Gastroenterology Flashcards
1
Q
What is Crohn’s disease?
A
Definition – chronic inflammatory disease occurring sporadically anywhere in the GI tract characterised by granulomatous transmural inflammation, most commonly affecting the terminal ileum. Typically presents in late adolescence or early adulthood
2
Q
What causes Crohn’s disease?
A
Cause – not fully understood but thought to be due to an abnormal reaction of the immune system to abnormal gut flora in those with a genetic susceptibility
3
Q
How does Crohn’s disease present? (think particularly about how this is different to UC)
A
Diarrhoea (less likely to be bloody than UC) and abdominal pain (often post-prandial)
Weight loss (more prominent than in UC)
Fatigue, malaise, malabsorption and vitamin deficiency and anorexia
Mouth ulcers
Perianal disease – abscess, fistulae, strictures, and skin tags
Abdominal mass
Bowel obstruction and fistulas
Lesions anywhere from mouth to anus with skip lesions
Clubbing
4
Q
What associated conditions and presentations might be seen alongside classical Crohn’s features?
A
Gallstones are more common secondary to reduced bile acid absorption
Oxalate renal stones and liver disease due to the above issue
Arthritis
Increased risk of bowel caner
Osteoporosis
Erythema nodosum and pyoderma gangrenosum
Episcleritis (more common in CD) and uveitis (more common in UC)
5
Q
How should suspected Crohn’s disease be investigated?
A
- Endoscopy (colonoscopy) showing deep ulcers, skip lesions and cobble stone appearance
- Biopsy/Histology – inflammation in all layers, increased goblet cells and granulomas
- Abdominal x-ray with small bowel enema showing strictures (Kantor’s string sign), proximal bowel dilation, rose thorn ulcers, skip lesions, fistulae, and thickened bowel wall
- Stool microscopy and culture
- Raised CRP/ESR, faecal calprotectin and WCC
- FBC, B12, folate and haematinics for anaemia
- LFTs and U&Es and vit D levels
6
Q
What two bits of general advice should be given to all Crohn’s disease patients?
A
Stop smoking and avoid NSAIDs as they can exacerbate
7
Q
How should you induce a remission in a Crohn’s patient?
A
- Glucocorticoids (prednisolone first line or hydrocortisone/methylprednisolone IV if severe) to induce remission with reducing regimen or 5-ASA drugs such as mesalazine are second line to induce remission
- Azathioprine/Methotrexate used as an add-on to induce remission but not alone
- Infliximab used in refractory disease and fistulating Crohn’s alongside azathioprine or methotrexate
- Metronidazole for isolated peri-anal disease
8
Q
What should you monitor during a hospital stay for someone with a Crohn’s flare?
A
- Stool chart for frequency and consistency
* Routine bloods as above
9
Q
How should remission be maintained in Crohn’s?
A
- Azathioprine or mercaptopurine
- Methotrexate
- 5-ASA drugs such as mesalazine if previous surgery
10
Q
What surgery is often required in Crohn’s?
A
Majority of patient will eventually require surgery, usually Ileocaecal resection.
Colonic resection is usually not indicated as recurrence rate is high.
11
Q
What is ulcerative colitis?
A
Definition – superficial inflammatory reaction that always starts at the rectum
and never extends past the Ileocaecal valve, continuous disease due to haemorrhagic colonic mucosa +/- pseudopolyps formed by inflammation. Peak incidence 15-25 years and 55-65 years.
12
Q
What causes ulcerative colitis?
A
Cause – thought to be inappropriate immune response against abnormal colonic flora in genetically susceptible individuals
13
Q
What are the clinical features of ulcerative colitis?
A
Bloody diarrhoea and mucus
Crampy abdominal pain, typically in left lower quadrant
Often painless as mucosa has no nerve endings
Urgency and tenesmus suggesting rectum involved
Weight loss (more prominent in CD), malaise, fever and anorexia
Inflammation does not spread beyond submucosa
Clubbing
14
Q
How are ulcerative colitis flares categorised?
A
Mild – <4 stools daily with/without blood, no systemic disturbance, and normal inflammatory markers
Moderate – 4-6 stools a days with minimal systemic disturbance
Severe – >6 stools a day containing blood and systemic disturbance – fever, tachycardia, abdominal pain, distention, reduced bowel sounds, anaemia, and hypoalbuminemia. Be aware of toxic megacolon.
15
Q
What are the associated conditions and features of someone with Ulcerative colitis?
A
Primary sclerosing cholangitis more common
Increased risk of colorectal cancer compared to CD
Erythema nodosum and pyoderma gangrenosum
Arthritis
Episcleritis (more common in CD) and uveitis (more common in UC)
Osteoporosis
16
Q
How should suspected ulcerative colitis be investigated?
A
- Endoscopy – widespread ulceration with preservation of adjacent mucosa causing a pseudopolyps appearance
- Biopsy/Histology – no spread beyond submucosa, inflammatory cell infiltrate in lamina propria, neutrophil migration to form crypt abscess, depletion of goblet cells, infrequent granulomas
- Abdominal X-ray with barium enema showing loss of haustra, superficial ulceration (pseudopolyps) and drainpipe colon as disease is long standing and to rule out toxic megacolon – transverse colon > 6cm in combination with systemic upset
- Stool microscopy and culture
- Raised CRP/ESR, faecal calprotectin and WCC
- FBC, B12, folate and haematinics for anaemia
- LFTs and U&Es and vit D levels
17
Q
How do you induce remission in someone with mild-moderate ulcerative colitis?
A
Inducing Remission
Mild-moderate disease
Proctitis
• Topical aminosalicylate
• If remission not achieved within 4 weeks, then add oral aminosalicylate
• If remission still not achieved, then add a topical or oral steroid.
Proctosigmoiditis and left sided UC
• Topical aminosalicylate
• If remission not achieved by 4 weeks adding high dose oral aminosalicylate OR switching to high dose aminosalicylate and 4-8 weeks of a topical corticosteroid
• If remission still not achieved stop topicals and add oral aminosalicylate and oral corticosteroid
Extensive disease
• Topical aminosalicylate and high dose oral aminosalicylate
• If remission not achieved within 4 weeks stop topicals and add oral corticosteroid for 4-8 weeks
18
Q
How do you induce remission in someone with severe ulcerative colitis?
A
Severe colitis
• Treat in hospital as can be life threatening
• IV steroids (IV hydrocortisone or methylprednisolone) or IV ciclosporin if steroids contraindicated
• If no improvement after 72 hours consider adding IV ciclosporin or surgery
• Infliximab can be used if ciclosporin cannot
• If toxic megacolon, then manage aggressively with medical treatment for 24-72 hours and if no improvement in this time then a colectomy is performed
19
Q
What should you monitor during a hospital admission for a ulcerative colitis flare?
A
- Stool chart for frequency and consistency
* Routine bloods as above
20
Q
How is remission maintained in ulcerative colitis?
A
Maintaining remission
Mild-moderate flare
• Proctitis and proctosigmoiditis – topical/oral aminosalicylate OR both
• Left sided and extensive UC – low maintenance dose oral aminosalicylate
Severe or >2 exacerbation in past year
• Oral azathioprine or oral mercaptopurine
• Infliximab or adalimumab if intolerant of immunomodulation
Methotrexate NOT RECOMMENDED
21
Q
What surgery is required in ulcerative colitis?
A
Needed in about 1/5 if total failure of medical therapy or fulminant colitis with toxic dilatation or perforation. Completion proctectomy (permanent stoma) or ileo-anal pouch (can have stoma reversal but can get infection so give antibiotics for 2 weeks).
