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6 Gastroenterology
Therapies in Crohn’s disease
AZA
TNF
https://t.me/med1917
Azathioprine (
steroid taper, or requiring ≥
develop
creatitis, leucopenia, abnormal
every
include
5-ASA
Biologics Anti-
ease, therefore monoclonal antibodies to
disease activity. They counter neutrophil accumulation and granuloma formation
and cause cytotoxicity to
sponse.
Avoid in people w ith known under lying malign ancy.
) (2– 2.5mg/ kg/ d PO) used if refractory to steroids, relapsing on
2
SE
requiring treatment cessation including abdominal pain, nausea, pan-
4
wks for 3 months, then at least 3- monthly. Alternative immunomodulators
6
- mercaptopurine and methotrexate (
steroid courses/ yr. Takes 6– 10wks to work. 30% will
LFT
S. Monitor
FBC, U&E, LFT
CI:
weekly for 4wks, then
of re produ ctive a ge).
Unlike in UC, have no role in the management of Crohn’s.
:
TNF
plays an important role in pathogenesis of Crohn’s dis-
CI
: sepsis, active/ latent TB,
CD4
+ T cells, thus clearing cells driving the immune re-
TNF
, eg infliximab and adalimumab, can
LFT
>3- fold above top end of normal. SE: rash.
Anti- integrin: monoclonal
antibodies targeting adhesion molecules involved in gut lymphocyte tracking,
eg vedolizumab, reduce disease activity and have a more gut- specific mechanism
of activity.
safety profile, eg ustekinumab.
Anti-
IL12/ 23
: another key pathogenic cytokine target with favourable
Nutrition Enteral is preferred (with tube feeding if malnourished and poor in-
take); consider
only if no enteral options. Elemental diets: (eg
E028
®.) Contain
TPN
amino acids and can induce remission.
Surgery 50– 80% need ≥1 operation in their life. It never cures. Indications: drug failure
GI
(most common);
aims are:
2
To control perianal or fistulizing disease. 3 Defunction (rest) distal disease, eg with a
obstruction from stricture; perforation; fistulae; abscess. Surgical
1
Resection of aected areas— but beware short bowel syndrome (p
580
temporary ileostomy. Pouch surgery is avoided in Crohn’s ( risk of recu rrenc e).
Perianal disease Occurs in about 50%.
EUA
) are an important part of assessment. Treatment includes oral antibiotics,
(
immunosuppressant therapy ± anti-
MRI
and examination under anaesthetic
TNF
, and local surgery ± seton insertion.
Poor prognosis Age <40yrs at diagnosis; steroids needed at 1st presentation;
perianal disease; isolated terminal ileitis; smoking.
Diagnosing
After full investigation,
IBD- U
involvement = Crohn’s). This situation is rare in adults but commoner in children. Over
time the phenotype tends to become clearer (generally
pouch formation may be needed, though pouch failure rate is higher than in
IBD
- unclassified (
IBD
may not obviously be Crohn’s or UC in 5– 15% of patients.
ref ers t o iso lat ed co loni c
IBD- U
)
IBD
where the diagnosis remains unknown (small bowel
UC >
Crohn’s). Colectomy ±
UC
.
261
).
Fig 6.
23
Beyond the gut... ‘I hate how this stupid
illness is crippling me...’ As well as erythema
nodosum on the shins (above; also caused by
sarcoid, drugs, streptococci, and
associate with sero −ve arthritis of large or small
joints, spondyloarthropathy, ankylosing spondylitis, sacroiliitis, pyoderma gangrenosum, conjunctivitis, episcleritis, and iritis.
TB
), Crohn’s can
Fig 6.
24
Deep fissured ulcers seen at colonoscopy. The end result? ‘My family does not or will
not even talk to me about the disease... I don’t
know when urgency to race for the bathroom
will happen so I don’t go out and have been
living a hermit life...’
© Dr A Mee.
6 Gastroenterology
Gastrointestinal malabsorption
B
OHCS
MRCP; AXR
https://t.me/med1917
262
Impaired absorption of nutrients, including electrolytes and water, but the term is
also used to incorporate maldigestion, the necessary precursor.
Symptoms Diarrhoea; weight; lethargy; steatorrhoea; bloating. Deficiency signs
B
Anaemia (Fe ,
bone disease (vit
Tests
‘Coeliac disease’).
elastase.
, folate); bleeding disorders (vit K); oedema (protein); metabolic
12
D
FBC
); neurological features, eg neuropathy.
( or
MCV
Stool Sudan stain for fat globules; stool microscopy (infestation);
Breath hydrogen analysis For bacterial overgrowth.21 Take samples of
end- expired air; give glucose; take more samples at ½h intervals; early exhaled
hydrogen = overgrowth.
Infectious malabsorption
cayetanensis, microsporidia.
occurring in the Far and Middle East and Caribbean— the cause is unknown.
