Gastroenterology Flash Cards

Question 1

Achalasia (features, investigations, therapeutic options).

Answer 1

Impaired lower oesophageal sphincter relaxation and peristalsis in distal oesophagus.
Chronic, often constant, dysphagia for solids and liquids.
Weight loss unusual unless end-stage disease.
Increased risk of SCC x 10.
Investigations - barium swallow, endoscopy, oesophageal manometry.
Therapeutic options:
- calcium channel blockers, ISM.
- peroral endoscopic myotomy (POEM) * preferred.
- pneumatic dilatation (PD).
- oesophagectomy.
- endoscopic botox injection.

Question 2

Eosinophilic Oesophagitis.

Answer 2

Younger patients; male > female.
- Food bolus obstruction.
- Chronic dysphagia solids > liquids.
- Refractory GORD.
Infiltration of eosinophils into oesophageal mucosa (15/hpf).
Therapeutic options:
1. PPI therapy - lack of evidence; usually high-dose for 8 weeks.
2. Swallowed topical steroids - eg budesonide 1mg orodispersive tablets.
3. Dietary elimination - difficult.

Question 3

Barrett’s Oesophagus.

Answer 3

Risks: male, Caucasian, overweight, age, chronic heartburn, smoking, positive family history.
Precursor to oesophageal adenocarcinoma.
Risk of progression 0.38% per year.
Medical therapy: evidence to suggest combination PPI and aspirin therapy reduces risk of cancer development (AspECT trial).

Question 4

Barrett’s Surveillance - confirmed LGD / HGD.

Answer 4

If LGD confirmed on 2 occasions 6 months apart by two expert pathologists -> endoscopic ablation therapy (or close surveillance).
If HGD confirmed, annual risk of progression to adenocarcinoma is 10%. Oesophagectomy vs. endoscopic resection preferred to ablative techniques.
Post-removal of HGD, need to treat the remainder of Barrett’s and RFA preferred.

Question 5

Malignant and Benign Features of Dysphagia.

Answer 5

Malignant:

1. Shorter duration.
2. Solids > liquids.
3. Constant and progressive.
4. Older age.
5. Accompanying alarm symptoms.

Benign:
1. Often long history.
2. Liquids + solids.
3. Intermittent/unpredictable.
4. Younger -> can have alarm symptoms e.g. weight loss, but this is often late in the clinical course.
(DDx: eosinophilic oesophagitis, achalasia, other dysmotility, benign stricture, globus hystericus).

Question 6

Oesophageal Cancer Types.

Answer 6

1. Squamous cell carcinoma.
   - 90% oesophageal cancer worldwide.
   - Male:female 1:1.
   - Associations: smoking, alcohol, 10x more likely in achalasia.
   - Most commonly in mid-oesophagus.
2. Adenocarcinoma.
   - Most common oesophageal cancer in N. America and Europe.
   - Male:female 3-4:1.
   - Associations: GORD, obesity, no link to alcohol.
   - Lower oesophageal distribution.

Question 7

Endoscopic Features of Benign and Malignant Ulcers.

Answer 7

Benign:

• Round/oval/punched out, flat, smooth base.
• Smooth margins and normal surrounding mucosa.
• Majority <2cm.
• Normal adjoining rugal margins that extend to margins of the ulcer base.

Malignant:

• Irregular outline with necrotic or haemorrhagic base.
• Irregular raised margin.
• Anywhere.
• Any size.
• Prominent and oedematous rugal folds that usually do not extend to the margins.

Question 8

H. pylori and disease.

Answer 8

<20% of those infected develop symptoms.
PUD: ~10% of infected patients.
Gastric Ca.: 1-3% of infected patients.
MALT lymphoma: <0.1% infected patients.
BUT
- HP gastritis in 80% of patients with gastric cancer.
- HP in 95% MALT lymphoma.

Question 9

H. pylori and peptic ulcer disease.

Answer 9

75% of duodenal ulcers are associated with HP; eradication heals 95-98% compared with 85-95% with acid suppression alone.
HP infection associated with 70-80% gastric ulcers, 85% heal with HP eradication.
In upper GI bleeding from peptic ulcers, 27-37% will suffer a a re-bleed annually without HP eradication.

