Hepatitis B
 Hepatitis C
3. Autoimmune
 Primary Biliary Cirrhosis {PBS)
 Primary Sclerosing Cholangitis (PSC)
 Autoimmune Hepatitis
4. Metabolic
 Non-alcoholic steatohepatitis
 Hemochromatosis
 Alfa 1 antitrypsin deficiency
 Wilsons disease
 Cystic fibrosis
5. Drugs
 Methotrexat
 Isoniazid
 Amiodorone
 Phenytoin
What ore the signs of alcohol misuse?
1. cachexia
2. Tremor
3. Parotid enlargement
4. Dupuytren contracture
5. Cerebellar syndrome
6. Peripheral neuropathy
7. Myopathy
What are! the consequences of cirrhosis?
1. Consequences of portal hypertension
 Esophageal variesis
 Ascites
 Hypersplenism /thrombocytopenia
2. Consequancea of liver dysfunction
o Coagulopathy
o Encephalopathy
o jaundice
 o Hypoalbuminaemia
3. Hepatocellular carcinoma
What are the causes of decompensation in cirrhosis?
1. Infection
2. Spontaneous bacterial peritonitis
3. Hypokalemia---decreases renal ammonia clearance
4. Gastrointestinal bleeding
5. Sedatives
6. Hepatocellular carcinoma
How do you classify the severity of hepatic encephalopathy?
 Hepatic encephalopathy is defined as reversible neurological dysfunction or coma due to liver
disease.
Grade 1-lnsomnia / reversal of day-night sleep pattern
Grade 2-Lethargy/disorientation
Grade 3-Confusion/somnolescence
Grade 4-Coma
 Asterixis may be present at any stage

How do you assess the severity of cirrhosis?

The Childs-Pugh score assesses disease severity and prognosis.
· Score 1 2 3
Bilirubin (mmoVL) <35 35-52 >50
Ascites Nil mild moderate
Encephalopathy Nil 1-2 3-4
PT (sec prolonged) 1-4 4-6 >7
Albumin (g/L) >35 28-35 <28
Child-Pugh >10 (grade C) -33% 1-year mortality
Child- Pugh 7-9 (grade B) - 80% survive 5 years
Child-Pugh 5-6 (grade A) -90% survive 5 years

Are you aware of any strategies for the management of cirrhosis?

1. Slowing or reversing liver disease
Treatment depends on the underlying disease. Abstinence in alcoholic liver disease·, antiviral
therapy in viral hepatitis, and immunosuppression in autoimmune hepatitis, all improve liver
fibrosis.
2. Preventing superimposed liver damage
Abstinence from alcohol improves prognosis in viral hepatitis and chronic liver disease.
All patients should be immunized against hepatitis A, and hepatitis B if risk factors are
present.
Pneumococcal and yearly influenza vaccines should also be considered.
3. Preventing complications
Surveillance for hepatoma involves 6-monthly abdominal ultrasound and alpha-fetoprotein
(AFP) measurement, although a survival benefit from this approach has not been conclusively
demonstrated. All patients should undergo endoscopy as surveillance for oesophageal varices.
Patients with medium or large varices, or any varices in the context of advanced (Child-Pugh
C)
liver disease are treated with non-selective beta blockers as primary prophylaxis. Following an
episode of spontaneous bacterial peritonitis, prophylactic antibiotics are indicated.
Liver transplantation
The decision to proceed to liver transplantation is taken by a transplant centre. Selection is a
balance of the severity of liver disease, against the presence of co-morbidity, which would
affect outcome. Most centres advocate 6 months of abstinence from alcohol, and age under 65
years. Alcohol abstinence is insisted upon not to 'ration' or gans, but because liver function
may improve considerably following alcohol cessation. Some conditions are considered for
transplantation independent of disease severity, due to the presence of symptoms that affect
quality of life.
_Examples include intractable pruritus in PBC, or recurrent cholangitis in PSC.
Clinical notes
1. lymphadenopathy in the presence of ascites suggests malignancy or infection such -as
tuberculosis. Haematological malignancy is associated with extra-hepatic portal vein
thrombosis causing portal hypertension and ascites. Furthermore, other causes of generalized
lymphadenopathy (infectious mononucleosis, cytomegalovirus (CMV), toxoplasmosis, HIV,
HHV-6, Brtonella, systemic lupus erythematosus (SLE) and sarcoidosis) may cause ascites if
retroperitoneal lymph nodes affect lymphatic duct drainage.
2. Cirrhosis is the most common cause of ascites; therefore it is important to look carefully for
the signs of chronic liver disease.
3. There are several causes of abdominal distension: obesity. ascites, abdominal mass, gravid
uterus, intestinal obstruction, or constipation. The absence of abdominal tenderness makes
intestinal obstruction unlikely. The candidate should palpate for an abdominal or pelvic mass
carefully. Obesity and ascites may be difficult to distinguish, however, patients with
significant ascites should demonstrate a fluid thrill or shifting dullness.
