INICAL MEDICINE

OR THE MRCP PACES

Volume 1: core clinical skills
G, utam Mehta ABDOMEN
Bilallqbal
Abdomen System

Case 1 • Chronic Liver Disease

CASE PRESENTATI ON
This pot.ient is Icteric,' with cachexla1 and abdominal distension. There is no evidence of anaemia.1
There is clubbing! leuconychia. 5 and palma•· erythema.6 Mult.iple spider naevi' are present
on the trunk and face. There are mult.iple petechiae and ecchymoses.8 There is gynoecamastlo
and loss of body hair. 9 On examinat.ion of the abdomen.' 0 caput·medusae'' are present There is
hepatosplenomegaly11 and ascltes.U There is a hepatic venous hum.'• There are no hepat.ic bruits' 5

The•e is peripheral oedema.' 6 There are no signs of hepatic encephalopathy.' 7

The diagnosis is cirrhosis of the liver w ith portal hypertension. ' 8

Clinical notes
1. Jaundice is a marker of severity of liver disease, as well as a consequence of decompensation.Yellow
discolouration is not usually seen until the serum bilirubin is ~oVL (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 (haemolysis and hyperlipidaemia in alcohol misuse), or biliar y obstruction.
2. C achexia 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. ~naemia 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 anaemia, it is an important negative to mention to the examiner. The principal causes of
anaemia 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 malabsorp~ion such as t~opical sprue and Whipple's disease .
5 . Leuconychia is a non-specific finding which is associated with hypoalbuminaemia as well as other
conditio ns such as heart failure. renal disease. Hodgkin's lymphoma (HL) and d iabetes mellitus
(see C ase 8--Nephrotic Syndrome).
6. Palmar erythema reflects the vasodilated state of cir rhosis. Other causes of palmar erythema include
hypercapnoea, rheumatoid arthr itis. thyrotoxicosis, pregnancy. fever; and exercise.
7. Spider naevi are vascular lesio n s. 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 ip the
oestradiol:free testosterone ratio. Carefully inspect the superior vena cava (SVC) distribution, and
reme mber not to miss inspecting the patient's back!
8. Petechiae and echymoses are a consequence of coagulopathy and thrombocytopenia.

3·
ABDOMEN SYSTEM

9. Gynaecomastia and loss of body hair a-re 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 t.issue.
10. Before proceeding to palpation and percussion, carefully inspect the abdomen. Many useful dinical 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 surge!')•
FuUness of the flanks su ~esting ascites
Distended abdominal W3ll veins (see below)
11. Caput medusae are a resutt 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 hypert.ension 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 non-alc:oholic 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 (see Case 2-Ascites). This can be done at
the end of the examination. after sitting the patient forward to inspect the back a nd 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 hepatoce llular
carcinoma. It results from collateral formation between the portal system and remnant of the umbilical
vein. It is best a ppreciated 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 art.eriovenous malformations, intestinal art.eriovenous
..1alformations, 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 fai:ure. Asterixis is almost always
bilateral; unilateral asterixis suggests a structural neurological lesion.
1 8. 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: hypcrplgmentation, xanthelesma, tendon xanthomata, excoriation marks

4
 CASE 1 • CHRONIC LIVER DISEASE

Humochromacosis: bronze pigmentauon. arthropatl~ ~

tel)
Co.ttutl'"' anflac ~raised \lenOUS ~third ~t &ouncl
Wikon'll ~-Re.scner- "'1&S (only oro ~~ eownillliUon).&ldnl!'uc-rigid syndlouoe
a, ·antitrypsin c:lefidenq: 1owoer zone etn;lh)'~
Budd-Chbrf syndrome_ loss of ~ c iu;:ubr n11lux (due to Inferior ava Involvement)
Questions commonly asked by examiners
What ore the couses of cirrhosis?
Alcohol
VIral
• Hepatitis B
• Hl'pntltls C
Autoimmune
• Primllry Blhllry CirrtlOSis {PBQ
• Pnmary Sclcros g Cholangitis (PSC)
• Autoimmune ~o:.s
MetaboUc
Non-alcohotic steatohepatitis
• Hacmachromatosls
• a, AntJtrypW! defiCienCy
• W.tsoo•s dlsea.se
• CystJc Abrosls
Drugs
• Methotrexat
• Isoniazid
• Amiodorone
• Phenytoin
What ore the signs of alcohol misuse?
c~chexla
Tremor
Parotid enlargement
Dupuytren\ contracture
Ccrcbetw syndrome
~··~ropathy
M)lop•lhy
What ON! the consequences of cirrhosis?
Consequences of portal hypertension
~vances
• Ascites
Hypersplenism/thrombocytopenia
Consequancea of liver dysfunction

Il •
•
Co,gulopo~thy
~ nc:cphfllop,trhy

5
ABDOMEN SYSTEM

• jaundice
• Hypoalbuminaemia
Hepatocellular carcinoma
What are the causes of decompensation in cirrhosis?
Infection
Spontaneous bacterial peritonitis
Hypokalaemia---decreases renal ammonia cl~arance
Gastrointestinal bleeding
Sedatives
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-lnsomnialreversal 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 d isease severity and prognosis.

· Score 2 3
Bilirubin (mmoVL) <35 35-52 >SO
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?
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 ~iver fibrosis.
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.

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 conte-,.t of advanced (Child-Pugh C)

6
 CASE· 2 • ASCITES

Figure 1.1 A patient with decompensated chronic liver disease.There is gross ascites with an umbilical hernia.
Note the mild degree of gynaecomastia.

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 advo cate 6 months of abstinence from alcohol, and age under 65 years.
Alcohol ab stinence is insisted upon not to 'ration' o r gans, but because liver function may improve
c o nsiderab ly following a lcoho l cessation. Some conditions are considered for transplantation

l
inde pende nt of d ise ase seve rity, due to the presence of symptoms that affect quality of life.
_Examples include intractable pruritus in PBC, or re current cholangitis in PSC.

\ Case 2 • Ascites

CASE PRESENTATION

t This pauent is not cadlectic. There is no eVIdence or lymphadenopathy' or stigmata or chronic liver
diseose.7 The abdomen Is distended,J but is soft and non-tender. The umbilicus Is everted.• There are
no collateral vessels visible on the abdominal wa/1.5 There is no evide~e or hepatosplenomegaly. The
abdomen 1s dull to percussion m the flanks, with shifting dullness.0 A fluid thrill can be demonstrated.'

t 7
ABDOMEN SYSTEM

The venous pressure is not elevated,8 and there is no peripheral oedema. There are no signs o(hepadc
encephalopathy.9
The diagnosis is oscites. 10

Clinical notes
1. ·lymphadenopathy in the presence of ascites suggests malignancy or infection such -as tuberculosis.
Haema~ological malignancy is associated with extra-hepatic portal vein thrombosis causing portal
hypertension and ascites. Further'Tlore, other cau•es of generalized lymphadenopathy (infectious
mononucleosis, cytomegalovirus (CMV), toxoplasmosis, HIV, HHV-6, B; rtonella, 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 thi! signs
of chronic liver disease (see Case 1 Chronic Uver 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 oth': 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 1 SOOml 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 1S 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 pres en~ Only o ne o f 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 OVP) nee d 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 absen<"e 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<hranlc 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 asc ites, it is important to consid er 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 ne phrotic
syndrome (membranous glomerulon ephritis).

8
 CASE 2 • ASCITES

Questions commonly asked by examiners

What ore the most common causes of ascites in developed countries?
Ol"'rllosl~(7S")
Malignancy (1'"')
Heart failure (3")
Tuberculosis(~)
~creatitis (1")
What lnitlol Investigations would you request to determine the aetiology
of the ascites?
Olapostk paracentesis
• ascitic fluid albumin and total protein
• ascitic fluid differential white cell count
• asc.ltJc fluid gram stain and culture (for conventional microbes and acid-fast baci~li)
• ascitic fluid cytology
Abdomin.t ukruound
• to exclude liver or intra-abdominal mass IH!oos suggestJve of malignancy
• splenomegaly suggests portal hypertension
• hepatic win and portal Yein dopp(er should be perlonned to exclude thrombosis
~c.-.
• o-r function tests (lFTs)
• prothrombin time
• full blood count (FBC) (thrombocytopenl suuestJ hypenplenlsm and portal
r hypenanslon)
How do you dassify tronsudcltiwe ond eJr1ldGWe tlldta1
J Since many patients with ascites also haYe decreased serum albwnln lewb, comparing the
ascitic fluid albumin with the serum albumin Is superior to comparing the ascitic fluid
albumin with a fixed value (I.e . 25gll). The serum asclte~lbumln ar;adlent (SA- AG) is
calculated as:

SA-AG = serum albumin (giL)-ascltlc fluid albumin (giL)

SA- AG > 11 giL suggests transudatlve ascites. and SA- AG < 11giL sugests exudative ascites.
Whac is the pachophyslology of CISCites and oedemcr ltl ckrltosis?
Ascites only occurs In clnilosis following the ~t of ponal hypertension. One cause
of ascites IS dl~rupdon of portal blood flow in the Wet- due to flbrosd, cauWn& fluid to accumulate
In the pentoneum..Another cause is vasodilAtation of the sptanchnlc di"Cutatlon.
The diseued liver produces vasodilatory compounds. which auw splanchnic vasodilatation.
an .ncrease in blood flow through the portal vein, and consequently an lncruse ., portal
vean pre:s~ure.This also causes a decrease in systemic vaKular resistance. and consequently a
decrease in effectNe circulating YOlu-ne and blood pressure.This leads to activation of the
ren~o-qtotensin-aldosterone systems, and the sympathetic neniOUS system. This Is also the
reason why the cardiac filling pressure is low. and the venous pressul"8 Is not elevated.
The net result Is avid ~lum and water retention. propaptlng the deYelopment of ascites
and oedema.

9
ABDOMEN SYSTEM

What is the initial therapy for ascites in cirrhosis?

Therapy is directed towards rever sing these physiological abnormalities.
Dietary sodium restriction
flu id restriction
Diuretic therapy---in~ially with aldosterone antagonists, such as ·spironolactone. O nce a
naturesis has been achieved (conf irm by m easuring urinary sodium). a loop diuretic can be
added to increase diuresis.
How does this relate to the development of the hepatorenal s yndrome?
The hE,patorenal syndrome is the end stage of the spectrum of ascites and portal hypertension.
Since systemic vasodilat< tion causes a progressive decrease in effe ctive circulating vo lume. this
results in t he activation of vasocoAstrictor systems which reduce renal blood flow. T his reduces
glomerular filtration rate. and causes progressive renal dysfuction in end-stage ;iver disease,
despite structurally normal kidneys.

.,
Case 3 • Hepatpmegaly

CASE PRESENTATION 2
This patient is cochectic.' There is no evidence of anaemia, 2 icterus, or stigmata of chronic liver disease. 3
There is no lymphodenapothy. 4 The abdomen is nat distended.' and there is no clinical evidence o f
osdtes. • There is hepatomegaly with a non-tender liver edge palpable 4an below the costal margin.'
There is also a palpable umbiUcol nodule.8 There is no evidence of splenomegaly. There are no audible
brurcs or a hepatic venous hum. 9 There are no signs· of encephalopathy to suggest hepatic failure' 0
This patient has hepatomegaly. The presence of cachexia and an umbilical nodule suggests
malignancy as the most lrke/y cause.

