Gastroenterology: Coeliac + rare conditions Flashcards
1
Q
What is coeliac disease?
A
T cell-mediated inflammatory autoimmune disease affecting the small bowel in which sensitivity to prolamin results in villous atrophy and malabsorption
2
Q
Which part of the immune system mediates coeliac disease?
A
T cells
3
Q
Which part of the bowel is affected in coeliac?
A
Small bowel
4
Q
Which gender is affected more by coeliac?
A
Females (2:1)
5
Q
Which nationality is more affected by coeliac?
A
Irish populations
6
Q
At which age does coeliac present?
A
Bimodal
1) Infancy
2) 50-60 years
7
Q
What are risk factors/associations with coeliac?
A
1) Family history
2) HLA-DQ2 allele
3) Other autoimmune disease e.g. T1D
8
Q
Which gene is associated with coeliac?
A
HLA-DQ2 allele
9
Q
What are the GI symptoms in coeliac?
A
1) Abdo pain
2) Distension
3) N&V
4) Diarrhoea
5) Steatorrhoea
10
Q
What are the systemic symptoms of coeliac?
A
1) Fatigue
2) Weight loss/failure to thrive in children
11
Q
What are the general signs of coeliac?
A
1) Pallor - anaemia
2) Short stature + wasted buttocks - malnutrition
3) Features of vitamin deficiency - malabsorption e.g bruising due to vitamin K deficiency
12
Q
What is the dermatological manifestation of coeliac?
A
Dermatitis herpetiformis
13
Q
How does dermatitis herpetiformis present?
A
Pruritic papulovesicular lesions over the buttocks and extensor surfaces of the arms, legs and trunks
14
Q
What are features of severe coeliac disease?
A
1) Weight loss or failure to thrive
2) Short stature + wasted buttocks
3) Dermatitis herpetiformis
15
Q
What are the complications of coeliac?
A
1) Unexplained iron deficiency (anaemia)
2) B12 or folate deficiency
3) Hyposplenism
4) Osteoporosis - DEXA scan may be required
16
Q
What diseases are associated with coeliac?
A
1) Type 1 diabetes
2) Autoimmune thyroid disease e.g. Graves disease or Hashimoto’s thyroiditis
3) Enteropathy associated T-cell lymphoma
17
Q
What malignancy are people with coeliac at risk of?
A
T cell lymphoma (enteropathy associated)
18
Q
What initial investigations should be done in coeliac disease?
A
1) Stool culture - to exclude infection
2) FBC - anaemia (can be any type)
3) U&E and bone profile (vitamin D absorption may be impaired)
4) LFT - albumin may be low (malabsorption)
5) Iron, B12, folate
19
Q
How do you diagnose coeliac?
A
OGD + duodenal/jejunal biopsy
20
Q
When should patients be referred for OGD + biopsy in suspected coeliac?
A
1) After positive serological testing
2) Negative serological testing but high suspicion
21
Q
When should OGD + biopsy for coeliac ideally be carried out?
A
Before gluten is withdrawn from the diet + repeat after gluten withdrawal (to demonstrate resolution)
22
Q
What are the histological features of coeliac on duodenal biopsy?
A
1) Sub-total villous atrophy
2) Crypt hyperplasia
3) Intra-epithelial lymphocytes
23
Q
What two serological blood tests are done first line in suspected coeliac?
A
1) Anti-TTG IgA antibody
2) IgA level - 2% of coeliac patients are IgA deficient so will have a false negative anti-TTG IgA
24
Q
What type of antibody is anti-TTG?
A
IgA
25
Which serological test can be measured in coeliac if the patient is found to be IgA deficient on initial testing?
Anti-TTG IgG
26
Which serological test can be measured in coeliac disease if anti-TTG IgG is weakly positive?
Anti-endomyseal (more specific but less sensitive)
27
Which two antibodies are associated with coeliac?
1) Anti-TTG (IgA and IgG)
2) Anti-endomyseal antibody
28
When can HLA-DQ2 testing be used for coeliac?
In specialist settings e.g. in children who are not having a biopsy
29
How is coeliac disease managed?
1) Life-long gluten free diet - patient education on which foods contain gluten
2) Regular monitoring to check adherence to gluten-free diet + screen for complications
30
What does the presence of hyposplenia as a complication of coeliac disease mean?
Patients have a susceptibility to encapsulated organisms
31
What is enteropathy associated T cell lymphoma (EATL)?