Tetracycline
250
mg/ 6h PO + folic acid 5mg/ d PO for 3– 6mths may help.
Coeliac disease
Suspect this if diarrhoea + weight loss or anaemia (esp. if iron or
sponses to gluten (alcohol- soluble proteins in wheat, barley, rye ± oats) in the small
bowel causes villous atrophy and malabsorption.
DQ8
rest are
Prevalence 1 in
50– 60
; autoimmune disease; dermatitis herpetiformis (
100– 300
yrs). : >1:1. Relative risk in 1st- degree relatives is 6×.
Presentation Steatorrhoea; diarrhoea; abdominal pain; bloating; nausea + vomiting;
aphthous ulcers; angular stomatitis (
malacia; failure to thrive (children).
Diagnosis Hb;
RCDW
preferred test (but is an
Where serology positive or high index of suspicion proceed to duodenal biopsy while on
a gluten- containing diet: expect subtotal villous atrophy, intra- epithelial
hyperplasia. Where doubt persists,
Treatment Lifelong gluten- free diet— patients become experts. Rice, maize, soya,
potatoes, and sugar are
in patients with mild disease. Gluten- free biscuits, flour, bread, and pasta are prescribable. Monitor response by symptoms and repeat serology.
Complications Anaemia; osteopenia/ osteoporosis; hyposplenism (oer 'flu and
pneumococcal vaccinations);
or weight); malignancy (lymphoma, gastric, oesophageal, colorectal); neuropathies.
Chronic pancreatitis
Epigastric pain ‘bores’ through to the back, eg relieved by sitting forward or hot
water bottles on epigastrium/ back (look for skin mottling of erythema ab igne);
bloating; steatorrhoea; weight; diabetes mellitus. Symptoms relapse and worsen.
Causes Alcohol; smoking; autoimmune; rarely: familial; cystic fibrosis; haemochroma-
tosis; pancreatic duct obstruction (stones/ tumour); congenital (pancreas divisum).
Tests Ultrasound ±
speckled calcification; faecal elastase.
Treatment Drugs Give analgesia (coeliac- plexus block may give relief); lipase, eg
Creon®; fat- soluble vitamins. Insulin needs may be high or variable (beware hypoglycaemia).
may be tried (no lipase needed for absorption, but diarrhoea may be worsened).
Surgery For unremitting pain; narcotic abuse (beware of this); weight: eg pancrea-
tectomy or pancreaticojejunostomy (a duct drainage procedure).
Complications Pseudocyst; diabetes; biliary obstruction; local arterial aneurysm;
splenic vein thrombosis; gastric varices; pancreatic carcinoma.
Diet No alcohol; low fat may help. Medium- chain triglycerides (
Causes See
2
+
); Ca
; Fe;
B
+ folate;
12
INR
; lipid profile; coeliac tests (see
Endoscopy + small bowel biopsy.
Giardia, Cryptosporidium, Isospora belli, Cyclospora
Tro pi ca l sp ru e Villous atrophy + malabsorption
12
Associations
HLA DQ2
p
438
).
(commoner if Irish). Any age (peaks in childhood and
p
327
, fig
8.21
~
(p
325
IgA
OK
30
);
B
, ferritin. Antibodies: anti- transglutaminase is single
12
antibody— check IgA levels to exclude subclass deficiency).
HLA DQ2
. Limited consumption of oats (≤50g/ d) may be tolerated
); weight; fatigue; weakness; osteo-
% less severe: may mimic
and
DQ8
gen otypin g may h elp.
IBS
.
WBC
10
GI T
- cell lymphoma (rare; suspect if refractory symptoms
CT:
pancreatic calcifications confirm the diagnosis,
BOX
.
). T- cell re-
in 95%; the
S + crypt
MCT
oil)
:
6 Gastroenterology
Causes of gastrointestinal malabsorption
https://t.me/med1917
Malabsorption results from a failure of any of the phases of digestion and absorption; luminal digestion, mucosal absorption, and postabsorptive transport into
the circulation. Disorders with diuse mucosal involvement cause global malabsorption of almost all nutrients (eg coeliac disease), while certain disorders result
in malabsorption that is selective to particular nutrients (eg pernicious anaemia).
Luminal phase
• Pancreatic insufficiency: chronic pancreatitis; pancreatic cancer; cystic fibrosis.
• Bile: p rim ar y b il ia ry c ho la ng it is; il ea l r es ect io n; bi li ary ob st ru ct ion ; c ol es ty ram in e.
Mucosal phase
• Small bowel mucosa: coeliac disease; Crohn’s disease; Whipple’s disease (see
BOX
); radiation enteritis; tropical sprue; small bowel resection; brush border
enzyme deficiencies (eg lactase insuciency); drugs (metformin, neomycin,
alcohol); amyloid (
• Bacterial overgrowth:21 spontaneous (esp. in elderly); in jejunal diverticula; post-
op blind loops.
