Medicine Flashcards
What is the treatment of choice for prophylaxis of variceal haemorrhage?
Propanolol
What causes achalasia?
Failure of oesophageal peristalsis and of relaxation of the lower oesophageal sphincter (LOS) due to degenerative loss of ganglia from Auerbach’s plexus i.e. LOS contracted, oesophagus above dilated.
What are the clinical features of achalasia?
- dysphagia of BOTH liquids and solids
- typically variation in severity of symptoms
- heartburn
- regurgitation of food
- may lead to cough, aspiration pneumonia etc
- malignant change in small number of patients
What are the investigations of achalasia?
- oesophageal manometry (excessive LOS tone which doesn’t relax on swallowing, considered the most important diagnostic test)
- barium swallow shows grossly expanded oesophagus, fluid level, ‘bird’s beak’ appearance)
- chest x-ray (wide mediastinum, fluid level)
What are the treatments available 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-effects
Inheritance mode of wilson’s disease
Autosomal recessive
What is Wilson’s disease?
Wilson’s disease is an autosomal recessive disorder characterised by excessive copper deposition in the tissues. Metabolic abnormalities include increased copper absorption from the small intestine and decreased hepatic copper excretion. Wilson’s disease is caused by a defect in the ATP7B gene located on chromosome 13.
Gene and chromosome defective in Wilson’s disease?
ATP7B chromosome 13
Age of onset and characteristics of Wilson’s disease
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
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’s the management for 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 are the features of Crohn’s disease?
- Diarrhoea usually non-bloody
- Weight loss more prominent
- Upper gastrointestinal symptoms, mouth ulcers, perianal disease
- Abdominal mass palpable in the right iliac fossa
- Gallstones are more common secondary to reduced bile acid reabsorption. Oxalate renal stones are formed as the impaired bile acid rebsorption (ileum) increases the loss calcium in the bile. Calcium normally binds oxalate.
Complications
- Obstruction, fistula, colorectal cancer (risk higher in UC)
Pathology
- Lesions may be seen anywhere from the mouth to anus
- Skip lesions may be present
Histology
- Inflammation in all layers from mucosa to serosa
- increased goblet cells
- granulomas
Endoscopy
- Deep ulcers, skip lesions - ‘cobble-stone’ appearance
Radiology (Small bowel enema)
- high sensitivity and specificity for examination of the terminal ileum
- strictures: ‘Kantor’s string sign’
- proximal bowel dilation
- ‘rose thorn’ ulcers
- fistulae
What are the features of Ulcerative colitis?
- Bloody diarrhoea more common than in crohns
- Abdominal pain in the left lower quadrant
- Tenesmus
- Primary sclerosing cholangitis more common
Complications
- Risk of colorectal cancer high in UC than CD
Pathology
- Inflammation always starts at rectum and never spreads beyond ileocaecal valve
- Continuous disease
Histology
- No inflammation beyond submucosa (unless fulminant disease) - inflammatory cell infiltrate in lamina propria
- neutrophils migrate through the walls of glands to form crypt abscesses
- depletion of goblet cells and mucin from gland epithelium
- granulomas are infrequent
Endoscopy
- Widespread ulceration with preservation of adjacent mucosa which has the appearance of polyps (‘pseudopolyps’)
Radiology (Barium enema)
- loss of haustrations
- superficial ulceration, ‘pseudopolyps’
- long standing disease: colon is narrow and short -‘drainpipe colon’
Bacterial classification of c diff
Gram positive bacillus
Clostridium difficile
It produces an exotoxin which causes intestinal damage leading to a syndrome called pseudomembranous colitis.
Risk factors for c diff
- Second and third-generation cephalosporins are now the leading cause of C. difficile
- clindamycin
- PPIs
Pathophysiology of c diff
- anaerobic gram-positive, spore-forming, toxin-producing bacillus
- transmission: via the faecal-oral route by ingestion of spores
- releases two exotoxins (toxin A and toxin B) that act on intestinal epithelial cells and inflammatory cells resulting in colitis
What are the features of c diff?
- diarrhoea
- abdominal pain
- a raised white blood cell count (WCC) is characteristic
- if severe toxic megacolon may develop
What’s the severity scale for c diff?
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 do you diagnose c diff?
- 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?
Current antibiotic therapy should be reviewed and antibiotics stopped if possible.
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
How do you prevent the spread of c diff?
- isolation in side room: the patient should remain isolated until there has been no diarrhoea (types 5-7 on the Bristol Stool Chart) for at least 48 hours
- all staff should wear disposable gloves and an apron during any contact with patients known to have C. difficile
- hand washing is also essential - alcohol gel does not kill the spores of C. difficile
How do aminosalicylate drugs work? What are they used for?
5-aminosalicyclic acid (5-ASA) is released in the colon and is not absorbed. It acts locally as an anti-inflammatory. The mechanism of action is not fully understood but 5-ASA may inhibit prostaglandin synthesis
Use: colitis and crohns
What is sulphasalazine? What are the side effects?
- a combination of sulphapyridine (a sulphonamide) and 5-ASA
- 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 (GI upset, headache, agranulocytosis, pancreatitis, interstitial nephritis)
- Aminosalicylates are associated with a variety of haematological adverse effects, including agranulocytosis - FBC is a key investigation in an unwell patient taking them.
What is mesalazine and what are the side effects?
- a delayed release form of 5-ASA
- sulphapyridine side-effects seen in patients taking sulphasalazine are avoided
- mesalazine is still however associated with side-effects such as GI upset, headache, agranulocytosis, pancreatitis*, interstitial nephritis
*pancreatitis is 7 times more common in patients taking mesalazine than sulfasalazine - Aminosalicylates are associated with a variety of haematological adverse effects, including agranulocytosis - FBC is a key investigation in an unwell patient taking them.
What is osalazine?
two molecules of 5-ASA linked by a diazo bond, which is broken by colonic bacteria
Features of whipples disease
Diarrhoea, weight loss, lymphadenopathy, arthralgia, fever
D WALF
What is the underlying aetiology of Budd-Chiari syndrome?
Thrombosis of the hepatic vein
Severe vomiting –> haematemesis in a question is most likely to indicate:
Mallory Weiss syndrome
What is gardners syndrome? What are the features of gardner’s syndrome?
A variant of FAP called Gardner’s syndrome can also feature osteomas of the skull and mandible, retinal pigmentation, thyroid carcinoma and epidermoid cysts on the skin
Multiple colonic polyps, osteomas, epidermoid cysts
What are the types of colon cancer?
- sporadic (95%)
- hereditary non-polyposis colorectal carcinoma (HNPCC, 5%)
- familial adenomatous polyposis (FAP, <1%)
