Gastro Flashcards
(201 cards)
1
Q
Features of Crohn’s Disease
A
Diarrhoea usually non-bloody
Weight loss more prominent
Upper gastrointestinal symptoms, mouth ulcers, perianal disease
Abdominal mass palpable in the right iliac fossa
2
Q
Features of UC
A
Bloody diarrhoea more common
Abdominal pain in the left lower quadrant
Tenesmus
3
Q
Extra-intestinal features of Crohn’s disease
A
Gallstones are more common secondary to reduced bile acid reabsorption
Oxalate renal stones*
4
Q
Extra-intestinal features of UC
A
Primary sclerosing cholangitis more common
5
Q
Complications of Crohns
A
Obstruction, fistula, colorectal cancer
6
Q
Pathology of Crohn’s
A
Lesions may be seen anywhere from the mouth to anus
Skip lesions may be present
7
Q
Pathology of UC
A
Inflammation always starts at rectum and never spreads beyond ileocaecal valve
Continuous disease
8
Q
Histology of Crohn’s
A
Inflammation in all layers from mucosa to serosa
increased goblet cells
granulomas
9
Q
Histology of UC
A
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
10
Q
Crohn’s endoscopy findings
A
Deep ulcers, skip lesions - ‘cobble-stone’ appearance
11
Q
UC endoscopy findings
A
Widespread ulceration with preservation of adjacent mucosa which has the appearance of polyps (‘pseudopolyps’)
12
Q
Crohn’s radiology findings
A
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
13
Q
UC radiology findings
A
Barium enema
loss of haustrations
superficial ulceration, ‘pseudopolyps’
long standing disease: colon is narrow and short -‘drainpipe colon’
14
Q
Hep B surface antigen
A
(HBsAg) is the first marker to appear and causes the production of anti-HBs
Usually indicates acute infection 1-6 months
If present >6 months = chronic infection
15
Q
Anti-HBs
Anti HB surface antigen
A
implies immunity - exposure or immunisation
absent in chronic infection
16
Q
Anti-HBc
Anti Hep B core antigen
A
previous or current infection
17
Q
IgM anti-HBc
A
Appears during acute or recent hepatitis B infection and is present for about 6 months.
18
Q
IgG anti-HBc
A
persistant infection
19
Q
HbeAg
A
results from breakdown of core antigen from infected liver cells as is, therefore, a marker of infectivity. Marker of HBV replication and infectivity
20
Q
Hep B
Previous immunisation
A
anti-HBs positive, all others negative
21
Q
Hep B
previous infection, not a carrier
A
anti-HBc positive, HBsAg negative
22
Q
previous hepatitis B, now a carrier:
A
anti-HBc positive, HBsAg positive
23
Q
Wilsons disease
Liver features
A
cirrhosis
hepatitits
24
Q
Wilsons disease
Neurological features
A
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
25
Wilson's disease
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
26
Wilson's disease
other
renal tubular acidosis
esp Fanconi's syndrome
Blue nails
haemolysis
27
Wilson's disease
Diagnosis
```
Slit lamp for Kayser-Fleischer rings
Serum caeruloplasmin - reduced
Serum total copper - reduced
free copper - increased
increased 24hr urinary copper secretion
```
28
Management of Wilsons disease
penicillamine
trientine hydrochloride
tetrathiomolybdate
29
Complications of coeliac disease
hyposplenism
anaemia - iron, folate, B12 deficiency
osteoporosis, osteomalacia
lactose intolerance
T-cell mediated gastric lymphoma
subfertility, unfavourable pregnancy outcomes
rare: oesophageal cancer, other malignancies
30
Primary biliary cholangitis (prev cirrhosis)
interlobular bile ducts become damaged by a chronic inflammatory process causing progressive cholestasis which may eventually progress to cirrhosis. The classic presentation is itching in a middle-aged woman