Don’t confuse with aerent loop syndrome (
• Infection: giardiasis; diphyllobothriasis (
p
364
).
DM & PPI
use are also risk factors. Try metronidazole
p
614
B
malabsorption); strongyloidiasis.
12
400
mg/ 8h PO.
).
Postabsorptive phase
• Lymphatic system obstruction: congenital (eg intestinal lymphangiectasia,
Milroy disease (
)), acquired (eg lymphoma, Whipple's disease (see
BOX
)).
p
692
Whipple's disease
A rare disease11 featuring GI malabsorption which usually occurs in middle- aged
white males, most commonly in Europe. It is fatal if untreated and is caused by
Tropheryma whippelii, which, combined with defective cell- mediated immunity,
produces a systemic disease.
Features Often starts insidiously with arthralgia (chronic, migratory, seronega-
GI
tive arthropathy aecting mainly peripheral joints).
symptoms commonly include colicky abdominal pain, weight loss, steatorrhoea/ diarrhoea, which leads to
malabsorption. Systemic symptoms such as chronic cough, fever, sweats, lymphadenopathy, and skin hyperpigmentation also occur. Cardiac involvement may
lead to endocarditis, which is typically blood culture negative.
a reversible dementia, ophthalmoplegia, and facial myoclonus (if all together, they
are highly suggestive)— also hypothalamic syndrome (hyperphagia, polydipsia, in-
NB: CNS
somnia).
involvement may occur without GI involvement.
CNS
features include
Tests Diagnosis requires a high level of clinical suspicion. Jejunal biopsy shows
stunted villi. There is deposition of macrophages in the lamina propria- containing
granules which stain positive for periodic acid– Schi (
CSF
found in aected samples, eg
The bacteria may be seen within macrophages on electron microscopy.
RNA
bacterial
can be performed on serum or tissue.
, cardiac valve tissue, lymph nodes, synovial fluid.
PAS
). Similar cells may be
MRI
may demonstrate
PCR
of
CNS
involvement.
Should include antibiotics which cross the blood– brain barrier. Current re-
commendations:
co- trimoxazole for
IV
ceftriaxone (or penicillin + streptomycin) for 2wks then oral
1
year. Shorter courses risk relapse. A rapid improvement in
symptoms usually occurs.
263
21
Bacterial overgrowth proximal to the colon causes diarrhoea, abdominal pain, and vitamin malabsorp-
tion. Causes: old age, autonomic neuropathy (eg diabetic), ileocaecal valve resection,
PPI
usage, amyloidosis.
6 Gastroenterology
Gastrointestinal motility disorders
IBS
https://t.me/med1917
264
Gut motility is essential to sustain life. As a result, there are multiple overlapping
mechanisms to ensure that the carefully synchronized wave of smooth muscle
contraction and relaxation continues to propel food and facilitate absorption of
nutrients in a variety of circumstances (even in the case of vagotomy or sympathectomy). Disorders of this coordinated peristaltic activity can occur in association
with abnormalities in a range of organ systems.
Gastroparesis Delayed gastric emptying in the absence of obstruction, resulting in
post- prandial bloating, nausea/ vomiting, abdominal pain, and early satiety.
⅓ cases are due to diabetes (
p
200
), ⅓ idiopathic, and ⅓ related to a range of other
conditions: post- surgical; post- viral (norovirus, rotavirus); medication- induced (opioids); neurological and systemic disorders (systemic sclerosis,
hypothyroidism).
epigastric distension/ tenderness and a succussion splash.
tigraphy with a
prokinetics (eg metoclopramide), anti- emetics,
Signs Look for signs of any underlying condition. There may be
99
technetium- labelled meal Treatment Alter diet (fat, fibre),
PEG
Diagnosis Gastric scin-
decompression if refractory.
Intestinal pseudo- obstruction This resembles mechanical GI obstruction (p
but in the absence of an obstructing lesion. Acute colonic pseudo- obstruction
is called Ogilvie's syndrome (
hemicolon. Chronic intestinal pseudo- obstruction is rare, presents with recurrent
p
694
) and usually involves the caecum and right
or chronic abdominal pain/ distension and weight loss from malabsorption, and has
similar pathogenic mechanisms to gastroparesis. Impaired motility is confirmed
with scintigraphy. Nutritional support and electrolyte replacement are important.
Irritable bowel syndrome (
IBS
is the most commonly diagnosed gastrointestinal condition. It is a chronic
functional disorder of the
)
GI
tract characterized by recurrent abdominal pain associated with altered bowel habits. The pathophysiology is uncertain but likely involves altered intestinal motility, visceral hypersensitivity, intestinal inflammation,
or microbial dysbiosis. Several diagnostic criteria exist.