CASE . PR ES ENTATION 2
This patient is well-naurished.1 There is no evidence ofanaemia, 1 icterus, or stigmata of chronic liver
disease. 3 There is no lymphade nopathy! The abdomen is not distended. 5 and there is no clinical e vidence
of asdtes.6 There is hepatomegaly with a tender liver edge palpable 4cm below the costal margin.'
There is no:> evidence of splenomegaly. There are no audible bruits or a hepatic venous hum • There are no
SJgns of encephalopathy to suggest hepatic failure. 10
This pauenc has tender hepatomegaly" . The differential d1agnosis includes:
(a) infectious disease, (e.g. viral hepatitis)
(b) alcoholic hepatitis
(c) malignoncy'2
(d) hepatic congestion. (e.g. cardiac foilure)JJ
(e) vascular liver disease. (e.g. Budd-Chiari syndrome. sickle cell disease)

10
 CASE 3 • H EPATOM EGALY

Clinical notes
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 temporalis 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.

i
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

r 11

t
I~

ABDOMEN SYSTEM
- ---· ---
low or normaL An elevated venous pressure indicates right heart failure, and thus hepatic congestion as
the cause of hepatomegaly. Look for the giant systolic waves of tricuspid regurgitation, which is
associated with pulsatile hepatomegaly.

Questions commonly asked by examiners

What are the causes of hepatomegaly (without splenomegaly)?
Malignancy---primary or secondary
Cirrhosis
Alcoholic liver disease
• Non-alcoholic fatty liver disease (NAFLD)
Primary biliary cirrhosis
Hepatic congestion
• Right heart failure
Constrictive pericarditis
Restrictive cardiomyopathy
Alcoholic hepatitis
Infectious disease
"-
Viral hepatitis
• Toxoplasmosis
Hydatid disease
-• Pyogenic liver abscess
Amoebic liver abscess
Infiltration
• Amyloidosis
Sarcoidosis
• G lycogen storage disorders
Vascular liver disease
Budd-Chian syndrome
• Sickle cell disease
Polycystic liver disease
Tertiary syphilis (due to syphilitic gumma)
Obstetric liver disease*
Which tumours commonly metastasise to the liver?
Colorectal cancers account for the majority of cases of metastatic liver disease. Others include
oesophageal, lung, gastric, breast, lymphatic, renal, endometrial, neuroendocrine, sarcomatous, and
bone tumours.
Do you know of any benign liver tumours?
Cavernous haemangioma-most common benign liver tumour. typically affecting women of
childbearing age.
Hepatic adenoma-associated with use of oestrogen-containing contraceptives.
Focal nodular hyperplasia-also affects women of childbearing age, although not associated
with oestrogen use.

« Acute fatty liver of pregnancy typically occurs in the third trimester, hence hepatomegaly Is obscured by the
gravid uterus.

12
 CASE 4 ·• SPLE N O MEG ALY

Nodular regenerative hyper plasia-affects elderly patients. often with systemic autoimmune
disease.
What are the infective causes of acute hepatitis?
Hepatitis A
Hepatitis B
Hepatitis C (until recently this was not thought to cause acute hepatitis, although outbreaks
have been reported in HIV-positive men)
Hepatitis E
EBV
CMV
Toxoplasmosis
Herpes Simplex virus
What are the causes and clinical manifestations of the Budd-Chlari syndrome?
The Budd-Chiat'i syndrome is characterized by obstruction to hepatic venous outflow, most
commonly due to thrombosis, which may occur at the level of the hepatic venules, the hepatic vein, or
the inferior vena cava.This causes venous stasis, congestion, and damage to hepatic parenchymal cells.
An underlying cause can be identified in 75% of patients, such as myeloproliferative disorders, or
[ t hrombophilias such as deficiency of protein C. proteinS, or antithrombin Ill, the factorY Leiden
mutation, the prothrombin-gene mutation, the antiphosp holipid syndrome, or paroxysmal
'· noctumal haemoglobinuria.
Patients either present acutely with jaundice and hepatic encephalopathy, or more commonly
w ith the subacute onset of abdominal pain and hepatomegaly. Ascites may be absent due to the

r development of a hepatic venous collateral circulation.

Diagnosis is usually by doppler ultrasound ofthe hepatic vein.Treatment 1nvolves anticoagulation
and the medical management of ascites, unless encephalopathy or liver failure are present, in
which case thrombolysis, angioplasty, or liver transplantation are indicated.
Wh•"1t are the hepatic manifestations o( sickle cell anaemia?
Gall stone disease- -due to chronic haemolysis causing pigment stones.
Sickle hepatic crisis--due to sickle thrombosis causing sinusoidal obstruction. Presents with
right upper quadrant pain, jaundice, and tender hepatomegaly.
Intrahepatic cholestasis--due to sickle thrombosis in sinusoids, causing hepatocyte swelling
and intrahepatic biliary obstruction.
Associated liver conditions--iron overload due to blood transfusion, viral hepatitis
contracted through blood transfusion.

Case 4 • Splenomegaly (with or without hepatomegaly)

------------------------------------~-----------------------

Examiner's note
Splenomegaly has a large number of causes. and these include non-gastrointestinal
causes. Despite the extensive list of causes, there are only a limited number that are

13
ABDOMEN SYSTEM

frequently encountered in the MRCP (PACES) examination. The most common causes to
appear are:
Haematological malignancy
Portal hypertension
Other less common causes that may be encountered include:
Haemolytic anaemia
Felty's ~yndrome
Strictly speaking this is an abdominal station, however it is important to make general
observations to determine the undenying cause. Although it may be acceptable to provide a
dia ~nos is of splenom egaly and then provide a differential diagnosis. if a clear cause can be
identified, it will impress examiners and gain valuable marks. In the final presentation, mentioning
important negatives demonstrates to the examiner a systematic and coherent approach to a
patient with splenomegaly.

CASE PRESENTATION 1
T11is patient is anaemic.1 There is no evidence of iaerus.2 There ore no stigmata of chronic liver disease 1
ond there is no evidence of rheumacologicol disease• There is no lymphadenopathy. 5 There are
excoriation marks to suggest pruritis.6 There IS splenomegaly w1th the splentc edge palpable 8cm
below the coswl margin. 1 Ther~ is no hepatomegaly, osdtes or penpherol oedema. There is no venous
hum.8 There ore no signs of hepatic encephalopathy.
This patient has anaemia and splenomegaly. In the absence of stigmata ofchronic liver disease and
portal hypertension, the most likely cause is a myeloproliferative disease. 9

CASE PRESENTATION 2
Tl ;is patient IS anaemic.' There is no evidence of icterus. 2 There ore no stigmata of chronic liver disease 3
and there is no evidence o( rheumotologicol disease. • There is widespread lymphadenopathy' and
there ore excoriation marks to suggest prurius. 6 There is hepatosplenomegaly with the liver edge
palpable Jcm below the costal margin and the splenic edge palpable 4cm below the costal margm. 7
There IS no osdtes or peripheral oedema. There IS no venous hum.8 There ore no signs of hepatic
encephalopathy.
This patient has hepatosplenomegaly with widespread lymphadenopathy. In the absence of
sttgmoto of chronic liver disease and portal hypertension, the most likely cause is a lymphoproliferative
disease.•

CASE PRESENTATION 3
This patient is anaemic. 1 There is no evidence of icterus. 2 There are no stigmata ofchronic liver disease. 3
There is a symmetrical deforming arthropathy affecting the small joints of the hands, with ulnar
dev10t1on and nodules on che foreonns• There is also a vas.cultic rash' There is splenomegaly with the

14
 CASE 4 • SPLENOMEGALY
----- - - - - - - - -- - - ---
splenic edge palpable 4cm below the costal margm. 1 There IS no hepatomegaly, ascites or peripheral
oedema. There is no venous hum.8 There are no signs ofhepatic encephalopathy.
This patient has rheumatoid arthritis. The presence of splenomegaly in the absence of stigmata of
chronic liver disease and portal hypertension makes Felty's syndrome the most likely diagnosis. I would
like to see evidence of neutropenia on the blood count to confirm the diagnosis.

Clinical notes
1. Anaemia is most reliably demonstrated by looking for conjunctival pallor. This is thou~ht to be more
sensitive than looking for pallor of skir creases, nails, or other mucosal membranes. If there is no
evidence of anaemia, it is an important negativ!! to mention in the final case presentation.
·2. In the absence of stigmata of chronic liver disease, the presence of jaundice with sp lenomegaly shou ld
raise the suspicion of haemolysis in the context of haematologkal malignancy, in particular 'cold'
autoimmune haemolytic anaemia associated w ith chronic lymphocytic leukaemia.
3. Look carefully for the stigmata of chronic liver disease (see Case 1 Chronic Liver Disease). The
presence of stigmata of chronic liver d isease lends support to portal hypertension as the cause of
splenomegaly.
4. Look for signs of m eumatological d isease. in particular meumatoid arthritis. In the context of
splenomegaly this would support a diagnosis of Felty's syndrome, which occurs in 5% of patients with
long-standing rheumatoid arthritis. Hyperuricaemia due to haematological malignancy may also occur,
causing acute gout. although signs of chronic tophaceous gout are u..rlikely to be present.
S. Lymphadenopathy must be carefully sought if splenomegaly or hepatosplenomegaly is fou nd, since
haematological disease is an important differential. Many tutors favour examining the cervical lymph
nodes witt-. the patient supine, prior to abdominal palpation. However. an alternative approach is to
examine for lymphadenopathy at the end of the routine, w ith the patient sitting upright. Not only does
this facilitate examination of all cervical lymph nodes, rather than just supraclavicular nodes, but the
candidate also has knowledge of the findings of abdominal palpation, and may therefore proceed to
examine the axillary. inguinal, and epitrochlear lymph nodes if haematological disease is suspecre::!
Lympahdenopathy can also occur in Felty's syndrome.
6. Pruritis occurs with cholestatic liver or biliary disease, but may also be a feature of haematological
malignancie s.
7. The spleen is typically 12cm in length, and lies in the left upper quadrant. In healthy state s, the spleen
cannot be palpated since it lies beneath the rib cage, but as it enlarges it becomes palpable below
the costal margin and towards the right iliac fossa. However. the spleen is only palpable below the
costal margin o nce it is greate r than 15cm in length. Subtle splenic e nlargement is therefore missed
by palpation. Percussion over Troube~ space may detect subtle splenic enlargement.This involves
percussion over the area between the left sixth rib, and the left costal margin, in the mid-axillary line.
The stomach, which is resonant to percussi.::>n, nor.nal\y o ccupies this area, however the percussion
note becomes dull In the presence of splenomegaly. This technique may be more sensitive than
palpation for subtle splenomegaly.
9. A venous hum is b est appreciated over the epigastriu m and indicates portal hypertension.This is an
important negative to mention in a patient with hepatosplenomegaly.
10. In the setting of haematological malignancy, there are two general patterns of presentation t o
be aware of;
(a) Splenomegaly without lymphadenopathy is most likely to be a myeloproliferative condition such
as chronic myeloid le u kaemia (CML).The spleen is more likely t o be markedly enlarged (see
below) and anaemia is more common. Remember that lymphadenopathy cannot be completely
excluded by t he bedside, and adequate imaging will be required.

Ir 15

;
ABDOMEN SYSTEM

(b) Splenomegaly and lymphadenopathy is most likely to be a lymphoproliferative condition such as

lymphoma or chronic lymphocytic leukaemia.The spleen is not typically as large as in
myeloproliferative disorders, and the patients are less likely to be anaemic. However,
hepatomegaly is more common.

