GI Fifth yr Flashcards
Features of acute liver failure?
Jaundice
Coagulopathy
Hypoalbuminaemia
Hepatic encephalopathy
Renal failure (hepatorenal syndrome)
Management of variceal bleeding?
ABC
Correct clotting - FFP, vitamin K
Terlipressin and prophylactic ABx at presentation (before endoscopy)
Band ligation for oesophageal varices. Injections of N-butyl-2-cyanoacrylate for gastric varices.
Sengstaken-Blakemore tube if uncontrolled haemorrhage
TIPS if not controlled with above measures
Prophylaxis - propranolol
LFTS for alcoholic liver disease
GGT elevated
AST:ALT normally >2, ratio >3 is suggestive of acute alcoholic hepatitis
Management of alcoholic hepatitis
Glucocorticosteroids during acute episodes (pt’s who will benefit determined by Maddrey’s discriminant function - using prothrombin time and bilirubin concentration)
Pentoxyphylline sometimes used
Causes of ascites with serum-ascites albumin gradient (SAAG) <11g/L
Hypoalbuminaemia (nephrotic syndrome, severe malnutrition, e.g., Kwashiorkor)
Malignancy (peritoneal carcinomatosis)
Infections (tuberculous peritonitis)
Pancreatitis
Bowel obstruction
Biliary ascites
Postop lymphatic leak
Serositis in CTD
Causes of ascites with serum-ascites albumin gradient (SAAG) >11g/L
Indicates portal hypertension
Liver disorders are most common cause (cirrhosis/alcoholic liver disease, acute liver failure, liver metastases)
Cardiac (right HF, constrictive pericarditis)
Budd-Chiari syndrome
Portal vein thrombosis
Veno-occlusive disease
Myxoedema
Management of ascites
Reduce dietary sodium
Fluid restriction if serum Na+ <125mmol/L
Aldosterone antagonists (+/- top diuretics)
Drainage if tense ascites - requires albumin cover to prevent paracentesis induced circulatory dysfunction
Offer prophylactic oral ciprofloxacin or norfloxacin for people with cirrhosis and ascites with an ascitic protein of 15 g/litre or less, until the ascites has resolved
TIPS in some pt’s
Epidemiology of autoimmune hepatitis
Young females
Associations with other autoimmune disorders, hypergammaglobulinaemia, HLA B8, DR3
Three types of autoimmune hepatitis
Type 1 - ANA and anti-SMA, affects both adults and children
Type 2 - Anti-liver/kidney microsomal type 1 antibodies (LKM1), Affects children only
Type 3 - Soluble liver-kidney antigen, Affects adults in middle-age
Investigations for autoimmune hepatitis
LFTs
ANA/SMA/LKM1 antibodies, raised IgG levels
liver biopsy: inflammation extending beyond limiting plate ‘piecemeal necrosis’, bridging necrosis
Management of autoimmune hepatitis
Steroids
Other immunosuppressants (e.g., azathioprine)
Liver transplantation
Causes of raised levels of unconjugated bilirubin
Overproduction - Haemolysis (autoimmune, Hb disordrers, RBC enzyme disorders, RBC membrane disorders, myeloproliferative neoplasms)
Reduced uptake (eg. drugs, port systemic shunt)
Hepatocyte dysfunction
Conjugation dysfunction - GGT deficiency (Gilberts, Crigler-Najjar syndrome)
Causes of raised levels of conjugated bilirubin
Predominantly elevated AST & ALT - viral hepatitis, AI hepatitis, toxin/drug related hepatitis, haemochromatosis, ischaemic hepatitis, alcoholic hepatitis
Normal AST, ALT and ALP - Defective excretion of bilirubin (Dubin-Johnson syndrome)
Predominantly elevated ALP - cholestasis of pregnancy, malignancy (pancreas), cholangiocarcinoma, PBC, PSC, choledocholithiasis
Summary of Budd-Chiari (causes, features, Ix)
Hepatic vein thrombosis - usually in haematological disease or procoagulant condition
Causes
polycythaemia rubra vera
thrombophilia: activated protein C resistance, antithrombin III deficiency, protein C & S deficiencies
pregnancy
combined oral contraceptive pill: accounts for around 20% of cases
The features are classically a triad of:
abdominal pain: sudden onset, severe
ascites → abdominal distension
tender hepatomegaly
Investigations
ultrasound with Doppler flow studies is very sensitive and should be the initial radiological investigation
Sx of gallstones?
colicky right upper quadrant pain
occurs postprandially
symptoms are usually worst following a fatty meal - when cholecystokinin levels are highest and gallbladder contraction is maximal.