31
Associations with primary biliary cholangitis
Sjogren's syndrome (seen in up to 80% of patients)
rheumatoid arthritis
systemic sclerosis
thyroid disease
32
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
33
Diagnosis of primary biliary cholangitis
Immunology
anti-mitochondrial antibodies (AMA) M2 subtype are present in 98% of patients and are highly specific
smooth muscle antibodies in 30% of patients
raised serum IgM
34
Diagnosis of primary biliary cholangitis
imaging
required before diagnosis to exclude an extrahepatic biliary obstruction (typically a right upper quadrant ultrasound or magnetic resonance cholangiopancreatography (MRCP)
35
Management of primary biliary cholangitis
ifrst-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
36
Complications of primary biliary cholangitis
cirrhosis → portal hypertension → ascites, variceal haemorrhage
osteomalacia and osteoporosis
significantly increased risk of hepatocellular carcinoma (20-fold increased risk)
37
Boerhaave syndrome
Severe vomiting → oesophageal rupture
38
Mallory-Weiss syndrome
Severe vomiting → painful mucosal lacerations at the gastroesophageal junction resulting in haematemesis. Common in alcoholics
39
Plummer-Vinson syndrome
Triad of:
dysphagia (secondary to oesophageal webs)
glossitis
iron-deficiency anaemia
Treatment includes iron supplementation and dilation of the webs
40
where is CCK secreted from
I cells in upper small intestine
41
Action of CCK
Increases secretion of enzyme-rich fluid from pancreas, contraction of gallbladder and relaxation of sphincter of Oddi, decreases gastric emptying, trophic effect on pancreatic acinar cells, induces satiety
42
Stimulation of CCK
Partially digested proteins and triglycerides
43
Source of Gastrin
G cells in antrum of the stomach
44
Stimulation of Gastrin
Distension of stomach, vagus nerves (mediated by gastrin-releasing peptide), luminal peptides/amino acids
Inhibited by: low antral pH, somatostatin
45
Action of Gastrin
Increases acid secretion by gastric parietal cells, pepsinogen and IF secretion, increases gastric motility, stimulates parietal cell maturation
46
Source of secretin
S cells in upper small intestine
47
Stimulation of secretin production
acidic chyme, fatty acids
48
Action of secretin
Increases secretion of bicarbonate-rich fluid from pancreas and hepatic duct cells, decreases gastric acid secretion, trophic effect on pancreatic acinar cells
49
Source of VIP
Small intestine, pancreas
50
Stimulation of VIP
Neural
51
Action of VIP
Stimulates secretion by pancreas and intestines, inhibits acid secretion
52
Source of somatostatin
D cells in the pancreas & stomach
53
Stimulation of somatostatin
Fat, bile salts and glucose in the intestinal lumen
54
Action of somatostatin
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
55
Ascending cholangitis
Presenting symptoms
Charcot's triad right upper quadrant (RUQ) pain, fever and jaundice occurs in about 20-50% of patients
fever is the most common feature, seen in 90% of patients
RUQ pain 70%
jaundice 60%
hypotension and confusion are also common (the additional 2 factors in addition to the 3 above make Reynolds' pentad)
Raised inflammatory markers
56
Management of ascending cholangitis
intravenous antibiotics
| endoscopic retrograde cholangiopancreatography (ERCP) after 24-48 hours to relieve any obstruction
57
What is whipple's disease
rare multi-system disorder caused by Tropheryma whippelii infection. It is more common in those who are HLA-B27 positive and in middle-aged men.
