Gastro Flashcards
What is Zollinger-Ellison syndrome?
Zollinger-Ellison syndrome is a condition characterised by excessive levels of gastrin secondary to a gastrin-secreting tumour.
. What is Zollinger-Ellison Syndrome?
Zollinger-Ellison Syndrome (ZES) is a rare condition caused by a gastrin-secreting tumor (gastrinoma), leading to excess stomach acid production and severe peptic ulcers.
📍 Location of Gastrinoma:
Pancreas (most common)
Duodenum
Lymph nodes
🔬 Association with MEN1 Syndrome:
25% of ZES cases are linked to Multiple Endocrine Neoplasia type 1 (MEN1)
MEN1 involves parathyroid, pituitary, and pancreatic tumors
- Pathophysiology
1️⃣ Gastrinoma secretes excess gastrin → Stimulates parietal cells → Increased HCl (acid) production
2️⃣ Severe acid hypersecretion → Multiple, recurrent peptic ulcers (often resistant to treatment)
3️⃣ Acid inactivates pancreatic enzymes → Malabsorption & diarrhea
Where are most of the tumors found in Zollinger-Ellison syndrome?
The majority of these tumours are found in the first part of the duodenum, with the second most common location being the pancreas.
What are the features of Zollinger-Ellison syndrome?
multiple gastroduodenal ulcers
diarrhoea
malabsorption
What are the most common glands affected in MEN1?
The most common glands affected are the parathyroids, pancreas, and pituitary.
What types of drugs cause drug-induced cholestasis?
oral contraceptive pill
Which drugs are known to cause a hepatocellular picture with a rise in alanine transaminase (ALT) to greater than two times the upper limit of normal?
Amiodarone
Methyldopa
Nitrofurantoin
Phenytoin
What is the management of First episode of C. difficile infection?
first-line therapy is oral vancomycin for 10 days
second-line therapy: oral fidaxomicin
third-line therapy: oral vancomycin +/- IV metronidazole
What is the management of recurrent infections of C. difficile infection?
recurrent infection occurs in around 20% of patients, increasing to 50% after their second episode
within 12 weeks of symptom resolution: oral fidaxomicin
after 12 weeks of symptom resolution: oral vancomycin OR fidaxomicin
What is the management of Life-threatening C. difficile infection?
oral vancomycin AND IV metronidazole
specialist advice - surgery may be considered
What on LFTS suggests alcoholic liver disease?
the ratio of AST:ALT is normally > 2, a ratio of > 3 is strongly suggestive of acute alcoholic hepatitis
What is the pathophysiology of pernicious anaemia?
antibodies to intrinsic factor +/- gastric parietal cells
intrinsic factor antibodies → bind to intrinsic factor blocking the vitamin B12 binding site
gastric parietal cell antibodies → reduced acid production and atrophic gastritis. Reduced intrinsic factor production → reduced vitamin B12 absorption
vitamin B12 is important in both the production of blood cells and the myelination of nerves → megaloblastic anaemia and neuropathy
What is perncious anaemia?
Pernicious anaemia is an autoimmune disorder affecting the gastric mucosa that results in vitamin B12 deficiency.
What are the causes of perncious anaemia?
Whilst pernicious anaemia is the most common cause of vitamin B12 deficiency, it’s not the only cause. Other causes include atrophic gastritis (e.g. secondary to H. pylori infection), gastrectomy, malnutrition (e.g. alcoholism).
What are the risk factors of pernicious anaemia?
more common in females (F:M = 1.6:1) and typically develops in middle to old age
associated with other autoimmune disorders: thyroid disease, type 1 diabetes mellitus, Addison’s, rheumatoid and vitiligo
more common if blood group A
What are the features of pernicious anaemia?
anaemia features
lethargy
pallor
dyspnoea
neurological features
peripheral neuropathy: ‘pins and needles’, numbness. Typically symmetrical and affects the legs more than the arms
subacute combined degeneration of the spinal cord: progressive weakness, ataxia and paresthesias that may progress to spasticity and paraplegia
neuropsychiatric features: memory loss, poor concentration, confusion, depression, irritabiltiy
other features
mild jaundice: combined with pallor results in a ‘lemon tinge’
atrophic glossitis → sore tongue
What major disease is pernicious anaemia associated with?
increased risk of gastric cancer
What is the treatment for achalasia?
pneumatic (balloon) dilation is increasingly the preferred first-line option
less invasive and quicker recovery time than surgery
patients should be a low surgical risk as surgery may be required if complications occur
surgical intervention with a Heller cardiomyotomy should be considered if recurrent or persistent symptoms
intra-sphincteric injection of botulinum toxin is sometimes used in patients who are a high surgical risk
drug therapy (e.g. nitrates, calcium channel blockers) has a role but is limited by side-effectsHeller cardiomyotomy
What are the adverse effects of PPIs?
hyponatraemia, hypomagnasaemia
osteoporosis → increased risk of fractures
microscopic colitis
increased risk of C. difficile infections
What are the early symptoms of Haemochromatosis?
early symptoms include fatigue, erectile dysfunction and arthralgia (often of the hands)
Which features of haemochromatosis is reversible with treatment?
which features are reversible with treatment:
Reversible complications
Cardiomyopathy
Skin pigmentation
Irreversible complications
Liver cirrhosis**
Diabetes mellitus
Hypogonadotrophic hypogonadism
Arthropathy
What is the management of Small bowel bacterial overgrowth syndrome (SBBOS)?
correction of the underlying disorder
antibiotic therapy:rifaximin is now the treatment of choice due to relatively low resistance. Co-amoxiclav or metronidazole are also effective in the majority of patients.
How to diagnose Small bowel bacterial overgrowth syndrome (SBBOS)?
hydrogen breath test
small bowel aspiration and culture: this is used less often as invasive and results are often difficult to reproduce
clinicians may sometimes give a course of antibiotics as a diagnostic trial
What are the risk factors for Small bowel bacterial overgrowth syndrome (SBBOS)?
neonates with congenital gastrointestinal abnormalities
scleroderma
diabetes mellitus
How to treat recurrent infection of C. difficile?
recurrent infection occurs in around 20% of patients, increasing to 50% after their second episode
within 12 weeks of symptom resolution: oral fidaxomicin
after 12 weeks of symptom resolution: oral vancomycin OR fidaxomicin
What is the management of C. difficile infection?
First episode of C. difficile infection
first-line therapy is oral vancomycin for 10 days
second-line therapy: oral fidaxomicin
third-line therapy: oral vancomycin +/- IV metronidazole
Recurrent episode
recurrent infection occurs in around 20% of patients, increasing to 50% after their second episode
within 12 weeks of symptom resolution: oral fidaxomicin
after 12 weeks of symptom resolution: oral vancomycin OR fidaxomicin
Life-threatening C. difficile infection
oral vancomycin AND IV metronidazole
specialist advice - surgery may be considered
Crohn’s disease affects mainly..?
Terminal illeum
Abdominal mass palpable in the right iliac fossa is associated with what condition?
Crohn’s disease
Crohn’s disease can affect any part of the gastrointestinal tract from mouth to anus, but it most commonly affects the terminal ileum. This can lead to inflammation and thickening of the bowel wall, leading to the formation of an abdominal mass that can often be palpated in the right iliac fossa. Furthermore, Crohn’s disease is characterised by transmural inflammation which may result in complications such as strictures, abscesses or fistulas, which could also contribute to a palpable mass.
What is the investigation of choice for suspected perianal fistulae in patients with Crohn’s?
MRI
Why do patients with coeliac disease require regular immunisations?
Functional hyposplenism. Patients with coeliac disease require regular immunisations due to functional hyposplenism. The spleen plays a crucial role in the immune system, particularly in filtering bacteria and producing antibodies. In patients with coeliac disease, there can be a decrease in splenic function, which increases their susceptibility to certain infections, especially those caused by encapsulated bacteria such as Streptococcus pneumoniae, Haemophilus influenzae type b, and Neisseria meningitidis. Therefore, it is essential for these patients to receive regular immunisations against these organisms.