22
Q
What is Coeliac’s disease?
A
Definition – Example of malabsorption caused by an autoimmune condition with sensitivity to gluten. Repeated exposure to gluten leads to villus atrophy and malabsorption. Affects 1 in 100 people and commonly misdiagnosed as irritable bowel syndrome. More common in women
23
Q
What are the risk factors for Coeliac’s disease?
A
Other autoimmune disease such as thyroid disease, T1DM, first degree relative with coeliac Dermatitis herpetiformis (itchy burning blisters on elbows, scalp, shoulders, and ankles) Usually presents prior to 3 years
24
Q
What are the clinical features of Coeliac’s disease?
A
Chronic or intermittent diarrhoea (often particularly smelly)
Failure to thrive or faltering growth
Persistent or unexplained GI symptoms
Prolonged fatigue
Recurrent abdominal pain cramping or distention
Unexplained iron deficiency anaemia
25
How is Coeliac's disease diagnosed?
Immunoglobulin A-tissue transglutaminase or anti-endomysial (NICE) and anti-gliadin (not recommended by NICE) antibodies
Duodenal or Jejunal biopsy showing subtotal villous atrophy, crypt hyperplasia and infiltration of lymphocytes
Note prior to testing patients need to be eating gluten for 6 weeks
Other investigations
FBC and blood smear
26
How is Coeliac's disease managed?
Gluten free diet
Check compliance by testing for antibodies
Pneumococcal vaccine due to Hyposplenism and influenza if patient requests
Calcium and vit D supplementation
27
What complications can occur as a result of Coeliac's disease?
Malabsorption and malnutrition
Anaemia from iron, folate (more common than B12) and B12
Hyposplenism
Osteoporosis and Osteomalacia
Lactose intolerance
Enteropathy-associated T-cell lymphoma of small intestine
Subfertility
28
How is a Coeliac's crisis managed?
Rehydration and correction of electrolyte balance
| Steroids if needed
29
What is the definition of traveler's diarrhoea and what are the common causes?
Traveller’s diarrhoea = 3 loose to watery stools in 24 hours with or without one or more of abdominal cramps, nausea vomiting or blood in the stools. Typically causes be E.Coli.
30
What is the definition of acute food poisoning, and what are the common causes?
Acute food poisoning =sudden onset of nausea, vomiting and diarrhoea after the ingestion of a toxin. Typically causes by staph aureus, bacillus cereus or clostridium perfingens.
31
What is the typical presentation of E.coli gastroenteritis?
E.Coli – recent travel, nausea, watery stools and abdominal cramps
32
What is the typical presentation of giardiasis gastroenteritis?
Giardiasis – prolonged non-bloody diarrhoea
33
What is the typical presentation of cholera gastroenteritis?
Cholera – profuse watery diarrhoea, severe dehydration, and weight loss
34
What is the typical presentation of shigella gastroenteritis?
Shigella – bloody diarrhoea, vomiting and abdominal pain
35
What is the typical presentation of staph aureus gastroenteritis?
Staph Aureus – severe vomiting and short incubation period
36
What is the typical presentation of campylobacter gastroenteritis?
Campylobacter – flu like prodrome, followed by abdominal pain, fever, diarrhoea (may be bloody), can mimic appendicitis and can cause Guillain barre syndrome
37
What is the typical presentation of bacillus cereus gastroenteritis?
Bacillus cereus – vomiting with 6 hours typically with rice OR diarrhoeal illness occurring after 6 hours.
38
What is the typical presentation of amoebiasis gastroenteritis?
Amoebiasis – gradual onset blood diarrhoea, abdominal pain and tenderness which may last for several week
39
What is norovirus?
AKA the winter vomiting bug. Transmitted by faecal oral route usually with virus becoming aerosolized with vomiting or flushing toilet
40
What are the clinical features of norovirus?
Nausea, vomiting, diarrhoea, headache, fever, and myalgia
| Vomiting is sudden onset and symptoms usually for a short duration
41
How should norovirus be investigated?
Stool culture and PCR
42
How should you manage a patient with norovirus in a hospital?
Limit transmission by isolation of infected and good hand hygiene
Symptoms usually self-resolve within 72 hours
Rehydration and electrolytes
43
What are the common differnetials for someone suspected of having norovirus?
Salmonella – often causes bloody diarrhoea and high fever
Rotavirus – predominantly in children
E. Coli – longer incubation period and causes severe abdominal cramping unlike norovirus
44
What is clostridium difficile
Gram positive rod that produces an exotoxin which causes intestinal damage leading to pseudomembranous colitis. Antibiotic use is a major cause of C.Diff diarrhoea in hospitals, particularly clindamycin and 2nd and 3rd generation cephalosporins. Other risk factors include PPIs.
45
What are the clinical features of clostridium difficile?
Diarrhoea
Abdominal pain
Raised WCC
Sever toxic megacolon
46
How should a potential c.diff infection be investigated?
Faecal culture and detection of clostridium difficile toxin (CDT)
C.Diff antigen positive only shows exposure rather than infection
47
Describe the severity index for classifying C.diff infection?
* Mild – normal WCC
* Moderate – WCC<15, 3-5 loose stools
* Severe – WCC > 15, acute creatinine rise >50% baseline, Temp > 38.5 or evidence of severe colitis from x-ray or examination
* Life-threatening – hypotension, partial or complete ileus, toxic megacolon or CT evidence of severe disease.
48
What is the management of C.Diff infections?
Isolation and barrier nursed with good hand hygiene
Oral metronidazole for 10-14 days if first episode
If severe, second episode or not responding, then oral vancomycin
Fidaxomicin – can also be trialed particularly if multiple co-morbidities
If life threatening then combination of oral vancomycin and IV metronidazole
49
Define diverticulas, diverticular disease and diverticulitis?
Diverticulitis – outpouchings of the bowl (diverticula) that are inflamed and ulcerated
Diverticulosis – presence of diverticula
Diverticula disease – diverticula that are symptomatic
50
How common are diverticula/diverticulosis?
Very common with 30% of westerners having diverticula by age 60, only 25% will experience symptoms and 75% of these will experience episode of diverticulitis.
51
What causes diverticula to form?
Occur due to increase intra-colonic pressure and usually occurs along the weaker portions of the wall such as where the penetrating arteries enter.
52
What are the risk factors for diverticula?
```
Age
Lack of dietary fibre
Obesity, especially in younger patients
Sedentary lifestyle
Smoking
NSAID use
```
53
How does diverticula disease present?
Diverticula Disease
Almost all diverticula are found in the sigmoid colon
Pain in left iliac region eases after passing wind or faeces
Usually the pain comes on after eating
Feeling bloated
Change in bowel habit – constipation or diarrhoea and mucus
54
How does diverticulitis present?
Severe pain in left lower quadrant +/- guarding (if perforation)
N&V due to ileus or colonic obstruction
Change in bowel habit – constipation more common but diarrhoea also seen
Urinary frequency – urgency or dysuria due to irritation of the bladder by inflamed bowel
PR bleeding
Pneumaturia or faecaluria suggesting colovesical fistula
Vaginal passage of faeces or flatus suggest colovaginal fistula
Pyrexia, tachycardia
Nausea and vomiting
55
How should diverticulitis and diverticular disease be investigated?
FBC + CRP, G&S if actively bleeding
Erect CXR for perforation
AXR – dilated bowel loops, obstruction, or abscesses (+ barium enema)
CT – best modality for abscesses
Colonoscopy – avoid initially in infective exacerbation due to risk of perforation
56
What is the Hinchey severity classification for diverticula disease?