58
Features of whipple's disease
malabsorption: diarrhoea, weight loss
large-joint arthralgia
lymphadenopathy
skin: hyperpigmentation and photosensitivity
pleurisy, pericarditis
neurological symptoms (rare): ophthalmoplegia, dementia, seizures, ataxia, myoclonus
59
Whipple's disease investigations
jejunal biopsy shows deposition of macrophages containing Periodic acid-Schiff (PAS) granules
60
Management of whipple's disease
guidelines vary: oral co-trimoxazole for a year is thought to have the lowest relapse rate, sometimes preceded by a course of IV penicillin
61
Features of billiary colic
Colicky abdominal pain, worse postprandially, worse after fatty foods
62
Management of billiary colic
imaging- gallstones and history compatible then laparoscopic cholecystectomy
63
Features of acute cholecystitis
Right upper quadrant pain
Fever
Murphys sign on examination
Occasionally mildly deranged LFT's (especially if Mirizzi syndrome)
64
Management of acute cholecystitis
Imaging (USS) and cholecystectomy (ideally within 48 hours of presentation)
65
Features of gallbladder abscess
Usually prodromal illness and right upper quadrant pain
Swinging pyrexia
Patient may be systemically unwell
Generalised peritonism not present
66
Management of gallbladder abscess
Imaging with USS +/- CT Scanning
Ideally, surgery although subtotal cholecystectomy may be needed if Calot's triangle is hostile
In unfit patients, percutaneous drainage may be considered
67
Features of cholecystitis
Patient severely septic and unwell
Jaundice
Right upper quadrant pain
68
Management of cholecysittis
Fluid resuscitation
Broad-spectrum intravenous antibiotics
Correct any coagulopathy
Early ERCP
69
Features of gallstone ileus
Patients may have a history of previous cholecystitis and known gallstones
Small bowel obstruction (may be intermittent)
70
Management of gallstone ileus
Laparotomy and removal of the gallstone from small bowel, the enterotomy must be made proximal to the site of obstruction and not at the site of obstruction. The fistula between the gallbladder and duodenum should not be interfered with.
71
Features of acalculous cholecystitis
Patients with intercurrent illness (e.g. diabetes, organ failure)
Patient of systemically unwell
Gallbladder inflammation in absence of stones
High fever
72
Management of aculous cholecystitis
If patient fit then cholecystectomy, if unfit then percutaneous cholecystostomy
73
Gilbert's syndrome
autosomal recessive
mild deficiency of UDP-glucuronyl transferase
benign
74
Crigler-Najjar syndrome, type 1
autosomal recessive
absolute deficiency of UDP-glucuronosyl transferase
do not survive to adulthood
75
Crigler-Najjar syndrome, type 2
slightly more common than type 1 and less severe
| may improve with phenobarbital
76
Dubin-Johnson syndrome
autosomal recessive. Relatively common in Iranian Jews
mutation in the canalicular multidrug resistance protein 2 (MRP2) results in defective hepatic excretion of bilirubin
results in a grossly black liver
benign
77
Rotor syndrome
autosomal recessive
defect in the hepatic uptake and storage of bilirubin
benign
78
Mechanism of action
Metoclopramide
D2 receptor antagonist
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
79
Metoclopramide
Uses
Nausea
gastro-oesophageal reflux disease
prokinetic action is useful in gastroparesis secondary to diabetic neuropathy
often combined with analgesics for the treatment of migraine (migraine attacks result in gastroparesis, slowing the absorption of analgesics)
80
Metoclopramide
adverse features
extrapyramidal effects: oculogyric crisis. This is particularly a problem in children and young adults
hyperprolactinaemia
tardive dyskinesia
parkinsonism
81
Metoclopramide
Ileus vs obstruction
Maybe helpful in ileus
Avoid in obstruction
82
Acute management of 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
83
Presenting features of haemochromatosis
early symptoms include fatigue, erectile dysfunction and arthralgia (often of the hands)
'bronze' skin pigmentation
diabetes mellitus
liver: stigmata of chronic liver disease, hepatomegaly, cirrhosis, hepatocellular deposition)
cardiac failure (2nd to dilated cardiomyopathy)
hypogonadism (2nd to cirrhosis and pituitary dysfunction - hypogonadotrophic hypogonadism)
arthritis (especially of the hands)
84
Reversible complications of haemochromatosis
cardiomyopathy
| skin discolouration
85
Irreversible complications of haemochromatosis
Liver cirrhosis**
Diabetes mellitus
Hypogonadotrophic hypogonadism
Arthropathy
86
Aminosalicylate drugs
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
Aminosalicylates are associated with a variety of haematological adverse effects, including agranulocytosis - FBC is a key investigation in an unwell patient taking them.