Which drugs may decrease the accuracy of a 13C-urea breath test?
no antibiotics in past 4 weeks, no antisecretory drugs (e.g. PPI) in past 2 weeks
Ranitidine is an H2-receptor antagonist that reduces gastric acid secretion but does not directly affect H. pylori. However, it may cause false-negative results if used within two weeks before testing as it can reduce bacterial load by decreasing acidity levels in the stomach.
PPIs may cause false-negative results if used within two weeks before testing as they can reduce bacterial load by decreasing acidity levels in the stomach, similar to H2-receptor antagonists. However, since lansoprazole was stopped six weeks ago, this should not be a concern.
Which investigations would be most helpful in monitoring treatment in haemochromatosis?
Ferritin and transferrin saturation are the most useful investigations for monitoring the adequacy of venesection. Transferrin saturation should be kept below 50% and the serum ferritin concentration below 50 ug/L. Please note that these figures are different from the haemochromatosis diagnostic values (transferrin saturation >55% in men and >50% in women, ferritin >500 ug/L). Ferritin is the primary intracellular iron-storage protein that directly correlates with the degree of iron overload in the blood. Transferrin saturation determines the proportion of transferrin (the primary iron transporter in the blood) that is occupied by iron. It therefore also correlates with the degree of iron overload and hence the effectiveness of venesection.
What is Dubin-Johnson Syndrome (DJS) and Rotor Syndrome?
Both Dubin-Johnson syndrome (DJS) and Rotor syndrome are rare genetic disorders that affect bilirubin metabolism, resulting in mild jaundice.
Dubin-Johnson syndrome is a benign disorder characterized by conjugated (direct) hyperbilirubinemia (elevated levels of direct bilirubin in the blood), leading to mild jaundice.
It is genetically inherited in an autosomal recessive manner.
Which antibody is present in primary sclerosing cholangitis?
p-ANCA
Spontaneous bacterial peritonitis is a key differential for abdominal pain and fever in patients with..
portal hypertension and liver cirrohosis
Spontaneous bacterial peritonitis (SBP) is an ascitic fluid infection without an evident treatable intra-abdominal source. SBP occurs almost always in patients with known cirrhosis and ascites, commonly as a result of alcoholic liver disease, hepatitis B, hepatitis C, and non-alcoholic fatty liver disease. SBP should be suspected in a patient with known liver disease who present with fever, abdominal tenderness, abdominal distention, vomiting and altered mental state.
What is the most common organism found in ascitic fluid of Spontaneous bacterial peritonitis?
the most common organism found on ascitic fluid culture is E. coli
What is the management of Spontaneous bacterial peritonitis?
intravenous cefotaxime is usually given
How is the diagnosis of Spontaneous bacterial peritonitis made?
paracentesis: neutrophil count > 250 cells/ul
the most common organism found on ascitic fluid culture is E. coli
Antibiotic prophylaxis should be given to patients with ascites if:
patients who have had an episode of SBP
patients with fluid protein <15 g/l and either Child-Pugh score of at least 9 or hepatorenal syndrome
NICE recommend: ‘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’
Alcoholic liver disease is a marker of poor prognosis in SBP.
What is the child pugh score?
The Child-Pugh score is a clinical scoring system used to assess the severity of chronic liver disease, particularly cirrhosis, and to predict prognosis and treatment decisions.
What is a common complication of Transjugular Intrahepatic Portosystemic Shunt (TIPSS)?
exacerbation of hepatic encephalopathy is a common complication
acute, life-threatening oesophageal or gastric variceal bleeding that is refractory to medical management, including endoscopic intervention and pharmacotherapy such as vasoconstrictors What should be offered?
insert a Sengstaken-Blakemore tube
Contraindications for the placement of this tube encompass cessation or deceleration of the bleed, recent surgical procedures involving the gastro-oesophageal junction, and established oesophageal strictures. Given that the patient has not responded to initial treatment and lacks a history of recent surgery affecting the gastro-oesophageal junction, inserting a Sengstaken-Blakemore tube would be most appropriate to manage the bleeding.
Before considering a Transjugular Intrahepatic Portosystemic Shunt (TIPS), it is advisable to insert a Sengstaken-Blakemore tube due to TIPS being associated with an elevated risk of precipitating hepatic encephalopathy
The patient’s presentation of multiple non-healing leg ulcers, feeling unwell for many months, pale conjunctivae, and poor dentition with bleeding gums are all suggestive of scurvy,….
scurvy, which is caused by a deficiency in vitamin C. Vitamin C is essential for collagen synthesis, and its deficiency can lead to impaired wound healing, gum disease, and other connective tissue abnormalities.
What drugs cause a hepatocellular picture?
paracetamol
sodium valproate, phenytoin
MAOIs
halothane
anti-tuberculosis: isoniazid, rifampicin, pyrazinamide
statins
alcohol
amiodarone
methyldopa
nitrofurantoin
What drugs tend to cause cholestasis (+/- hepatitis)
combined oral contraceptive pill
antibiotics: flucloxacillin, co-amoxiclav, erythromycin*
anabolic steroids, testosterones
phenothiazines: chlorpromazine, prochlorperazine
sulphonylureas
fibrates
rare reported causes: nifedipine
What drugs cause liver cirrhosis?
methotrexate
methyldopa
amiodarone
What are the Early signs of haemochromatosis ?
Fatigue, erectile dysfunction and arthralgia
What is bud-Chiari syndrome?
Budd-Chiari syndrome, or hepatic vein thrombosis, is usually seen in the context of underlying haematological disease or another procoagulant condition.
Budd-Chiari syndrome is a rare condition caused by obstruction of hepatic venous outflow, leading to liver congestion, hepatomegaly, and portal hypertension. The blockage occurs due to thrombosis or stenosis of the hepatic veins or inferior vena cava.
What are causes of Bud-chiari syndrome?
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
What are the features are classically a triad of in bud chiari syndrome:
abdominal pain: sudden onset, severe
ascites → abdominal distension
tender hepatomegaly
What investigations should be done for bu chiari syndrome?
ultrasound with Doppler flow studies is very sensitive and should be the initial radiological investigation
What is the management of Primary billary cholangitis?
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
What is the first line investigation in Acute mesenteric ischaemia?
Venous blood gas is the most useful of the listed investigations. Approximately 90% of patients with ischaemic bowel will have elevated lactate and associated metabolic acidosis. This will confirm suspicion for the diagnosis and also give information about the severity. However, lactate is not specific. A CT angiography abdomen and pelvis with contrast is needed urgently to assess for ischaemic bowel.
Acute mesenteric ischaemia causes a raised lactate and is the first-line investigation
Ishaemic colitis vs mesenteric colitis?
🩸 Definition: A transient, self-limiting ischemia of the colon due to low blood flow, often from hypoperfusion rather than complete blockage.
📍 Location: Colon (especially watershed areas like splenic flexure & rectosigmoid junction)
🩸 Definition: A life-threatening condition caused by severe reduction or blockage of blood flow to the small intestine.
📍 Location: Small intestine (Jejunum & Ileum)
64 year old patient has presented with a 3-month history of dull abdominal pain (radiating to/worse at the back), weight loss and grey-coloured stools (steatorrhoea) and fatigue what are u thinking?
Steatorrhoea is caused by fat malabsorption and can occur if a tumour blocks the pancreatic duct meaning insufficient pancreatic juices are secreted hence, there is a reduction in lipase and bile salts. This, coupled with the history of smoking/alcohol intake and history of type 2 diabetes mellitus increases the likelihood of underlying presentation of pancreatic cancer. While pancreatic cancer classically presents as ‘painless jaundice’, often presentations are less clear cut. NICE guidelines advise referring a patient for a high-resolution CT scan of the pancreas if aged 60 or over with weight loss and any one of diarrhoea, back pain, abdominal pain, nausea, vomiting, constipation or new-onset diabetes. This patient is aged 64 and has presented with evidence of weight loss and upper abdominal pain radiating to the back. Therefore, a high-resolution CT scan of the pancreas is indicated as this can provide detailed imaging of the pancreas and surrounding structures, helping to identify any abnormalities and explore the possible differential diagnosis of a pancreatic picture such as pancreatic cancer
What is the blood marker for pancreatic cancer?