```
Hinchey Severity Classification for diverticula Disease
I – para-colonic abscess
II – pelvic abscess
III – purulent peritonitis
IV – faecal peritonitis
```
57
How are acute exacerbations or diverticulitis managed?
Oral antibiotics, NBM and liquid diet and analgesia
| If severe or does not settle within 72 hours, then admit for IV antibiotics
58
How is an acute bleed from diverticula disease managed?
```
Acute Bleed
ABCDE
Fluids
Transfusion if needed
Check clotting
Monitor conservatively
Usually stops of its own accord if not then may not be diverticula related
```
59
What general management is there for diverticular disease?
Increase dietary fibre intake
Drainage of colonic abscess surgically or radiologically
Segmental resection if recurrent episode of diverticulitis
Hinchey IV – resection and stoma, often requiring HDU admission
60
What is GORD?
Symptoms of oesophagitis secondary to refluxed gastric contents. This can be mild reflux at least twice a week or moderate to severe reflux at least once a week.
61
If left untreated what can GORD cause?
```
Oesophagitis
Ulcers
Anaemia
Benign strictures
Barrett’s oesophagus
Oesophageal cancer
```
62
What are the clinical features of GORD?
Burning retrosternal pain (heartburn) usually after eating and worse at night
Chest pain
Regurgitation of food or sour liquid
Sensation of lump in the throat
Dysphagia
Night time acid reflux can cause hoarseness, chronic cough, laryngitis, new or worsening asthma or disrupted sleep
63
How should GORD be investigated?
Upper GI endoscopy
| 24hr oesophageal pH monitoring (gold standard test for diagnosis
64
What are the indications for an upper GI endoscopy in GORD?
* Age > 55yrs
* Symptoms > 4 weeks or persistent symptoms despite treatment
* Dysphagia
* Relapsing symptoms
* Weight loss
65
How is GORD managed?
GORD which has not been investigated with endoscopy should treated as dyspepsia
1. Review medications for possible causes
2. Lifestyle advice
3. Trial of full dose proton pump inhibitor for one-month OR test and treat H-pylori. If symptoms persist after either of these then an alternative approach should be tried.
Testing for H-pylori – carbon-13 urea breath test or stool antigen test. Treat with a proton pump inhibitor + amoxicillin + clarithromycin OR a proton pump inhibitor + metronidazole + clarithromycin.
If GORD is endoscopically proven
• Full dose proton pump inhibitor 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 low dose treatment as required
• If no response, then H2RA (cimetidine/ranitidine) or prokinetic (metoclopramide) for one month
66
What is Barrett's oesophagus?
Metaplasia of lower oesophageal mucosa from squamous cell to columnar epithelium. This causes an increased risk of oesophageal carcinoma of about 50-100-fold. Barrett’s can be subdivided into short (<3cm) and long (>3cm).
67
What are the risk factors for Barrett's oeosphagus?
GORD
Male (7:1)
Smoking
Central obesity
68
How is Barrett's oesophagus managed?
Endoscopic surveillance with biopsies – every 3-5yrs
High dose proton pump inhibitor
If dysplasia of any grade is identified intervention is offered
Endoscopic mucosal resection or radiofrequency ablation
69
What are gastric/duodenal ulcers?
Definition – erosion of the stomach or duodenal wall due to excess acid/pepsin/bile salts/Helicobacter Pylori or inadequate levels of mucus/bicarbonate/blood flow/cell turnover.
70
Which type of ulcers are most common and how many are associated with H-pylori?
Duodenal ulcers are 4x more common than gastric and 95% are associated with H-pylori. Gastric ulcers generally occur in elderly on the lesser curvature of the stomach and only 75% are associated with H-pylori.
71
What causes gastric/duodenal ulcers?
```
H-Pylori
Smoking
Drugs: NSAIDs, steroids, SSRIs, and bisphosphonates
Zollinger Ellison syndrome
Increased gastric emptying (duodenal)
Delayed gastric emptying (gastric)
Increase stomach acid secretion
```
72
What are the clinical features of peptic ulcers?
Duodenal ulcers – epigastric pain usually worst 2-5 hours after eating and related to hunger, types of food and time of day may be relieved by eating
Gastric ulcers – epigastric pain that is exacerbated by eating
```
Fullness after meals
Heartburn (retrosternal pain)
Tender epigastrium
Alcohol
Nausea
```
(ALARMS symptoms – Anaemia, Loss of weight, Anorexia, Recent onset, Malaena/haematemasis and swallowing difficult
73
How are peptic ulcers investigated?
Routine bloods
Test for H-Pylori. Testing for H-pylori – carbon-13 urea breath test or stool antigen test.
Endoscopy
Gastrin secretions (when off PPI) for Zollinger Ellison Syndrome
74
How are peptic ulcers managed?
H-Pylori – PPI and 2 antibiotics (clarithromycin and amoxicillin/metronidazole)
If H-Pylori test is negative, then PPI until ulcer healed
Reduction in weight
Change of diet and lifestyle (alcohol)
75
How does a perforated peptic ulcer present?
Sudden onset epigastric pain preceded by a history of upper abdominal pain, pain made worse by any kind of movement, especially coughing, or sneezing. May have clinical evidence of peritonitis. Erect CXR may show free air under the diaphragm.
76
How are perforated peptic ulcers managed?
Management is via laparotomy or laparoscopy to give wash out, primary repair or resection
77
What is achalasia?
Definition – failure of the oesophageal peristalsis and of the lower oesophageal sphincter muscle fibres to relax due to degenerative loss of ganglia from Auerbach’s plexus. This results in the LOS contracted and oesophagus above dilated.
78
Who does achalasia most commonly affect?
Usually affecting middle-aged adults equally between men and women.
79
What are the clinical features of achalasia?
Dysphagia of both liquids and solids
Regurgitation leading to cough and aspiration pneumonia
Epigastric and sternal pain (heartburn)
Weight loss
Very small number of patients show a malignant change
80
How is achalasia investigated?
Oesophageal manometry – excessive LOS tone which does not relax on swallowing
Barium swallow – grossly expanded oesophagus, fluid level, bird’s beak appearance
CXR – wide mediastinum and fluid level
Endoscopy
81
How is achalasia managed?
Lifestyle changes – eat slowly and small portions, chewing well with plenty of water
Sleep with extra pillows
Intra-sphincteric injection of botulinum toxin
Pneumatic (balloon) dilation – forceful dilation of the sphincter
Heller Myotomy – dissecting away the outer tough muscle layer
Drug therapy
Sublingual nifedipine
Isosorbide mononitrate
82
What is Primary Sclerosing cholangitis
Definition – inflammation of the intra and extra hepatic bile ducts (inside and outside the liver) that eventually causes scaring and restructuring resulting in cholestasis and biliary fibrosis, cirrhosis and liver failure. Cause is unclear but potentially autoimmune
83
Who does primary sclerosing cholangitis occur in?
It is very common that people with PSC also have some form of Inflammatory bowel disease. 4% of UC patients have PSC and 80% of PSC have UC, Crohn’s much less common. HIV also associated with PSC. Otherwise very rare but most common in those aged 40 and twice more common in men.
84
What are the clinical features of primary sclerosing cholangitis
```
Most commonly no signs
Cholestasis resulting in jaundice and pruritis
Right upper quadrant abdominal pain
Fatigue
Hepatomegaly and Splenomegaly
```
85
What investigations should be done if you are considering primary sclerosing cholangitis?