*pancreatitis is 7 times more common in patients taking mesalazine than sulfasalazine
87
Sulphasalazine
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 (see mesalazine)
88
Mesalazine
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
89
Hydatid cysts
Hydatid cysts are endemic in Mediterranean and Middle Eastern countries. They are caused by the tapeworm parasite Echinococcus granulosus. An outer fibrous capsule is formed containing multiple small daughter cysts. These cysts are allergens which precipitate a type 1 hypersensitivity reaction.
90
Clinical features of hydatid cysts
Up to 90% of cysts occur in the liver and lungs
Can be asymptomatic, or symptomatic if cysts > 5cm in diameter
Morbidity caused by cyst bursting, infection and organ dysfunction (biliary, bronchial, renal and cerebrospinal fluid outflow obstruction)
In biliary rupture, there may be the classical triad of; biliary colic, jaundice, and urticaria
91
Investigation of hydatid cysts
imaging
ultrasound if often used first-line
CT is the best investigation to differentiate hydatid cysts from amoebic and pyogenic cysts
serology
useful for primary diagnosis and for follow-up after treatment
wide variety of different antibody/antigen tests available
92
Peutz-Jagher's syndrome
autosomal dominant condition characterised by numerous hamartomatous polyps in the gastrointestinal tract. It is also associated with pigmented freckles on the lips, face, palms and soles. Although the polyps themselves don't have malignant potential, around 50% of patients will have died from another gastrointestinal tract cancer by the age of 60 years.
Genetics
autosomal dominant
responsible gene encodes serine threonine kinase LKB1 or STK11
93
Peutz-Jeghers syndrome
Features
hamartomatous polyps in GI tract (mainly small bowel)
pigmented lesions on lips, oral mucosa, face, palms and soles
intestinal obstruction e.g. intussusception
gastrointestinal bleeding
94
What is carcinoid syndrome
usually occurs when metastases are present in the liver and release serotonin into the systemic circulation
may also occur with lung carcinoid as mediators are not 'cleared' by the liver
95
Features of carcinoid syndrome
flushing (often 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
96
Investigations of carcinoid syndrome
urinary 5-HIAA
| plasma chromogranin A y
97
Management of carcinoid syndrome
somatostatin analogues e.g. octreotide
| diarrhoea: cyproheptadine may help
98
Primary causes of bile acid malabsorption
excessive production of bile acid, or secondary to an underlying gastrointestinal disorder causing reduced bile acid absorption. It can lead to steatorrhoea and vitamin A, D, E, K malabsorption.
99
Secondary causes of bile acid malabsorption
ileal disease e.g. Crohn's
cholecystectomy
coeliac disease
small intestinal bacterial overgrowth
100
Investigations of bile acid malabsorption
the test of choice is SeHCAT
nuclear medicine test using a gamma-emitting selenium molecule in selenium homocholic acid taurine or tauroselcholic acid (SeHCAT)
scans are done 7 days apart to assess the retention/loss of radiolabelled 75SeHCAT
101
Management of bile acid malabsorption
bile acid sequestrants e.g. cholestyramine
102
Threadworms
Enterobius vermicularis
103
Management of enterobius vermicularis
CKS recommend a combination of anthelmintic with hygiene measures for all members of the household
mebendazole is used first-line for children > 6 months old. A single dose is given unless infestation persists
104
Crigler-Najjar syndrome, type 1
autosomal recessive
absolute deficiency of UDP-glucuronosyl transferase
do not survive to adulthood
causes unconjugated hyperbilirubinaemia
105
Crigler-Najjar syndrome type 2
slightly more common than type 1 and less severe
may improve with phenobarbitol
unconjugated hyperbilirubinaemia
106
Dubin-Johnson syndrome
autosomal recessive. Relatively common in Iranian Jews
mutation in the canalicular multidrug resistance protein 2 (MRP2) results in defective hepatic excretion of bilirubin
results in a grossly black liver
benign
Conjugated hyperbilirubinaemia
107
Rotor syndrome
autosomal recessive
defect in the hepatic uptake and storage of bilirubin
benign
conjugated hyperbilirubinaemia
108
Gilbert's syndrome
autosomal recessive
mild deficiency of UDP-glucuronyl transferase
benign
unconjugated hyperbilirubinaemia
109
Wilson's disease - genetics
Defect in the ATP7B gene
110
adverse effects of sulfasalazine
sulphapyridine moiety: rashes, oligospermia, headache, Heinz body anaemia, megaloblastic anaemia, lung fibrosis, GI upset, headache, agranulocytosis, pancreatitis*, interstitial nephritis
111
Typical history of Whipple's disease
a 45-year-old man is being investigated for diarrhoea, weight loss and arthralgia. Jejunal biopsy shows deposition of macrophages containing PAS-positive granules
112
What is whipple's disease
Whipple's disease is a rare multi-system disorder caused by Tropheryma whippelii infection. It is more common in those who are HLA-B27 positive and in middle-aged men.