CA19-9
What is the diagnostic marker for HCC Hepatocellular carcinoma?
Raised AFP Alpha-fetoprotein
What are Small bowel enema findings in crohns disease?
high sensitivity and specificity for examination of the terminal ileum
strictures: ‘Kantor’s string sign’
proximal bowel dilation
‘rose thorn’ ulcers
fistulae
Right heart failure is actually one of the most common causes of hepatomegaly. It is characterised by
Right heart failure is actually one of the most common causes of hepatomegaly. It is characterised by a firm, smooth and tender to touch liver edge. The real clue in this question is that it is also pulsatile, which is due to the back-up of blood due to the failure of the right side of the heart to work effectively. The fact that it is pulsatile, distinguishes it from the other possible answers.
COPD is a common cause of right-sided heart failure. This is often referred to as cor pulmonale. Some other features of right-sided heart failure include; a raised JVP, ascites, and peripheral oedema.
Which test is more sensitive for haemochromatosis ?
The correct answer is transferrin saturation. The diagnosis here is haemochromatosis, given the presentation and investigations - the bronze tint to the skin, chondrocalcinosis of the finger joints, raised glucose suggesting iron deposition in the pancreas, and liver disease suggesting iron deposition in the liver too. In the general population, transferrin saturation is considered the most useful marker initially. Ferritin is often also measured but is not as sensitive. If the transferrin saturation indicates a diagnosis of haemochromatosis, genetic testing may then be undertaken.
What is key in determining the severity of C. difficile infection?
white cell count
In young men the two most common causes of lower abdominal pain are…
appendicitis and testicular problems (infection and torsion). Therefore it is imperative to examine the testes to ensure you do not miss a source of referred pain. A digital rectal examination is also important to perform but for someone with abdominal pain and no pelvic pain it would be less important than a scrotal examination. The key thing you would be looking for is a perianal abscess which would always present with pain around the anus and in the pelvis as well as a fever which is why this is a less correct answer, remember the question is seeking the single best answer and so although many of the answers may be plausible it is the best one that is correct.
What is the management of h-pylori infection?
eradication may be achieved with a 7-day course of
a proton pump inhibitor + amoxicillin + (clarithromycin OR metronidazole)
if penicillin-allergic: a proton pump inhibitor + metronidazole + clarithromycin
Which patients require urgent referral?
All patients who’ve got dysphagia
All patients who’ve got an upper abdominal mass consistent with stomach cancer
Patients aged >= 55 years who’ve got weight loss, AND any of the following:
upper abdominal pain
reflux
dyspepsia
Which patients require non urgent referral?
Patients with haematemesis
Patients aged >= 55 years who’ve got:
treatment-resistant dyspepsia or
upper abdominal pain with low haemoglobin levels or
raised platelet count with any of the following: nausea, vomiting, weight loss, reflux, dyspepsia, upper abdominal pain
nausea or vomiting with any of the following: weight loss, reflux, dyspepsia, upper abdominal pain
How to Manage patients who do not meet referral criteria (‘undiagnosed dyspepsia’)
This can be summarised at a step-wise approach
1. Review medications for possible causes of dyspepsia
2. Lifestyle advice
3. Trial of full-dose proton pump inhibitor for one month OR a ‘test and treat’ approach for H. pylori
if symptoms persist after either of the above approaches then the alternative approach should be tried
What is another name for chronic mesenteric ischaemia?
Intestinal angina
What is the classic triad for Intestinal angina/chronic mesenteric ischaemia?
classically characterised by a triad of severe, colicky post-prandial abdominal pain, weight loss, and an abdominal bruit - by far the most common cause is atherosclerotic disease in arteries supplying the GI tract
What is the management of Pyogenic liver abscess?
drainage (typically percutaneous) and antibiotics
amoxicillin + ciprofloxacin + metronidazole
if penicillin allergic: ciprofloxacin + clindamycin
What malignancies are associated with HNPCC
the second most common malignancy following colorectal cancer is endometrial cancer.
Primary biliary cholangitis - the M rule
IgM
anti-Mitochondrial antibodies, M2 subtype
Middle aged females
What are the clinical features of Primary biliary cholangitis ?
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
What is the management of primary billary cholangitis?
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
What conditions are asscoiated with primary billary cholangitis?
Sjogren’s syndrome (seen in up to 80% of patients)
rheumatoid arthritis
systemic sclerosis
thyroid disease
What is the pathophysiology pf HRS?
The most accepted theory regarding the pathophysiology of HRS is that vasoactive mediators cause splanchnic vasodilation which in turn reduces the systemic vascular resistance. This 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.
What are the two types of HRS?
Type 1 HRS
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 HRS
Slowly progressive
Prognosis poor, but patients may live for longer
What is the management of HRS?
vasopressin analogues, for example terlipressin, have a growing evidence base supporting their use. They work by causing vasoconstriction of the splanchnic circulation
volume expansion with 20% albumin
transjugular intrahepatic portosystemic shunt
What is the mechanism of loperamide?
µ-opioid receptor agonist which does not have systemic effects as it is not absorbed through the gut
The mechanism by which loperamide works is through stimulation of µ-opioid receptors in the submucosal neural plexus of the intestinal wall. This, in turn, reduces peristalsis of the intestines decreasing gastric motility.
Ongoing diarrhoea in Crohn’s patient post-resection with normal CRP →
diagnosis of bile acid malabsorption as a complication of the ileocecal resection
What is the treatment for bile acid malabsorption?
cholestyramine
Cholestyramine is a bile acid sequestrant used in the management of hyperlipidaemia. It decreases bile acid reabsorption in the small intestine, therefore upregulating the amount of cholesterol that is converted to bile acid. The main effect it has on the lipid profile is to reduce LDL cholesterol. It is also occasionally used in Crohn’s disease for treatment diarrhoea following bowel resection
What are the adverse effects of Cholestyramine?
abdominal cramps and constipation
decreases absorption of fat-soluble vitamins
cholesterol gallstones
may raise level of triglycerides
What is a key investigation for a suspected perforated peptic ulcer?
An erect chest x-ray
What is the mechanism of action of metaclopramide?
whilst metoclopramide is primarily a D2 receptor antagonist, the mechanism of action is quite complicated:
it is also a mixed 5-HT3 receptor antagonist/5-HT4 receptor agonist
the antiemetic action is due to its antagonist activity at D2 receptors in the chemoreceptor trigger zone. At higher doses the 5-HT3 receptor antagonist also has an effect
the gastroprokinetic activity is mediated by D2 receptor antagonist activity and 5-HT4 receptor agonist activity
What is a common complication of constipation and may increase falls risk?
Acute urinary retention
What is Courvoisier’s law?
A palpable, non tender, enlarged gallbladder accompanied with painless jaundice is unlikely to be due to gallstones. Instead consider malignancy
1️⃣ Pancreatic Head Cancer (Most Common)
Compresses the common bile duct, leading to obstruction
Causes progressive, painless jaundice and weight loss
2️⃣ Cholangiocarcinoma (Bile Duct Cancer)
Tumor in the bile duct causing obstruction
3️⃣ Periampullary Tumors
Tumors near the ampulla of Vater
4️⃣ Benign Causes (Rare)
Strictures (e.g., post-surgical, autoimmune)
Which antibiotics are most likely to cause pseudomembranous colitis?
Cephalosporins such as ceftriaxone, not just clindamycin, are strongly linked to C.difficile
What is Mackler triad for Boerhaave syndrome?
vomiting, thoracic pain, subcutaneous emphysema
What is Boerhaave syndrome?
Boerhaave syndrome is a spontaneous esophageal rupture due to forceful vomiting or retching, leading to full-thickness (transmural) perforation of the esophagus. It is a life-threatening surgical emergency.