Ix and Tx of gallstones?
abdominal ultrasound
LFTs
stones in bile duct - MRCP or intraoperative imaging
Tx - laparoscopic cholecystectomy
Features and Tx of acute cholecystitis?
Right upper quadrant pain
Pain may radiate to back or right shoulder
Fever
Murphys sign on examination
Occasionally mildly deranged LFT’s (especially if Mirizzi syndrome)
Imaging (USS) and cholecystectomy (ideally within 48 hours of presentation) (2)
Features and Tx of gallbladder abscess?
Usually prodromal illness and right upper quadrant pain
Swinging pyrexia
Patient may be systemically unwell
Generalised peritonism not present
Imaging with USS +/- CT Scanning
Ideally, surgery although subtotal cholecystectomy may be needed if Calot’s triangle is hostile
In unfit patients, percutaneous drainage may be considered
Features and Tx of gallbladder abscess?
Patient severely septic and unwell
Jaundice
Right upper quadrant pain
Fluid resuscitation
Broad-spectrum intravenous antibiotics
Correct any coagulopathy
Early ERCP
Features and Tx of gallbladder abscess?
Patients may have a history of previous cholecystitis and known gallstones
Small bowel obstruction (may be intermittent)
Laparotomy and removal of the gallstone from small bowel, the enterotomy must be made proximal to the site of obstruction and not at the site of obstruction. The fistula between the gallbladder and duodenum should not be interfered with.
Features and Tx of acalculous cholecystitis?
Patients with intercurrent illness (e.g. diabetes, organ failure)
Patient of systemically unwell
Gallbladder inflammation in absence of stones
High fever
If patient fit then cholecystectomy, if unfit then percutaneous cholecystostomy
Features and Tx of Gilbert’s syndrome?
autosomal recessive* condition of defective bilirubin conjugation due to a deficiency of UDP glucuronosyltransferase
prevalence is approximately 1-2% in the general population.
Sx
unconjugated hyperbilirubinaemia (i.e. not in urine)
jaundice may only be seen during an intercurrent illness, exercise or fasting
Investigation: rise in bilirubin following prolonged fasting or IV nicotinic acid
No treatment required
What is haemochromatosis?
autosomal recessive disorder of iron absorption and metabolism resulting in iron accumulation. It is caused by inheritance of mutations in the HFE gene. prevalence in people of European descent = 1 in 200, making it more common than cystic fibrosis
Features of haemochromatosis?
early symptoms (non-specific) include fatigue, erectile dysfunction and arthralgia (often of the hands)
‘bronze’ skin pigmentation
diabetes mellitus
liver: stigmata of chronic liver disease, hepatomegaly, cirrhosis, hepatocellular deposition)
cardiac failure (2nd to dilated cardiomyopathy)
hypogonadism (2nd to cirrhosis and pituitary dysfunction - hypogonadotrophic hypogonadism)
arthritis (especially of the hands)
Complications of haemochromatosis?
Reversible:
Cardiomyopathy
Skin pigmentation
Irreversible:
Liver cirrhosis
DM
Hypogonadotrophic hypogonadism
Arthropathy
Ix for haemochromatosis?
general population:
transferrin saturation is considered the most useful marker, ferritin should also be measured but is not usually abnormal in the early stages of iron accumulation
testing family members:
genetic testing for HFE mutation
Iron study profile:
transferrin saturation > 55% in men or > 50% in women
raised ferritin (e.g. > 500 ug/l) and iron
low TIBC
LFTS
molecular genetic testing for the C282Y and H63D mutations
MRI is generally used to quantify liver and/or cardiac iron
liver biopsy is now generally only used if suspected hepatic cirrhosis
Management of haemochromatosis?
