Gastro Flashcards
What is Eosinophilic Oesophagitis?
Eosinophilic oesophagitis is characterised by an allergic inflammation of the oesophagus. An oesophageal biopsy will show dense infiltrate of eosinophils in the epithelium. Although this disease is relatively poorly understood, it is thought to be caused by an allergic reaction to ingested food. The resulting oesophageal inflammation results in pain and dysphagia, amongst other symptoms.
Which gender and age group is Eosinophilic oesophagitis common in?
3:1 male:female ratio
Average age at diagnosis is 30-50 years old
what are the risk factors for developing eosinophilic oesophagitis?
Allergies/ asthma: suffering from food/ environmental allergies or atopic dermatitis and asthma increases the risk of diagnosis
Male sex
Family history of eosinophilic oesophagitis or allergies
Caucasian race
Age between 30-50
Coexisting autoimmune disease e.g. coeliac disease
what are the symptoms and signs of eosinophilic oesophagitis?
Patients typically present with a subacute onset of:
In children, disease presents with failure to thrive due to food refusal
Adults often experience dysphagia, strictures/ fibrosis (56%), food impaction (55%), regurgitation/ vomiting, anorexia
Signs:
Signs are minimal and suspicion of this diagnosis relies mainly on the reported symptoms, past medical history and exclusion of other differential diagnoses e.g. GORD
Weight loss
What are the investigations of eosinophilic oesophagits?
Endoscopy - histological analysis.
There must be more than 15 eosinophils per high power microscopy field to diagnose the condition. Other findings on endoscopy include reduced vasculature, thick mucosa, mucosal furrows, strictures and laryngeal oedema. Histologically, the diagnosis is made more likely in the presence of epithelial desquamation, eosinophilic microabscesses, and abnormally long papillae
PPI trial: persistence of eosinophilia and no improvement of symptoms after trialling a proton pump inhibitor. This can help the clinician differentiate between eosinophilic oesophagitis and GORD, which can be a tricky task
How is eosinophilic oesophagitis managed?
dietary modification
There are three methods available to begin excluding food from the diet. The elemental diet (involves taking an amino acid mixture for six weeks), exclusion of six food groups (involves avoiding foods commonly associated with allergy e.g. nuts, soy, egg, seafood), and the targeted elimination diet (involves excluding foods that have been identified as allergy-triggering during allergy testing).
Topical steroids e.g. fluticasone and budesonide are options when dietary modification fails. This requires the patient to swallow solutions of the steroid to line the oesophagus. This should be done for eight weeks before being reassessed
Oesophageal dilatation: 56% of patients require this at some point in their treatment to reduce the symptoms associated with oesophageal strictures
what are the complications of eosinophilic oesophagitis
Strictures of the oesophagus (56%)
Impaction: 55% of patients experience this, and 38% of these require endoscopic removal of the impaction
Mallory-Weiss tears
what is ocreotide and when is it used?
A synthetic somatostatin analogue that is licensed to treat symptoms associated with carcinoid tumours with features of carcinoid syndrome, particularly flushing and diarrhoea. It reduces the secretion of serotonin which is responsible for these symptoms. This peptide hormone is naturally produced by D (delta) cells in the pancreas and stomach and is thought to act to reduce acid secretion from gastric parietal cells.
what are the hormones involved in food digestion?
Gastrin, CCK, Secretin, VIP, somatostatin,
Where is gastrin produced, what it the stimulus and what are its actions?
Produced - G cells in the antrum of the stomach
Stimulus - distension of the stomach, vagus nerves (mediated by gastrin releasing peptide), luminal peptides/amino acids. Inhibited by low antral pH, somatostatin.
Actions - increases acid secretion by gastric parietal cells, pepsinogen and IF secretion, increases gastric motility, stimulates parietal cell maturation
Where is CCK produced, what it the stimulus and what are its actions?
Produced - I cells in the upper small intestines
Stimulus - patirally digested proteins and triglycerides
Actions - increases secretion of enzyme rich fluid from the pacreas, contraction of the gallbladder and relaxation of sphincter of Oddi, decreases gastric emptying, trophic effect on the pancreatic acinar cells, induces satiety.
Where is Secretin produced, what it the stimulus and what are its actions?
Source: S cells in upper small intestine
Stimulus - acidic chyme, fatty acids
Actions - Increases secretion of bicarbonate-rich fluid from pancreas and hepatic duct cells, decreases gastric acid secretion, trophic effect on pancreatic acinar cells
Where is VIP produced, what it the stimulus and what are its actions?
Source: small intestine, pancreas
Stimulus: Neural
Actions: stimulates secretion by pancreas and intestines, inhibits acid production
Where is Somatostatin produced, what it the stimulus and what are its actions?