LFTs – ALP and bilirubin raised
Magnetic resonance cholangiopancreatography (MRCP) is first line. Can also consider Endoscopic retrograde Cholangiopancreatography (ERCP). They will both show a beaded appearance
p-ANCA may be positive
Liver biopsy showing signs consistent with PSC can be used to diagnose
86
How is primary sclerosing cholangitis managed?
No treatment only management of symptoms
Cholestyramine to stop skin itching.
Liver transplant if eligible but in 1/5 of cases it will reoccur.
Eat healthy diet with NO alcohol
87
What complications can occur as a result of primary sclerosing cholangitis?
```
Liver cirrhosis and failure
Vitamin Deficiency
Infection of the bile ducts
Cholangiocarcinoma in 10%
Increased risk of colorectal cancer
```
88
What is primary biliary cholangitis?
Definition – autoimmune disease that causes destruction of the small bile ducts of the liver resulting in bile and other toxins accumulating in the liver and so fibrosis.
Often occurs in people with other autoimmune disease. Affects 1 in 4000 people and much more common in women (9:1), usually middle aged.
89
What causes primary biliary cholangitis?
Autoimmune cause (the large majority contain anti-mitochondrial antibodies against pyruvate dehydrogenase complex).
90
What other conditions is primary biliary cholangitis associated with?
Associated with Sjogren’s syndrome (80% of patients)
Rheumatoid arthritis
Systemic sclerosis
Thyroid disease
91
What are the clinical features of primary biliary cholangitis?
Classic presentation is itching in a middle-aged woman
Fatigue
Pain in URQ (only seen in 10%)
Xanthelasmas and xanthomas
Clubbing
Hepatosplenomegaly
Cholestatic Jaundice
Hyperpigmentation, especially around pressure points
Sjogren’s features such as dry eyes and dry mouth
92
How should someone suspected of having primary biliary cholangitis be investigated?
LFTs – raised ALP and GGT as well as bilirubin
Test for anti-mitochondrial antibodies (AMA M2 subtype) against pyruvate dehydrogenase
Smooth muscle antibodies seen in 30%
Raised serum IgM
Bilirubin levels indicate prognosis – if 2-6mg/dl then 4 years, 6-10mg/dl about 2 years and if greater than10mg/dl usually about 1.5 years.
USS and CT to rule out blockages of the bile ducts and a liver biopsy can be helpful
93
How is primary biliary cholangitis managed?
Ursodeoxycholic acid and obeticholic acid – slows disease progression and improves symptoms. Cholestyramine (bile acid sequestrant) can also help with pruritis.
Fat soluble vitamin Supplements
Liver transplant if needed in advanced cases e.g. bilirubin >100. Recurrence in graft can occur but not usually a problem
94
What complications can occur from primary biliary cholangitis?
Cirrhosis – portal hypertension – ascites and variceal haemorrhage
Osteomalacia and osteoporosis
Significantly increased risk of hepatocellular carcinoma (20-fold increase)
95
Why does pancreatic cancer carry a poor prognosis and what type of caner is pancreatic cancer histologically?
Often diagnosed late as it presents in non-specific ways. 80% of pancreatic cancers are adenocarcinomas, typically occurring at the head of the pancreas.
96
What are the risk factors for pancreatic cancer?
```
Increasing age
Smoking
Diabetes
Chronic pancreatitis (alcohol not independent risk factor though)
Hereditary non-polyposis colorectal carcinoma
Multiple endocrine neoplasia
Multiple endocrine neoplasia
BRCA2 gene
KRAS gene mutation
```
97
What are the clinical features of pancreatic cancer?
```
Painless jaundice is pancreatic cancer until proven otherwise
Pale stools, dark urine and pruritis
Cholestatic liver function tests
Anorexia and weight loss
Epigastric pain
Diabetes
Atypical back pain
Migratory thrombophlebitis (Trousseau sign) more common than in other cancers
```
98
How should suspected pancreatic cancer be investigated?
USS has a sensitivity of 60-90%
CT scan is investigation of choice if diagnosis suspected
Double duct sign – simultaneous dilation of the common bile and pancreatic ducts
99
How is pancreatic cancer managed?
Very few suitable for surgery
Whipple’s resection (pancreaticoduodenectomy) is performed for resectable lesions in the head of the pancreas. SE include dumping syndrome and peptic ulcer disease.
Adjuvant chemotherapy us usually given following surgery
ERCP with stenting is often used for palliation
100
What can cause acute liver failure?
Paracetamol overdose
Alcohol
Viral hepatitis (usually A or B)
Acute fatty liver of pregnancy
101
What are the clinical features of acute liver failure?
```
Jaundice
Coagulopathy – raised PT
Hypoalbuminaemia
Hepatic encephalopathy
Renal failure (hepatorenal syndrome)
```
102
What investigations should be done in someone with acute liver failure?
Coagulation screen and Albumin are best markers of liver ‘function’
LFTs are good at suggesting the cause and showing where inflammation is occurring
103
How is acute alcoholic hepatitis managed?
* Glucocorticoids such as prednisolone. Maddrey's discriminant function (DF) is used during acute episodes to determine who would benefit from glucocorticoid therapy, it is calculated from a formula using prothrombin time and bilirubin concentration
* Pentoxyphylline is also sometimes used but has less evidence for increasing survival
104
What is hepatic encephalopathy?
Excess absorption of ammonia and glutamine from bacterial breakdown of proteins in the gut is thought to be the cause. Trans jugular intrahepatic portosystemic shunting (TIPSS) may precipitate encephalopathy. Most commonly this is seen with acute liver failure but can also be seen in chronic disease.
105
What can precipitate hepatic encephalopathy?
```
Infections especially spontaneous bacterial peritonitis
GI bleeds
Post trans jugular intrahepatic portosystemic shunt
Constipation
Drugs – sedatives and diuretics
Hypokalaemia
Renal failure
Increased dietary protein
```
106
What are the clinical features of hepatic encephalopathy?
Confusion and altered GCS
Asterix – ‘liver flap’, arrhythmic negative myoclonus with a frequency of 3-5Hz
Constructional apraxia – inability to draw a 5-pointed star
Triphasic slow waves on EEG
Raised ammonia levels (but very rarely measured)
107
How is hepatic encephalopathy graded?
```
Grading
Grade 1 – irritability
Grade 2 – confusion, inappropriate behaviour
Grade 3 – incoherent and restless
Grade 4 – coma
```
108
How is hepatic encephalopathy managed and prevented?
Treat underlying precipitating cause
Lactulose with addition of rifaximin for secondary prophylaxis of hepatic encephalopathy. Lactulose works by promoting excretion of ammonia and increasing metabolism of ammonia by gut bacterial whilst antibiotics such as rifaximin modulate gut flora resulting in decreased ammonia production.
Embolization of portosystemic shunts and liver transplantations in selected patients
109
What is cirrhosis?
Progressive destruction of the liver over time involving destruction and regeneration of the liver parenchyma until the tissue scaffold is damaged leading to cirrhosis.
110
What can cause chronic liver disease?
Alcoholic cirrhosis
Viral Hepatitis from hepatitis B and C
(Acute live disease caused by hepatitis A, E and D and also EBV but this is only relevant in pregnancy and when B is also present)
Wilson’s disease – copper metabolism disorder causing build up in the liver
Haemochromatosis – iron overload due to metabolic disorder
Primary Biliary Cholangitis/cirrhosis
Primary Sclerosing Cholangitis
Non-alcoholic fatty liver disease (NAFLD)
Right heart failure
Drugs
111
Which drugs induce a hepatocellular type chronic liver failure?