113
Features of Whipple's disease
malabsorption: diarrhoea, weight loss
large-joint arthralgia
lymphadenopathy
skin: hyperpigmentation and photosensitivity
pleurisy, pericarditis
neurological symptoms (rare): ophthalmoplegia, dementia, seizures, ataxia, myoclonus
114
Investigation findings of Whipple's disease
jejunal biopsy shows deposition of macrophages containing Periodic acid-Schiff (PAS) granules
115
Management of Whipple's disease
oral co-trimoxazole for a year is thought to have the lowest relapse rate, sometimes preceded by a course of IV penicillin
116
Bile acid malabsorption: causes
primary, due to excessive production of bile acid, or secondary to an underlying gastrointestinal disorder causing reduced bile acid absorption. It can lead to steatorrhoea and vitamin A, D, E, K malabsorption.
Secondary causes are often seen in patients with ileal disease, such as with Crohn's. Other secondary causes include:
cholecystectomy
coeliac disease
small intestinal bacterial overgrowth
117
Bile acid malabsorption investigations
the test of choice is SeHCAT
nuclear medicine test using a gamma-emitting selenium molecule in selenium homocholic acid taurine or tauroselcholic acid (SeHCAT)
scans are done 7 days apart to assess the retention/loss of radiolabelled 75SeHCA
118
Bile acid malabsorption management
bile acid sequestrants e.g. cholestyramine
119
Hormones that decrease gastric H+ secretion
secretin
VIP
somatostatin
120
familial adenomatous polyposis chromosome
chromosome 5
121
Genetic causes of colorectal cancer
sporadic (95%) ( half of colon cancers show allelic loss of the APC gene) 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
hereditary non-polyposis colorectal carcinoma (HNPCC, 5%)
familial adenomatous polyposis (FAP, <1%)
122
HNPCC- hereditary non-polyposis colorectal carcinoma
an autosomal dominant condition, is the most common form of inherited colon cancer. Around 90% of patients develop cancers, often of the proximal colon, which are usually poorly differentiated and highly aggressive. 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%)
123
Typical history of Plummer-Vinson syndrome
a 60-year-old woman presents with dysphagia and lethargy. On examination she has a smooth, swollen tongue and pale conjunctivae
124
What is Plummer-Vinson syndrome
dysphagia (secondary to oesophageal webs)
glossitis
iron-deficiency anaemia- managed with iron replacement and dilatation of the webs
125
Stereotypical history of Meckle's diverticulum
a 1-year-old boy with a recent history of rectal bleeding presents with intestinal obstruction. During surgery he is found to have a omphalomesenteric band
126
What is Meckle's diverticulum
congenital diverticulum of the small intestine. It is a remnant of the omphalomesenteric duct (also called the vitellointestinal duct) and contains ectopic ileal, gastric or pancreatic mucosa
127
Rule of 2 - Meckle's diverticulum
occurs in 2% of the population
is 2 feet from the ileocaecal valve
is 2 inches long
128
Presentation of Meckle's diverticulum
abdominal pain mimicking appendicitis
rectal bleeding
Meckel's diverticulum is the most common cause of painless massive GI bleeding requiring a transfusion in children between the ages of 1 and 2 years
intestinal obstruction
secondary to an omphalomesenteric band (most commonly), volvulus and intussusception
129
Management of Meckle's diverticulum
removal if narrow neck or symptomatic. Options are between wedge excision or formal small bowel resection and anastomosis.