What are the complications of primary sclerosing cholangitis?
cholangiocarcinoma (in 10%)
increased risk of colorectal cancer
What serology is done to test for celiac disease?
tissue transglutaminase (TTG) antibodies (IgA) are first-choice according to NICE
endomyseal antibody (IgA)
needed to look for selective IgA deficiency, which would give a false negative coeliac result
Requires IgA sufficiency (check total IgA levels first)
What are the three types of colon cancer?
sporadic (95%)
hereditary non-polyposis colorectal carcinoma (HNPCC, 5%)
familial adenomatous polyposis (FAP, <1%)
What genetic mutations are involved in sporadic colon cancer?
more than half of colon cancers show allelic loss of the APC gene.
It is believed a further series of gene abnormalities e.g.
activation of the K-ras oncogene,
deletion of p53 and DCC tumour suppressor genes lead to invasive carcinoma.
What genetic mutations are involved in hereditary non polyposis colorectal carcinoma (HNPCC)/lynch syndrome?
Currently seven mutations have been identified, which affect genes involved in DNA mismatch repair leading to microsatellite instability. The most common genes involved are:
MSH2 (60% of cases)
MLH1 (30%)
What genetic mutations are involved in familial adenomatous polyposis ?
It is due to a mutation in a tumour suppressor gene called adenomatous polyposis coli gene (APC), located on chromosome 5.
What antibodies are present in primary sclerosing cholangitis?
positive anti-neutrophil cytoplasmic antibody (ANCA) pANCA and anti-smooth muscle cell antibodies.
What are the characteristic electrolyte disturbances seen in patients with refeeding syndrome
Hypophosphataemia, hypokalaemia and hypomagnesaemia
hypophosphataemia
this is the hallmark symptom of refeeding syndrome
may result in significant muscle weakness, including myocardial muscle (→ cardiac failure) and the diaphragm (→ respiratory failure)
hypokalaemia
hypomagnesaemia: may predispose to torsades de pointes
abnormal fluid balance
What is refeeding syndrome?
Refeeding syndrome describes the metabolic abnormalities which occur on feeding a person following a period of starvation. It occurs when an extended period of catabolism ends abruptly with switching to carbohydrate metabolism.
Pathophysiology of Hypophosphatemia in Refeeding Syndrome?
Shift from Fat to Carbohydrate Metabolism: In refeeding syndrome, the reintroduction of carbohydrates leads to a shift from fat to carbohydrate metabolism. This switch activates insulin secretion, which in turn increases cellular uptake of glucose.
Intracellular Movement of Phosphate: Insulin and increased glucose uptake stimulate the intracellular movement of phosphate, which is used in the synthesis of ATP and 2,3-diphosphoglycerate in erythrocytes. This intracellular shift reduces serum phosphate levels.
Decreased Phosphate Stores: Patients with chronic malnutrition often have depleted phosphate stores, although their serum phosphate levels may initially be normal. When refeeding starts, the sudden demand for phosphate in anabolic processes exceeds the supply, leading to hypophosphatemia.
Clinical Consequences of Hypophosphatemia?
Cardiac Dysfunction: Hypophosphatemia can impair myocardial contractility, leading to heart failure. It may also cause arrhythmias due to its role in maintaining normal cellular electrophysiology.
Respiratory Failure: Phosphate is essential for ATP production, necessary for respiratory muscle function. Severe hypophosphatemia can lead to muscle weakness, including the diaphragm and intercostal muscles, potentially resulting in acute respiratory failure.
Neurological Complications: These can range from confusion and seizures to coma, attributable to disturbed ATP metabolism in the central nervous system.
Haematological Effects: Reduced 2,3-diphosphoglycerate levels in erythrocytes affect oxygen release from haemoglobin, leading to tissue hypoxia. Hypophosphatemia can also result in hemolysis.
Rhabdomyolysis: Phosphate depletion impairs ATP production in muscles, which can lead to muscle breakdown and rhabdomyolysis.
Patients are considered high-risk if one or more of the following:
BMI < 16 kg/m2
unintentional weight loss >15% over 3-6 months
little nutritional intake > 10 days
hypokalaemia, hypophosphataemia or hypomagnesaemia prior to feeding (unless high)
If two or more of the following:
BMI < 18.5 kg/m2
unintentional weight loss > 10% over 3-6 months
little nutritional intake > 5 days
history of: alcohol abuse, drug therapy including insulin, chemotherapy, diuretics and antacids
NICE recommend that if a patient hasn’t eaten for > 5 days, aim to
NICE recommend that if a patient hasn’t eaten for > 5 days, aim to re-feed at no more than 50% of requirements for the first 2 days.
What are the classical biochemical features associated with tumour lysis syndrome
hyperkalaemia, hyperphosphataemia, and hypocalcemia.
What is the managment of Wilsons disease?
penicillamine (chelates copper) has been the traditional first-line treatment
trientine hydrochloride is an alternative chelating agent which may become first-line treatment in the future
tetrathiomolybdate is a newer agent that is currently under investigation
What are the investigations for Wilsons disease?
slit lamp examination for Kayser-Fleischer rings
reduced serum caeruloplasmin
reduced total serum copper (counter-intuitive, but 95% of plasma copper is carried by ceruloplasmin)
free (non-ceruloplasmin-bound) serum copper is increased
increased 24hr urinary copper excretion
the diagnosis is confirmed by genetic analysis of the ATP7B gene
slit lamp examination for Kayser-Fleischer rings
reduced serum caeruloplasmin
reduced total serum copper (counter-intuitive, but 95% of plasma copper is carried by ceruloplasmin)
free (non-ceruloplasmin-bound) serum copper is increased
increased 24hr urinary copper excretion
the diagnosis is confirmed by genetic analysis of the ATP7B gene
What are the features of Wilsons disease?
Features result from excessive copper deposition in the tissues, especially the brain, liver and cornea:
liver: hepatitis, cirrhosis
neurological:
basal ganglia degeneration: in the brain, most copper is deposited in the basal ganglia, particularly in the putamen and globus pallidus
speech, behavioural and psychiatric problems are often the first manifestations
also: asterixis, chorea, dementia, parkinsonism
Kayser-Fleischer rings
green-brown rings in the periphery of the iris
due to copper accumulation in Descemet membrane
present in around 50% of patients with isolated hepatic Wilson’s disease and 90% who have neurological involvement
renal tubular acidosis (esp. Fanconi syndrome)
haemolysis
blue nails
What is a common cause of hyperferritinaemia
Alcohol excess
In pancreatic cancer, 3 different abdominal masses may be present:
hepatomegaly (metastases)
gallbladder (Courvoisier’s law)
epigastric mass (primary)
What is the Complete Management of Acute Variceal Bleeding?
1️⃣ Resuscitation:
IV fluids, but avoid excessive resuscitation (risk of worsening portal hypertension).
Blood transfusion: Aim for Hb 7-8 g/dL (restrictive strategy).
Correct coagulopathy (vitamin K, FFP, platelets if needed).
2️⃣ Terlipressin/Octreotide:
Start immediately before endoscopy.
3️⃣ Prophylactic Antibiotics:
IV Ceftriaxone (or oral Norfloxacin if mild).
4️⃣ Urgent Endoscopy (within 12 hours):
Endoscopic variceal band ligation (EVL) = first-line treatment.
Sclerotherapy if EVL is not possible.
5️⃣ Consider Balloon Tamponade (Sengstaken-Blakemore tube):
If bleeding is massive & uncontrolled before definitive therapy.
6️⃣ Transjugular Intrahepatic Portosystemic Shunt (TIPS):
Considered if bleeding persists despite endoscopic therapy & medical management.
7️⃣ Long-term Prevention (Secondary Prophylaxis):
Non-selective beta-blockers (e.g., Propranolol, Carvedilol) to reduce portal pressure.
Repeat band ligation until varices obliterated.
What is the Complete Management of Acute non Variceal Bleeding?