* Paracetamol
* Sodium valproate and phenytoin
* MAOIs
* Halothane
* Anti TB durgs
* Statins
* Alcohol
* Nitrofurantoin
112
Which drugs induce a cholestatic type chronic liver failure?
* Anabolic steroids and testosterone
* COCP
* Antibiotics – flucloxacillin, co-amoxiclav and erythromycin
* Phenothiazines – chlorpromazine and prochlorperazine
* Sulphonylureas
* Fibrates
* Nifedipine
113
Which drugs induce a cirrhotic type chronic liver failure?
* Methotrexate
* Amiodarone
* Methyldopa
114
What are the clinical signs of chronic liver failure?
* Nail clubbing
* Palmer erythema
* Spider nevi
* Gynaecomastia
* Testicular atrophy
* Anaemia
* Dupuytren’s contracture (permeant flexion of fingers at MCP joint)
* Caput medusae.
115
What are the clinical features of decompensated chronic liver disease?
* Encephalopathy: drowsiness, hyperventilation, hepatic flap, and confusion
* Jaundice
* Ascites due to portal hypertension and hypoalbuminemia
* Leukonychia
* Peripheral oedema
* Bruising
* Varices
* Renal failure (portal hypertension)
* Respiratory alkalosis.
116
How should chronic liver disease be investigated?
LFTs, Albumin and bilirubin
Abdominal USS
Liver biopsy – adverse effects of pain and bleeding so done less now
Transient elastography and acoustic radiation force impulse imagining (both US based)
Transient elastography offered to:
• Hepatitis C infected
• Men who drink > 50 units a week and women who drink > 35 units a week
• Previously diagnosed with alcohol related liver disease
Upper GI endoscopy to check for varices in patients with new diagnosis of cirrhosis
Liver USS every 6 months +/- AFP to check to hepatocellular carcinoma
117
What specific tests/scores might be considered when looking for causes of chronic liver disease?
Ferritin is an acute phase protein and so transferrin is more useful for detecting haemochromatosis.
Anti-mitochondrial antibodies and anti-smooth muscle antibody (autoimmune hepatitis)
Alpha fetoprotein can be raised in hepatocellular
Enhanced Liver fibrosis score for NAFLD
118
How is chronic liver disease graded?
Child-Pugh classification grades Liver cirrhosis into A, B and C. MELD used more often now. MELD – Model for End-Stage Liver Disease – uses a formula including bilirubin, creatinine, and INR to predict mortality.
119
How are the problems from chronic liver disease managed?
Ascites – treat with drain and spironolactone. Portosystemic shunts can be used but can exacerbate encephalopathy. Also use albumin transfusions and diuretics
Varices treatment – If small propranolol to reduce blood pressure, if medium-large then endoscopic variceal band ligation (EVL), performed two-weekly until all varices have been eradicated.
Encephalopathy – affects conscious level from muddled to coma. Treat precipitates such as dehydration, constipation, and infection.
Vitamin K to help coagulation
Transplant is the only real cure
120
What complications of chronic liver disease should you be aware of
```
Spontaneous bacterial peritonitis – infection of ascites
Hepatorenal syndrome (rapid deterioration of kidney function)
```
121
Why is the serum-ascites albumin gradient (SAAG) important?
Ascites is classified based on whether this score is > or < 11g/l
122
What causes an ascites with a SAAG > 11g/l
```
This indicates portal hypertension
• Cirrhosis
• Alcoholic hepatitis
• Cardiac ascites
• Mixed ascites
• Massive liver metastases
• Fulminant hepatic failure
• Budd-Chiari syndrome
• Portal vein thrombosis
• Veno-occlusive disease
• Myxoedema
• Fatty liver of pregnancy
```
123
What causes ascites with a SAAG < 11g/l
* Peritoneal carcinomatosis
* Tuberculous peritonitis
* Pancreatic ascites
* Bowel obstruction
* Biliary ascites
* Postoperative lymphatic leak
* Serositis in connective tissue diseases
124
How should ascites be managed?
Reducing dietary sodium or fluid restriction is sometimes recommended if the sodium is < 125mmol/L
Aldosterone antagonists such as spironolactone – loop diuretics are often added
Drainage if tense ascites (therapeutic abdominal paracentesis)
• Large-volume paracentesis requires albumin cover as it can cause induced circulatory dysfunction and mortality which is associated with a high rate of ascites recurrence, development of hepatorenal syndrome, dilutional hyponatraemia and high mortality rate
Transjugular intrahepatic portosystemic shunt (TIPS) may be considered in some patients
125
What is spontaneous bacterial peritonitis and how is it diagnosed?
This is effectively where ascites caused by liver failure becomes infected with bacterial. This presents as abdominal pain and fever. The most common causes is E. coli.
Diagnosis is made via paracentesis with a neutrophil count > 250cell/ul.
126
How is spontaneous bacterial peritonitis managed?
IV cefotaxime
Prophylaxis should be offered to patients with ascites if they have had a previous episode or a fluid protein < 15g/l. Also consider with child pugh score >/=9 or hepatorenal syndrome.
Prophylactic antibiotics are oral ciprofloxacin or norfloxacin until ascites has resolved.
127
What is hepatorenal syndrome and why does it occur?
Vasoactive mediators cause splanchnic vasodilation which in turn reduced the systemic vascular resistance. This results in reduced perfusion to the kidneys and so the juxtaglomerular apparatus activates the renin-angiotensin-aldosterone system causing renal vasoconstriction which is not enough to counterbalance the effects of the splanchnic vasodilation.
128
What are the two types of hepatorenal syndrome?
Type 1 HRS
Rapidly progressive
Doubling of serum creatinine to >221 umol/L or a halving of the creatinine clearance to < 2mml/min over a period of less than 2 weeks. Very poor prognosis.
Type 2 HRS
Slowly progressive. Prognosis poor but patient may live for longer than in type 1
129
How is hepatorenal syndrome managed?
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 a 20% albumin
Transjugular intrahepatic portosystemic shunt
130
What is non alcoholic fatty liver disease?
Most common cause of liver disease in the developed world, largely due to obesity and ranges from steatosis (fat in the liver), steatohepatitis – fat with inflammation and then progressive disease with cirrhosis. This is effectively the hepatic manifestation of metabolic syndrome and insulin resistance is an important mechanism.
131
What is non-alcohlic steatohepatitis
Non-alcoholic steatohepatitis is a term commonly used to describe liver changes seen similar to those of an alcoholic but with the absence of alcohol abuse. Most patient will have little progression in disease however some progress to liver fibrosis and cirrhosis.
132
What are the risk factors for non alcohlic fatty liver disease?
Obesity
T2DM
Hyperlipidaemia
Sudden weight loss/starvation
133
What are the clinical features of non alcoholic fatty liver disease?
```
Usually asymptomatic
Hepatomegaly
ALT typically > AST
Increased echogenicity on US
Eventually liver failure
```
134
How should suspected non alcoholic fatty liver disease be investigated?
Typically found on USS as incidental fatty changes
If found an enhanced liver fibrosis blood test should be done to check for advanced fibrosis, the ELF test is a combination of hyaluronic acid + procollagen III + tissue inhibitor of metalloproteinase. Algorithm is used to form a score similar to triple testing in Down’s.
If ELF not available can use the NALFD fibrosis score in combination with transient elastography to predict fibrosis.
Liver biopsy to stage the disease more accurately
135
How is non alcoholic fatty liver disease managed?