Question 10

H. pylori therapy.

Answer 10

Increased clarithromycin resistance.
Triple therapy should not be prescribed unless H. pylori clarithromycin resistance rates are known to be <15%.
If clarithromycin resistance rates are not known, do not use triple therapy.
First-line if clarithromycin resistance >15% or unknown:
- Quadruple therapy with clarithromycin + metronidazole + amoxicillin + PPI.
- Treatment duration: 14 days.

Question 11

Post-eradication H. pylori testing.

Answer 11

Everyone.
No sooner than 4 weeks after completion of treatment.
If repeat endoscopy is clinically unnecessary - urea breath test or faecal antigen testing is acceptable.
Pre-breath test: withhold antibiotics for >28 days, withhold PPI for 7-14 days.
Pre-faecal antigen test: withhold PPI 14 days.

Question 12

Guidelines on anti-platelet agents in high-risk patient with GI bleed.

Answer 12

Restart APA on day 3 post-endoscopy -> relook gastroscopy up to discretion of endoscopist.

If DAPT -> continue aspirin; clopidogrel/ticagrelor continuation/resumption decided on case-by-case basis with cardiologist. If low-risk stigmata, single or DAPT can continue.

Question 13

Warfarin and GI Bleed.

Answer 13

Scope when INR = 2.5.
Don’t delay to correct coagulopathy.
If INR supra-therapeutic - no evidence. Therefore, partial or complete reversal indicated in cases of serious/life threatening bleeding.
If risk of reversal very high and bleed not severe - delaying endoscopy may be reasonable option.

Question 14

DOAC and GI Bleed.

Answer 14

If patient stable/responds to resuscitation, reasonable to delay 12-24 hours.
If persistently hypotensive:
a) Dabigatran -> Idarucizumab.
b) Xa inhibitors
- Andexanet alpha (US).
- Combination of clotting factors have been used (PCC/4F PCC).
Resumption same as warfarin.

Question 15

Coeliac Testing.

Answer 15

Anti-TTG
- Test of choice provided patient consuming gluten-containing diet and sufficient IgA.
If anti-TTG IgA weakly positive, anti-endomysial IgA.
- Very specific but technically difficult test.
In IgA deficiency -> use IgG tests.
** must always test for IgA deficiency.

Question 16

Refractory Coeliac Disease (subtypes).

Answer 16

Type 1 (85%)

• Lymphocyte infiltrate is the same as that in untreated CD.
• Steroids +/- steroid-sparing agents e.g. azathioprine.
• ?budesonide, ?mesalazine.

Type 2 (15%)

• CD3 intra-epithelial T cells with abnormal surface markers /- oligoclonal T cell expansion.
• Less favourable prognosis.
• Malnutrition can be profound, may need TPN.
• Multitude of therapies tried -> best evidence for Cladribine (chemotherapy used in haematological malignancies).

Question 17

Whipple’s Disease.

Answer 17

Triad: weight loss, chronic diarrhoea (which can be bloody), arthralgia.
+ prolonged fever and peripheral lymphadenopathy.
SB biopsy shows PAS-positive macrophages in sub-mucosa.

Question 18

Jaundice (DDx).

Answer 18

1. Elevated haeme load.
   - Haemolysis.
   - Inadequate erythropoiesis.
   - Haematoma.
2. Hepatocellular dysfunction.
   - Hepatitis.
   - Hepatic failure.
   - Cirrhosis.
   - Drug injury.
3. Biliary obstruction.
   - Malignant.
   - Parasitic.
   - Stone disease.
   - Extrinsic compression.

Question 19

Screening for HCC in Cirrhosis.

Answer 19

USS + AFP 6-monthly.

Question 20

Cutaneous and extremity manifestations of cirrhosis.

Answer 20

Increase in estradiol:
- spider angiomas.
- gynecomastia.
- feminization: inversion of male pubic hair pattern, loss of axillary or chest hair.
- palmar erythema (central palmar sparing).
- testicular atrophy.
Jaundice.
Nail changes: terry nails, muehrchke nails, clubbing.
Hypertrophic osteoarthropathy.
Dupytren’s contractures.