1️⃣ Resuscitation (If Hemodynamically Unstable)
IV Access: Two large-bore (⩾18G) cannulas
Fluid Resuscitation: Crystalloids (if hypotensive)
Blood Transfusion:
Hb target: 7–8 g/dL (restrictive strategy, unless cardiac history)
Correct Coagulopathy:
FFP if INR >1.5 (or PCC for warfarin)
Platelets if <50 × 10⁹/L
Oxygen and Monitor Vitals
2️⃣ Risk Stratification (Predicts Mortality & Need for Endoscopy)
Glasgow-Blatchford Score (GBS) → Determines need for hospital admission
Rockall Score → Predicts mortality risk
3️⃣ Medications Before Endoscopy
IV Proton Pump Inhibitor (PPI) – Omeprazole 80 mg IV bolus → 8 mg/hr infusion
Helps stabilize clot formation but does not prevent rebleeding.
Stop NSAIDs, anticoagulants if possible (restart if essential).
4️⃣ Endoscopy (Within 24 Hours, or Urgent if Unstable)
Peptic Ulcer Bleeding → Treat as per Forrest Classification
High-risk ulcers (active bleeding, visible vessel, clot) → Endoscopic therapy
Options: Injection of adrenaline, thermal coagulation, or hemoclips
Mallory-Weiss Tear → Usually self-limiting, but may need adrenaline injection.
Dieulafoy’s Lesion (arterial malformation) → Requires endoscopic coagulation or clipping.
🔄 Post-Endoscopic Management & Prevention
1️⃣ High-Dose IV PPI for 72 Hours
Omeprazole IV infusion (reduces rebleeding in peptic ulcers).
2️⃣ Eradicate H. pylori (If Peptic Ulcer Disease)
Triple therapy: PPI + Clarithromycin + Amoxicillin (or Metronidazole if allergic).
3️⃣ Restart Anticoagulation (If Indicated)
Wait ~48-72 hours after hemostasis if needed (balance rebleeding vs. thrombotic risk).
4️⃣ Secondary Prevention
Stop NSAIDs if possible or use PPI protection if essential.
For high-risk patients: Consider long-term PPI therapy.
Management of non-variceal bleeding
NICE do not recommend the use of proton pump inhibitors (PPIs) before endoscopy to patients with suspected variceal upper gastrointestinal bleeding although PPIs should be given to patients with non-variceal upper gastrointestinal bleeding and stigmata of recent haemorrhage shown at endoscopy
if further bleeding then options include repeat endoscopy, interventional radiology and surgery
Antibiotic prophylaxis should be given to patients with ascites if:
patients who have had an episode of SBP
patients with fluid protein <15 g/l and either Child-Pugh score of at least 9 or hepatorenal syndrome
NICE recommend: ‘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’
What is the commonest cause of liver failure in the UK?
Paracetamol
A lemon tinge to the skin is associated with what condition?
pernicious anaemia. The light yellow tinge is caused by the combination of pallor (due to the anaemia) and mild jaundice (caused by the haemolysis).
What is the management of primary biliary cholangitis?
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
What are the complications of primary biliary cholangitis?
cirrhosis → portal hypertension → ascites, variceal haemorrhage
osteomalacia and osteoporosis
significantly increased risk of hepatocellular carcinoma (20-fold increased risk)
What is used for the prophylaxis of oesophageal bleeding?
A non-cardioselective B-blocker (NSBB) propanol
Portal hypertension secondary to liver cirrhosis is common due to the scarred liver causing increased pressure in the portal venous system. In order to accommodate the pressure, the oesophageal, gastric and rectal veins enlarge and form thin-walled varices.
Beta-blockers that are non-cardioselective (i.e. they act on beta-2 adrenoreceptors on vascular smooth muscle as well as cardiac beta-1 adrenoreceptors) will cause vasodilation in these engorged vessels and reduced heart rate which lowers the blood pressure in the variceal veins and reduces the risk of rupture.
What is the most appropriate way to treat this hypophosphataemia?
Hypophosphatemia is recognised by a serum phosphate level <0.80 mmol/L. It is further classified as mild (ˆ¼0.64-0.80 mmol/L), moderate (ˆ¼0.32-0.64 mmol/L) and severe (<0.32 mmol/L).
In mild to moderate hypophosphataemia where patients are asymptomatic, enteral replacement is required using Phosphate Sandozµ effervescent tablets. Each tablet contains 16.1mmol of phosphate, 20.4mmol of sodium and 3.1mmol of potassium. An adult dose is usually up to 6 tablets daily in divided doses, which is dissolved in water to produce a solution that can safely be administered via feeding tubes. Dose adjustments to be made according to response.
Intravenous phosphate replacement is required for patients with severe hypophosphataemia or when symptomatic. Phosphate Polyfusorµ is a commonly used 500ml solution which contains 50mmol of phosphate, 81mmol of sodium and 9.5mmol of potassium. The maximum dose is 500ml Polyfusorµ per infusion and maximum infusion rate is 150ml Polyfusorµ per hour.
Difference between iron deficiency and anaemia of chronic disease?
What is the most common symptom of Crohn’s disease in children?
commonly presents with abdominal pain in children. The pain is typically crampy and often located in the right lower quadrant, reflecting ileal involvement. This symptom is due to transmural inflammation caused by the disease.
What is the management of non alcholic fatty liver disease?
the mainstay of treatment is lifestyle changes (particularly weight loss) and monitoring
there is ongoing research into the role of gastric banding and insulin-sensitising drugs (e.g. metformin, pioglitazone)
What is the gold standard investigation for the diagnosis of coeliac disease?
Endoscopic intestinal biopsy, however, is the gold standard for the diagnosis of coeliac disease and should be offered to all adult patients if the diagnosis is suspected following serology. Jejunal biopsy is correct, as the duodenum and jejunum are the most affected portions of bowel in coeliac disease, while the ileum is not as affected (unlike in Crohn’s disease), and would not be an appropriate place for a biopsy sample from a professional.
What is a treatment option for Barrett’s esophagus with high-grade dysplasia (HGD)?
if dysplasia of any grade is identified endoscopic intervention is offered. Options include:
radiofrequency ablation: preferred first-line treatment, particularly for low-grade dysplasia
Endoscopic mucosal resection (EMR)
This has a high risk of progression to adenocarcinoma of the oesophagus. An alternative is oesophagectomy. NICE recommend considering endoscopic therapy as an alternative to oesophagectomy in people with high-grade dysplasia and intramucosal cancer, especially in patients who are considered unsuitable for surgery.
What is the management of barretts oesophagus?
high-dose proton pump inhibitor
whilst this is commonly used in patients with Barrett’s the evidence base that this reduces the change of progression to dysplasia or induces regression of the lesion is limited
endoscopic surveillance with biopsies
for patients with metaplasia (but not dysplasia) endoscopy is recommended every 3-5 years
if dysplasia of any grade is identified endoscopic intervention is offered. Options include:
radiofrequency ablation: preferred first-line treatment, particularly for low-grade dysplasia
endoscopic mucosal resection
What is barretts oeasophagus?
Barrett’s refers to the metaplasia of the lower oesophageal mucosa, with the usual squamous epithelium being replaced by columnar epithelium. There is an increased risk of oesophageal adenocarcinoma, estimated at 50-100 fold. There are no screening programs for Barrett’s - it’s typically identified when patients have an endoscopy for evaluation of upper gastrointestinal symptoms such as dyspepsia.
What are the risk factors for barretts oesophagus?
gastro-oesophageal reflux disease (GORD) is the single strongest risk factor
male gender (7:1 ratio)
smoking
central obesity
What can barretts oesophagus be subdivided into?
Barrett’s can be subdivided into short (<3cm) and long (>3cm). The length of the affected segment correlates strongly with the chances of identifying metaplasia. The overall prevalence of Barrett’s oesophagus is difficult to determine but may be in the region of 1 in 20 and is identified in up to 12% of those undergoing endoscopy for reflux.
Patients with ascites secondary to liver cirrhosis should be given an
aldosterone antagonist spironolactone
What is osteomalacia?