Prevalence 10– 20%, but depends on the criteria used; age at onset: 40yrs; : ≥2:1.
Diagnosis The diagnosis is defined by symptom- based criteria but symptoms are
IBS
not specific for
guish from transient gut symptoms. Rome
intestinal dysfunction’,
in the last
altered stool frequency • altered stool form. Other features: urgency; incomplete
evacuation; abdominal bloating/ distension; mucus
food. Symptoms are chronic (onset ≥
bated by stress, menstruation, or gastroenteritis (post- infectious
IBS- C
predominant constipation;
classified.
common. Insuation of air during lower
reproduce the pain.
disorders, eg functional dyspepsia (
tions, eg migraine (
, therefore these must use the frequency and duration to distin-
IV
3
months, associated with ≥2 of: • relieved or worsened by defecation •
): recurrent abdominal pain ≥ 1 day/ week on average
6
months prior to diagnosis), and often exacer-
IBS- D
predominant diarrhoea;
PR
fig
criteria12 (see
6.25
BOX
; worsening of symptoms after
Signs Examination is usually normal, but mild abdominal tenderness is
GI
endoscopy (not usually needed) may
Associated conditions The presence of other functional bowel
p
248
p
454
), chronic fatigue syndrome (p
), and other commonly associated condi-
556
), fibromyalgia (p
pression, dyspareunia, adds further support to the diagnosis.
When to investigate Diagnostic tests are rarely required when the criteria are
FBC, CRP
met and alarm features are absent;
coeliac serology (
of alarm features: age of onset >
anaemia; nocturnal diarrhoea; family history of
CRP, ESR
toms in ‘known
therapy,
p
262
) in
IBS- D & IBS- M
50
yrs; history <6 months; unexplained weight or
. Refer if 1 Diagnostic uncertainty (you or the patient!). 2 Changing symp-
IBS
OHCS
’. 3 Refractory to management (here,
p
754
).
or faecal calprotectin (p
are sucient. Colonoscopy in the presence
IBD
or colorectal cancer, abnormal
NICE
favours cognitive
Causes
SLE
, amyloidosis,
602
‘Defining gastro-
IBS
). Subtypes
IBS- M
mixed; un-
556
), de-
260
), and
)
6 Gastroenterology
Managing
IBS- C
IBS- D
OHCS
IBS- D
https://t.me/med1917
IBS
Initial treatment Like the diagnosis, treatment is based on the type and severity
of symptoms. All patients should be given a positive diagnosis, an explanation of
the condition, and reassurance about its benign natural history. In patients with
mild intermittent symptoms, lifestyle/ dietary measures are sucient. Since it is
non- fatal, safety of treatment is a priority.
Lifestyle advice Exercise (inverse association with colonic transit time), stress
reduction, and sleep hygiene.
Dietary modification Take a careful dietary history; 9/ 10 patients report that cer-
tain foods trigger symptoms. Much of the evidence is weak, but some specific
dietary interventions may be recommended under dietician supervision:
FODMAP
(fermentable carbohydrates; poorly absorbed and gas producing) diet,
but stop if no improvement after
tation; potential benefits are restricted to soluble fibre (psyllium/ ispaghula), avoid
increasing wheat bran intake.
these are triggers, gluten- free diet not recommended.
1
month of strict adherence. 2 Fibre supplemen-
3
Dietary exclusions; spicy foods and excess fat if
4
Probiotics; 1- month trials
1
Low
can be considered, but may not provide substantial benefit.
Pharmacotherapy
•
: if there is no response to soluble fibre, try osmotic laxatives (polyethelene
glycol preferred to lactulose which can aggravate bloating). If this fails, try
prosecretory agents linaclotide, prucalopride, or plecanatide.
•
: try loperamide 2mg 45 minutes before meals.
• Colic/ bloating: oral antispasmodics: mebeverine
• Psychological symptoms/ visceral hypersensitivity: emphasize the positive! You
10
bromide
have excluded sinister pathology and over time, symptoms tend to improve.
Consider cognitive behavioural therapy (
amitriptyline
at a low dose for visceral pain (ie you are not prescribing the higher licensed
dose for depression), and that it improves
mg/ 8h (over the counter).
10– 20
mg at night (SE: drowsiness, dry mouth); explain that this is
135
mg/ 8h or hyoscine butyl-
p
754
), hypnosis, and tricyclics, eg
by slowing GI transit.
Defining gastrointestinal dysfunction— all roads lead to Rome
265
Fig 6.
25
There is nothing romantic about functional bowel disorders, other than the association
of the definitions of these conditions with the eternal c ity. The fourth iteration of the Rome criteria classifies these into
functional bloating/ distension, and unspecified) but they exist on a continuum; a predominance of
pain or diarrhoea versus constipation can help to point us in the right direction. Following patients'
journeys through multiple evolving symptoms and negative investigations that lead to apparent
dead ends can be complex, but arriving at a clear clinical diagnosis is therapeutically invaluable.