4. An everted umbilicus occurs when ascites is tense, due to fluid within a hernial sac. Para-
umbilical herniae. or other abdominal wall herniae, may also be apparent.
5. Prominent abdominal wall collateral vessels may be a consequence of portal hypertension,
termed-caput medusae, or of inferior vena caval obstruction.These can be distinguished by
occluding the vessels below the umbilicus.The direction of flow in caput medusae is away
from the umbilicus,towards the legs. In inferior vena caval obstruction, flow is towards the
head.
6. Ascites can be detected clinically by assessing for shifting dullness to percussion or a fluid
thrill. The absence of flank dullness on percussion has been shown to be the most accurate
predictor of ascites (probability of ascites without flank dullness is less than 1 0%).
Approximately 1500 ml of fluid must be present before dullness is present. Once dullness has
been demonstrated in the flanks, the patient is asked to roll towards the examiner (to prevent
the patient falling off the bed), and after 15 seconds percussion is repeated to demonstrate a
change in note to resonant.
7. A fluid thrill is elicited by tapping the abdomen on one side, and feeling the transmitted wave
by placing the other hand flat on the other side of the abdomen. large volume ascites is
required for a fluid thrill to be present Only one of these tests need be performed. i.e. shifting
dullness need not be performed if a fluid thrill is present.
8. Assessment of the jugular venous pressure JVP) need not be performed routinely during the
abdominal examination. However, if ascites of unknown cause is found, volume status must
be assessed. Cirrhosis is typically associated with systemic vasodilatation, hence the cardiac
 filling pressure is low or normal. An elevated venous pressure. in the absence of tense ascites
or renal insufficiency. Suggests heart failure. atrial myxoma, or constrictive pericarditis as the:
cause of ascites.
9. Signs of hepatic encephalopathy suggest the presence of liver failure. This is an important
negative to mention, since ascites may occur due to reversible acute on chronic liver failure in
which encephalopathy is invariably present. This should be distinguished from progressive
liver disease and portal hypertension, which is irreversible although encephalopathy may not
be present.
10.When presenting a diagnosis of ascites, it is important to consider the underlying cause and
consider potential aetiologies. Mentioning relevant negative findings demonstrates to the
examiner your lateral thinking and active thought processes. Remember hypoalbuminaemia
can be caused by malnutrition,chronic liver disease and nephrotic syndrome. Throughout your
general observations. note the presence of rheumatological disease. i.e. rheumatoid arthritis
and SLE, as this can result in nephrotic syndrome (membranous glomerulonephritis).
What ore the most common causes of ascites in developed countries?
1. Cirrhosis (7S%)
2. Malignancy (1%)
3. Heart failure (3%)
4. Tuberculosis (2%)
5. pancreatitis (1%)
What lnitial Investigations would you request to determine the aetiology of the ascites?
diagnostic paracentesis
• ascitic fluid albumin and total protein
• ascitic fluid differential white cell count
• ascitic fluid gram stain and culture (for conventional microbes and acid-fast bacilli)
• ascitic fluid cytology
Abdomin.t ultrasuound
• to exclude liver or intra-abdominal mass lesion suggestive of malignancy
• splenomegaly suggests portal hypertension
• hepatic vein and portal vein Doppler should be performed to exclude thrombosis
Blood test
• liver function tests (LFTs)
• prothrombin time
• full blood count (FBC) (thrombocytopenia suggests Hypersplenism and portal hypertension)
How do you classify transudative and exudative ascites
 Since many patients with ascites also have decreased serum albumin level, comparing the
ascitic fluid albumin with the serum albumin Is superior to comparing the ascitic fluid
albumin with a fixed value (25g/l). The serum ascitec~albumin gradient (SA- AG) is
calculated as:
SA-AG = serum albumin (g/L)-ascitic fluid albumin (g/L)
SA- AG > 11 g/L suggests transudate ascites. and
SA- AG < 11 g/L suggests exudative ascites.
What is the pathophysiology of ascites and edema in cirrhosis?
 Ascites only occurs In cirrhosis following the development of portal hypertension. One cause
of ascites IS disruption of portal blood flow in the liver due to flbrosis, causing fluid to
accumulate In the peritoneum. Another cause is vasodilatation of the splanchnic circulation.
 The diseased liver produces vasodilator compounds. which cause splanchnic vasodilatation.
an .increase in blood flow through the portal vein, and consequently an increase ., portal vein
pressure. This also causes a decrease in systemic vacuolar resistance. and consequently a
decrease in effective circulating volume and blood pressure. This leads to activation of the
renin-angiotensin-aldosterone systems, and the sympathetic nervous system. This Is also the
reason why the cardiac filling pressure is low. and the venous pressure Is not elevated. The net
result Is avid sodume and water retention. propagating the development of ascites and
oedema.
What is the initial therapy for ascites in cirrhosis?