Osteomalacia is a condition characterised by the softening of bones due to inadequate mineralisation, primarily caused by vitamin D deficiency
Pathophysiology: In coeliac disease, the ingestion of gluten leads to an autoimmune response that damages the intestinal mucosa, impairing nutrient absorption. This malabsorption can result in low serum levels of vitamin D and calcium, crucial for bone health.
Clinical Features: Patients may present with bone pain, muscle weakness, and increased susceptibility to fractures. Symptoms can be subtle and may include fatigue and difficulty walking.
Diagnosis: Diagnosis involves serum biochemistry showing low calcium and phosphate levels, elevated alkaline phosphatase, and low 25-hydroxyvitamin D levels. A bone biopsy may show unmineralised osteoid.
Treatment: Management includes a strict gluten-free diet to promote intestinal healing and supplementation with vitamin D and calcium. Regular monitoring of bone density is recommended.
What blood test results is most likely to indicate haemochromatosis?
Raised transferrin saturation and ferritin, with low TIBC is the characteristic iron study profile in haemochromatosis
What is the most important next investigation to perform in ulcerative colitis flare with systemic upset?
abdominal x ray, This patient may have developed a toxic megacolon, which is classically demonstrated by the transverse colon being > 6 cm in diameter in combination with signs of systemic upset. Patients identified as having a toxic megacolon are usually treated aggressively with medical therapy for 24-72 hours. If there is no sign of improvement during this time a colectomy is performed.
What is Plummer-Vinson syndrome/also known as Paterson-Brown-Kelly syndrome?
Plummer-Vinson syndrome, also known as Paterson-Brown-Kelly syndrome, is a rare condition characterized by the triad of iron deficiency anaemia, dysphagia due to esophageal webs, and atrophic glossitis. The patient’s symptoms of pain in her tongue and pain on swallowing, along with angular stomatitis and a red smooth tongue, are consistent with this disorder. Additionally, her blood tests reveal microcytic anaemia (low Hb and low MCV), which is suggestive of iron deficiency.
Treatment includes iron supplementation and dilation of the webs
What should be assessed before commencing azathioprine or mercaptopurine?
Thiopurine methyltransferase (TPMT) activity
is an enzyme involved in the metabolism of azathioprine and mercaptopurine. Some people have a deficiency of TPMT due to genetic mutations, and these people are at a greater risk of experiencing severe side effects from conventional doses of azathioprine or mercaptopurine.
Which medication should be avoided in bowel obstruction?
Metoclopramide should be avoided as it is a pro-kinetic anti-emetic so could cause a perforation in bowel obstruction.
What is the is the investigation of choice for suspected carcinoid tumours?
Urinary 5-HIAA
plasma chromogranin A y
What is the investigation of choice for liver cirrhosis?
Transient elastography, also known as Fibroscan
Diagnosis
traditionally a liver biopsy was used. This procedure is however associated with adverse effects such as bleeding and pain
other techniques such as transient elastography and acoustic radiation force impulse imaging are increasingly used and were recommended by NICE in their 2016 guidelines
for patients with NAFLD, NICE recommend using the enhanced liver fibrosis score to screen for patients who need further testing
What is transient elastography?
brand name ‘Fibroscan’
uses a 50-MHz wave is passed into the liver from a small transducer on the end of an ultrasound probe
measures the ‘stiffness’ of the liver which is a proxy for fibrosis
In terms of screening for cirrhosis NICE made a specific recommendation, suggesting to 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
What are further investigations for patients newly diagnosed with liver cirrhosis?
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
What are the complications of Primary sclerosing cholangitis?
cholangiocarcinoma (in 10%)
increased risk of colorectal cancer
What deficiency causes angular cheilitis?
Riboflavin
It is caused by a variety of reasons, including infection, mechanical factors, drug-related side effects and nutritional deficiencies. In the case of the latter, deficiencies of iron, zinc and vitamins from the B group are the most common causes. Of those in the vitamin B group, deficiencies of riboflavin (B2), niacin (B3), pyridoxine (B6), folate (B9) and cyanocobalamin (B12) are typically linked to the condition.
Riboflavin is a cofactor of flavin adenine dinucleotide (FAD) and flavin mononucleotide (FMN) and is important in energy metabolism.
Ascorbic acid
vitamin c
Colecalciferol
vitamin D3
Pantothenic acid
vitamin B5
Thiamine
vitamin B1
What are the side effects of Mesalazine?
GI upset, headache, agranulocytosis, pancreatitis*, interstitial nephritis
*pancreatitis is 7 times more common in patients taking mesalazine than sulfasalazine
What are the side effects of Aminosalicylates ?
Aminosalicylates are associated with a variety of haematological adverse effects, including agranulocytosis - FBC is a key investigation in an unwell patient taking them.
What are the side effects of Sulphasalazine?
many side-effects are due to the sulphapyridine moiety: rashes, oligospermia, headache, Heinz body anaemia, megaloblastic anaemia, lung fibrosis
other side-effects are common to 5-ASA drugs (see mesalazine)
mesalazine:
GI upset, headache, agranulocytosis, pancreatitis*, interstitial nephritis
*pancreatitis is 7 times more common in patients taking mesalazine than sulfasalazine
How does Zollinger-Ellison Syndrome characteristically present?
Zollinger-Ellison Syndrome characteristically presents with multiple peptic ulcers as well as diarrhoea, along with a family history of multiple endocrine neoplasia. The patient has no family history or mention of diarrhoea.
What is used in the management of severe alcoholic hepatitis?
Corticosteroids
Selected management notes for alcoholic hepatitis:
glucocorticoids (e.g. prednisolone) are often used during acute episodes of alcoholic hepatitis
Maddrey’s discriminant function (DF) is often used during acute episodes to determine who would benefit from glucocorticoid therapy
it is calculated by a formula using prothrombin time and bilirubin concentration
pentoxyphylline is also sometimes used
the STOPAH study (see reference) compared the two common treatments for alcoholic hepatitis, pentoxyphylline and prednisolone. It showed that prednisolone improved survival at 28 days and that pentoxyphylline did not improve outcomes
What are features of gastric cancer?
abdominal pain
typically vague, epigastric pain
may present as dyspepsia
weight loss and anorexia
nausea and vomiting
dysphagia: particularly if the cancer arises in the proximal stomach
overt upper gastrointestinal bleeding is seen only in a minority of patients
if lymphatic spread:
left supraclavicular lymph node (Virchow’s node)
periumbilical nodule (Sister Mary Joseph’s node)
What investigations are done for gastric cancer?
diagnosis: oesophago-gastro-duodenoscopy with biopsy
signet ring cells may be seen in gastric cancer. They contain a large vacuole of mucin which displaces the nucleus to one side. Higher numbers of signet ring cells are associated with a worse prognosis
staging:
CT scan of the chest, abdomen, and pelvis is indicated in all patients to look for metastatic disease
other modalities they may be used for staging include endoscopic ultrasound, (FDG)-PET scanning and pre-operative staging laparoscopy
What are the scoring systems for for liver cirrhosis and what values do they use?
For many years the Child-Pugh classification was used to classify the severity of liver cirrhosis. However, in recent years the Model for End-Stage Liver Disease (MELD) has been increasingly used, particularly patient’s who are on a liver transplant waiting list
Child-Pugh classification
Score 1 2 3
Bilirubin (µmol/l) <34 34-50 >50
Albumin (g/l) >35 28-35 <28
Prothrombin time,
prolonged by (s) <4 4-6 >6
Encephalopathy none mild marked
Ascites none mild marked
Summation of the scores allows the severity to be graded either A, B or C:
< 7 = A
7-9 = B
> 9 = C
MELD
Uses a combination of a patient’s bilirubin, creatinine, and the international normalized ratio (INR) to predict survival. A formula is used to calculate the score:
MELD = 3.78×ln[serum bilirubin (mg/dL)] + 11.2×ln[INR] + 9.57×ln[serum creatinine (mg/dL)] + 6.43
The 3-month mortality based on MELD scores:
40 or more: 71.3% mortality
30 - 39: 52.6% mortality
20 - 29: 19.6% mortality
10 - 19: 6.0% mortality
< 9: 1.9% mortality
What is the treatment for autoimmune hepatitis?
steroids, other immunosuppressants e.g. azathioprine
liver transplantation
What are the features of autoimmune hepatitis?
may present with signs of chronic liver disease
acute hepatitis: fever, jaundice etc (only 25% present in this way)
amenorrhoea (common)
ANA/SMA/LKM1 antibodies, raised IgG levels
liver biopsy: inflammation extending beyond limiting plate ‘piecemeal necrosis’, bridging necrosis
What conditions are associated with autoimmune hepatitis?