Questions commonly asked by examiners

What are the characteristics of the spleen on palpation?
Enlarges towards the right iliac fossa
Possesses a medial notch
I~ dull to percussion (unlike a kidney, which is resonant due to overlying colon)

One cannot palpate 'above' a sple ~n--between the spleen and the costal margin
The spleen is not ballotable (unlike a kidr.ey)
What are the causes of splenomegaly?
In order of frequency:*
Portal hypertension-33%
Haematological malignancy-27%
Infection (e.g. HIV, endocarditis)-23%
Congestion or inflammation (e.g. cardiac failure)-8%
Primary splenic disease (e.g. splenic vein thrombosis)----4%_
Other-S%
By degree of splenic enlargement
Massive splenomegaly (crossing the midline)
• CML
• Myelofibrosis
• Kala-azar (visceral leishmaniaisis)
• Malaria
AIDS with Mycobacterium avium complex
Moderote splenomegaly
Portal hypertension
• Lymphoma
• Leukaemia (acute or chronic)
• Thalassaemia
• Glycogen and lipid storage diseases (e.g. Gaucher's disease)
Mild splenomegaly
• Other myeloproliferative diseases (e.g. polycythaemia rubra vera)
• Haemolysis
• Infection (e.g. EBV. infec:tive endocarditis)
Autoimmune disease (e.g. rheumatoid arthritis, SLE)
• Infiltrative conditions (e.g. amyloid, sarcoid)
Which of these conditions cause isolated splenomegaly without hepatomegaly?
This distinction is often over-emphasized, since all haematological causes of splenomegaly may
also cause hepatomegaly, due to extramedullary haematopoiesis. The infective and infiltrative

" From series of 449 patients attending a single medical centre in San Francisco~ USA West J Med 1998:
169(2):88-97.

16
 CASE 4 • SPLENOMEGALY

causes of splenomegaly may also cause hepatomegaly. The conditions which are most likely to
cause isolated splenomegaly are autoimmune diseases, and primary splenic diseases such splenic
vein thrombosis or splenic abscess.

How would you evaluate this patient?

History
• Ask about constitutional symptoms-fever; night sweats. malaise. weight loss. These
suggest an underlying infective, malignant, or autoimmune condition. They also
represent 'B symptoms' in non-Hodgkin's lymphoma (NHL).
• Ask specifically about risk factors for HIV infection.
• Ask about risk factors for lymphoma, particulariy family history of lymphoma, use of
radiation therapy. immunosuppressive therapy, chemotherapy, or crgan transplantation.
• Ask about bone and joint pain. This may occur in myeloproliferative disease due to
increased haematopoiesis, or due to secondar y hyperuricaemia causing acute gout.
• Ask about symptoms of pancytopaenia, such as bruising (thrombocytopaenia). or
fatigue (anaemia). These are unusual in myeloproliferative disease, but may signify the
transformation of CML to acute myeloid leukaemia (AML) (blast crisis).
• Ask about a history of autoimmune disease.
• Ask about a history of liver disease.
• Take a thorough travel history, including malaria risk and prophylaxis.
Investigations
• FBC, blood film, tFTs, serum LDH, beta-2 microglobulin, and autoimmune profile.
• Chest X-ray (CXR)
• HIV testing
• Imaging (ultrasound initially to evaluate splenomegaly, but axial imaging of the chest,
abdomen and pelvis will be required to evaluate for lymphadenopathy or disseminated
malignancy. Positron Emission Tomography is highly sensitive for non-Hodgkin's
lymphoma, although not specific, and may also be positive in infection or metastatic
malignancy.)
Lymph node excision biopsy (rather than fine needle aspirate, since intact tissue is
required for histological assessment).
• Bone marrow biopsy-will diagnose conditions such as lipid storage diseases,
mycobacterial infection, granulomatous disease, and lymphoid or myeloid disorders.
It is also required to evaluate for extra-nodal disease during staging of non-Hodgkin's
lymphoma.
What is the significance of 8-symptoms in non-Hodgkin's lymphoma?
Apprvximately 40% of patients with NHL present with B-symptoms.These have been forr.-;ally
defined as:
Fever >38°C
Weight loss >10% of body weight over 6 months
Drenching night sweats
If one of these symptoms is present, then the patient's clinical staging is altered accordingly.
What do you know of the cytogenetics of CML?
The Philadelphia chromosome is present in 90-95% of ratients with CML This is a chromosomal
translocation, characterized by the fusion of the oncogene c-obl on chromosome 9, with bcr on
chromosome 22.This fusion leads to increased oncogene activity through tyrosine kinase
signalling, and eventually leads to malignancy.

17
ABDOMEN SYSTEM

Detection of the bcr-abt gene product mRNA is used for the diagnosis of CML, and for
monitoring disease activity. Furthermore, monoclonal antibodies to tyrosine kinases have
revolutionized the treatment of CML
What do you understand by the term 'blast crisis'?
This phase of the disease is similar to acute leukaemia, and survival is 3-6 months. Blast cells are
found in the bone marrow and peripheral blood. Skin or tissue infiltration also defines blast crisis.

What ore the causes of hyposplenism?

Splenic infarction (e.g. sickle cell anaemia, vascultitis)
Splenic artery thrombosis
:nfiltrative conditions (e.g. amyloid, sarcoid)
Coe:iac disease
Autoimmune disease
What advice would you give a patient with hyposplenism, or following splenectomy?*
Vaccinatians-Pneumococca~ Haemophilus influenzae B, and Meningococcal group C. Ensure
that repeat vaccinations are administered every 5-10 years.
Prophylactic antibiotics----<:>ral phenoxymethylpenicillin or erythromycin for at least two years,
and '!lay be continued lifelong. ·
Patients who develop infection despite these measures should attend hospital urgently, for
consideration of parenteral antibiotics.
Patients should be colf"nselled regarding malaria prophylaxis and travel advice.
Patients should carry an information card, or wear a medic-alert bracelet, to inform
healthcare practitioners of their condition.
What do you understand by Felty's syndrome?
Felty's syndrome was originally described as seropositive rheumatoid arthritis complicated by
neutropenia and splenomegaly. However, since splenomegaly may occur in rheumatoid a-r thritis in
the absence of neutropenia, and splenomegaly is not always clinically detectable, splenomegaly is
no longer considered an absolute diagnostic requirement.

Case 5 • Haemochromatosis
CASE PRESENTATION
This patient is not icteric. 1 There is evidence of skin pigmentation2 and koilonychic;. 3 There is
gynaecamastia and decrt!ased body hair.• There is hepatomegaly with the liver edge palpable 4cm
below the costal margin.' There is no evidence of splenomegaly, ascites, or peripheral oedema. There are
no hepatic bruits and there is no hepatic venous hum. 6 There are no signs of hepatic encephalopathy.
The walking aid suggests the presence of arthropathy.' Furthermore, the blood glucose meter and
finger-prick marks suggest the presence of diabetes mellitus.8
The diagnosis is haemachromatosis. 9

* From British Committee for Standards in Haematology guidelines, 2002.

18
 CASE 5 • HAEMOCHROMATOSIS
-------
Clinical notes
The classical description of'bronze diabetes' with cirrhosis. diabetes mellitus, and 'slate-grey'
pigmentation is increasingly rare, due to improved diagnosis and treatment of the condition.
Indeed, the combination of diabetes mellitus and cirrhosis is more like ly to represent NAFLD
than haemochromatosis. However, patients with advanced haemochromatosis do tend to crop up
in the MRCP (PACES) examination, hence this is presented as a separate case to chronic liver
disease.
1. jaundice may or may not be present. Although liver function abnormalities occur in 75% of patients,
jaundice is absent early in the course of disease.
2. Cutaneous pi3mentation is seen in >90% of patients with idiopathic haemochromatosis. and is onP. of
the earliest signs of the disease (th >ugh it may be mild). It is more evident on sun-exposed areas of the
skin, i.e. the face and hands. The pigmentation c~.n vary from bronze to slate-grey to metallic grey
discoloration. Other skin changes that can occur are ichthyosiform changes and skin atrophy
(particularly on the anterior surface oflegs).
3. Haemochromatosis is a cause of koilonychia. Koilonychia affecting the thumb and index finger has been
reported to occur in SO% of patients. Prominent koilonychia affecting all nails o ccurs in 25% of patients.
Look for stigmata of chronic liver disease. These are absent early in the course of disease. Cirrhosis
occurs in 13% of patients and occurs late.
4. Gynaecomastia and decreased body hair can be manifestations of chronic liver disease or
hypogonadism. Hypogonadism occurs due to iron deposition in pituitary gland. Any pituitary deficit may
be present. however hypogonadism is the most common.Visual field defects do not occur:
Amenorrhoea in women is much less common than hypogonadj;;m in men. Partial loss of body hair •s
seen in 60% of patients. Complete loss of body hair is seen in 12% o f patients. The pubic region is the
most commonly affected area.
5. Hepatomegaly is common at presentation and is firm and regular: Whilst cirrhosis only occurs in
10-1 5% of patients, the risk of hepatocellular carcinoma in patients with haemochromatosis and
cirrhosis is greater than for other liver diseases .. Some specialists advocate increased frequency of
hepatocellular carcinoma surveillance in these patients (3-monthly rather than 6-monthly).
6. A hepatic bruit in the context of haemochromatosis signifies the development of hepatocellular
carcinoma, and a hepatic venous hum indicates portal hypertension.
7 Arthropathy (pseudogout) is due to calcium pyrophosphate crystal deposition. The most common
distribution is a symmetrical, small-joint arthropathy, similar to rheumatoid arthritis. However, arthralgia
is more common than synovitis.The most commonly affected joints are the metacarpophalangeal
(MCP) and proximal interphalangeal (PIP) joints. Inspect the hips and knees for joint replacement scars
when examining the legs for oedema.
8. Look at the lateral aspects of the fingertips for skin pricks. which indicate glucose testing. Furthermore,
when palpating the abdomen for masses look for evidence of lipoatrophy and lipohypertrophy in the
subcutaneous tissue as a clue to suggest insulin administration.
9 If the diagnosis of haemochromatosis is presented, then tell the examiner you would like to look for:
(a) Diabetes: finger pricks (glucose testing). fundoscopy( retinopathy). urinalysis (glycosuria)
(b) Restrictive or dilated cardiomyopathy: raised venous pressure, third or fourth heart sound

Questions commonly asked by examiners

What is the mode of inheritance of hereditary haemochromatosis?
Hereditary haemochromatosis is inherited as an autosomal recessive trait. The HFE gene has
been localized to the short arm of chromosome 6 ( 6p21.3).

t
~ 19
r
ABDOMEN SYSTEM

Most Ci\ucasian patients with haemochromatosis a re homozygous fo r the cysteine-to-tyrosine

substitution at position 282 (C282Y).A smaller proportion are homozygous for the histidine-to-
aspartate substitution at position 63 (H63D). A minority are compound heterozygotes for these
mutations.
How ·does one diagnose haemochromatosis?
Diagnosis of iron overload
Iron overload is suggested by serum iron studies. A fasting transferrin saturation >60% in males,
or >50% in females. has a high specificity for !ron overload. In clinical practice, a transferrin
saturation >45% is considered significant enough to warrant investigation. The serum ferritin is
also elevated in iron overload, how.,ver since ferritin is an acute phase prote1n, the specificity of
this test is less than for transferrin ~aturation.
Liver biopsy. to confirm parenchymal iron deposition, is considered if the blood tests suggest
abnormal liver function.