venesection is the first-line treatment:
monitoring adequacy of venesection: transferrin saturation should be kept below 50% and the serum ferritin concentration below 50 ug/l
desferrioxamine may be used second-line
Aetiology of hepatic encephalopathy?
excess absorption of ammonia and glutamine from bacterial breakdown of proteins in the gut
acute and chronic liver disease
TIPS may precipitate
Features of hepatic encephalopathy?
confusion, altered GCS
asterix: ‘liver flap’, arrhythmic negative myoclonus with a frequency of 3-5 Hz
constructional apraxia: inability to draw a 5-pointed star
triphasic slow waves on EEG
raised ammonia level (not commonly measured anymore)
Grading of hepatic encephalopathy?
Grade I: Irritability
Grade II: Confusion, inappropriate behaviour
Grade III: Incoherent, restless
Grade IV: Coma
Precipitating factors for hepatic encephalopathy?
infection e.g. spontaneous bacterial peritonitis
GI bleed
post transjugular intrahepatic portosystemic shunt
constipation
drugs: sedatives, diuretics
hypokalaemia
renal failure
increased dietary protein (uncommon)
Management of hepatic encephalopathy?
treat any underlying precipitating cause
NICE recommend lactulose first-line, with the addition of rifaximin for the secondary prophylaxis of hepatic encephalopathy
lactulose is thought to work by promoting the excretion of ammonia and increasing the metabolism of ammonia by gut bacteria
antibiotics such as rifaximin are thought to modulate the gut flora resulting in decreased ammonia production
other options include embolisation of portosystemic shunts and liver transplantation in selected patients
Summary of hepatitis B serology?
surface antigen (HBsAg) - causes the production of anti-HBs
Anti-HBs implies immunity (either exposure or immunisation). It is negative in chronic disease
HBsAg normally implies acute disease (present for 1-6 months)
if HBsAg is present for > 6 months then this implies chronic disease (i.e. Infective)
Anti-HBc implies previous (or current) infection. IgM anti-HBc appears during acute or recent hepatitis B infection and is present for about 6 months. IgG anti-HBc persists
HbeAg results from breakdown of core antigen from infected liver cells as is, therefore, a marker of infectivity. Marker of HBV replication and infectivity
Example results:
previous immunisation: anti-HBs positive, all others negative
previous hepatitis B (> 6 months ago), not a carrier: anti-HBc positive, HBsAg negative
previous hepatitis B, now a carrier: anti-HBc positive, HBsAg positive
Features of viral hepatitis?
nausea and vomiting, anorexia
myalgia
lethargy
right upper quadrant (RUQ) pain
RFs - recent travel, IVDU
Features of viral hepatitis?
nausea and vomiting, anorexia
myalgia
lethargy
right upper quadrant (RUQ) pain
RFs - recent travel, IVDU
Features of cholangiocarcinoma?
Persistent biliary colic symptoms, associated with anorexia, jaundice and weight loss.
A palpable mass in the right upper quadrant (Courvoisier sign), periumbilical lymphadenopathy (Sister Mary Joseph nodes) and left supraclavicular adenopathy (Virchow node) may be seen
Features of acute pancreatitis?
Usually due to alcohol or gallstones
Severe epigastric pain
Vomiting is common
Examination may reveal tenderness, ileus and low-grade fever
Periumbilical discolouration (Cullen’s sign) and flank discolouration (Grey-Turner’s sign) is described but rare
Risk factors for hepatocellular carcinoma?
iver cirrhosis, for example secondary to hepatitis B & C, alcohol, haemochromatosis and primary biliary cirrhosis.
Chronic hepatitis B is the most common cause of HCC worldwide with chronic hepatitis C being the most common cause in Europe.