130
Pathophysiology of Meckle's diverticulum
normally, in the foetus, there is an attachment between the vitellointestinal duct and the yolk sac. This disappears at 6 weeks gestation
the tip is free in the majority of cases
associated with enterocystomas, umbilical sinuses, and omphaloileal fistulas.
arterial supply: omphalomesenteric artery.
typically lined by ileal mucosa but ectopic gastric mucosa can occur, with the risk of peptic ulceration. Pancreatic and jejunal mucosa can also occur.
131
Actions of somatostatin
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
132
Wilson's disease chromosome
Chromosome 13
133
Prophylaxis of variceal haemorrhage
propranolol, endoscopic banding and ligation
134
Treatment of variceal haemorrhage
Telipressin, IV abx (quinolones), ABCDE, banding
135
Kantor's string sign
gastrointestinal string sign (also known as the string sign of Kantor) refers to the string-like appearance of a contrast-filled bowel loop caused by its severe narrowing
136
Stereotypical history of Gardener's syndrome
multiple colonic polyps, osteomas, epidermoid cysts
137
What is Gardener's syndrome
sub-type of familial colorectal polyposis
138
stereotypical history of Gilbert syndrome
a young man is noted to have an elevated unconjugated bilirubin level on a fasting blood sample
139
Stereotypical history of Dubin-Johnson syndrome
a 20-year-old man of Iranian Jewish descent is investigated for jaundice and found to have an elevated conjugated bilirubin level
140
Haemochromatosis chromosomal abnormalities
Haemochromatosis is an autosomal recessive disorder of iron absorption and metabolism resulting in iron accumulation. It is caused by inheritance of mutations in the HFE gene on both copies of chromosome 6
141
Management of Hepatorenal syndrome
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 shun
142
pathophysiology of hepatorenal syndrome
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.
143
Type 1 hepatorenal syndrome
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
144
Type 2 hepatorenal syndrome
Slowly progressive
| Prognosis poor, but patients may live for longer
145
Stereotypical history of Peutz-Jeghers syndrome
a man who presents with intussusception is noticed to have multiple polyps on colonoscopy. These are later shown to be hamartomatous. He also has pigmented lesions on his lips and palms
146
Stereotypical history of Villous adenoma
a 75-year-old man presents with passing large amounts of a mucous-like diarrhoea. Bloods demonstrate hypokalaemia
147
What is Peutz-Jeghers syndrome
Autosomal dominant condition characterised by numerous hamartomatous polyps in the gastrointestinal tract. It is also associated with pigmented freckles on the lips, face, palms and soles. Although the polyps themselves don't have malignant potential, around 50% of patients will have died from another gastrointestinal tract cancer by the age of 60 years.
148
Genetics of Peutz-Jeghers syndrome
autosomal dominant
| responsible gene encodes serine threonine kinase LKB1 or STK11
149
Features of Peutz-Jeghers syndrome
hamartomatous polyps in GI tract (mainly small bowel)
pigmented lesions on lips, oral mucosa, face, palms and soles
intestinal obstruction e.g. intussusception
gastrointestinal bleeding
150
Aetiology of Dubin-Johnson syndrome
Mutation in the canalicular multidrug resistance protein 2 (MRP2) results in defective hepatic excretion of bilirubin
151
Stereotypical history of biliary colic
an obese 50-year-old woman presents with pain in the RUQ which radiates to the interscapular region. She is apyrexial and not jaundiced
152
Tropheryma whippelii
Jejunal biopsy shows periodic acid-Schiff positive macrophages
153
Anatomy of direct inguinal hernia
Protrudes through Hesselback triangle
| Passes medial to the inferior epigastric artery
154
Anatomy of indirect inguinal hernia
Protrudes through the inguinal ring
| Passes lateral to the inferior epigastric artery
155
Anatomy of femoral hernia
Protrudes below the inguinal ligament, lateral to the pubic tubercle
more common in women
156
Contra indications of liver biopsy
```
deranged clotting (e.g. INR > 1.4)
low platelets (e.g. < 60 * 109/l)
anaemia
extrahepatic biliary obstruction
hydatid cyst
haemoangioma
uncooperative patient
ascites
```
157
What is Whipple's disease
Whipple's disease is a rare multi-system disorder caused by Tropheryma whippelii infection. It is more common in those who are HLA-B27 positive and in middle-aged men.