 Therapy is directed towards rever sing these physiological abnormalities.
o Dietary sodium restriction
o fluid restriction
o Diuretic therapy---initially with aldosterone antagonists, such as ·spironolactone. Once
a naturesis has been achieved (confirm by measuring urinary sodium). a loop diuretic
can be added to increase diuresis.
How does this relate to the development of the hepatorenal syndrome?
 The hepatorenal syndrome is the end stage of the spectrum of ascites and portal hypertension.
Since systemic vasodilation causes a progressive decrease in effective circulating volume. this
results in the activation of vasoconstrictor systems which reduce renal blood flow. This
reduces glomerular filtration rate. and causes progressive renal dysfunction in end-stage liver
disease, despite structurally normal kidneys.
1. Assessment of nutritional state is a key part of the gastrointestinal examination. and should be
mentioned during presentation even if the patient is well-nourish<'d. Formal methods Include
weight and anthropometry. However; a subjective assessment <:an be mad.: in the examination
setting (see
Vol 2. Case 3 Weight loss). Wasting of the temporali s muscle os an early sign of generalized muscle
atrophy, and subjective assessment of triceps fat fold thickness goves an indication of loss of
subcutaneous fat.
2. Anaemta can be present in chronic liver disease, haematological disease (i.e. sickle ce ll anaemia)
and in
malignancy. If it is not present. it is an'important negative to mention in the case presentation.
3. look for jaundice and other stigmata of chronic liver disease. Hepatomegaly. in the absence of
stigmata
of chronic liver disease o- portal hypertension, does not necessarily mean that parenchymal liver
disease or cirrhosis can l-. excluded.Whilst the liver is typically 'shrunken' in advanced cirrhosis,
other
con~itions such as primary bilial')· clrrho:;is and liver diseases chara~'terized by fat deposition
(alcoholic
liver disease or non-alcoholic fatty liver disease) may present with isolated hepatomegaly.
4. lymphadenopathy suggests infection or malignancy. Generalized lymphadenopathy can occur with
infection mononucleosis, CMV, toxoplasmosis, and sarcoidosis.
5. Carefully inspect the abdomen. Look for scars (paracentesis and liver biopsy). In thin patients
there may
be fullness of the right upper quadrant indicating hepatomegaly. Ascites may be present in
disseminated
malignancy, and in portal hypertension due to chronic liver disease or vascular liver disease. The
d~rection of flow In distended abdominal veins may differentiate inferior vena cava (IVC)
obstruction
due to disseminated malignancy, and portal hypertension (see Case 2 Ascites).
6. Approximately 1500ml of fluid must be present before flank dullness is present. Therefore in the
absence of dullness, it is best to present the absence <:If flank dullness as 'there is no clini<:al
evidence of
ascttes' as opposed to 'there is no osdtes'.
7. Remember to percuss the superior and inferior borders of the liver. following palpation of the
inferior
margin, since hyper-expanded lungs may displace the liver inferiorly. By percussing in the mid-
clavicular Une,
one can measure the liver span.The mean wer span in healthy subjects is 10.5cm in men and 7cm in
women
It is important to comment if the liver edge Is tender; as tender hepatomegaly has a specific
differential
diagnosos (see below).The presence of an 'irregular' liver edge is thought to suggest malignancy,
although this
sign is subtle and has poor sensitivity, and we therefore suggest that this description is avoided!
8. An umbilical nodule, the Sister Mary joseph nodule,ls a metastatic deposit found most commonly
in
gastric or colon adenocarcinoma, hepatocellular carcinoma, or lymphoma.
9. A hepatic bruit over the liver can be heard with alcoholic hepatitis or hepatic carcinoma (primary
or
secondary). The hepatic venous hum is a cc>ntinuous murmur that is audible in portal hypertension.
10. The presence of encephalopathy with liver dysfunction raises the possibility of acute liver
failure, and it
is therefore an important negative to mention.Tender hepatomegaly and jaundice may suggest
hepatic
necrosis. These patients also have systemic vasdtlilatation with hypotenscon and tachycardia, similar
to
the clinical presentation of septic shock. However, the presence of hepatic encephalopathy is
required
for the diagnosis (see Case 1 Chronic liver Disease for the grading of hepatic encephalopathy).
11. Tender hepatomegaly suggests stretch of the liver capsule. by a process that has caused recent
hepatic
enlar£ement. such as hepatitis (infectious or alcoholic), malignancy, co.-.gestion, or vascular disease.
If the
venoo..s pressure is not elevated, then it is best to omit congestion. I.e. cardiac failure from the
differential diagnosis list (see below).
12. If suspecting malignancy as the underlying cause. then it is important to consider both primary
and
serondary malignancies. Tell the examiner you would like to examine other systems to look for
possible
promary tumours that may metastasize to the liver. In female patients it would be important to
examine
for breasts lumps.
13. At the end of the examination, ask the examiner for pt.. mission to examine the venous pressure.
Th•s should be done at the end of the Gl examination if the patient has ascites or hepatomegaly.
C it-rhosis is typically associated with systemic vasodilatation, hence the cardiac filling pressure is