A rare type of non-Hodgkin lymphoma
32
What is the link between EATL and coeliac?
The likelihood or acquiring this malignancy is directly proportional to the strength of overall adherence to a gluten free diet - i.e. the more a patient breaks adherence, the more likely they are to get EATL
33
What is gastroparesis (delayed gastric emptying)?
Delayed gastric emptying caused by decreased activity of the stomach muscles, causing food to be held in the stomach for a longer period than usual
34
Which condition is gastroparesis associated with?
Diabetes
35
What causes the delayed gastric emptying in gastroparesis?
Decreased activity of the stomach muscles (food held in stomach longer than usual)
36
Why does gastroparesis develop in diabetes?
Due to autonomic neuropathy
37
How does gastroparesis present?
1) N&V
2) Feeling of fullness after a few bites
3) Abdominal pain
4) Bloating
5) ± poor glucose control due to lack of absorption of indigested food in diabetic patients
38
Why does gastroparesis in diabetes lead to poor glucose control?
Due to lack of absorption of indigested food
39
How do you diagnose gastroparesis?
Solid meal gastric scintigraphy (radionuclide studies of gastric emptying)
40
How do you manage gastroparesis?
1) Dietary modification - low fibre, smaller/more frequent meals, pureed/mashed food
2) Domperidone
3) Metoclopramide or erythromycin (motility agents)
41
Which medications can be used to manage gastroparesis?
1) Domperidone
2) Metoclopramide or erythromycin (motility agents)
42
What dietary modifications are recommended in gastroparesis?
1) Low fibre
2) Smaller/more frequent meals
3) Pureed/mashed food
43
What is Zollinger-Ellison syndrome?
The development of several ulcerations in the stomach + duodenum due to uncontrolled release of gastrin from a gastrinoma in the pancreas or less commonly duodenum
44
Where does the ulceration occur in Zollinger-Ellison syndrome?
Stomach + duodenum
45
What causes Zollinger-Ellison syndrome?
Uncontrolled release of gastrin from a gastrinoma
46
What does the uncontrolled release of gastrin in Zollinger-Ellison syndrome result in?
Ulcers (gastric + duodenal)
47
Where does the gastrinoma usually present in Zollinger-Ellison syndrome?
Pancreas (can also occur in duodenum)
48
Which condition is Zollinger-Ellison syndrome associated with?
MEN-1 (multiple endocrine neoplasia 1)
49
What is MEN-1 (multiple endocrine neoplasia 1)?
Part of a group of genetically inherited diseases that result in proliferative lesions of multiple endocrine organs
50
Which organs do the abnormalities in MEN-1 affect?
3 Ps = pancreas, parathyroid, pituitary (endocrine organs)
51
How does Zollinger-Ellison syndrome present?
1) Abdominal pain - typically epigastric
2) Diarrhoea
3) GI bleeding - due to ulceration of the duodenum
52
How can you differentiate Zollinger-Ellison syndrome from other causes of duodenal/gastric ulcers?
Patients will not respond to simple PPIs
53
What is the initial screening test for Zollinger-Ellison syndrome?
Gastric pH or gastrin levels - both raised
54
How do you diagnose Zollinger-Ellison syndrome?
Secretin stimulation test (provocative test - give secretin and observe a v large increase in gastrin)
55
What is the best imaging modality to identify Zollinger-Ellison syndrome?
Somatostatin receptor scintigraphy - CT scans can often miss the tumour
56
What additional investigation is performed in Zollinger-Ellison syndrome?
Endoscopy - to identify duodenal ulcers
57
How is Zollinger-Ellison syndrome treated?
Resection of tumour (if no metastases)
58
Which type of ulcer is most common in Zollinger-Ellison syndrome?
Duodenal
59
What is hereditary haemochromatosis?
Disorder of iron metabolism
60
What happens in hereditary haemochromatosis?
Excessive iron accumulates in the body (due to disordered iron metabolism) and is deposited in a number of sites incl. liver, heart, joints, pituitary, pancreas and skin
61
What is the most common hereditary haemochromatosis genotype?
Homozygosity for HFE C282Y
62
Which protein is affected in hereditary haemochromatosis, causing iron overload?
HFE protein
63
What are liver complications of hereditary haemochromatosis?
1) Liver fibrosis
2) Cirrhosis
3) Hepatocellular carcinoma
64
What is a cardiac complication of hereditary haemochromatosis?