158
Features of Whipple's disease
malabsorption: diarrhoea, weight loss
large-joint arthralgia
lymphadenopathy
skin: hyperpigmentation and photosensitivity
pleurisy, pericarditis
neurological symptoms (rare): ophthalmoplegia, dementia, seizures, ataxia, myoclonus
159
Autoimmune hepatitis- features
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
160
Types of autoimmune hepatitis - type 1
Anti-nuclear antibodies (ANA) and/or anti-smooth muscle antibodies (SMA)
Affects both adults and children
161
Types of autoimmune hepatitis - type 2
Anti-liver/kidney microsomal type 1 antibodies (LKM1)
Affects children only
162
Types of autoimmune hepatitis - type 3
Soluble liver-kidney antigen
Affects adults in middle-age
163
Second line management of C. diff
oral fidaxomicin
164
Features of c.diff
diarrhoea
abdominal pain
a raised white blood cell count (WCC) is characteristic
if severe toxic megacolon may develop
165
Metabolic consequences of re-feeding syndrome
hypophosphataemia
hypokalaemia
hypomagnesaemia: may predispose to torsades de pointes
abnormal fluid balance
166
How to prevent vertical transmission of Hep B
give baby Hep B vaccine and immunoglobulin after birth
167
Bile malabsorption investigations
is SeHCAT
nuclear medicine test using a gamma-emitting selenium molecule in selenium homocholic acid taurine or tauroselcholic acid (SeHCAT)
scans are done 7 days apart to assess the retention/loss of radiolabelled 75SeHCAT
168
Monoclonal antibody for treatment of c.diff
Bezlotoxumab is a monoclonal antibody which binds to Clostridium difficile toxin B and neutralises it to prevent recurrence of infection.
169
Features of severe pancreatitis
```
age > 55 years
hypocalcaemia
hyperglycaemia
hypoxia
neutrophilia
elevated LDH and AST
```
170
Plummer Vinson Syndrome
Triad of:
dysphagia (secondary to oesophageal webs)
glossitis
iron-deficiency anaemia
Treatment includes iron supplementation and dilation of the webs
171
Gilbert syndrome
isolated hyperbilirubinaemia in relation to physiological stress- student revising for exams
172
Features of haemochromatosis
early symptoms include fatigue, erectile dysfunction and arthralgia (often of the hands)
'bronze' skin pigmentation
diabetes mellitus
liver: stigmata of chronic liver disease, hepatomegaly, cirrhosis, hepatocellular deposition)
cardiac failure (2nd to dilated cardiomyopathy)
hypogonadism (2nd to cirrhosis and pituitary dysfunction - hypogonadotrophic hypogonadism)
arthritis (especially of the hands)
173
Genetics of Haemochromatosis
inheritance of mutations in the HFE gene on both copies of chromosome 6*. It is often asymptomatic in early disease and initial symptoms often non-specific e.g. lethargy and arthralgia
Epidemiology
1 in 10 people of European descent carry a mutation in the genes affecting iron metabolism, mainly HFE
prevalence in people of European descent = 1 in 200, making it more common than cystic fibrosis
174
Function of luminal peptide
trigger secretion of Gastrin
175
Features of Whipple's disease
HLA-B27 positive
malabsorption: diarrhoea, weight loss
large-joint arthralgia
lymphadenopathy
skin: hyperpigmentation and photosensitivity
pleurisy, pericarditis
neurological symptoms (rare): ophthalmoplegia, dementia, seizures, ataxia, myoclonus
176
Investigations of Whipple's disease
Jejunal biopsy shows deposition of macrophages containing Periodic acid-Schiff (PAS) granules
177
Conditions associated with H Pylori
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
178
Histology of Barrett's oesophagus
the columnar epithelium may resemble that of either the cardiac region of the stomach or that of the small intestine (e.g. with goblet cells, brush border)
179
Secondary haemochromatosis
iron overload from multiple transfusions