Question 21

Physical Findings of Cirrhosis.

Answer 21

Parotid gland enlargement (alcohol).
Fetor hepaticus.
Ascites.
Caput medusae.
Splenomegaly.
Cruveilhier-Baumgarten murmur.
Asterixis.

Question 22

Hepatic Encephalopathy (staging, features).

Answer 22

Reversible neuropsychiatric abnormalities associated with liver dysfunction and/or portosystemic shunting.
Staging:
- Minimal.
- Grade 1: sleep/wake reversal, change in behaviour, mild confusion..
- Grade 2: lethargy, moderate confusion.
- Grade 3: stupor, arousable, incoherent.
- Grade 4: unresponsive to pain, intubate.
Hyperreflexia, bradykinesia, myoclonus, rigidity, nystagmus, decerebrate posturing, focal neurological defects.
NB: caused by ammonia penetration into the CNS. A healthy liver clears ammonia by conversion to glutamine. Measurement of venous ammonia is often not helpful. Not useful prognostically.

Question 23

Causes of Hepatic Encephalopathy.

Answer 23

Infection.
Bleeding.
Medication - anticholinergics, narcotics/benzodiazepines.
Metabolic derangement - alkalosis, hypokalaemia, hyponatraemia.
Hypovolaemia/hypoxia.
Constipation.

Question 24

Treatment of Hepatic Encephalopathy.

Answer 24

Lactulose.

• decrease GI transit time.
• decrease pH of gut lumen, trapping NH4.
• alternative metabolic substance for gut bacteria - less ammonia production.
• 30-45mL 2-4 times per day.
• goal is 2-3 soft stools per day.

Rifaximin.

• 400mg tds or 550mg bd.
• novel antibiotic - decontamination of the gut.

Question 25

Ascites and Albumin-Gradient.

Answer 25

High gradient = portal hypertension.

• Serum albumin to ascites gradient >/= 11g/L.
• Not specific for cirrhosis.
• Alcoholic hepatitis, heart failure, massive hepatic metastases, Budd-Chiari, portal vein thrombosis, portal fibrosis, schistosomiasis.

Low gradient = leaky capillaries/tumour.

• Serum albumin to ascites albumin gradient <11g/L.
• Peritoneal carcinomatosis, peritoneal tuberculosis, pancreatitis, serositis, nephrotic syndrome.

Question 26

Ascitic Fluid Analysis.

Answer 26

Cell count and differential is the single most useful test to perform on ascites fluid.
>500WBC is abnormal.
>250/mm3 neutrophils is consistent with peritonitis.
Total protein - values <10g/L indicate high-risk for SBP.
LDH increased in infection.
Consider perforation if 2 out of 3 present:
1. Total protein >10.
2. Glucose <2.8.
3. LDH > ULN for serum.

Question 27

Spontaneous Bacterial Peritonitis.

Answer 27

Infection in the ascitic fluid in the absence of a surgical source.
>/=250 PMNs/mm3.
Empiric treatment with fever (T 37.8, abdominal pain, altered mental status, positive paracentesis).
Gut bacteria: E. coli, Klebsiella common pathogens.
Use broad-spectrum antibiotics without nephrotoxicity for five days: Cefotaxime 2g 8 hourly.
Discontinue non-selective beta-blockers. These are associated with 58% increase in mortality.

** NB: IV Albumin in patients with SBP (1.5g/kg) at diagnosis and 1gm/kg on Day 3.

Question 28

SBP Prophylaxis.

Answer 28

History of SBP:
- Prolonged/indefinite use of TMP/SMX or daily Fluoroquinolone.
- Inpatients with ascites fluid total protein <10 or 15 -> antibiotics during the hospitalisation.
Cirrhosis with GI bleeding:
- Ceftriaxone 1g daily, followed by TMP/SMX twice a day or Ciprofloxacin 500mg bd for seven days.

Question 29

Gastrooesophageal Varices Treatment.

Answer 29

Pre-primary prophylaxis: treat underlying liver disease (HCV, HBV, NASH).