Produced - D Cells in the pancreas & Stomach
Stimulus - Fat, bile salts and glucose in the intestinal lumen
Action: Decreases acid and pepsin secretion, decreases gastrin secretion, decreases pancreatic enzyme secretion, decreases insulin and glucagon secretion
inhibits trophic effects of gastrin, stimulates gastric mucous production
How is Wilson’s disease inherited?
AR
what is Wilson’s disease?
characterized by excessive copper deposition in the tissues
Metabolic abnormalities include increased copper absorption from the small intestine and decreased hepatic copper excretion
The onset of symptoms is usually between 10 - 25 years. Children usually present with liver disease whereas the first sign of disease in young adults is often neurological disease
What gene and chromosome is the defect in Wilsons disease?
Wilson’s disease is caused by a defect in the ATP7B gene located on chromosome 13.
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 are the investigations for Wilson’s 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
What is the management of Wilson’s 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 is Purtscher retinopathy?
A condition that may be seen following head trauma and in conditions such a acute pancreatitis, fat embolization, amniotic fluid embolization and vasculitic disease.
Cotton wool spots are seen on fundoscopy
What are the scoring systems to identify the cases of severe acute pancreatitis?
Ranson score, Glasgow score and APACHE II.
Common factors in these scoring systems include:
age > 55 years
hypocalcaemia
hyperglycaemia
hypoxia
neutrophilia
elevated LDH and AST
How is drug induced liver disease devided?
epatocellular, cholestatic or mixed.
what drugs cause a hepatocellular liver injury?
paracetamol
sodium valproate, phenytoin
MAOIs
halothane
anti-tuberculosis: isoniazid, rifampicin, pyrazinamide
statins
alcohol
amiodarone
methyldopa
nitrofurantoin
what drugs 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 is the most common type of inherited colorectal cancer?
Hereditary non-polyposis colorectal carcinoma (HNPCC), also known as Lynch syndrome.
what are the three types of colon cancer?
sporadic (95%)
hereditary non-polyposis colorectal carcinoma (HNPCC, 5%)
familial adenomatous polyposis (FAP, <1%)
what is sporadic colon cancer due to?
Studies have shown that sporadic colon cancer may be due to a series of genetic mutations. For example, 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 in Lynch syndrome?
AD condition
patients usually develop cancers in the proximal colon, which are poorly differentiated and highly aggressive.
The most common genes involved are
MSH2 (60% of cases)
MLH1 (30%)
What is the criteria used to aid the diagnosis of Hereditary non-polyposis colorectal carcinoma
The Amsterdam criteria are sometimes used to aid diagnosis:
at least 3 family members with colon cancer
the cases span at least two generations
at least one case diagnosed before the age of 50 years
What is FAP?
Familial adenomatous polyposis
AD condition
hundreds of polyps form by the age of 30-40.
Patients inevitably develop a carcinoma
due to a mutation in a tumour suppressor gene celled adenomatous polyposis coli gene (APC), located on chromosome 5.
Genetic testing can be done by analysing DNA from a patient’s white blood cells
How is FAP managed?
Patients generally have a total proctocolectomy with ileal pouch anal anastomosis (IPAA) formation in their twenties.
However they are also at risk from duodenal tumours
What is the management for FAP
Patients generally have a total proctocolectomy with ileal pouch anal anastomosis (IPAA) formation in their twenties.
How can ascites be devided?
The causes of ascites can be grouped into those with a <11 g/L or a gradient >11g/
What does anascitic fluid with a SAAG >11g/L indicates
portal hypertension
what causes acites with a SAAG > 11g/L
Liver disorders are the most common cause
cirrhosis/alcoholic liver disease
acute liver failure
liver metastases
Cardiac
right heart failure
constrictive pericarditis
Other causes
Budd-Chiari syndrome
portal vein thrombosis
veno-occlusive disease
myxoedema
What causes ascites with a SAAG < 11g/L
Hypoalbuminaemia
nephrotic syndrome
severe malnutrition (e.g. Kwashiorkor)
Malignancy
peritoneal carcinomatosis
Infections
tuberculous peritonitis
Other causes
pancreatitis
bowel obstruction
biliary ascites
postoperative lymphatic leak
serositis in connective tissue diseases
How are ascites managed?
reducing dietary sodium
fluid restriction is sometimes recommended if the sodium is < 125 mmol/L
aldosterone antagonists: e.g. spironolactone
loop diuretics are often added. Some authorities only add loop diuretics in patients who don’t respond to aldosterone antagonists whereas other authorities suggest starting both types of diuretic on the first presentation of ascites
drainage if tense ascites (therapeutic abdominal paracentesis)
large-volume paracentesis for the treatment of ascites requires albumin ‘cover’. Evidence suggests this reduces paracentesis-induced circulatory dysfunction and mortality
paracentesis induced circulatory dysfunction can occur due to large volume paracentesis (> 5 litres). It is associated with a high rate of ascites recurrence, development of hepatorenal syndrome, dilutional hyponatraemia, and high mortality rate
prophylactic antibiotics to reduce the risk of spontaneous bacterial peritonitis. 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’
a transjugular intrahepatic portosystemic shunt (TIPS) may be considered in some patients
How is the severity of UC classified?