Lifestyle changes, particularly weight loss and monitoring
| Gastric banding and insulin-sensitising drugs such as metformin and pioglitazone are up an coming in research
136
Who is autoimmune hepatitis usually seen in?
Most commonly this is seen in young females, associated with other autoimmune disorders, hypergammaglobulinaemia, HLA B8 and DR3.
137
What are the 3 classifications of autoimmune hepatitis?
Type 1 – anti-nuclear antibodies (ANA) and/or anti smooth muscle antibodies (SMA). This affects both adults and children
Type 2 – anti-liver/kidney microsomal type 1 antibodies (LKM1). This affects children only.
Type 3 – soluble liver kidney antigen. This affects adults in middle age.
138
What are the clinical features of autoimmune hepatitis?
May present as signs of chronic liver disease
Acute hepatitis with fever, jaundice, and amenorrhoea
ANA/SMA/LKM1 antibodies and raised IgG levels
Liver biopsy – inflammation extending beyond limiting plate (piecemeal necrosis) and bridging necrosis.
139
What is the management of autoimmune hepatitis?
Steroids and other immunosuppressants e.g. azathioprine
| Liver transplantation
140
What causes ALT/AST to rise?
ALT/AST – Aminotransferases, released in the bloodstream after hepatocellular injury. ALT is more specific for hepatocellular injury whilst AST is also expressed in the heart, skeletal muscles, and RBCs.
In alcoholic hepatitis the ALT rarely goes above 200
141
What causes ALP to rise?
ALP – alkaline phosphatase (canaliculi lining the bile ducts). Rise if there is a blockage in the drainage of the biliary system. Also, can be raised due to direct damage to the canaliculi. Also present in bones and placenta and always raised in growing children. Usually there is overlap of raised ALT and ALP due to bile ducts travelling through the liver
142
What causes GGT to rise?
GGT – gamma glutamyltranspeptidase also released due to cholestatic damage. Found in the liver, pancreas, renal tubules and intestines but not the bone so useful in combination with ALP. If raised in junction with ALP, then this is very indicative of biliary tree obstruction. Also markedly raised in chronic alcohol toxicity.
143
Why are LFTs misnomers?
LFTs are actually inflammatory liver markers, the real LFTs are INR, Albumin and Bilirubin
144
What is the LFT picture for hepatocellular predominant liver injury?
Hepatocellular predominant liver injury AST and ALT will be raised
145
What is the LFT picture for alcoholic liver disease?
Alcoholic liver disease AST/ALT ratio typically 2:1 or more. Normal ALP and raised GGT with macrocytosis strongly suggestive of alcoholic liver disease
146
What is the LFT picture for viral hepatitis?
Viral hepatitis – ALT raised and normal bilirubin, AST could be very raised
147
What is the LFT picture for non-alcoholic fatty liver disease?
Non alcoholic fatty liver disease – ALT typically > AST
148
What kind of primary cancers are seen in the liver?
The most common two primary cancers associated with the liver are hepatocellular carcinoma and cholangiocarcinoma. Other rarer primary cancer includes: hepatoblastoma, sarcomas, lymphomas, and carcinoids.
149
What is hepatocellular carcinoma and what causes it?
These make up 75% of all primary liver cancers and are almost always occur as a result to chronic inflammatory activity. This can be due to cirrhotic livers or chronic hepatitis B infection (which is the most common cause).
150
What are the risk factors for hepatocellular carcinoma?
```
Alpha-1 antitrypsin deficiency
Hereditary tyrosinosis
Glycogen storage disease
Aflatoxin
Drugs – COCP and anabolic steroids
Porphyria cutanea tarda
Male sex
DM and metabolic syndrome
```
151
What are the clinical features and common presentation of hepatocellular carcinoma?
Presentation is generally late and usually as patients with existing liver cirrhosis where a mass is discovered on screening USS.
Jaundice, ascites, RUQ pain, hepatomegaly, pruritis, splenomegaly and raised AFP.
152
How are hepatocellular carcinomas usually diagnosed and investigated?
Staging CT/MRI – usually both
Alpha-fetoprotein is a useful marker
Biopsy should be avoided as it seeds tumours through a resection plane
If there is any doubt, then serial a-fetoprotein and CT scan are the preferred strategy
Check testis in males as testicular tumours can release AFP
153
Who is screened for hepatocellular carcinoma?
Screening for US +/- AFP considered for at risk groups – cirrhosis secondary to hepatitis B and C or hemochromatosis and men with liver cirrhosis secondary to alcohol.
154
What is the management of hepatocellular carcinoma?
Surgical resection is mainstay although high risk due to most having already diseased livers
In small primary disease whole resection and transplantation may be considered
Palliative chemo and radiotherapy can be used
Radiofrequency ablation
Transarterial chemoembolization
Sorafenib – multikinase inhibitor
155
What is cholangiocarcinoma?
Second most common type of liver malignancy which arise in the bile ducts, the majority (80%) arise in the extra hepatic ducts.
156
How does cholangiocarcinoma usually present?
Presentation is late, usually due to jaundice and often means the disease is non resectable. The main risk factors is primary sclerosing cholangitis and in less well developed countries typhoid and liver flukes.
157
How is a diagnosis of cholangiocarcinoma made?
Obstructive jaundice picture
CA19-9, CEA and CA-125 are often elevated
CT/MRI and MRCP identify and stage the cancer
158
How is cholangiocarcinoma managed?
Surgical resections offer best chance of cure although is usually contraindicated due to peri hilar invasion coupled with lobar atrophy.
Palliation of jaundice but not with metallic stents if being considered for resection
159
What type of cancers do you get in the gall bladder and how common are they?
Rare with only 1000 new cases in the UK each year. The majority are adenocarcinomas and due to nonspecific symptoms almost always present late.
160
What are the risk factors for gall bladder cancer?
```
Female
Caucasians, Native Americans, and Koreans
Gallstones and so Obesity
Porcelain gallbladder (calcification due to chronic cholecystitis)
Gallbladder adenomas
Congenital gallbladder abnormalities
Primary sclerosing cholangitis
Smoking and industrial chemicals
```
161
What are the clinical features of gall bladder cancer?
```
Asymptomatic in early stages and so usually found incidentally during surgery.
RUQ pain
Anorexia, nausea and vomiting
Malaise and weight loss
Palpable RUQ mass
Jaundice
Pale stools and dark urine
Pruritis
```
162
How should gall bladder cancer be investigated?
LFTs and Ca 19-9 and CEA but all non specific
USS
CT scan and MRI pre operatively
Endoscopic USS + biopsy is gold standard
T1 – invades laminae propria/muscle of gallbladder
T2 – invades perimuscular connective tissue but no viscera of the liver/peritoneum
T3 – invades visceral peritoneum and/or liver and/or adjacent organ
T4 – invades vascular structures and/or invades two or more adjacent organs
163
How are gall bladder cancers managed?
Surgical resection but this is contraindicated if:
• Metastatic disease
• Malignant ascites
• Vascular invasion
Chemoradiotherapy but this is mainly for palliation
Endoscopic common bile duct stents in obstructive jaundice
164
What are hemangiomas in the liver?
Haemangiomas – most common benign tumour of the liver with an incidence of around 8%. Cavernous haemangiomas can be enormous. They appear reddish purple and are hyper vascular, they are normally separated from the normal liver tissue by a ring of fibrous tissue. On US they are hyperechoic.
165
what are liver cell adenomas?
Liver cell adenoma – very common in middle aged women and linked to oral contraceptives. Well demarcated from liver but lack a fibrous capsule. On US they have mixed echoity and on CT are hypodense. If symptomatic or bleeding removal may be required.