Other risk factors include:
alpha-1 antitrypsin deficiency
hereditary tyrosinosis
glycogen storage disease
aflatoxin
drugs: oral contraceptive pill, anabolic steroids
porphyria cutanea tarda
male sex
diabetes mellitus, metabolic syndrome
Features of hepatocellular carcinoma?
tends to present late
features of liver cirrhosis or failure may be seen: jaundice, ascites, RUQ pain, hepatomegaly, pruritus, splenomegaly
possible presentation is decompensation in a patient with chronic liver disease
raised AFP
Screening with ultrasound (+/- alpha-fetoprotein) should be considered for high risk groups such as:
- patients liver cirrhosis secondary to hepatitis B & C or haemochromatosis
- men with liver cirrhosis secondary to alcohol
Management of hepatocellular carcinoma?
early disease: surgical resection
liver transplantation
radiofrequency ablation
transarterial chemoembolisation
sorafenib: a multikinase inhibitor
Causes of hepatomegaly?
Cirrhosis: if early disease, later liver decreases in size. Associated with a non-tender, firm liver
Malignancy: metastatic spread or primary hepatoma. Associated with a hard, irregular. liver edge
Right heart failure: firm, smooth, tender liver edge. May be pulsatile
Other causes:
viral hepatitis
glandular fever
malaria
abscess: pyogenic, amoebic
hydatid disease
haematological malignancies
haemochromatosis
primary biliary cirrhosis
sarcoidosis, amyloidosis
Pathophysiology of hepatorenal syndrome?
vasoactive mediators cause splanchnic vasodilation
in turn reduces the systemic vascular resistance
results in ‘underfilling’ of the kidneys.
This is sensed by the juxtaglomerular apparatus which then activates the renin-angiotensin-aldosterone system, causing renal vasoconstriction which is not enough to counterbalance the effects of the splanchnic vasodilation.
Types of hepatorenal syndrome?
Type 1
Rapidly progressive
Doubling of serum creatinine to > 221 µmol/L or a halving of the creatinine clearance to less than 20 ml/min over a period of less than 2 weeks
Very poor prognosis
Type 2
Slowly progressive
Prognosis poor, but patients may live for longer
Management of hepatorenal syndrome?
vasopressin analogues, for example terlipressin - work by causing vasoconstriction of the splanchnic circulation
volume expansion with 20% albumin
transjugular intrahepatic portosystemic shunt
Inherited causes of jaundice?
Unconjugated hyperbilirubinaemia:
Gilbert’s syndrome - AR, mild deficiency of UDP-glucuronyl transferase
Crigler-Najjar syndrome - AR, type 1 = absolute deficiency of UDP-glucuronosyl transferase, do not survive to adulthood, type 2 = less severe, may improve with phenobarbital
Conjugated hyperbilirubinaemia:
Dubin-Johnson syndrome - AR, mutation in the canalicular multidrug resistance protein 2 (MRP2) results in defective hepatic excretion of bilirubin, results in a grossly black liver
Rotor syndrome - autosomal recessive, defect in the hepatic uptake and storage of bilirubin
Summary of ischaemic hepatitis?
diffuse hepatic injury resulting from acute hypoperfusion (sometimes known as ‘shock liver’)
diagnosed in the presence of an inciting event (e.g. a cardiac arrest) and marked increases in aminotransferase levels (exceeding 1000 international unit/L or 50 times the upper limit of normal).
Often occurs in conjunction with acute kidney injury (tubular necrosis) or other end-organ dysfunction.
Diagnosis of liver cirrhosis
traditionally a liver biopsy was used - however associated with adverse effects such as bleeding and pain
other techniques such as transient elastography ‘Fibroscan’ and acoustic radiation force impulse imaging are increasingly used
for patients with NAFLD, NICE recommend using the enhanced liver fibrosis score to screen for patients who need further testing
Further investigations
NICE recommend doing an upper endoscopy to check for varices in patient’s with a new diagnosis of cirrhosis
liver ultrasound every 6 months (+/- alpha-feto protein) to check for hepatocellular cancer
Screening for liver cirrhosis?
Offer transient elastography to:
people with hepatitis C virus infection
men who drink over 50 units of alcohol per week and women who drink over 35 units of alcohol per week and have done so for several months
people diagnosed with alcohol-related liver disease
Summary of NAFLD
describes a spectrum of disease ranging from:
steatosis - fat in the liver
steatohepatitis - fat with inflammation, non-alcoholic steatohepatitis (NASH)
progressive disease may cause fibrosis and liver cirrhosis
hepatic manifestation of the metabolic syndrome and hence insulin resistance is thought to be the key mechanism leading to steatosis.
thought to affect around 3-4% of the general population.