Diagnosis of haemochromatosis
Genetic testing for the C282Y and H63D mutations will confirm the diagnosis of
haemochromatosis in over 90% of cases. However, other mutations are responsible for some
cases of haemochromatosis, particularly in non-Caucasian populations. First-degree relatives of
patients with haemochromatosis should uns:fergo screening with genetic testing.
What is the treatment of haemochromatosis?
Phlebotomy is the mainstay of treatment for haemochromat9sis. Initially, one unit of blood should
be rem oved once to twice weekly, until the transferrin saturation falls below SO%, or the ferritin
falls below SOng/mL Maintenance phlebotomy should then be performed every three months.
Iron removal through phlebotomy improves insulin sensitivity, fatigue, and skin pigmentation. However.
arthropathy, hypogonadism, and cirrhosis do not respond to treatment. Hepatocellular cancer (HCC)
accounts for 30% of all deaths in haemochromatosis, therefore all patients with cirrhosis should
undergo HCC surveillance with six-monthly ultrasound and a-fetoprotein measurement.
What are the cardiac complications of haemochromatosis?
Haemochromatosis can cause a restrictive or dilated cardiomyopathy. Cardiac MRI (magnetic
resonance imaging) is a sensitive modality for detecting myocardial iron deposition.
Do you know any other causes of iron overload?
Conditions requiring regular blood transfusion (haemoglobinopathy or refractory anaemia) are a cause
of transfusional iron overload If phlebotomy cannot be used to treat these patients, iron chelators such
as desferrioxamine are used to decrease body iron. Porphyria cutanea tarda, most commonly
associated with hepatitis C infection, is also associated with iron overload and abnormal liver function.

Case 6 + Prim~ry Biliary Cirrhosis

CASE PRESENTATION
This m iddle-aged lady' is icteric, 1 with generoUsed hyperpigmentation.1 There is no evidence of anoem1a.•
There is clubbing. xanthelasma,5 tendon xanthomotaS and multiple excoriation marks. • There are

20
 CASE 6 • PRIMARY BILIARY CIRRHOSIS

multrpie petechiae and echymoses. 1 Multiple spider naevi are present on the upper limbs, rrunk. and
(OCP There is hepatosplenomegaly with the liver edge palpable 3cm below the costal margin8 and the
splenic edge palpable Jcm below the costal margin.• There are no hepatic bruits but there is a hepatic
venous hum.'0 There IS no osci!eS, peripheral oedema, or signs of hepatic encephalopathy.

Th1s pat1ent has kyphos~> and there is evidence of old fractures, suggestive of metabolic bone disease.
There 1S proximal muscle wasting and weakness. There ore fearures to suggest autoimmune disease.''
1he diagnOSIS is primary biliary cirrhosis with portal hypertension.

Clh lical notes

1. A middle-aged female patient with chronic liver disease is highly suggestive of primary biliary cirrhosis. It is
important to remember that approximately 75-90% of patients are female . although mates can be affected.
2. jaundice is a late feature ofthe disease.
3 Pigmentation is due to melanin deposition rather than jaundice.
4 T he causes of anaemia in primary biliary cirrhosis include Gt blood loss (oesophageal varices and
pept1c ulcers) and t hose related to additional underlying autoimmune disorde rs (pernicious anaemia,
atrophic gastritis, and Coeliac's disease). It is important to remember that there is an increased
incidence of peptic ulcer disease in patients with primary biliary cirrhosis.
5. Xanthalesma occur in 10% of patients, and often o ccur late in the disease. Tendon xanthomata can
occur, but are uncommon. B,9th are a consequence of hypercholestero laemia.
6. Prurttis is a common presenting symptom, even in the absence of advanced liver disease.
Dermatological manifestations are the presenting feature in a third of patients. These include xerosis,
dermographism, and fungal nail infection. Be aware of skin findings that would relate to additional
underlying autoimm une diseases (see below).
7. C oagulopathy and thrombocytopenia are features of chronic liver disease and portal hypertension (see
Case 1 Chronic Liver Disease). However. primary biliary cirrhosis is also associated with malabsorption
of fat-soluble vitamins (A. D, E, and K). Therefore, vitamin K malabsorption contributes to the
coagulopathy seen in primary biliary cirrhosis.
8. H epatomegaly occurs in 70% of patients and is often smooth and non-tender. It is Important to note
that in 10% of patients there is unexplained right upper quadrant discomfort, thus one should be
especially careful to avoid causing discomfort when examining these patients!
9. Splenomegaly and ascites are late features of the disease and indicate portal hypertension. Of note,
patients with primary biliary cirrhosis may develop oesophageal varices and variceal haemorrhage early
in the course of d1sease, even in the absence of established cirrhosis.
10. Hepatic bruits would signify malignancy, which is a complication of the disease.A venous hum would
signify portal hypertension.
11. Although this case is similar to other cases of chronic liver disease, the successful detection of
additional clinical features will enable the candidate to make the correct d iagnosis of primary biliary
Cirrhosis. If additional features are not present. then it would be best to present the d1agnosis as
'chronic liver disease' or 'isolated hepatomegaly/splenomegaly' and provide a differential diagnosis.
T hroughout your examination look for the following features:
(a) Kyphosis and evidence of old fractures (osteopenia and osteoporosis}
(b) Proximal myopathy (osteomalacia)
(c) Features of other autoimmune diseases:
Graves d isease: goitre (?thyroidectomy sc_.r), eye signs, thyroid acropachy, pretibial
myxoedema, features of hypo- or hyperthyroidism
Sjogren's syndrome: dry mouth, dry eyes
Rheumatoid arthritis: symmetrical deforming arthropathy, eye signs

21
ABDOMEN SYSTEM
- - -- - - - ---------- - -- -------
Scleroderma: telangiectasia, tight shiny skin, sclerodactyly, calcinosis, dystrophic nails
Dermatomyositis: heliotrope rash, Gottron papules
Idiopathic pulmonary fibrosis: bibasal crepitations
Myasthenia gravis: myasthenic facies, ptosis, diplopia, proximal weakness, a nd fatigability
Vitiligo: hypopigmented patches
Atrophic gastritis: pallor, koilonychia-iron deficiency anaemia

Questions commonly asked by examiners

What are the clinical features of primary biliary cirrhosis?
Fatigue, pruritis, and hypercholesterolaemia occur at all stages. Liver diselse occurs late, and is
rarely a presenting feature, particularly with recent advances in diagnosi~ and treatment.
How does one diagnose primary biliary cirrhosis?
Serum anti-mitochondrial (M2) antibodies are present in 95%. ln the presence of cholestasis and
positive antibodies, liver biopsy may not be required. The histological lesion is portal t ract
granuloma, progressing to cirrhosis. Ultrasound and ERCP,'MRCP (endoscopic retrograde
cholangiopancreatography/magnetic resonance cholangi9pancreatography) are often performed
to exclude extra-hepatic cholestasis.
Which drugs con cause cholestasis?
Phenothiazines
Sulphonamides
Penicillins
Rifampicin
Macrolides
Carbamazepine
Synthetic androgenic steroids
Didofenac
What is the prognosis of primary biliary cirrhosis?
It is associated with increased mortality, however less than half of deaths are liver-related.
Fatigued patients have a worse outcome, and are more likely to have a non-liver related death.
What is the management of primary biliary cirrhosis?
Supplementation of fat soluble vitamins
Due to fat malabsorption, and subsequent loss of fat-soluble vitamins, vitamins A, D, E, and
K should be supplemented.
Treatment of bone disease
Patients should also undergo bone densitometry to screen fo r metabolic bone disease.
Osteoporosis occurs in up to a third of patients. Severe bone d isease that resulted in multiple
fractures is now uncommon. There is no proven treatment for bone disease associated with
primary biliary cirrhosis except liver transplantation. Vitamin D and calcium supplementation
should be given. Bisphosphonates may increase bone density. Oestrogen replacement may
improve osteoporosis in post-menopausal women.
Treatment of hypercholesterolaemia
The serum cholesterol may be markedly elevate d in patients with primary biliary cirrhosis.
lnt:erestingly. patients with primary biliary cirrhosis do not appear to have an increased mortality
secondary to atherosclerosis. Cholesterol lowering agents (statins) may be used if the LFTs are
monitored appropriately.

22
 CASE 7 • A 'RENAL' ABDOMEN

Tre atment of liver disease

Ursodeoxycholic acid has been shown to improve liver biochemistry a nd po ssibly retard dise ase
progression. It is the only d rug approved by the US "Food and Drug Administration (FDA) in the
t reatment o f primary biliary cirrhosis. However, a convincing effect on histology or transplant-
free survival has not been demonstrated.
Management of pruritis
Pruritis is thought not to be a result of bile acid deposition in the skin but rather a consequence
of bile acids on sensory nerve fibres. Biliary obstruction must be excluded. Colestyramine has
limite d data on e fficacy, but it is safe and frequently used. However, it will prevent absorption of
othe ~ a rugs taken simult•neously, such as ursodeoxycholic acid. Rifampicin has been shown to be
effe ctive in four placebt -controlle d trials. Naltrexone has a lso been demonstrated to be effective
in tl"oree trials, although the antl·opio ic:l mechanism of action often exacerbates ch ronic pain.
Anti-histamines d o not work, and may worsen encephalopathy.
Manage ment of fatigue
Fatigue is not a consequence of co-morbid depression. Co-existent hypothyroidism or anaemia
must be excluded. Naltrexone may be of some benefit.
Referral for transplantation
Patients are referred fo r transplant c onsiderat ion when the serum bilirubin >501Jmol/L, or in the
prese nce of refractory fatigue or pruritis. Recurrence in the graft may occur (15% at 3 years and
30% at 10 years).

Case 7 • A 'Renal' Abdomen

--- - - - · - - - - - - - - - - - - - - - - - - - - - - - - - --
Examine r's note
A 'renal' abdomen is a common case at the abdomen statio n in the MRCP(PACES) clinical
examination. These patients are often stable on their renal replaceme nt the rapy and have many
clinical signs, and thus are good for clinical examinations. The method of renal replacem ent
therapy is often very clear or, otherwise, can be easily deduced .To obtain a ' pass' at this station is
straightforward. but these patients display many clinical signs that relate to previous methods of
renal replacement therapy: previous complications of renal replacement therapy; complications of
immunosuppressive therapy; and pos~ibly underlying aetiology of re nal d isease. The refor e , many
additional marks can be gained, and transforming a 'pass' into a 'clear pass' is very simple.
Candida tes are often poorly prepared for t his station, and it is important to be aware of the
different methods of re nal re placement therapy and the multiple clinical signs one m ust lo ok fo r
whe n examining such patients.
When presenting a case at the abdome n station, a ge neric approach that has been adopte d in
this book and one that is commo nly favoured by e xaminers starts periphe ra lly from the hands to
the face and ending on the abdomen. However, in a renal abdomen, the approach to presentation
iS different, and the following structured framework should be used:
1 . C urrent mode of renal replacement therapy
2 . Previous modes of renal replacement therapy (o ld scars)
3. Adequacy of re nal replacement therapy (uraemia and 'volume status)

23
ABDOMEN SYSTEM

4. Complications ·of renal failure , i.e. anaemia

5. Complications immunosuppressive therapy (often with renal transplantation)
6. Aetiology of renal disease {this may not be possible) ·

CASE PRESENTATION 1
This patient has a tunnelled central venous catheter in the right subclavian vein, with no evidence ·o f
catheter-site infection. 1 There are also scors on ·the chest wall from previous sites of vascular access for
haemodialysis, and there is a functioning and immature arteriovenous fistula in the left arm. 2
. There is no asterixis of the out-stretched hc.nds and there are no signs ofuroemlo. The venous pressure
is r.ot elevated, there is no peripheral oedema, and the patient ·is euvolaemic. 3
There is no clinical evidence of anaemia.• There are pinpricks at the lateral aspects of the fingertips,
indicating frequent glucose testing. There is llpohypertrophy of the subcutaneous tissues indi.::ating
subcutaneous insulin ·use. 6 ·

This patient has end-stage renal failure and receives renal replacement therapy through hoemodiolysis.
The patient currently receives haemodialysis through a tunnelled venous catheter whilst the arteriovenous
fistula matures. The most likely aetiology of renal disease is diabetes. 7

CASE PRESENTATION 2
This patient has a peritoneal dialysis catheter in the abdomen. with no evidence of catheter-site
infection. The abdomen is distended. soft and non-tender. There is a midline laparotomy scar. There is
flank dullness that shifts with rotation of the patient. consistent with dialysis fluid within the peritoneal
cavity. There are no abdominal wall herniae. 1 There are also scars from previous sites of vascular access
for haemodialysis. 2
There is no asterixis of the out-stretched hands and there are no signs ofuroemla. The venous pressure
is not elevated, there is no peripheral oedema. and the patient is euvolaemlc. 3 ·

There is no clinical evidence of anaemia.• There ore no peripheral stigmata of systemic disease•
Th.is patient has end-stage renal failure and receives renal replacement therapy through peritoneal dialysis. ·
The aetiology or renal disease is not clear (but has a differential diagnosis).'