5
distinct groups (
IBS,
functional constipation (FC) and diarrhoea (
Artwork by Gillian Turner.
FDR
),
6 Gastroenterology
Neuroendocrine tumours
https://t.me/med1917
266
A diverse group of epithelial neoplasms with neuroendocrine dierentiation that
can form almost anywhere. Well- dierentiated tumours arise predominantly in
GI
tract, are of enterochroman cell (neural crest) origin, and are capable
the
of producing
ileum (
elsewhere in the
5HT
. These have been known as carcinoid tumours (appendix (45%),
30
%), rectum (20%)22) and islet cell tumours (pancreas). They also occur
GI
tract, ovary, testis, and bronchi. 80% of tumours >2cm across
will metastasize.
Symptoms and signs Initially few. GI tumours can cause appendicitis, intussuscep-
RUQ
tion, or obstruction. Hepatic metastases may cause
bradykinin, tachykinin, substance
P, VIP
, gastrin, insulin, glucagon,
syndrome), parathyroid, and thyroid hormones.
p
217
); 10% occur with other neuroendocrine tumours.
(
pain. Tumours may secrete
10
% are part of
Carcinoid syndrome Occurs in ~5% and implies metastatic hepatic involvement
90
%, inactivation of bioactive substances secreted into the portal circulation).
(>
Symptoms and signs Bronchoconstriction; paroxysmal flushing especially in upper
CCF
body (± migrating weals); diarrhoea;
stenosis from
5HT
- induced fibrosis). Carcinoid crisis See
Te st s 24h urine 5- hydroxyindoleacetic acid (
change with drugs and diet: discuss with lab).
cate and stage primary tumours. Plasma chromogranin
PET/ CT
(p
722
) with novel tracers;
also have a role. Echocardiography and
(tricuspid incompetence and pulmonary
BOX
5-HIAA
CXR
111
Indium octreotide scintigraphy (Octreoscan™)
BNP
(p
135
) can be used to investigate car-
.
, a
5HT
metabolite; levels
+ chest/ pelvis
A
(reflects tumour mass);
cinoid heart disease.
Treatment Carcinoid syndrome Octreotide (somatostatin analogue) blocks re-
lease of tumour mediators and counters peripheral eects. Long- acting alternative: lanreotide. Loperamide for diarrhoea.
cure for carcinoid tumours so it is vital to find the primary site. At surgery, tumours
are an intense yellow. Procedures depend on site, eg rectal carcinoid tumours
1
cm can be resected endoscopically. Debulking (eg enucleating), embolization, or
<
radiofrequency ablation of hepatic metastases can symptoms. Give octreotide
Tumour therapy Resection is the only
cover to avoid precipitating a massive carcinoid crisis.
Median survival 5– 8yrs (~3yrs if metastases are present, but may be up to 20yrs;
so beware of giving up too easily, even in metastatic disease).
Carcinoid crisis
When a tumour outgrows its blood supply or is handled too much during surgery,
mediators flood out. There is life- threatening vasodilation, hypotension, tachycardia, bronchoconstriction, and hyperglycaemia. It is treated with high- dose
octreotide, supportive measures, and careful management of fluid balance.
ACTH
( Cushing’s
MEN- 1
MRI/ CT
syndrome
help lo-
22
Some are never clinically detected: 1 in
300
autopsies have a small bowel carcinoid tumour.
6 Gastroenterology
Zollinger– Ellison syndrome
https://t.me/med1917
This is the ass ociation of peptic ulcers with a gastrin- secreting adenoma
(gastrinoma), a neuroendocrine tumour arising in the pancreas, stomach, or duodenum. Gastrin excites excessive gastric acid production, which may produce multiple
ulcers in the duodenum and stomach.
disease. Suspect in those with multiple peptic ulcers, ulcers distal to the duodenum,
or a family history of peptic ulcers (or of islet cell, pituitary, or parathyroid adenomas).
Most cases are sporadic;
1
(
MEN1
, p
217
). 60% are malignant; metastases are found in local lymph nodes and the
Symptoms Include abdominal pain and dyspepsia, from the ulcers, and chronic
liver.