1) Severe myocardial siderosis (deposition of excess iron) leading to cardiac dysfunction
2) May manifest as dyspnoea, orthopnoea or arrhythmia that improves after iron depletion
65
What is a pancreatic complication of hereditary haemochromatosis?
Diabetes - often unchanged by phlebotomy therapy
66
What is the dermatological complication of hereditary haemochromatosis?
Skin hyperpigmentation (bronze) - often decreases after phlebotomy
67
How does hereditary haemochromatosis present?
1) Bronze skin
2) Type 2 diabetes
3) Fatigue
4) Joint pain (arthropathy)
5) Liver cirrhosis
6) Adrenal insufficiency
68
What is the initial investigation done for hereditary haemochromatosis?
Blood tests + iron studies
69
What do blood tests + iron studies show in hereditary haemochromatosis?
1) Deranged LFTs
2) Raised serum ferritin
3) Raised transferrin saturation
70
What further investigations are done in hereditary haemochromatosis?
1) Genetic testing - can reveal HFE gene defects
2) Brain and heart MRI - may show evidence of iron deposition
3) Liver biopsy - show increased iron stores
71
What is the primary goal of therapy in hereditary haemochromatosis?
Iron depletion to normalise body iron stores + prevent/decrease iron-mediated tissue injury and organ dysfunction
72
What is the first line/primary therapy to normalise iron stores in hereditary haemochromatosis?
Phlebotomy/venesection - stimulates erythropoiesis and mobilises iron from parenchymal cells and other storage sites
73
What is a second line treatment option for hereditary haemochromatosis?
Desferrioxamine - an iron chelating agent
74
How does phlebotomy treat hereditary haemochromatosis?
Phlebotomy stimulates erythropoiesis and mobilises iron from parenchymal cells and other storage sites
75
What is desferrioxamine?
Iron chelating agent
76
How do you treat dermatitis herpetiformis?
Dapsone (antibiotic)
77
What is porphyria?
Spectrum of disorders caused by defects in haem synthesis due to alterations in enzyme function or structure
78
What are the types of acute porphyria?
1) Acute intermittent porphyria
2) Variegate porphyria
3) ALA deficiency
79
What are triggers of acute porphyria?
1) Antibiotics - Rifampicin, Isoniazid, Nitrofurantoin
2) Anaesthetic agents - Ketamine, Etomidate
3) Sulfonamides
4) Barbiturates
5) Antifungal agents
80
How does acute porphyria attack present?
1) Abdominal pain
2) Nausea
3) Confusion
4) Hypertension
81
How do you diagnose porphyria?
Urinary porphobilinogen levels (a product in the pathway of haem metabolism) - urine samples need to be protected from light to prevent the breakdown of PBG
82
How do you management acute porphyria attacks?
Largely supportive - haem arginate can also be given IV to replenish haem levels
83
What is alpha-1 antitrypsin deficiency?
Inherited condition that affects the lungs and liver
84
How does alpha-1 antitrypsin deficiency affect the lungs?
Emphysema - without alpha-1 antitryptase there is less defence against neutrophil elastase, which destroys the alveoli (this process is exacerbated in smokers)
85
What does alpha-1 antitrypsin deficiency cause in the liver?
Cirrhosis + hepatocellular carcinoma
86
What does alpha-1 antitrypsin deficiency cause in the lungs?
Emphysema
87
How does alpha-1 antitrypsin deficiency present?
1) COPD presenting at 30-40 years old
2) Neonatal jaundice at birth
3) Deranged LFTs in adults with no other identified cause
88
How do you diagnose alpha-1 antitrypsin deficiency?
1) Alpha-1 antitrypsin levels
2) Genotyping
3) Liver biopsy
89
What do you see on liver biopsy in alpha-1 antitrypsin deficiency?
Periodic acid Schiff positive globules
90
What does CXR show in alpha-1 antitrypsin deficiency?
Hyperinflation
91
How is alpha-1 antitrypsin deficiency managed?
Few management options
1) Advise patients to stop smoking
2) Liver transplant may be required in cases of decompensation
3) IV A1AT pooled from human donors is expensive and not widely used
92
What makes alpha-1 antitrypsin deficiency worse?
Smoking
93
What happens in Wilson's disease?
Impaired copper metabolism and build up of copper in tissues
94
What is the genetic cause of Wilson's disease?