CASE PRESENTATION 3
This patient has a scor in the right IUoc fossa. This overlies a smooth. firm. and non-tender moss. ' It has
a dull percussion note. There is no associated bruit There are scars on the chest wan from previous sites of
vascular access for haemodiafysjs. There is a non-functioning arteriovenous fistula in the right arm. 2
There is no asterixis of the out-stretched hands'and there ore no signs ofuroemla. The venous pressure
is not elevated. there is no peripheral oedema, and the patient is euvolaemic.3
There is no clinical evidence of anaemia! There is evidence of gum hypertrophy. There are no stigma ta
of active infection.' There is on erythematous. maculopapular rash in a butterfly dktrlbution over
the cheeks and the bridge of the nose, sporing the nasolabial folds. with scaling and follicular plugging.
There is also a symmetrical arthropathy o f the small joints of the hands.6 .

24
 CASE 7 • A 'RENAL' ABDOMEN

Thr~ paoent has end-stage renal failure and has a renal transplant Gwen rhe patient rs etNolaemic
an<J in the absence of other signs of active renal replacement therapy. the renal transplant '-' functioning.
The patrent is currendy on cyclosporin immunosuppresswe therapy. The most likely aetiology or renal
drsease rs systemic lupus erythematosus.'

Clinical notes
1. Current mode' of renal replacement therapy. This should be obvious from the end of the bed, or
otherwise can easily be deduced.
(a) Tunnelled cen!rol venous catheter. These are usually sited in the left or right subclavi< ular area
throufh the subclavian vein.Tunnelled lines are typically silastic. double-lumen catheters that allow
intermediate-duration haemodialysis whilst an arteriovenou~ frstula matures. It is Important to
comment on the absence or presence of catheter-site infection.
(b) Arteriovenous fistula. Arteriovenous fistulae are the preferred form of vascular access for
haemodialysrs. and are typically placed in the non-dominant upper limb. The fistula requires
months to mature. hence referral for haemodialysis must be made welt in advance of clinical need,
and temporary haemodialysis through a venous catheter may be necessary. The absence of a
palpable thrill suggests non-function.
(c) Peritoneal dialysis. A peritoneal dialysis catheter should be obvious during examination ofthe
abdomen and provides tong-term access to the peritoneal cavity. It is important to comment on
the absence and presence of catheter site infection. Clinical examination may indicate fluid in the
peritoneal cavity. Look for abdominal walt and inguinal herniae.
(d) Renal tmnsplom. Look carefully for scars in the right iliac fossa (Ruit~rford-Morrison Scar), and
carefully feel for the presence of a smooth mass below the scar: O~casionalty there may be ar.
additional scar in the left iliac fossa with a palpable mass.This will baffle candidates, and the most
likely explanation for this would be a repeat transplantation following failure of the old renal
transplant. Remember, a scar in the right iliac fossa DOES NOT ALWAYS imply the presence of a
renal transplant. as patients may have previously had an appendicectomy! It is therefore important
to fell carefully for fullness or a mass below the scar. Once the mass is identified;
Palpate the margins (often smooth)
Estimate the size (this can vary, but usually Scm >< Scm)
Comment on whether it is tender or non-tender
Comment on the consistency (often a firm mass)
Percuss over the mass (usually a dull percussion note)
Auscultate for bruits
2. Previous modes of renal replacement therapy. Look carefully for scars In the subctavicular areas for
previous tunnelled lines scars. Look carefully o n the arms for arteriovenous fistulae. Look carefully for
scars on the abdorninal walt indicating previous peritoneal dialysis. Mal<"' particular note of the
presence of laparotomy scars that may indicate previous surgery for peritonitis, an established
complication of peritoneal dialysis.
3. Adequacy of renal replacement therapy. Assessing fluid status is important. Clinical signs of uraemia
include:
(a) Altered mental status
(b) Asterixis (metabolic encephalopathy)
(c) Excoriation marks (secondary to pruritis)
(d) Tachypnoea (metabolic acidosis with respiratory compensation)
(e) Pericardia! rub (uraemic pericarditis)
-4. Complications of renal replacement therapy.The absence or presence of anaemia should be
included in the final presentation.The absence of anaemia is an important negative.

25
ABDOMEN SYSTEM

5. Complications of immunosuppressive therapy. This is relevant in patients with renal transplantation.

although it could be argued that end-stage renal failure itself is an 'immunocompromised' state.
Complications for im~unosupression should be sought for In the following manner:
(a) Stigmata of infection
(b) Presence of skin lesions (benign and malignant)
(c) Complications relating to specific drugs:
Cyclosporin: gum hypertrophy, hirsutism. coarse tremor. hypertension. diabetes mellitus
Steroids: purpura. cushingoid features, di"'betes mellitus
Tacrolimus: diabetes mellitus
6. Aetiology of renal failure. This may not be clear, but look for common causes:
(a) Diabetes: fingertips for pinpricks glucose testing), lipodystrophy. d iabetic retinopathy
(b) Hypertension: ask for the blood pressure
(c) Vasculitis: skin lesions. stigmata of rheumatological dise~e
(d) Polycystic kidney disease: palpable kidneys. look for nephreaamy scars
and rarities:
(e) A/port's syndrome: hearing aid
(f) Tuberous selenosis: subungal fibromas sebacuous aderomas
(g) membranoproliferative glomerulonephritis type 2 lipodystrophy (face/upper trunk/arms)
7. Final presentation.This is important, and should summarize your clinical findings. If the aetiology of
renal disease is not clear, then provide a differential diagnosis for renal failure (given below). Tell the
examiner you would like to
(a) Measure the blood pressure
(b) Check a urinalysis (glycosuria. haematuria. and proteinuria)
(c) Auscultate the heart for a pericardia! rub (uraemic pericarditis)

Questions commonly asked by examiners

What ore the major causes of chronic renal disease in developed countries?
Diabetes metliws 34%
Glomerulonephritis 21%
Hypertension 12%
Miscellaneous ' 10%
(including drugs. paraproteinaemia, obstructive uropathy)
Polycystic kidney disease 6%
Reflux nephropathy 6%
Analgesic nephropathy 6%
Uncertain 5%
What ore the principles of the management of chronic renal disease?
Treatment of reversible ca...ses of renal dysfunctioro
• Diagnosis of treatable glomerular disease (e.g. vasculitis. glomerulonephritis)-renal
biopsy is indicated unless both kidneys are small (suggesting irreversible disease). or
there is a specific contraindication.
• Cessation of nephrotoxic drugs (e.g. diur·etics, nonsteroidal a nti-inflammatory drugs
(NSAIDs), antibiotics).
• Exclusion of obstructive uropathy and renovascular disease--ultrasound of the renal
tract +/- MR angiography.

26
 CAS E 7 • A 'RENAL' ABDOMEN

Slowing disease progression

Treatment ofhyperte nsoon--the target blood pressure for patients with proteinuria is
130/SOmmHg. The first line agents should be ACE (angiotensin converting enzyme)
Inhibitors or angootensln-11 receptor antagonists {In the absence of significant renovascular
disease).
• Treatment of cardiovascular risk factors--Consider cardiovascular protection with aspirin
and lipid lowering therapy if 10 ~ar risk of CHD is >20%.Advise about smoking cessation.
Treatment of the complications of chronic renal disease
• Volume overload--dietary sodium restriction and loop d iuretics.
• Hyperkalaemia--dietary potassium restriction, loop diuretics. and oral sodium
bicarl:>onate.
• Hyperphosphataemia-phosphate binders, such as calci•Jm carbonate, limit the
development of renal osteodystrophy. Patients with hypercalcaemia due to
hyperparathyroidism should receive alternative phosphate binders.
• Metabolic acidosis-treatment of acidosis with oral sodium bicarl:>onate limits renal
osteodystrophy and symptomatic uraemia.
• Renal osteodystrophy--treatment of hyperphosphataemia, and the administration of
vitamin D analogues, limit the development of secondary hyperparathyroidism, which
predisposes to renal osteodystrophy. Parathyroidectomy should be considered if the
patient develops symptomatic hypercalcaemia due to hyperparathyroidism, refractory
to medical therapy.
• - Anaemia-normochromic, normocytic anaemia OCC\Jrs due to reduced ptoduction
of erythropoietin by the kidney. Following the adequate treatment of concomitant
iron-deficiency. almost invakbly with Intravenous Iron if necessary, regular administra-
tion of erythropoietin improves symptoms and cardiovascular morl:>idity.
What are the indications for renal replacement therapy?
Preparation for renal replacement should begin when the glomerular filtration rate decreases to
30mUmin, or between 30 and 40mUmin in diabetics. The clinical indications for acute
haemodialysis are:
Pericarditis or pleuritis due to uraemia
Uraemic bleeding diathesis (due to platelet dysfunction)
Volume overload refractory to diuretics
Hypertension refractory to antihypertensive drugs
Refractory hyperkalaemia
Refractory acidosis
Encephalopathy or decline in mental status due to uraemia
Removal of toxins (lithium, salicylates etc.)
Can you think of any problems associated with dialysis?
Haemodia\ysls
Dialysis washout--due to removal of too much fluid (excessive ultrafiltration), or too rapid
Ouod removal. This may cause hypotension. fatigue. chest pain. leg cramps. nausea. and headache.
Bocteraemlo-particularty associated with wnnelled or non-tunnelled venous catheters.
MetaStatic infection may occur, especially with staphylococcus aureus infection. causing osteomy-
elitis, endocarditis, e ndopthalmitis, or hepatic and splenic abscesses. These complications must
be actively sought a nd e xcluded in the presence of staphylococcus aureus bacteraemia.
Bleeding--may o ccur due to the use of hepa rin as an anticoagulant during haemodialysis.
inor ble eding is generally self-limiting with the cessation of anticoagulation. Rarely. prqtamine

27
ABDOMEN SYSTEM

sulphate may be required to reverse anticoagulation in the context of major bleeding.