Recognised associations include other autoimmune disorders, hypergammaglobulinaemia and HLA B8, DR3.
What are the three types of autoimmune hepatitis?
What are the are first-line investigations which are expected to be normal in patients with suspected irritable bowel syndrome.
Full blood count, ESR, CRP, antibody testing for coeliac disease - endomysial antibodies or tissue transglutaminase
During infection what is an unreliable indicator of iron stored in the body ?
During infection, ferritin is an unreliable indicator of iron stored in the body as it is an acute phase protein. Transferrin saturation should be used instead
What are the causes of increased ferritin levels into 2 distinct categories?
The best test to see whether iron overload is present is transferrin saturation. Typically, normal values of < 45% in females and < 50% in males exclude iron overload.
The NICE guidelines for anaemia-iron deficiency (2013), state the following investigations:
1) Check full blood count: This has already been done as this patient has been identified as having anaemia so is a distractor answer.
2) If results show a low Hb and low MCV in a non-pregnant person check the ferritin level
Serum ferritin levels correlate with the total amount of iron stored in the body, with low levels indicating low iron stores and therefore iron deficiency anaemia. Iron deficiency anaemia can be caused by gastrointestinal causes such as blood loss from GI tract, peptic ulcers, gastric carcinoma or angiodysplasia. Gynaecological causes include menstruation and pregnancy. Malabsorption from Coeliac disease, gastrectomy or H.Pylori infection can also cause iron deficiency. As there are many causes, some more sinister than others, it is always good to investigate the causes of an anaemia.
It is important to note that ferritin levels can be elevated when inflammation or co-existing conditions such as liver disease, malignancy or hyperthyroidism are present thus giving spurious readings. In this case, as stated by NICE guidelines, a different measure of iron status should be considered such as iron, total iron binding capacity or transferrin saturation.
What is the cause of reduced ferritin levels?
Because iron and ferritin are bound the total body ferritin levels may be decreased in cases of iron deficiency anaemia.
Measurement of serum ferritin levels can be useful in determining whether an apparently low haemoglobin and microcytosis is truly caused by an iron deficiency state.
What is Pellagra?
Pellagra is a disease caused by a severe deficiency of niacin (vitamin B3) and/or tryptophan (an amino acid that can be converted into niacin). It’s characterized by the “four Ds”: dermatitis, diarrhea, dementia, and death (if untreated).
What are the characteristics of Pellagra?
It’s characterized by the “four Ds”: dermatitis, diarrhea, dementia, and death (if untreated).
What is beri beri and its subtypes?
Beriberi is a deficiency disease resulting from a lack of thiamine, also known as vitamin B1. Thiamine is essential for energy metabolism, nerve function, and heart health.
Beriberi is due to a thiamine (vitamin B1) deficiency and can be further categorized into wet beriberi (presenting with tachypnoea, dyspnoea and pedal oedema) and dry beriberi (presenting with pain, paresthesia and confusion). Wernicke-Korsakoff syndrome is a subtype of dry beriberi.
What is niacin/Vitamin B3 ?
Niacin is a water soluble vitamin of the B complex group. It is a precursor to NAD+ and NADP+ and hence plays an essential metabolic role in cells.
Biosynthesis
Hartnup’s disease: hereditary disorder which reduces absorption of tryptophan
carcinoid syndrome: increased tryptophan metabolism to serotonin
What are the features of
carcanoid tumour?
flushing (often the earliest symptom)
diarrhoea
bronchospasm
hypotension
right heart valvular stenosis (left heart can be affected in bronchial carcinoid)
other molecules such as ACTH and GHRH may also be secreted resulting in, for example, Cushing’s syndrome
pellagra can rarely develop as dietary tryptophan is diverted to serotonin by the tumour
What cardiac abnormalities are associated with carcanoid syndromes?
Carcinoid syndrome can affect the right side of the heart. The valvular effects are tricuspid insufficiency and pulmonary stenosis
What is the management of carcanoid syndromes?
somatostatin analogues e.g. octreotide
diarrhoea: cyproheptadine may help
What are the investogations for carcanoid syndromes?
urinary 5-HIAA
plasma chromogranin A y
What are carcanoid tumors?
A carcinoid is a slow-growing type of neuroendocrine tumor originating in the cells of the neuroendocrine system. In some cases, metastasis may occur. Carcinoid tumors of the midgut are associated with carcinoid syndrome.
What is Pauciarticular arthritis?
refers to arthritis affecting fewer than five joints. It can occur in both ulcerative colitis and Crohn’s disease as an extra-intestinal manifestation, without a significant difference in prevalence between the two conditions.
What are the extra-intestinal manifestations of inflammatory bowel disease?
Pauciarticular arthritis refers to arthritis affecting fewer than five joints. It can occur in both ulcerative colitis and Crohn’s disease as an extra-intestinal manifestation, without a significant difference in prevalence between the two conditions.
Osteoporosis, defined as a reduction in bone mineral density leading to an increased risk of fracture, can also occur as a complication of both UC and Crohn’s disease due to factors such as chronic inflammation, steroid use and malnutrition. However, there isn’t a clear distinction between these two diseases regarding their association with osteoporosis.
Episcleritis, which involves inflammation of the episclera (a thin layer on top of the white part of the eye), is another extra-intestinal manifestation that can be seen in both UC and Crohn’s disease. Again, there isn’t a significant difference in its occurrence between these two conditions.
Lastly, Erythema nodosum, a skin condition that results in red tender lumps usually on the shins, can occur as an extra-intestinal manifestation of inflammatory bowel diseases (IBD). It is more commonly associated with Crohn’s disease rather than ulcerative colitis.
Therefore, out of these options presented, primary sclerosing cholangitis stands out as being much more common in ulcerative colitis compared to Crohn’s disease.
What condiions are associated with Helicobacter pylori infection?
peptic ulcer disease
95% of duodenal ulcers
75% of gastric ulcers
gastric cancer
B cell lymphoma of MALT tissue (eradication of H pylori results causes regression in 80% of patients)
atrophic gastritis
What is the pathophysiology of Helicobacter pylori infection?
Helicobacter pylori is a Gram-negative bacteria associated with a variety of gastrointestinal problems, principally peptic ulcer disease.
Pathophysiology
Helicobacter pylori has 2 main mechanisms to survice in the acidic gastric environment:
chemotaxis away from low pH areas, using its flagella to burrow into the mucous lining to reach the epithelial cells underneath
secretes urease → urea converted to NH3 → alkalinization of acidic environment → increased bacterial survival
pathogenesis mechanism:
Helicobacter pylori releases bacterial cytotoxins (e.g. CagA toxin) → disruption of gastric mucosa
Where can can carcanoid tumors occur?
After confirming elevated urinary 5-HIAA levels, further investigations such as colonoscopy and CT abdomen should be considered for localisation of the primary carcinoid tumour and staging of disease. They would not be diagnostic of a carcinoid in the absence of a positive urinary 5-HIAA. Further investigations should be tailored to the patient’s clinical presentation as carcinoid tumours can arise from a variety of sources relating to the embryonic development of the gut. Foregut tumours (lung, thymus, stomach, or proximal duodenum) account for up to 25% of cases. Midgut tumours (small intestine, appendix or proximal colon) account for up to 50% and hindgut tumours (distal colon or rectum) account for approximately 15%.
What vitamin deficiencies is associated with cealiac disease?