20
diarrhoea due to inactivation of pancreatic enzymes (also causes steatorrhoea) and
damage to intestinal mucosa.
mL). Measure three fasting levels on dierent days and o
(reduced acid production, eg in chronic atrophic gastritis) should be excluded as this
also causes a raised gastrin level: gastric pH should be <
test is useful in suspected cases with only mildly raised gastrin levels (
The adenoma is often small and dicult to image; a combination of somatostatin receptor scintigraphy, endoscopic ultrasound, and
OGD
adenoma.
evaluates gastric/ duodenal ulceration. High- dose proton pump inhibitors, eg omeprazole: start with
intragastric pH helps determine the best dose (aim to keep pH at
have malignant potential and require resection (with lymph node clearance generally
recommended if >
multiple, and metastatic disease is rare. If well- dierentiated (
analogues may be
rubicin/ fluorouracil is
bolization may be done for hepatic metastases.
resectable lesion,
2
cm in size). Surgery may be avoided in
1
st line and chemotherapy with streptozotocin (if available) + doxo-
2
nd line. In
~
20
% with hepatic metastases. Screen all patients for
Incidence ~0.1% of patients with peptic ulcer
% are associated with multiple endocrine neoplasia, type
Te st s (fig
6.26
) Fa st in g se ru m g a st ri n l ev e l ( >
PPI
therapy. Hypochlorhydria
2
. The secretin stimulation
CT
is used to localize and stage the
60
mg/ d and adjust according to response. Measuring
2– 7
MEN1
, as adenomas are often
G1
and G2) somatostatin
G3,
etoposide + cisplatin is possible.13 Selective em-
1000
pg/
100– 1000
pg/ mL).
). All gastrinomas
Prognosis 5yr survival: 80% if single
MEN1
.
267
Fig 6.
26
Octreoscan™ in patient with metastatic
deposit (thin arrow), gastric neuroendocrine tumour (thick arrow).
Reproduced from Wass et al., Oxford Textbook of Endocrinology and Diabetes,
MEN 1
gastrinoma. Solitary hepatic metastatic
permission from Oxford University Press.
2011
, with
6 Gastroenterology
Jaundice
OHCS
ERCP
MRCP
CT/ MRI
https://t.me/med1917
268
Jaundice refers to yellowing of skin, sclerae, and mucosae from plasma bilirubin
60
(visible at
µmol/ L; fig
(pre- hepatic, hepatocellular, or cholestatic/ obstructive) or by the type of circulating bilirubin (conjugated or unconjugated;
Unconjugated hyperbilirubinaemia
Overproduction
Haemolysis (p
Impaired hepatic uptake Drugs (paracetamol, rifampicin), ischaemic hepatitis.
Impaired conjugation Gilbert’s syndrome:
the gene promoter. A common (
noticed for many years. Usually presents in adolescence with intermittent jaundice
occurring during illness, exercise or fasting. Mild bilirubin; normal
cytes (ie no haemolysis).
unconjugated hyperbilirubinaemia presenting in the
CNS
signs. Gene mutations causing
2
) ability to excrete bilirubin. T1: phototherapy and plasmapheresis; liver trans-
(type
plant before irreversible kernicterus (
Conjugated hyperbilirubinaemia Dark urine, pale stools. When severe, it can be
associated with an intractable pruritus (best treated by relief of the obstruction).
Hepatocellular dysfunction There is hepatocyte damage, usually with some
cholestasis. Causes: viruses: hepatitis (
6.10
; alcohol; cirrhosis (see
haemochromatosis; autoimmune hepatitis (
- antitrypsin deficiency (p
ilis;
1
failure to excrete conjugated bilirubin (Dubin– Johnson
p
696
); right heart failure; toxins, eg carbon tetrachloride; fungi (fig
Impaired hepatic excretion (cholestasis) Primary biliary cholangitis; primary
sclerosing cholangitis; drugs (
atic cancer; compression of the bile duct, eg lymph nodes at the porta hepatis;
cholangiocarcinoma; choledochal cyst; Caroli’s disease;
structive jaundice from common bile duct compression by a gallstone impacted in
the cystic duct, often associated with cholangitis).
The patient Ask Ab out b loo d tra nsfu sion s, IV drug use, body piercing, tattoos, sexual
activity, travel abroad, jaundiced contacts, family history, alcohol use, and all medications (eg old drug charts;
p
272
), hepatic encephalopathy (p
(
megaly, ascites, and a palpable gallbladder (if seen with painless jaundice the cause
is not gallstones— Courvoisier’s law).
Tests See p
is absent in pre- hepatic causes; in obstructive jaundice, urobilinogen is absent.
Haematology
for haemolysis (
Bunnell (
Microbiology Blood and other cultures; hepatitis serology. Ultrasound Are the bile
ducts dilated? Are there gallstones, hepatic metastases, or a pancreatic mass?
(See
scopic ultrasound (
common bile duct stones.
abdominal
272
for screening tests in suspected liver disease. Urine Bilirubin
FBC
, clotting, film, reticulocyte count, Coombs test and haptoglobins
p
332
EBV
). Chemistry
p
726
.) If bile ducts are dilated and
EUS)
if abdominal malignancy is suspected.
What to do? Tre a t t he ca u se pr om pt ly . Ensure adequate hydration; broad- spectrum
antibiotics if obstruction. Monitor for ascites, encephalopathy; call a hepatologist.