Associated factors
obesity
type 2 diabetes mellitus
hyperlipidaemia
jejunoileal bypass
sudden weight loss/starvation
Features of NAFLD
usually asymptomatic
hepatomegaly
ALT is typically greater than AST
increased echogenicity on ultrasound
Investigations for NAFLD
no evidence to support screening
based on incidental finding of NAFLD
NICE recommends the use of the enhanced liver fibrosis (ELF) blood test to check for advanced fibrosis
FIB4 score or NALFD fibrosis score
FibroScan
advanced fibrosis should be referred to a liver specialist. They will then likely have a liver biopsy to stage the disease more accurately
Management of NAFLD
lifestyle changes (particularly weight loss) and monitoring
?gastric banding and insulin-sensitising drugs (e.g. metformin, pioglitazone)
Summary of pancreatic cancer?
Often diagnosed late due to non-specific presentations
80% of pancreatic tumours are adenocarcinomas which typically occur at the head of the pancreas.
Associations:
increasing age
smoking
diabetes
chronic pancreatitis (alcohol does not appear an independent risk factor though)
hereditary non-polyposis colorectal carcinoma
multiple endocrine neoplasia
BRCA2 gene
KRAS gene mutation
Features of pancreatic cancer?
classically painless jaundice
pale stools, dark urine, and pruritus
cholestatic liver function tests
Courvoisier’s law states that in the presence of painless obstructive jaundice, a palpable gallbladder is unlikely to be due to gallstones
however, patients typically present in a non-specific way with anorexia, weight loss, epigastric pain
loss of exocrine function (e.g. steatorrhoea)
loss of endocrine function (e.g. diabetes mellitus)
atypical back pain is often seen
migratory thrombophlebitis (Trousseau sign) is more common than with other cancers
Ix for pancreatic cancer?
USS
high-resolution CT scan - ‘double duct’ sign - the presence of simultaneous dilatation of the common bile and pancreatic ducts
Management of pancreatic cancer?
less than 20% are suitable for surgery at diagnosis
a Whipple’s resection (pancreaticoduodenectomy) is performed for resectable lesions in the head of pancreas. Side-effects of a Whipple’s include dumping syndrome and peptic ulcer disease
adjuvant chemotherapy is usually given following surgery
ERCP with stenting is often used for palliation
Summary of primary biliary cholangitis?
typically seen in middle-aged females (female:male ratio of 9:1)
autoimmune condition
Interlobular bile ducts become damaged by a chronic inflammatory process causing progressive cholestasis which may eventually progress to cirrhosis
“itching in middle-aged woman”
Associations: Sjogrens, RA, systemic sclerosis, thyroid disease
Complications:
cirrhosis > portal HTN > ascites, vatical haemorrhage
osteomalacia, osteoporosis
^ risk of hepatocellular carcinoma
Features of PBC
early: may be asymptomatic (e.g. raised ALP on routine LFTs) or fatigue, pruritus
cholestatic jaundice
hyperpigmentation, especially over pressure points
around 10% of patients have right upper quadrant pain
xanthelasmas, xanthomata
also: clubbing, hepatosplenomegaly
late: may progress to liver failure
Diagnosis of PBC
immunology:
anti-mitochondrial antibodies (AMA) M2 subtype are present in 98% of patients and are highly specific
smooth muscle antibodies in 30% of patients
raised serum IgM
imaging:
required before diagnosis to exclude an extrahepatic biliary obstruction (typically a right upper quadrant ultrasound or magnetic resonance cholangiopancreatography (MRCP)
Management of PBC
first-line: ursodeoxycholic acid
(slows disease progression and improves symptoms)
pruritus: cholestyramine
fat-soluble vitamin supplementation
liver transplantation
e.g. if bilirubin > 100 (PBC is a major indication)
recurrence in graft can occur but is not usually a problem