Coeliac disease commonly presents with anaemia, but it is often a mixed picture. It causes a deficiency in iron, folate and vitamin B12 (although folate deficiency is more common than vitamin B12 deficiency).
B12 is absorbed in the terminal ileum. It requires the presence of intrinsic factor to be absorbed (absent in pernicious anaemia).
Folate is absorbed in the duodenum and jejunum.
Iron is mainly absorbed in the duodenum.
Other conditions associated with diarrhoea include:
thyrotoxicosis
laxative abuse
appendicitis
radiation enteritis
A 22-year-old man presents with crampy abdominal pain diarrhoea and bloating. He has just returned from a holiday in Egypt. He had been swimming in the local pool three weeks ago. He reports that he is opening his bowels 5 times a day. The stool floats in the toilet water, but there is no blood. What is the most likely cause?
Giardia lamblia causes fat malabsorption, therefore greasy stool can occur. It is resistant to chlorination, hence risk of transfer in swimming pools.
What is the most sensitive and specific lab finding for diagnosis of liver cirrhosis in those with chronic liver disease?
Thrombocytopenia (platelet count <150,000 mm^3)
‘Multiple factors, including splenic sequestration, reduced activity of the hematopoietic growth factor thrombopoietin, bone marrow suppression by chronic hepatitis C virus infection and anti-cancer agents, and antiviral treatment with interferon-based therapy, can contribute to the development of thrombocytopenia in cirrhotic patients’.
What are common causes of liver cirrhosis?
alcohol
non-alcoholic fatty liver disease (NAFLD)
viral hepatitis (B and C)
How can gastric carcinoma present?
Gastric carcinoma is the correct answer. The fatigue and weight loss, alongside the anaemia and elevated urea levels, make this the most likely answer. Gastric cancer can present with an upper gastrointestinal (GI) bleed which would result in raised urea due to digestion of blood. The patient’s dark, foul-smelling stools are indicative of digested blood being passed in the stool.
What is the gold standard investigation to cealiac disease diagnosis?
Small bowel biopsy is the correct answer. This patient is presenting with features of coeliac disease. Coeliac disease is an autoimmune condition that affects the small bowel causing villous cell atrophy. Whilst carrying out the IgA-tTG test is considered the first-line investigation, endoscopy and biopsy are the gold standard investigation for confirmation as histological examination can reveal the presence of typical changes associated with coeliac such as villous atrophy. This patient has signs of coeliac disease such as bloating, diarrhoea, and fatigue. The fatigue and pallor (as seen in this patient) often stem from the fact iron deficiency is common in patients with coeliac disease. Type 1 diabetes and coeliac disease are both autoimmune conditions and there is a well-established association between the two due to the shared genetic and autoimmune nature.
While haemochromatosis can certainly manifest in abnormal liver function tests with a raised ferritin, the transferrin saturation - calculated as (iron / TIBC) x 100 - is well below the 40% threshold for females (based on British Society of Haematology guidelines) which would prompt consideration of iron overload. Furthermore we would normally expect ferritin to be even higher (>1000 ug/L) in haemochromatosis. Note that milder elevations of serum ferritin is commonly seen in NAFLD, as seen here.
Alcoholic hepatitis is unlikely given her level of alcohol intake. NICE guidelines state that consumption of less than 20g (2.5 units) per day in women, and less than 30g (3.75 units) per day in men, is used as the cut-off to diagnose NAFLD
What are associating factors of non alcoholic fatty liver disease?
obesity
type 2 diabetes mellitus
hyperlipidaemia
jejunoileal bypass
sudden weight loss/starvation
What investigations are done for NAFLD?
NICE produced guidelines on the investigation and management of NAFLD in 2016. Key points:
there is no evidence to support screening for NAFLD in adults, even in at risk groups (e.g. type 2 diabetes)
the guidelines are therefore based on the management of the incidental finding of NAFLD - typically asymptomatic fatty changes on liver ultrasound
in these patients, NICE recommends the use of the enhanced liver fibrosis (ELF) blood test to check for advanced fibrosis
the ELF blood test is a combination of hyaluronic acid + procollagen III + tissue inhibitor of metalloproteinase 1. An algorithm based on these values results in an ELF blood test score, similar to triple testing for Down’s syndrome
An excellent review by Byrne et Al1 in 2018 reviewed the diagnosis and monitoring of NAFLD. It made the following suggestions if the ELF blood test was not available:
non-invasive tests may be used to assess the severity of fibrosis
these include the FIB4 score or NALFD fibrosis score
these scores may be used in combination with a FibroScan (liver stiffness measurement assessed with transient elastography)
this combination has been shown to have excellent accuracy in predicting fibrosis
Patients who are likely to have advanced fibrosis should be referred to a liver specialist. They will then likely have a liver biopsy to stage the disease more accurately.
What is the management of non alcoholic fatty liver disease?
the mainstay of treatment is lifestyle changes (particularly weight loss) and monitoring
there is ongoing research into the role of gastric banding and insulin-sensitising drugs (e.g. metformin, pioglitazone)
What is the Rockall score?
the Rockall score is used after endoscopy
provides a percentage risk of rebleeding and mortality
includes age, features of shock, co-morbidities, aetiology of bleeding and endoscopic stigmata of recent haemorrhage
Fluid restriction may be indicated for patients with ascites with…
serum sodium < 125mmol/L, but would not be appropriate as a stand-alone intervention for this patient.
What are the complications of GORD?
oesophagitis
ulcers
anaemia
benign strictures
Barrett’s oesophagus
oesophageal carcinoma
The correct answer is Achalasia. Achalasia is a primary oesophageal motility disorder characterised by the failure of relaxation of the lower oesophageal sphincter and absence of normal peristalsis in the body of the oesophagus. It is not a complication of gastro-oesophageal reflux disease (GORD).
Now let’s discuss each incorrect answer:
Oesophageal carcinoma can indeed be a complication of GORD. Chronic exposure to gastric acid can lead to metaplastic changes in the oesophageal epithelium, known as Barrett’s oesophagus, which increases the risk for development of oesophageal adenocarcinoma.
Barrett’s oesophagus is a well-recognised complication of chronic GORD. It occurs due to repeated injury to the squamous epithelium lining the lower oesophagus from refluxed gastric acid, leading to replacement with columnar epithelium that predisposes to malignancy.
Anaemia could also be a complication of GORD, although it is less common than others. This could happen due to chronic blood loss from erosive esophagitis or from iron deficiency secondary to poor absorption caused by proton pump inhibitor therapy often used in treating GORD.
Lastly, benign strictures, also known as peptic strictures, are another recognised complication of GORD. They occur due to fibrotic healing following repeated episodes of inflammation caused by acid reflux, leading to narrowing and potential obstruction in the lower part of the oesophagus.
What is management of GORD?
Gastro-oesophageal reflux disease (GORD) may be defined as symptoms of oesophagitis secondary to refluxed gastric contents
NICE recommend that GORD which has not been investigated with endoscopy should be treated as per the dyspepsia guidelines.
Endoscopically proven oesophagitis
full dose proton pump inhibitor (PPI) for 1-2 months
if response then low dose treatment as required
if no response then double-dose PPI for 1 month
Endoscopically negative reflux disease
full dose PPI for 1 month
if response then offer low dose treatment, possibly on an as-required basis, with a limited number of repeat prescriptions
if no response then H2RA or prokinetic for one month
Wiskott-Aldrich syndrome
is an X-linked recessive disorder that primarily affects males. It presents in infancy or early childhood with eczema, recurrent infections (due to immunodeficiency), and thrombocytopenia with small platelets leading to bleeding problems.
Friedreich’s ataxia
is a neurodegenerative disorder that typically presents before adolescence with progressive gait instability (ataxia), dysarthria, loss of deep tendon reflexes and hypertrophic cardiomyopathy.
What drug causes haemolytic anaemia?
Sulphasalazine. This drug, used in the treatment of ulcerative colitis and rheumatoid arthritis, can cause haemolytic anaemia with Heinz bodies.