Defective ATP7B protein product
95
Which gender is more affected by Wilson's disease?
Equally affects men and women
96
What are the different ways that Wilson's disease can present?
1) Diseases manifestations can be pleomorphic
2) May be predominantly hepatic, neurological or psychiatric
3) Manifestations may range from asymptomatic state to life-threatening fulminant hepatic failure
97
What are the liver manifestations of Wilson's disease?
1) Asymptomatic disease with transaminase elevation
2) Acute hepatitis
3) Acute on chronic liver failure
4) Cirrhosis
5) Liberation of copper into the bloodstream causes Coomb's negative haemolytic anaemia, with transient episodes of low-grade haemolysis and jaundice
98
What are the neurological manifestations of Wilson's disease?
1) An akinetic-rigid syndrome similar to Parkinson's disease
2) Pseudosclerosis dominated by tremor
3) Ataxia
4) A dystonic syndrome, which often leads to severe contractures
5) Other findings = drooling, spasticity, chorea, athetosis, myoclonus, micrographia, dyslalia, hypomimia, and dysarthria
99
What are the psychiatric manifestations of Wilson's diease?
May present before hepatic or neurological signs in up to ⅓ of patients
1) Decreased academic performance or personality changes
2) Sexual exhibitionism
3) Impulsiveness
4) Labile mood
5) Inappropriate behaviour
6) Depression
7) Paranoia
8) Schizophrenia
- Leads also to suicide in a discrete number of cases
100
What are the ocular manifestations of Wilson's disease?
1) Kayser-Fleischer ring (deposition of copper in the Descemet's membrane)
2) Sunflower cataracts in the lens (deposition of copper in the anterior and posterior capsule of the lens, sparing epithelial and cortical cells)
101
What is the first line investigation of choice when screening for Wilson's disease?
24h urine collection - test for urinary copper (will be high)
102
Which other tests can be done in Wilson's disease?
Serum caeruloplasmin and serum copper - usually low (despite copper deposits in tissues) but may be normal
103
How is the diagnosis of Wilson's disease confirmed?
Genetic analysis of the ATP7B gene
104
How is Wilson's disease managed?
1) Chelators e.g. D-penicillamine and trientine
2) Zinc salts act as inductors of methallothioneins, which favour a negative copper balance and a reduction of free plasmatic copper
3) Screening in first and second relatives of index cases is mandatory
105
What are the levels of serum caeruloplasmin and serum copper in Wilson's disease?
Usually low (or normal)
106
What are carcinoid tumour/syndrome?
Rare, slow growing malignant tumours that develop in the neuroendocrine system
107
Carcinoid tumours are cancers of which system?
Neuroendocrine system
108
What are two common primary origin sites of carcinoid tumours?
1) Appendix
2) Small intestine
109
What % of carcinoid tumours secrete hormones?
5-10%
110
Which hormone is most commonly secreted by carcinoid tumours?
Serotonin
111
How do carcinoid tumours present?
1) Abdominal pain
2) Diarrhoea
3) Flushing
4) Wheeze
5) Pulmonary stenosis
112
What causes the symptoms in carcinoid tumours?
1) Symptoms are caused by the effects of serotonin and its breakdown products on the systemic circulation
2) Patients with gastrointestinal carcinoid tumours only experience these symptoms if they have liver metastases, as the products of the tumour can drain straight into the hepatic vein without undergoing metabolism in the liver itself
113
When do gastrointestinal carcinoid tumours cause more systemic symptoms?
If they have liver metastases, as the products of the tumour can drain straight into the hepatic vein without undergoing metabolism in the liver itself
114
How do you treat carcinoid tumours?
1) Octreotide (somatostatin analogue) - to inhibit tumour products
2) Surgical resection - to decrease tumour size
115
What is Whipple's disease?
Rare, systematic disease
116
What causes Whipple's disease?
Tropheryma whipplei (gram positive bacteria)
117
How does Whipple's disease present?
1) Diarrhoea
2) Abdominal pain
3) Joint pain
But can affect any part of the body incl. cardiac and nervous systems
118
Which gender is more affected by Whipple's disease?
Males
119
How do you diagnose Whipple's disease?
Small bowel biopsy
120
What do you see on small bowel biopsy in Whipple's disease?
Presence of acid-Schiff (PAS)-positive macrophages, which are seen to contain the causative bacteria on electron microscopy
121
How do you treat Whipple's disease?
Long term course of co-trimoxazole