Tan
New onset DM
180
Features of carcinoid tumours
flushing (often 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
181
Primary biliary cholangitis
```
the M rule
IgM
anti-Mitochondrial antibodies, M2 subtype
Middle aged females
Commonly presents with itching
```
182
Complications of primary biliary cirrhosis
cirrhosis → portal hypertension → ascites, variceal haemorrhage
osteomalacia and osteoporosis
significantly increased risk of hepatocellular carcinoma (20-fold increased risk)
183
Management of primary biliary cirrhosis
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
184
Diagnosis of primary biliary cirrhosis
immunology
anti-mitochondrial antibodies (AMA) M2 subtype are present in 98% of patients and are highly specific
smooth muscle antibodies in 30% of patients
raised serum IgM
imaging
required before diagnosis to exclude an extrahepatic biliary obstruction (typically a right upper quadrant ultrasound or magnetic resonance cholangiopancreatography (MRCP)
185
Features of Child Pugh score
```
bilirubin
albumin
prolonged prothrombin
encephalopathy
ascites
```
186
Drugs causing dyspepsia
```
NSAIDs
bisphosphonates
steroids
calcium channel blockers*
nitrates*
theophyllines
```
187
Post-cholecystectomy syndrome
dyspepsia, vomiting, pain, flatulence and diarrhoea
Pain related to sphincter of oddi dysfunction
low fat diet and cholestyramine
188
Primary sclerosing cholangitis
ulcerative colitis: 4% of patients with UC have PSC, 80% of patients with PSC have UC
Crohn's (much less common association than UC)
HIV
189
Features of primary sclerosing cholangitis
```
cholestasis
jaundice, pruritus
raised bilirubin + ALP
right upper quadrant pain
fatigue
```
190
Investigations of primary sclerosing cholangitis
endoscopic retrograde cholangiopancreatography (ERCP) or magnetic resonance cholangiopancreatography (MRCP) are the standard diagnostic investigations, showing multiple biliary strictures giving a 'beaded' appearance
p-ANCA may be positive
there is a limited role for liver biopsy, which may show fibrous, obliterative cholangitis often described as 'onion skin'
191
Intestinal causes of malabsorption
```
coeliac disease
Crohn's disease
tropical sprue
Whipple's disease
Giardiasis
brush border enzyme deficiencies (e.g. lactase insufficiency)
```
192
pancreatic causes of malabsorption
chronic pancreatitis
cystic fibrosis
pancreatic cancer
193
Diagnosis of small bowel overgrowth
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
194
Features of small bowel overgrowth
Chronic diarrhoea
bloating, flatulence
abdominal pain
195
Peutz-Jeghers syndrome
hamartomatous polyps in GI tract (mainly small bowel)
pigmented lesions on lips, oral mucosa, face, palms and soles
intestinal obstruction e.g. intussusception
gastrointestinal bleeding
196
VIP - vasoactive intestinal peptide
source: small intestine, pancreas
stimulation: neural
actions: stimulates secretion by pancreas and intestines, inhibits acid and pepsinogen secretion
197
VIPoma
```
90% arise from pancreas
large volume diarrhoea
weight loss
dehydration
hypokalaemia, hypochlorhydia
```
198
Zollinger-Ellison syndrome
```
Excessive gastrin production
usually from a gastrin secreting tumour usually of the duodenum or pancreas. Around 30% occur as part of MEN type I syndrome
multiple gastroduodenal ulcers
diarrhoea
malabsorption
```
199
Melanosis coli
Melanosis coli is a disorder of pigmentation of the bowel wall. Histology demonstrates pigment-laden macrophages
It is associated with laxative abuse, especially anthraquinone compounds such as senna
200
Autoimmune hepatitis
young women
amennorrhoea
derranged LFTs
201
Purtscher retinopathy
cotton wool spots on fundoscopy
| associated with acute pancreatitis