Haemodialysis can be performed w ithout anticoagulation in patients at h igh r isk of bleeding.
Dialysis related amyloidosis-occurs due to decreased clearance of !32-microglobulin.The
musculoskeletal manifestations include carpal tunnel syndrome, scapulo humeral arthropathy,
spondyloarthropathy. bone cysts, and pathological fractures. Systemic manifestations are less
common, b ut are characterized by amyloid deposits around blood vessels in the mucosa of
the gastrointestinal tract. heart, lungs, and urinary tract. Rarely, gastrointe.s tinal haemorrhage.
cardiac arrhthymias and renal vein thrombosis have been described.
Peritoneal dialysis
Bacterial peritonitis- is a common complication of perito,...nal peritonitis, occurring
approximately once every patient year.The typical presenta tion is with abdominal pain,
which may be mild, or with cloudy dialy~ates. Fever is frequently ab$ent.Treatment is
typically with intraperitoneal antibiotics, although occasionally removal of the dialysis
catheter and a change in dialysis modality may be necessary.
Solute clearance or ultrafiltration failure--as a consequence of peritoneal sclerosis, may
necessitate a change in dialysis modality.
Diabetes mell.itus---may occur due to systemic absorption of glucose from the peritoneal
dialysate.
Local compUcations-such as a bdominal wall hernias. fluid leakage .into surrounding soft
tissue. or catheter exit site infections.
What are the jTlanifestotions of renal osteodystrophy?
Osteitis fibrosa-increased bone turnover, due to secondary hyperparathyroidism. This is
usually asymptomatic, although bone pain and tenderness may occur, and bone cysts may
develop which are termed 'brown tumours·.
Osteomalacia--decreased mineralization of bone, predominantly due to alumin ium
d eposition in bone, from aluminium-containing phosphate binders.
Adynamic bone disease--is the most common bone lesion in haemodialysis and perito-
neal dialysis patients. Bone turnover is markedly redu ced. although there is no defect in

Figul"'e 7.1 A mature radio-cephalic arteriovenous fistula fo r haemodialysis.

. Reproduced from Barratt et al. Oxford Desk Reference Nephrology. 2009. with permission from Oxford
University Press.

28
 CASE 8 • NEPHROTIC SYNDROME

mineralization as in osteomalacia. Patients have decreased serum parathyroid honnone

(PTH), due to the use of phosphate binders and vitamin D analogues.
What is the differential diagnosis of bone pain in patients with renal disease?
Osteitis fibrosa
Osteomalacia
Dialysis-related amyloid
Myeloma or skeletal metastases
Osteomyelitis due to bacteraemia from infected vascular_access-
Neuropathic pain from nerve compression by arteriovenous fistulae

Case 8 • Nephrotic S:~ndrome

Examiner's n~es
Nephrotic syndrome is an uncommon case in the MRCP (PACES) examination, however it has
been reported to appear and candidates should therefore be prepared for this case.The key
clinical p9inters to the d iagnosis are features of hypoatbuminaemia and evidence _pf fluid
overload (ascites, pleural effusions, and oedema).The case presentation below is similar to the
case presentation for ascites (see Case 2 Ascites), and should therefore be read in conjunction
with the ascites clinical notes.
Throughout your examination, look for clues for the underlying aetiology and evidence of underlying
systemic disease. Often in the examination, the patient will have ascites, and it is important to look
thoroughly for signs and complications of chronic liver disease (as this is the most common cause for
ascites).The following case presentation is typical for a patient with nephrotic syndrome and has
been adapted from the case presentation for ascites. When preparing for this case, please read in
conjunction with the case presentation and clinical notes for ascites (see page).

CASE PRESENTATION
This patient has marked peripherof oedemo and periorbltol oedemo. ' There is feuconychio and
Muehrcl<e's lines ore visible across the nail beds.1 There are no splinter haemorrhages. nail-fOld infarcts
or rash/ There are no stigmata ofchronic liver disease.• There is no evidence C'flymphadenopathy.' The
venous pressure is elevated.• The obdomen is distended, with dinicol evidence of ascites. There is no
evidence o( hepatosplenomegaly. There are no signs of hepatic encephalopathy.
This patient demonstrates features of hypoolbuminaemio with fluid retention and oscites.
The unifying diagnosis is nephrotic syndrome. 7

Clinical notes
1. Peripheral oedema in renal disease is forst seen in tissues with low resistance , such as the periorbital
region or the scrotum and labia. This is unlike right-sided heart failure, where the peripheral oedema is
more generalized.

29
ABDOMEN SYSTEM

2. Examine the hands cat·efully, looking for signs of hypoalbuminaemia. Look for Muehrcke's lines, wh•ch
are pairs of transverse lines extending all the way across the nail bed, and occurring in more than one
digit. This sign is specific for hypoalbumlnaemia, as a consequence of the nephrotic syndrome, liver
disease, or enteropathy.These should not be confused with Mee's lines, which are also transverse lines
across the nail, associated with heart failure. Hodgkin's lymphoma. chemotherapeutic agents, and
arsenic poisoning. Muehrcke's lines affect the nail bed. and hence do not move with nail growth, unlike
Mee's lines, which are defects in the nail matrix. Leukonychia is non-specific finding associated with
hypoalbuminaemia as weH as other systemic conditions such as heart failure, liver disease. renal disea$e,
Hodgkin's lymphoma, and diabetes mellitus.
3. Also look for signs of underlying vasculitis or rheumatological disease as a cause of glomerular disease
(membranous glomerulonephritis).
4. Look carefully for signs of chronic liver disease. Hypoalbuminae ia occurs in chronic. liver disease, and
thus it rnay be more appropriate to state 'there are no or.her stigmata of chronic liver diseas~·. 45
opposed to 'there are no stigmata of chronic liver disease'.
5. Lymphadenopathy indicates infection or haematological malignancy as causes of nephrotic syndrome.
6. Assessment of the JVP is essential in patients with peripheral oedema or ascites. In patients with
significant oedema, assessment of the volume status and distrib ution of oedema can aid differential
diagnosis.The venous pressure will be elevated in nephrotic syndrome only with marked fluid overload
(as in patients with renal failure). Such patients are unlikely to appear In the MRCP (PACES) examination.

jVP Peripheral Oedema/Ascites

Right heart failu r e Elevated +

Renal failure -Variable +
Nephrotic syndrome Variable +
Uver disease Not elevated +
Venous insufficiency Not e levated +
Peripheral oedema may be asymmetrical

7. After having presented a unifying diagnosis of nephrotic syndrome, tell the examiner you would like to:
(a) Confirm the presence of proteinuria*
(b) Measure the blood pressure
(c) Look for evidence of underlying aetiology (see below for causes)
(d) Exan1ine the chest for pleural effusions
If the venous pressure were elevated (unlikely in the MRCP (PACES) examination). then another
important differential would be right heart failure. In such cases. tell the examiner you would like
to examine the cardiovasc•Jlar system.
'
Questions commonly asked by examiners
What is the definition of the nephrotic syndrome?
The nephrotic syndrome is a clinical syndrome, characterized by heavy proteinuria (> 3g/24
hours), hypoalbuminaemia (<30g/L), and oedema. Hyperlipidaemia and thrombotk: disease is
frequently observed, but are not essential for the diagnosis.

What is the difference between proteinuria and the nephrotic syndrome?

Proteinuria is a manifestation of glomerular disease. Urinary protein excretion in the normal adult
should be less than 150mg per day, of which 30mg is albumin. An alternative to 24-hour urine

" Proteinuria Is required for the diagnosis of the nephrotic syndrome, although non-nephrotic range proteinun a may
occur ln other conditions. Urinalysis is a useful bedside test to demonstrate proteinuria. but will not reliably q uantify
proteinuria.The demonstration of heavy proteinuria. greater than 3g in 24 hours. is required for the diagnosis.

30
 CASE 8 • NEPHROTIC SYNDROME
·- -- - --·-- --- - ·-··-------- --
collection is the estimation of the total protein:creatinine ratio (normal < 1 Smg/mmol).This
correlates with daily protein excretion. and is less cumbersome than a 24-hour collection, although
the limitations of the tests include variations with time of day. with race, and with body mass.
Any condition causing glomerular disease can cause a spectrum ranging from asymptomatic
prot einuria, to heavy pro teinuria wit hout symptoms, or to the nephrotic syndrome. Patients w ith
the nephrotic syndrome are at greater risk of complications such as thrombotic disease or
infection, than those w ith isolated proteinuria.
What are the way$ in which glomerular disease may present?
Focal nephritic disease--This is characterized by inflammatory lesions in less than one-half of
glo meruli o; light microscopy. Urinalysis reveals haematuria, mild proteinuria, and occasirnally
red cell cas..s. Findirgs of advanced disease, such as oedema, hypertension, and renal insl..ffi·
d e ncy, are absent.These patients typically present with asymptomati~ haematuria.
Diffuse nephritic disease--Diffuse glomerulonephritis affects most. or all, of the glomeruli.
These patients may present w ith features of advanced disease, such as oedema,
hypertension, renal insufficiency, or the nephrotic syndrome: ·
Nephrotic syndrome.
What is the differential diagnosis.ofthe nephrotic syndrome?
In adults, approximately 30% have a systemic disorder, such as diabetes mellitus, amyloidosis,'
o r SLE. The remainder are due to intrinsic renal disease, such as minimal change disease, focal
glomerulosclerosis, and membranous glomerulonephritis. Minimal change disease accounts for
the vast majority of nephrotic syndrome irt children.
Minimal change disease--This has typically normal light microscopic appearances, with no
evidence of immune complex deposition on immunofluorescence. The disorder is most
common in children, but may also occur in adults as either an idiopathic condition, or
associated with diabetes, lgA nephropathy, NSAIDs, HIV infection, or as a paraneoplastic
effect of malignancy most commonly Hodgkin's lymphoma.
Focal segmental glomeruloscerosis-This is characterized by segmental glomerular mesa ngial
collapse and sclerosis on light microscopy. It accounts for over 35% of cases of nephrotic
syndrome in developed countries, and ove r 50% amongst Afro-Caribbean populations.
The disorder can be Idiopathic. but is also associated with HIV infection, NSAID use, and
massive obesity.
Membranous glomerulonephritis--This disorder is characterized by basement membrane
thickening on light microscopy, with little cellular infiltration. Causes include infection (hepatitis B
and C, malaria, schistosomiasis. and syphilis), autoimmune disease (SLE, rheumatoid arthritis,

I
dermatomyositis. and Sjogren's syndrome), paraneoplastic syndrome to a solid organ malignancy
(lung. colon. stomach, breast. and lymphoma), and drugs (gold, penicillamine, and NSAIDs).
M esangiocapillary glomerulonephritis-This is characterized by proliferation of mesangial and
e ndothelial cells and expansion of the mesangial matrix and a double -contour or tram-track
appearance on light microscopy. It can be divided into primary (idiopathic) and secondary

I
types. The secondary types are more common than the idiopathic types. In idiopathic type.
immune complex deposition occurs within the glomerulus and can be further sub-categorized
a s type 1 (subendothe lial deposits) or type 2 (basement membrane deposits). Causes
include infection (chronic hepatitis B a nd C. leprosy, endocarditis), cryoglobulinaemia , and
autoimmune disease (SLE, rheumatoid arthritis, scleroderma. and Sjogren's syndrome).