mild: < 4 stools/day, only a small amount of blood
moderate: 4-6 stools/day, varying amounts of blood, no systemic upset
severe: >6 bloody stools per day + features of systemic upset (pyrexia, tachycardia, anaemia, raised inflammatory markers)
How do you induce remission in mild-moderate UC?
proctitis
topical (rectal) aminosalicylate: for distal colitis rectal mesalazine has been shown to be superior to rectal steroids and oral aminosalicylates
if remission is not achieved within 4 weeks, add an oral aminosalicylate
if remission still not achieved add topical or oral corticosteroid
proctosigmoiditis and left-sided ulcerative colitis
topical (rectal) aminosalicylate
if remission is not achieved within 4 weeks, add a high-dose oral aminosalicylate OR switch to a high-dose oral aminosalicylate and a topical corticosteroid
if remission still not achieved stop topical treatments and offer an oral aminosalicylate and an oral corticosteroid
extensive disease
topical (rectal) aminosalicylate and a high-dose oral aminosalicylate:
if remission is not achieved within 4 weeks, stop topical treatments and offer a high-dose oral aminosalicylate and an oral corticosteroid
how do you induce remission in severe UC?
should be treated in hospital
IV steroids are usually given first-line
IV ciclosporin may be used if steroids are contraindicated
if after 72 hours there has been no improvement, consider adding IV ciclosporin to IV corticosteroids or consider surgery
How do you maintain remission in UC?
Following a mild-to-moderate ulcerative colitis flare
proctitis and proctosigmoiditis
topical (rectal) aminosalicylate alone (daily or intermittent) or
an oral aminosalicylate plus a topical (rectal) aminosalicylate (daily or intermittent) or
an oral aminosalicylate by itself: this may not be as effective as the other two options
left-sided and extensive ulcerative colitis
low maintenance dose of an oral aminosalicylate
Following a severe relapse or >=2 exacerbations in the past year
oral azathioprine or oral mercaptopurine
what kind of bacteria is c-diff
Clostridioides difficile is a Gram positive rod
How is C-diff severity classified?
Mild -normal WCC
Moderate - ↑ WCC ( < 15 x 109/L)
Typically 3-5 loose stools per day
Severe - ↑ WCC ( > 15 x 109/L)
or an acutely ↑ creatinine (> 50% above baseline)
or a temperature > 38.5°C
or evidence of severe colitis(abdominal or radiological signs)
Life-threatening - Hypotension
Partial or complete ileus
Toxic megacolon, or CT evidence of severe disease
How is C.diff diagnosed
is made by detecting C. difficile toxin (CDT) in the stool
C. difficile antigen positivity only shows exposure to the bacteria, rather than current infection
How is c.diff managed?
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
Other therapies
bezlotoxumab is a monoclonal antibody which targets C. difficile toxin B
NICE do not currently support its use to prevent recurrences as it is not cost-effective
faecal microbiota transplant
may be considered for patients who’ve had 2 or more previous episodes
what are the features of hepatic encephalopathy?
confusion, altered GCS (see below)
asterixis: ‘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)
what is the grading of hepatic encephalopathy?
Grade I: Irritability
Grade II: Confusion, inappropriate behaviour
Grade III: Incoherent, restless
Grade IV: Coma
what are the 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)
How is hepatic encephalopathy managed?
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
What are the features of auto-immune hepatitis?
commonly seen in young females
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 are the 3 types of autoimmune hepatitis?
Type 1 - Anti-nuclear antibodies (ANA) and/or anti-smooth muscle antibodies (SMA)
Affects both adults and children
Type II - Anti-liver/kidney microsomal type 1 antibodies (LKM1)
Affects children only
Type III - Soluble liver-kidney antigen
Affects adults in middle-age
How do you manage auto-immune hepatitis?
steroids, other immunosuppressants e.g. azathioprine
liver transplantation
what are the features of Crohn’s disease?
presentation may be non-specific symptoms such as weight loss and lethargy
diarrhoea
the most prominent symptom in adults
Crohn’s colitis may cause bloody diarrhoea
abdominal pain: the most prominent symptom in children
perianal disease: e.g. Skin tags or ulcers
extra-intestinal features are more common in patients with colitis or perianal disease
what are exta-intestinal features of Crohn’s?
Related to disease activity
Arthritis: pauciarticular, asymmetric
Erythema nodosum
Episcleritis
Osteoporosis
Unrelated to disease activity
Arthritis: polyarticular, symmetric
Uveitis
Pyoderma gangrenosum
Clubbing
Primary sclerosing cholangitis