23
Multiple segmental cystic or saccular dilatations of intrahepatic bile ducts with congenital hepatic fi-
brosis. It may present in
24
Pancreatic or gallbladder cancer is more likely, as stones lead to a fibrotic, unexpandable gallbladder.
25
Albumin &
hepatocyte damage.
nant infiltration, pregnancy (placental isoenzyme), Paget’s disease, and childhood (bone isoenzyme).
20
INR
are the best indicators of hepatic synthetic function. Transaminases (
ALP
suggests obstructive jaundice, but also occurs in hepatocellular jaundice, malig-
6.27
). Jaundice is classified by the site of the problem
fig
6.28
).
334
, eg malaria/
9
% prevalence) benign condition that may go un-
DIC
, etc.); ineective erythropoiesis.
UGT
activity (see
BOX
) due to a defect in
FBC
and reticulo-
Crigler- Najjar syndrome: two rare syndromes of inherited
1
UGT
activity result in absent (type 1) or impaired
p
p
BOX
GP
records). Examine For signs of chronic liver disease
274
‘Causes of jaundice’); liver metastases/ abscess;
286
); Budd– Chiari (p
table
6.10
); common bile duct gallstones; pancre-
271
), lymphadenopathy, hepatomegaly, spleno-
24
Pale stools + dark urin e ≈ cho lestat ic jau ndice.
st days of life with jaundice ±
294
) develops. T2: usually no needed.
),
CMV
(p
401
),
EBV
(p
401
); drugs (table
AIH
); septicaemia; leptospirosis; syph-
686
); Wilson’s disease (p
&
Rotor syndromes, p
6.29
23
Mirrizi’s syndrome (ob-
281
688
).
), malaria parasites (eg if unconjugated bilirubin/ fever); Paul
U&E, LFT
, - GT, total protein, albumin.25 Paracetamol levels.
LFT
not improving.
(See p
726
.) or endo-
if conventional ultrasound shows gallstones but no definite
Liver biopsy (See p
yr- olds, with portal hypertension ± recurrent cholangitis/ cholelithiasis.
244
.) If bile ducts are normal. Consider
ALT, AST
) indicate
);
,
6 Gastroenterology
Fig 6.
https://t.me/med1917
27
It’s easy to miss mild jaundice, especially under fluorescent light, so take your patient to the window, and as you both
gaze at the sky, use the opportunity to broaden the horizons of
your enqui ries... where have you been... where are you going...
who are you with... what are you taking...? In the gaps, your patient may tell you the diagnosis— alcohol or drug abuse, sexual
infections/ hepatitis, or worries about the side eects of their
TB
or
HIV
medication or a spreading cancer ‘from this lump here
which I haven’t told anyone about yet’.
Roper, Clinical Skills,
2014
, with permission from Oxford University Press.
Reproduced from
The pathway of bilirubin metabolism
Unconjugated bilirubin is waterinsoluble. In the liver, bilirubin
is conjugated with glucuronic
acid by hepatocytes mediated
by a family of enzymes called
uridine- diphosphoglucuronate
glucuronosyltransferase (
making it water- soluble. Conjugated bilirubin is secreted
in bile and passes into the gut.
Some is taken up again by the
liver (via the enterohepatic circulation) and the rest is converted to urobilinogen by gut
bacteria. Urobilinogen is either
reabsorbed and excreted by the
kidneys, giving urine its colour,
or converted to stercobilin,
Fig 6.
28
Bilirubin is formed by the breakdown of
3
haemoglobin in a
gation, and excretion.
- step process: hepatic uptake, conju-
which colours faeces brown.
Causes of jaundice in a previously stable patient with cirrhosis
• Sepsis (esp.
• Malignancy: eg hepatocellular carcinoma. • GI bleeding.
Signs of decompensation Jaundice; ascites;
Table 6.
Haemolysis
Hepatitis
Cholestasis
UTI
, pneumonia, or peritonitis). • Alcohol; drugs (table
10
Examples of drug- induced jaundice
• Antimalarials (eg dapsone)
• Paracetamol overdose (p
• Isoniazid, rifampicin, pyrazinamide
• Monoamine oxidase inhibitors
• Flucloxacillin (may be weeks after )
• Fusidic acid, co- amoxiclav, nitrofurantoin
• Steroids (anabolic; the Pill)
UGI
bleed; encephalopathy.
824
)
• Sodium valproate
• Halothane
• Statins
• Sulfonylureas
• Prochlorperazine
• Chlorpromazine
6.10
UGT
).
),
269
Fig 6.
29
Amanita phalloides (Latin for ‘phallic toadstool’;
also known as the ‘death cap’) is a lethal cause of jaundice. It
is the most toxic mushroom known. After ingestion (its benign
appearance is confusing), amatoxins induce hepatic necrosis
leaving few options other than transplantation.
© Ian Herriott. NB: don’t use this image for identification!