I
How would you assess a patient with proteinuria?
Confirm presence of-proteinuria--Urinalysis should be performed on at least two separate
occasions to exclude proteinuria due to intercurrent illness.

t
~
31
ABDOMEN SYSTEM

Look for other signs of glomerular disease--The urine sediment should be examined for
haematuria and red cell casts. Also look for hypertension, diabetes mellitus, and impaired
renal function. Ask about symptoms suggestive of an underlying systemic vasculitis, or about
a family history of renal disease. (see Vol 2. Station 2 History taking skills).
Exclude orthostatic proteinuria-Th is is a benign condition, typically affecting young adults
under 30 years of age. In this condition, an overnight urine collection shows normal protein
excretion (i.e. <SOmg during an 8 hour period).
Establish degree of proteinuria-Protein excretion can be measured. with a 24-hour urine
collection. However, the protein:creatinine ratio from a single urine specimen is the most
commonly used screening test for pro teinuria. The albumin:creatinine ratio should be used
to detect microalbuminuria.
Microalbuminuria-This describes pathological albuminuri:i..which is not detectable by
dipstick urinalysis. It is defined as a 24-hour urine albumin excretion of 3o-300mg. or a
urinary albumin:creatinine ratio >2.5mg/mmol (men), and > 3.5mg/mmol (women).
Proteinuria-This is defined as between 300mg and 3g of proteinuria in 24 hours. or a
protein:creatinine ratio > 30mg/mmol.
Nephrotic range proteinuria-This is defined as proteinuria > 3g/day. or a
protein:creatinine ratio >300mg/mmoi.The nephrotic syndrome is diagnosed if
hypoalbuminaemia and oedema are a lso present.
Look for treatable causes ofglomerular disease:
Autoimmune profile--including antinuclear antibodies (ANAs), anti-DNA antibodies,
c~mplement levels, and cryoglobulins.

• Viral serology-including hepatitis B, hepatitis C. and HIV.

• Urine and plasma protein electrophoreisis.
• Antistreptococcal antibodies.
• Renal biopsy--is usually indicated to guide specific therapy if nephrotic syndrome is
present, and the kidneys are not small on imaging (suggesting irreversible renal disease).
What crre the complications of the nephrotic syndrome?
Oedema-controlled by salt restriction and diuretics
Hypertension--should be treated to a target of 125/75. using ACE inhibitors and
angiotensin-II receptor antagonists in the first instance.
Hypercholesterolaemia--t.Jsually requires lipid lowering therapy.
Thrombosis-routine prophylactic anticoagulation is not recommended, however immobile
patients should receive heparin prophylaxis.
lnfection---patie~ts should receive Pneumococcal and Meningococcal vaccinations. Penicillin
prophylaxis has not been shown to be beneficial.
How would you initiate treatment in a patient with significant oedema?
High doses of loop diuretics are often required, since patients with nephrotic syndrome are
often r e!atively resistant to diuretics. Thiazide diuretics. such as bendroflumethiazide or
metolazone, may be added for synergistic diuresis.
Monitor diuresis by measuring weight and postural blood pressure. Aim for weight loss of
between 0 .5--1 kg/day. Over-diuresis is signalled by excess weight loss, or the presence of
poswral hypotension >20mmHg.

32
 CASE 9 • POLYCYSTIC KIDNEYS

Case 9 .• Polycystic, KiCineys

--------------------------~------~--------------------------------------

CASE PRESENTATION
This patient has no stigmata of chronic liver disease.' There is no evidence ofanaemia. 2 The venous
pressure is not elevated.3 The abdomen is distended with fullness in the.flanks4 There is an irregular;
non-tender liver edge palpable ]em below the costal margin.5 There is no evidence of splenomegaly.•
There are bilateral flank masses. TJ-.P.se mosses are ballotable; it is possible to palpate above
these masses, and the overlying percussion note Is reso 1ant.7 There are no signs of uraemia or
encephalopathy" There is no evidence of renal replacement thernpy9
The diagnosis is polycystic kidney disease. 10

- -· ---·- -- -- - - -- - - ---'--- - - -- - -- - -- -- - ---

Clinical notes
1. Look for stigmata of chronic liver disease. Although hepatic cysts and hepatomegaly is common in
polycystic kidney disease, the liver function is usually normal and cirrhosis is rare.
2. Mention the presence or absence of anaemia. Anaemia is a complication of chronic renal disease. Also
Jook for plet horic facies that would suggest polycythaemia. Polycystic kidney diseas<;_ is associated with
increased erythropoietin production and is therefore an important secordary cause of polycythaemia.
3 . It is important to comment on volume status in a patient with chronic renal d isease.
4. When inspecting the abdomen look carefully for nephrectomy scars. Nephrectomy scars can be
unilateral or bilateral. Nephrectomy is often necessary in the context of trauma and haemorrhage. as
polycystic kidneys are very prone to traumatic injury. Other indications include pain, recurrent
infections, and cyst rupture. Nephrectomy is frequently undertaken at the time of renal transplantation.
Also look carefully in the right and left iliac fossae for scars suggesting a renal transplant.
5. Hepatic cysts occur in up to 70% of patients, but this may not always result in palpable hepatomegaly.
If hepatomegaly is present, the liver will have an irregular nodular edge. It is common for hepatomegaly
to be missed in patients with large polycystic kidneys. When palpating the liver, start from the left iliac
fossa with the hand placed firmly flat over the abdomen, aiming to feel the liver edge with the radial
border of the index finger as it descends with inspiration. Continue to do this as you successively move
up to the right costal margin. By placing the hand firmly on the abdomen, the renal mass is displaced
posteriorly, and attention can be paid to feeling for the descent of t he liver edge. A common error is
where the lower border of the enlarged kidney is mistaken for the liver edge in thin patients. In such
cases it is important to remember that the kidney will not descend with inspiration.
6. Splenic cysts can al>o occur (5% of patients), but are less common th<.n hepatic cysts.
7. The liver and spleen can be diffe•<:ntiated dinicalty from renal masses by the following general rules:

Liver and spleen Renal mass

-···------- - - -- - · - - - - -- - -- -
Percussion note Dull Usually resonant
Movement with respiration Yes No
Palpate above No Yes
Batlotable No Yes

Although these are taught as golden rules for differentiating kidneys from liver and spleen, there are
some exceptions _!lnd the following clinical points should be noted:
In patients with hepatomegaly AND a large right renal mass, it may be difficult to palpate
-, h..-...o. t-hQ. r-o n~ I rn-:~c-<' Thio;; m":lv f~h:Piv inr4ir::11tP 1'h,. nr.,..u ::,..nrP nf ::11 dno)P l::a r oP rPn:::tl rn::ao;;~

33
ABDOMEN SYSTEM

However, detecting the presence of a descending liver edge in inspiration, the resonant percussion
note over the mass BELOW the liver edge and the baUotable nature of the mass will help
diagnose both hepatomegaly AND a renal mass.
In thin patients with large kidneys, especially in cases where the kidneys are visible during
inspection (flank fullness) and easily palpable during light palpation of the abdomen, the percussion
note can be dull (as opposed to resonant)!
13. Asterixis of the out-stretched hands indicates a metabolic encephalopathy. Metabolic encephalopathies,
especially hepatic and renal, are the most common causes of bilateral aste_rixls. Other causes of
asterixis include hypercapnoea, electrolyte abnormalities (hypoglycaemia, hypokalaemia, and
hypomagnesaemia) and drug intoxication (barbiturate, phenytoin. and primidone).
9. Throughout yc:.ur examination look carefully for evidence of previous or current renal replacemfl•t
therapy. Patte lts may have stable polycystic kidney disease, and may not have reached end-stage
renal failure. Mentionfc,g :he lbsence or presence of renal replacement therapy is an Important
negative.
10. The above case presentation is appropriate when presenting a patient with polycystic kidney disease
who has not reached end-stage renal failure. In patients with evidence of renal replacement therapy,
we suggest using the presentation framework for a renal abdomen (see Case 7 Renal Abdomen).

Polycystic kidney disease is a multi-system disorder. Tell the examiner you would like to look for
other features and associations of the disease, and proceed as follows:
Measure the blood pressure (hypertension predates the onset of renal failure)
Examine the c ardiovascular system (mitral valve prolapse, aortic regurgitation, left
ventricular heave [hypertension])
Examine the neurological system: (evidence of old stroke; third nerve palsy
[Ber. y aneurysm])

Questions commonly asked by examiners

What other diseases cause bilateral renal cysts?
Multiple simple cysts
Tuberous sclerosis
Von Hippe! Lindau syndrome
Meckel-Gruber syndrome
Laurence-Moon-Bardet-Biedl syndrome
Trisomies 13 (Patau syndrome). 18 (Edward syndrome), and 21 (Down syndrome)
What is the differential diagnosis of a single palpable kidney?
Polycystic kidney disease (with only one palpable kidney)
Hydronephrosis
Hypertrophy of a single functioning kidney
Renal cell carcinoma
What is the differential diagnosis for bilateral palpable kidneys?
Bilateral renal cysts (see above)
Bilateral hydronephrosis
Amyloidosis
Bilateral renal cell carcinoma (occurs in von Hippel-lindau syndrome)
What da you know about the genetics of adult polycystic kidney disease?
Polycystic kidney disease is typically autosomal dominant (ADPKD). A variety of genetic
defects have been described. ADPKD1 accounts for 90% of cases, and has been mapped to

34
 CASE 9 • POL.:YCYSTIC KIDNEYS
--- ----- - - - - ---- - - - - - - -- - -- -·------ --..,----
chromosome 16. Most of the remainr!er of cases are ADPKD2, which has been mapped to
chromosome 4. and has a less severe phenotype. In 10% of patients, the disease arises from
a spontaneous mutation.
Autosomal recessive kidney disease (ARPKD) is a rare disease, presenting in infancy and
frequently causing severe liver and renal disease.
What are the features of ADPKD?
Flank and abdominal pain is common, caused by stretching of the capsule or traction of the
renal pedicle.
Acute pain suggests haemorrhage, infection, or torsion of a cyst. Kidney stones also occur in
20%, and may cause obstructive uropathy.
Nocturia occur: due to impaired ability to concentrate urine
Renal call carcinoma is ~.ot more common in ADPKD. However. the tumours are more likely
to be bilateral, and are more difficult to diagnose.
What ore the extra-renal manifestations of ADPKD?
Cerebr al aneurysms
Subarachnoid haemorrhage as a consequence of a ruptured cerebral aneurysm is the most
serious complication of ADPKD.Aneurysms occur in 4% of younger patients, and up to 10%
of older patients.
The role of magnetic resonance angiography has not been settled, and is probably only
desirable for high risk patients with a family history of haemorrhage. This is because of the
dilemma of treating small aneurysms ( <71'1"1m) whose r isk of rupture may be less than the
risk from neurosurgical treatment.
Liver cysts
Liver cysts occur later than kidney cysts in ADPKD, and are present in up to 70% of cases.
They rarely cause symptoms. although local symptoms, cholestasis, portal hypertension, and
venous obstruction have been described.
Autosomal dominant polycystic liver disease is a separate disorder, not associated with
kidney cysts or cerebral aneurysms.
Other extra-renal cysts
Pancreatic cysts occur in 9% and splenic cysts occur in 5% of patients. Cysts have also been
.reported in the thyroid, parathyroid, lung, pituitary gland, ovary, uterus, testis, seminal
vesicles, epididymis, bladder, and peritoneum. ·
Valvular heart disease
Mitral valve prolapse and aortic regurgitation are more common in this population,
although the clinical significance of these lesions is uncertain.
What are the principles of management of ADPKD?
Management of acute flank pain
Distinguishing infection, haemorrhage or renal stones may be difficult. Infection rarely causes
a positive urine culture, since the cysts are not in continuity with the collecting system.
Imaging may not distinguish infection or haemorrhage, but will exclude renal stones.
Infected cys~ must be treated with lipid-soluble antimicrobials that penetrate the cyst, since
~
they are not in contact with the glomerular system.Aminoglycosides and penicillins should
I not be used, but quinolones and vancomycin are suitable.
I Cyst aspiration is rarely performed, since it does not improve renal function, and the lesions
fL are multiple.