166
What are mesenchymal hamartomas?
Mesenchymal hamartomas – congenital and benign, usually present in infants and may compress the liver.
167
What is a liver abscess?
Liver abscess – common after biliary sepsis, symptoms include fever, RUQ pain and jaundice. US shows fluid filled cavity and hyperechoic walls. Most common cause is Staph aureus in children and E. coli in adults. Managed by drainage and antibiotics – amoxicillin, + ciprofloxacin + metronidazole. If Penicillin allergic, then ciprofloxacin and clindamycin.
168
What is an amoebic abscess?
Amoebic abscess – liver abscess is most common extra intestinal manifestations of amoebiasis, and majority are seen in the right lobe. Symptoms include fever and RUQ pain. US shows fluid filled stricture with poorly defined borders. Aspiration gibes a sterile odourless fluid with a thick consistency. Treat with metronidazole.
169
What is polycystic liver disease?
Polycystic liver disease – occurs in association with polycystic kidney disease, autosomal dominant and symptoms may occur as a result of capsular stretch.
170
What is a cystadenoma?
Cystadenoma – rare lesion with some malignant potential, usually a solitary multiloculated lesion with normal LFTs. US shows large anechoic fluid filled area with irregular margins. Surgical resection should be done in all cases.
171
How should a paracetamol overdose be managed?
If presenting within 1 hour of consumption, then may benefit from activated charcoal to reduce absorption of the drug.
Acetylcysteine given if:
1. Staggered overdose (not all taken within 1 hour) or there is doubt over the time of paracetamol ingestion regardless of the plasma concentration
2. The plasma paracetamol concentration is on or above the single treatment line regardless of risk factors for hepatotoxicity
This is given as an infusion over 1 hour. Adverse effects to be aware of – anaphylactoid reaction (non-IgE mediated mast cell release)
172
What are the King's college hospital criteria for liver transplant in paracetamol and non paracetamol overdose acute liver failure?
Criteria for Liver transplantation in paracetamol liver failure
Arterial pH < 7.3 24 hours after ingestion or all 3 of:
• PT > 100 seconds
• Creatinine > 300umol/l
• Grade III or IV encephalopathy
```
Non paracetamol failure
PT > 100
OR 3/5 of the following
1. Drug induced liver failure
2. Age < 10 or > 40yrs
3. >1-week form 1st jaundice to encephalopathy
4. PT > 50s
5. Bilirubin > 300umol/l
```
173
What would be deemed a high risk overdose?
```
Patients taking liver enzyme inducing drugs such as rifampicin, phenytoin, carbamazepine, chronic alcohol excess and St john’s wart.
Malnourished patients (anorexia) or patients who have not eaten for a long time
```
174
What dose/weight of patient can be fatal?
150mg/kg can be fatal, for overweight never use weight above 110kg to calculate this as it can lead to errors.
If underweight 75mg/kg can be fatal.
175
What is alcoholic ketoacidosis?
This occurs due to poor dietary intake in people who regularly drink large volumes of alcohol, often resulting in them vomiting up any food they do it. This enters the body into a starvation state of ketosis.
176
How does alcoholic ketoacidosis present?
Metabolic acidosis
Elevated anion gap
Elevated ketone levels
Normal or low glucose concentrations
177
How is alcoholic ketoacidosis managed?
Saline and Thiamine infusion
| 5% dextrose
178
What are aminosalicylates?
5-aminosalicylate acid (5-ASA) is released in the colon and not absorbed, it acts locally as an anti-inflammatory possibly by inhibiting prostaglandin synthesis.
179
What is sulphasalazine and what are its side effects?
Sulphasalazine – combination of sulphapyridine (sulphonamide) and 5-ASA
SE from sulphapyridine – rashes, oligospermia, headache, Heinz body anaemia, megaloblastic anaemia, and lung fibrosis. Many other SE are common to 5-ASA drugs such as GI upset, headache, agranulocytosis, pancreatitis and interstitial nephritis.
180
What are mesalazine and osalazine and what are their side effects?
Mesalazine – delayed release form of 5-ASA
Osalazine – two moleculesof 5-ASA joined together which is broken by bacteria
Avoids SE of sulphapyridine seen in sulphasalazine.
Common 5-ASA SE still present: GI upset, headache, agranulocytosis, pancreatitis, and interstitial nephritis.
181
What blood test should always be performed on a patient who is unwell on 5-ASA drugs?
Due to the risk of agranulocytosis FBC should always be checked in unwell patient on 5-ASA.
182
What is angiodysplasia?
This is a vascular deformity of the GI tract which predisposes to bleeding and iron deficiency anaemia. It is associated with aortic stenosis and is generally seen in elderly patients. It is worth considering in relation to unexplained GI bleeding.
183
How is angiodysplasia diagnosed?
Colonoscopy
| Mesenteric angiography if acutely bleeding
184
How is angiodysplasia managed?
Endoscopic cautery or argon plasma coagulation
Antifibrinolytics such as TXA
Oestrogen may also be used.
185
What is bile acid malabsorption?
This can cause chronic diarrhoea and occurs due to excessive production (primary) or reduced absorption of bile acid (secondary). It can lead to steatorrhea and vitamin A, D, E and K malabsorption.
186
What are some secondary causes of bile acid malabsorption?
Ileal disease such as with Crohn’s
Cholecystectomy
Coeliac disease
Small intestinal bacterial overgrowth
187
How is bile acid malabsorption investigated and diagnosed?
SeHCAT – nuclear medicine tests done 7 days apart to assess for retention/loss
188
How is chronic diarrhoea due to bile acid malabsorption managed?
Bile acid sequestrants such as cholestyramine
189
What is Budd chiari disease?
An extremely rare acute, subacute, or chronic cause of liver failure due to hepatic vein thrombosis and is usually seen in the context of haematological disease or another procoagulant condition.
190
What can cause Budd chiari disease?
Polycythaemia rubra vera
Thrombophilia
Pregnancy
COCP (20% of cases)
191
What are the clinical features of budd chiari disease?
Classically a triad of:
Abdominal pain which is sudden onset and severe
Ascites causing abdominal distention
Tender hepatomegaly
192
How should you investigate for budd chiari disease?
FBC LFT’s
Clotting screen
USS with doppler flow studies
193
What are the adverse effects of cholestyramine?
Abdominal cramps and constipation
Decreased absorption of fat-soluble vitamins
Cholesterol gallstones
Rise in triglycerides
194
What is haemochromatosis?
Autosomal recessive disorder of iron absorption and metabolism resulting in iron accumulation due to a mutation of chromosome 6.
195
What are the clinical features of haemochromatosis and which of these are reversible?
Early symptoms include fatigue, erectile dysfunction and arthralgia (often the hands)
Bronze skin pigmentation
Diabetes mellitus
Liver – chronic liver disease, hepatomegaly, cirrhosis and hepatocellular disposition
Cardiac failure (due to cardiomyopathy)
Hypogonadism (liver failure and pituitary dysfunction)
Arthritis
Reversible complications – Cardiomyopathy and skin pigmentation
Irreversible complications – liver cirrhosis, diabetes mellitus, hypogonadism and arthropathy
196
What investigations can be done when suspected haemochromatosis?
```
Transferrin saturations
Ferritin (not usually abnormal in early stages)
Genetic testing for family members
Liver biopsy – pearl stain
Joint x-rays show chondrocalcinosis
```
197
How is haemochromatosis managed?