6 Gastroenterology
Liver failure
OHCS
https://t.me/med1917
270
Definitions Liver failure may be recognized by the development of coagulopathy
INR
>1.5) and encephalopathy. This may occur suddenly in the previously healthy
(
liver = acute liver failure (hyperacute = onset ≤
26
wks.) More often it occurs on a background of cirrhosis = chronic liver failure.
7
d; acute = 8– 21d; subacute = 4–
Fulminant hepatic failure is a clinical syndrome resulting from massive necrosis of
liver cells leading to severe impairment of liver function.
Causes Infections Viral hepatitis (esp. B, C,
CMV
), yellow fever, leptospirosis.
Drugs Paracetamol overdose, halothane, isoniazid. Tox i ns Amanita phalloides
fig
6.29
, p
269
mushroom (
veno- occlusive disease.
angitis, primary sclerosing cholangitis, haemochromatosis, autoimmune hepatitis
- antitrypsin deficiency, Wilson’s disease, fatty liver of pregnancy (
1
malignancy.
Signs Jaundice, hepatic encephalopathy (see
fetor hepaticus (smells like pear drops), asterixis/ flap (
apraxia (cannot copy a
), carbon tetrachloride. Vascu lar B udd– Chiari syn. (p
Others Alcohol, fatty liver disease, primary biliary chol-
BOX
‘Hepatic encephalopathy’),
p48), constructional
5
- pointed star?). Signs of chronic liver disease (p
gest acute- on- chronic hepatic failure.
Te st s Blood
cetamol level, hepatitis,
autoantibodies (
MC&S
p
272
(
(and hepatic vein in suspected Budd– Chiari syndrome,
FBC
(?infection,26 ?GI bleed),
CMV
p
and
550
). Microbiology Blood culture; urine culture; ascitic tap for
of ascites— neutrophils >
). Radiology
CXR
; abdominal ultrasound; Doppler flow studies of the portal vein
U&E
,27
LFT
EBV
, clotting (PT/
serolo gy, ferr itin, 1- antitrypsin, caeruloplasmin,
250
/ mm3 indicates spontaneous bacterial peritonitis
INR
p
686
). Neurophysiology
evoked potentials (and neuroimaging) have a limited role.
Management Beware sepsis, hypoglycaemia, GI ble eds/ varices, & enc ephalop athy:
• Nurse with a 20° head- up tilt in
NG
tube to avoid aspiration and remove any blood from stomach.
an
• Insert urinary and central venous catheters to help assess fluid status.
• Monitor T°, respirations, pulse,
• Check
FBC, U&E, LFT
• 10% glucose IV, 1L/ 12h to avoid hypoglycaemia. Do blood glucose every 1– 4h.
• Treat the cause, if known (eg GI bleeds, sepsis, paracetamol poisoning, p
• If malnourished, get dietary help: good nutrition can decrease mortality. Give thia-
mine and folate supplements (
• Treat seizures with phenytoin (p
• Haemofiltration or haemodialysis, if renal failure develops (
syndrome?’).
• Try to avoid sedatives and other drugs with hepatic metabolism (
in liver failure’ and
• Consider
• Liaise early with nearest transplant centre regarding appropriateness.
, and
BNF
PPI
as p rophylaxis against st ress ul cerati on, eg omeprazo le 40mg/ d IV/ PO.
ITU
. Protect the airway with intubation and insert
BP,
pupils, urine output hourly. Daily weights.
INR
daily.
p
700
).
810
).
14
BOX
‘What is hepatorenal
).
Treat complications
Cerebral oedema On
Ascites Restrict fluid, low- salt diet, weigh daily, diuretics (p
Bleeding Vitamin K 10mg/ d IV for 3d, platelets,
ITU
: 20% mannitol IV; hyperventilate.
FFP
272
).
+ blood as needed ± endoscopy.
Blind of infection Ceftriaxone 1– 2g/ 24h IV, not gentamicin (risk of renal failure).
Blood glucose If 2mmol/ L or symptomatic, 50mL of 50% glucose IV; check often.
Encephalopathy Avoid sedatives; 20° head- up tilt in
lose
30– 50
mL/ 8h (aim for 2– 4 soft stools/ d) is catabolized by bacterial flora to short-
chain fatty acids which colon ic pH and tra p NH
12
h is a non- absorbable oral antibiotic that numbers of nitrogen- forming gut bacteria.
Wor se prog nos is if Grade
III– IV
encephalopathy, age >40yrs, albumin <30g/ L,
ITU;
correct electrolytes; lactu-
in t he col on as NH
3
+
; Rifaximin
4
drug- induced liver failure, late- onset hepatic failure worse than fulminant failure.
686
p29),
272
) sug-
), glucose, para-
EEG
824
).
BOX
‘Prescribing
550
mg/
INR
),
,
,
,
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