r
L

35

r
ABDOMEN SYSTEM

Management of r e nal failure

Control hyperte nsion.
Ensure adequate nut rit ion-there is no evide nce fo r protein restriction.
Treat anaemia. Re ple nish iron stores, and consider erythropoietin o nly after controlling
hypert ension.
Phosphate binders if the serum phosphat e is elevated.
Vitamin D supple mentation if the serum PTH is e levated.
For persistent hyper parathyroidism, consider calcimimetics or parathyroidectomy.
Early specialist referral for renal replacement therapy.
Screening for ADPKD
Cysts are present in infancy. and increase in size with age. However, onset of clinical d isease
is rare in children, and cysts may be missed radiologically when small. Therefore, screening in
those with a fam ily history occurs after the age of 20.
What do you know about Von-Hippel-Lindau syndrome?
Autosomal dominant condition (chromosome 3) with 80-90% penetrance
Cerebellar; retinal, and spinal haemangioblastomas
Cysts occur in the kidneys, liver, spleen, and epididymis
Increased risk of renal cell carcinoma (bilateral in 40% of cases) and phaechromocytoma

Case 10 • Abdominal Mass

CASE PRESENTATION 1
This patient is cachectic.' There is e vidence of anaemia. There is no evidence of clubbing 7 and there
are no stigmata of chrr'~•c liver disease. There is a pa lpable left supraclavicular lymph nodeJ The
abdomen is soft and non-tender. There is no organomegaly. There is a palpable mass in the left upper
quadrant. It is non-tender. firm. and ill-defined. It does not move with respiration, and 1s not (1xed to the
abdominal wall. The moss 1S not pulsatile. and is not ballocoble. The overlying percussion note is dull. It is
possible to palpate berween the moss and the left costal margm. On auscultation of the mass. there are
no bowel sounds, brwts, or rubs.•
Th1s patient has a left upper quadrant moss-most likely colonic or gastric in origin. The presence of
cachex1o and lymphadenopathy raises the susPicion of malignancy.5

CASE PRESEN T ATION 2

This patient is cachectic.' There is evidence of anaemia. On examination of the hands there is
clubbingl and leu conychio. There is oral ulceration. There is no lymphadenopathy.J There is a m idline
laparotomy scar. The abdomen is soft but tender in the right lower quadrant. There IS no orgonomegaly.
There is a palpable mass in the right lower quadra nt. It is tender, (lrm. and 1/1-de(med. It does not
move With respiration. • and is not fixed to the abdominal wall. The moss 1s not pulsatile, and is nor

36
 CASE 10 • ABDOMINAL MASS
--------·--·--
ballocable' The overlying percussion note is dull. It is possible to palpate between the m ass and the left
co stu/ margin. On auscultation o{ the mass. bowel sounds are aud1ble. but there are no bruits, or rubs!
Thts patient has a right lower quadrant mass-most likely colonic In origin. The presence of dubbing.
om/ ulceration. and abdominal tenderness suggests an inflammatory mass due to Crohn's disease.5

Clinical notes
1. Cachexia may be noticeable from standing at the end of the bed. Otherwise, a cachectic state may be
demonstrated by a poor nutritional status from a reduced tricep fat fold thickness that can be easily
assessed during the examination. Wasting of the temporalis nuscle is an early sign of generalized
muscle atrophy.
2. Gastrointestinal causes of clubbing include chronic liver disease, inflammatory bowel disease,
gastrointestinal lymphoma. coeliac disease, tropical sprue, parasitosis. Whipple's disease. and achalasia.
3. In the conte>et of an abdominal mass. lymphadenopathy suggests malignancy. Virchow's node (or signal
node) is an enlarged, hard, left supraclavicular lymph node which can contain metastasis of visceral
(abdominal) malignancy. Malignancies of the lntemal organs can reach an advanced stage before giving
symptoms. The left supraclavicular node, orVirchow's node, is an earty site of metastatic Gl cancer
because it is on the left side of the neck where thelymphatic drainage of most of the body (from the
tho racic duct) enters the venous circulation via the left subclavian vein. The differential diagnosisof an
enlarged Virchow's node includes lymphoma, other intra-abdominal malignancies, breat cancer, lung
canc:r. and infection(e.g. of the arm). An enlarged Virchow's node is also referred to as Troisier's sign.
4. Look below for differential diagnoses for masses in the four quadrants of the abdomen. Having
established the presence of an abdominal mass it is important to look for the following features:

FEATURE CliNICAL NOTES

Size Comment on the size. This need not be accurate, and a rough
estimate will suffice.
Consistency Is it soft or firm?
Border Well-defined or ill (poorly) -defined~ Ensure to define the contour of the
mass by inspection, percussion, and palpation. A well-defined mass may be
an intra-abdo minal organ (e.g. liver, spleen), whilst an ill-defined mass may
be matted loops of bowel or mesentery. or a neoplastic mass.
Tender Tender or non-tender
Attached to This suggests either an abdominal wall mass (e.g. lipoma or rectus
abdominal wall sheath haematoma). or an inflammatory or neoplastic mass that is
fixed to the abdominal wall.
Movement with A mobile intra-abdominal mass will move with respiration (e.g. liver,
respiration spleen), whilst relroperitoneal structures (e.g. aorta, kidney) or an
abdominal wall mass will not.
Pulsatile A pulsatile mass is suggestive of a vascular lesion , such as an aneurysm
or arterio-venous fistula.
Ballotable The kidneys are the only ballotable masses in the abdomen.
Percussion note Solid masses with a firm consistency will give a dull percussion note.
A uscultatory The presence of bowel sounds suggests that the mass is intestinal in
findings origin.The presence of a bruit suggests a vascular origin, w hilst a rub
suggests an inflammatory o r neoplastic origin.

37
ABDOMEN SYSTEM
------------------------
Remember with right/left upper quadrant masses, it is Important to establish if it is possible to palpate
above the mass. This will differentiate the mass from a liver/spleen (not possible to palpate above the
liver or spleen).
5. When presenting the final diagnosis, t ry to establish the location of the mass. Use other clinical signs to
make a diagnosis. If this is not possible, then provide a differential diagnosis based on the four quadrants
in which the mass lies (see below).

Questions commonly asked by examiners

What are the causes of:
A right upper quadrant mass
Liver--moves Nith respiration.
Right kidney--o-etroperitoneal and ballotable, but does not move with respiration.
Riedel's lobe of liver--this is a sessile projection of the right lobe of the liver, which
descends to the right of the gallbladder. It is considered a normal variant.
Gallbladder--moves with respiration.
Colon--does not move with respiration. High-pitched bowel sounds suggest obstruction.
A left upper quadrant mass
Spleen--moves with respiration. Possesses a medial notch. and enlarges towards the right
iliac fossa.
Left kidney--distinguished from the spleen by being ballotable and resonant to percussion.
Colon/pancreas/stomach-these are impossible to differentiate by clinical examination.
Pancreatic masses include cystic neoplasms, pseudocysts, and solid tumours.
A right lower quadrant mass
Colon/small intestine/appendix--inflammatory masses may be tender, although neoplastic
masses are usually painless.
Pelvic mass--bimanual palpation may distinguish an intestinal and pelvic mass.
A left lower quadrant mass
Sigmoid colon--an inflammatory mass may be due to diverticular disease or inflammatory
bowel disease. Neoplastic lesions are more common in the left colon than the right colon.
Pelvic mass
Do you know of any inherited conditions predisposing to colorectal cancer?
Hereditary Nonpolyposis Colorectol Cancer (HNPCC) or Lynch syndrome--An autosomal
dominant disorder with high penetrance, caused by mutations in one of several DNA
mismatch repair genes. Lynch syndrome accounts for 1-3% of colonic adenocarcinomas,
and is also associated with extra-colonic tumours such as endometrium, ovary, stomach,
$mall intestine, hepatobiliary, and urogenital. The Amsterdam Crite:-ia have been proposed
for the cliilical diagnosis of HNPCC:
• <!:3 relatives with colorectal cancer, one of whom is a first-degree relative of the
other two.
• Involvement of at least two generations
• One or more cancers diagnosed before the age of SO
A problem with this approach is the low sensitivity, so a significant number of patients with
hered itary syndromes may be missed. An alternative approach is to use molecular methods
to detect microsatellite instability, or mutation o f DNA repair genes, in tumours of patients
with colorectal cancer. Relatives can then be screened for these mutations from blood tests.
However. the cost-effectiveness of this approach remains to be assessed.

38
 CASE 10 • ABDOMINAL MASS

Familial Adenomatous Polyposis (FAP)-An autosomal dominant disorder. caused by mutation

in the adenomatous polyposis coli (APC) gene. Approximately one-third of patients with
FAP have no fam ily history of the disease, and probably represent new mutations. The
diagnosis of FAP is based upon the presence of more than 100 adenomatous colorectal
polyps. Almost all patients develop colorectal cancer by the age of 45, unless colectomy is
perfo rmed. Patients remain at risk of extra-colonic tumours, including duodenal ampullary
cancer, gastric cancer, follicular or papillary thyroid cancer, and CNS tumours. Gordner's
syndrome is a variant of FAP with extraintestinal lesions such as desmoid tumours, seba-
ceous cysts, lipomas, osteomas, and supernumerary teeth. Turcot's syndrome is a rare FAP
variant, associated with medulloblastoma.
Peutz-jeghers Syndrome-An autosomal dominant condition, characterized by multiple
hamartomatous polyps in the small intestine, colon, and stomach. Clinically, patients develop
numerous pigmented lesions on the lips and buccal mucosa. The overall cancer risk is
increased 9-fold for both gastrointestinal, and non-gastrointestinal sites, including breast,
lung, uterus, and ovary. (See volume 1, case f:amity History of Cancer)
What are the most common small intestinal tumours?
Small intestine tumours are rare, accounting for less than 2% of all gastrointestinal cancers. In
order of frequency. the most common small intestinal tumours are:
Neuroendocrine tumour-often termed carcinoid tumours, although they represent a
heterogenous group of cell types. These tumours typically present late due to a tack of
specific symptoms, and may present with intestinal perforation or obstruction. Secretory
tumours may cause the carcinoid syndrome if liver metastases are present. due to bioactive
products bypassing hepatic inactivation.
Lymphoma-These are usually non-Hodgkin's lymphomas. Presentation with abdominal
pain is common, although an abdominal mass is rare.T-celllymphomas may occur as a
c<Jnsequence of celiac disease.
Adenocordnoma- These occur most commonty in the duodenum. Coeliac disease, Crohn's
disease. and polyposis syndromes are risk factors.
Sarcoma and gastrointestinal stromal tumour- These originate from interstitial cells of
the intestine, and were previously referred to as smooth muscle tumours.Thef ~ypicatly
express the kit oncogene, which encodes a tyrosine kinase. Biological drugs, which inhibit
this tyrosine kinase (e.g.lmatinib), have revolutionized the treatment of these tumours.

39