Venesection – should aim to keep transferrin below 50% and ferritin below 50ug/l
Desferrioxamine – second line
198
What are the key point about Gilbert's disease?
Autosomal Recessive and benign, unconjugated bilirubin build-up
Mild deficiency of UPD-glucuronyl transferase
199
What are the key points about Crigler-Najjar syndromes?
Crigler-Najjar syndrome, type 1
Autosomal recessive and do not survive to adulthood unconjugated bilirubin build-up
Absolute deficiency of UDP-glucuronosyl transferase
Crigler-Najjar syndrome, type 2
Slightly more common than type 1 and less severe may improve with phenobarbital
200
What are the key points about Dubin-Johnson syndrome?
Autosomal recessive, relatively common in Iranian Jews and is benign, conjugated bilirubin build-up
Mutation in the canalicular multidrug resistance protein 2 (MRP2) results in defective hepatic excretion of bilirubin. Results in a grossly black liver
201
What are the key points about Rotor syndrome
Autosomal recessive and benign. Defect in the hepatic uptake and storage of bilirubin. Conjugated bilirubin build-up
202
What are the classic clinical features and diagnostic criteria for a diagnosis of irritable bowel syndrome?
Diagnosis requires any of the following 3 features for at least 6 months
Abdominal pain
Bloating (more common in women) – distension, tension or hardness
Change in bowel habit
OR
Abdominal pain relieved by defecation or altered frequency/form and 2/4 of the following:
Altered stool passage (straining, urgency, incomplete evacuation)
Symptoms made worse by eating
Passage of mucus
```
Other features
Lethargy
Nausea
Headache
Bladder symptoms
```
203
How should suspected IBS be investigated?
FBC
CRP
Coeliac screen
204
What are the management options for IBS?
First line according to predominant features
Pain – antispasmodic agent e.g. mebeverine
Constipation – laxatives but avoid lactulose. If resistant and persistent for 12 months trial Linaclotide but only after exhausting other classes
Diarrhoea – loperamide
Second line
Low dose TCAs
Psychological intervention such as CBT, hypnotherapy, or psychological therapy
205
What general dietary advice should be given to people with IBS?
Regular meals, avoiding missing meals or leaving long gaps
Drink plenty (8 cups) of fluid each day)
Reduce caffeine/alcohol/fizzy drink intake
Limit high fibre
Reduce resistant starches such as those in processed foods
For wind and bloating consider oats and linseed
206
What are the indications for bowel surgery in Crohn's?
Fistulae
Abscess formation
Strictures
207
What are the indications for bowel surgery in UC?
Disease requiring maximal therapy or prolonged course of steroids
Dysplastic transformation of the colonic epithelium with mass lesions
Emergency presentation of poorly controlled colitis failing to respond to medical therapy
208
What is small bowel overgrowth syndrome?
Disorder characterised by excessive amounts of bacteria in the small bowel resulting in GI symptoms
209
What are the risk factors for small bowel overgrowth syndrome?
Neonates with congenital gastrointestinal abnormalities
Scleroderma
Diabetes mellitus
210
What are the clinical features of small bowel overgrowth syndrome?
Lots of overlap with IBS
Chronic diarrhoea
Bloating, flatulence
Abdominal pain
211
How should suspected small bowel overgrowth syndrome be investigated?
Hydrogen breath test
Small bowel aspiration and culture
Give course of antibiotics as a diagnostic trial
212
How is small bowel overgrowth syndrome manage?
Correction of underlying disorder
Antibiotics therapy - rifaximin
Co-amoxiclav or metronidazole also effective in majority of patients
213
What is Vitamin A and what are its functions?
Vitamin A is a fat-soluble vitamin.
Functions
• Converted into retinal, an important visual pigment
• Important in epithelial cell differentiation
• Antioxidant
214
What does vitamin A deficiency cause?
Night blindness
215
What is vitamin B1?
Thiamine is a water-soluble vitamin of the B complex group. One of it's phosphate derivates, thiamine pyrophosphate (TPP), is a coenzyme in the many enzymatic reactions. Thiamine is therefore important in the catabolism of sugars and amino acids. The clinical consequences of thiamine deficiency are therefore seen first in highly aerobic tissues such as the brain (Wenicke-Korsakoff syndrome) and the heart (wet beriberi).
216
What are the two main causes of thiamine deficiency?
* Alcohol excess
| * Malnutrition
217
Which conditions can thiamine deficiency cause?
* Wernicke's encephalopathy: nystagmus, ophthalmoplegia and ataxia
* Korsakoff's syndrome: amnesia, confabulation
* Dry beriberi: peripheral neuropathy
* Wet beriberi: dilated cardiomyopathy
218
What is vitamin B 3 and what are its functions?
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.
219
What does vitamin B3 deficiency cause?
Pellagra: dermatitis, diarrhoea, dementia
220
What is vitamin B6 and what are its functions?
Vitamin B6 is a water-soluble vitamin of the B complex group. It is converted to pyridoxal phosphate (PLP) which is a cofactor for many reactions including transamination, deamination, and decarboxylation. Vitamin B6 deficiency can be caused by isoniazid therapy.
221
What are the consequences of vitamin B6 deficiency?
Peripheral neuropathy
| Sideroblastic anaemia
222
What is vitamin C and what are its functions?
Vitamin C is a water-soluble vitamin
```
Functions
• Antioxidant
• Collagen synthesis: acts as a cofactor for enzymes that are required for the hydroxylation proline and lysine in the synthesis of collagen
• Facilitates iron absorption
• Cofactor for norepinephrine synthesis
```
223
What happens in vitamin C deficiency?
Vitamin C deficiency (scurvy) leads to defective synthesis of collagen resulting in capillary fragility (bleeding tendency) and poor wound healing
```
Features vitamin C deficiency
• Gingivitis, loose teeth
• Poor wound healing
• Bleeding from gums, haematuria, epistaxis
• General malaise
```
224
What is refeeding syndrome?
During starvation state – very low blood glucose so very low insulin. Also, very low phosphate intake so intracellular phosphate used up by ATP synthesis
When refeeding occurs – rapid increase in glucose and so rapid increase in insulin, as tissues are regenerated phosphate is rapidly taken up into cells causing an abrupt decrease in phosphate (and magnesium) which is potentially fatal. Hypokalaemia is also seen as well as large fluid shifts.
225
Which patients are at high risk of refeeding syndrome?
High risk Patients with one of:
• BMI < 16
• Unintentional weight loss > 15% over 3-6 months
• Little nutritional intake for > 10 days
• Hypokalaemia, hypophosphataemia, hypomanesaemia prior to feeding
Or two of:
• BMI < 18.5
• 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
226
How is refeeding syndrome managed?
Replacement of electrolytes, thiamine and vitamin supplementation and MARSIPAN guidelines help with managing refeeding
If no intake for > 5 days re-feed at no more than 50% of requirement for the first 2 days.
227
What are the side effects/adverse effects of a gastrectomy?
```
Side effect/adverse effects following gastrectomy
• Small capacity and so early satiety
• Dumping syndrome
• Bile gastritis
• Afferent loop syndrome
• Efferent loop syndrome
• Anaemia (due to B12 deficiency)
• Metabolic bone disease
```
228
What is dumping syndrome?
Early
Food of high osmotic potential moves into the small bowel causing fluid shifts.
Late (rebound hypoglycaemia)
Surge of insulin following food of high glucose, 2-3 hours later this insulin overshoots causing hypoglycaemia
229
What causes GORD?
```
H-Pylori
Hiatal Hernias
Obesity
Obstructive sleep apnoea
Gallstones
```