Primary prophylaxis (varices present, but never bleed): screening endoscopy every 1-3 years, non-selective beta blocker (nadolol or propranolol) or Carvedilol or endoscopic variceal ligation.

Secondary prophylaxis: endoscopic variceal ligation and NSBB.

Acutely:

1. Resuscitation.
2. Antibiotic prophylaxis.
3. Lower the portal pressure:
   - octreotide/terlipressin.
   - avoid over-transfusion (goal Hb 70-80).
   - TIPSS.

** an INR >3 in a patient with cirrhosis does not indicate an increased risk for bleeding due to rebalanced haemostasis in CLD.

Question 30

Management of Haemostatic Abnormalities in Liver Disease with Bleeding.

Answer 30

Vitamin K.
Treat infection.
Consider DIC (diminished factor VIII level).
Cryoprecipitate - given for hypofibrinogenaemia or dysfibrinogenaemia.
PCC and recombinant activated factor VII expensive and not proven to improve outcomes.
Avoid FFP due to large volume.
Transfuse platelets to keep count >50,000.

Question 31

Hepatorenal Syndrome.

Answer 31

Progressive rise in creatinine >150mg/L.
Absence of shock.
Urine Na <10.
Cirrhosis with ascites.
No response to two days of volume expansion and withdrawal of diuretics.
No nephrotoxic drugs.

Type 1:

• Twofold increase in creatinine to >250mg/L during a period of less than 2 weeks.
• Median survival is a few weeks without treatment.
• Always fix the volume -> albumen 1g/kg/d up to 100g/d.
• Terlipressin 1-2m g IV every 4-6 hours with albumen 25-50g/day.
• norepinephrine and albumen in the critically ill.
• dialysis only as a bridge to transplant or acute injury recovery.

Type 2:

• Diuretic-resistant ascites.
• Slow increase in Cr >150mg/L.
• Median survival 6 months.

Question 32

Causes of Cholestatic Liver Disease.

Answer 32

A. Non-obstructive.

• PBC.
• Drugs.
• Pregnancy/oestrogens.
• CF.

B. Obstructive.

• PSC.
• Tumours.
• Cholelithiasis.
• Biliary cysts.
• Pancreatic disease.

Question 33

Primary Biliary Cholangitis.

Answer 33

95% women; usually 30-65 years.
Half asymptomatic at time of diagnosis.
Fatigue and pruritus most common symptoms - itching worse at night.
25-50% have hyperpigmentation.
Elevated ALP.
GGT and 5'Nucleotidase elevation.
Eosinophilia early.

Anti-mitochondrial antibodies (M2 subtype) present in 95% of patients with PBC. Specificity of 98%. Titre of 1:40 or higher.

Associated: ANA +ve in 70%, high incidence of other autoimmune disease (Sjogren’s, autoimmune thyroid disease, RA).

Treatment:

1. Ursodeoxycholic acid (13-15mg/kg/day).
   - improved LFTs, reduced disease progression, no effect on pruritus or fatigue.

Monitoring:

• LFTs every 3-6 months; TFTs annually.
• BMD every 2-4 years.
• Monitor vitamin A, D, K annually if Br >20.
• Appropriate monitoring of cirrhosis if present.

Question 34

Primary Sclerosing Cholangitis.

Answer 34

Inflammation, fibrosis and stricturing of the medium and large bile ducts.
Majority have UC (90%).
Only 5% of patients with UC have PSC.
Half asymptomatic, pruritus common.
Atypical P-ANCA 30-80%; hypergammaglobulinaemia in 30%.
May be positive for ANA, ASMA, RF.

Diagnosis:

• MRCP first test of choice.
• ERCP allows therapeutics.

IgG4-associated cholangitis (usually associated with autoimmune pancreatitis) is steroid-responsive and indistinguishable from PSC. Always measure IgG4 in new dx. of PSC.

Complications: cholangiocarcinoma (10-15% risk); gallbladder cancer (screening recommended); cirrhosis/portal hypertension; fat soluble vitamin deficiency/steatorrhoea; colon cancer; metabolic bone disease; cholangitis.

Treatment:

• Endoscopic treatment of dominant biliary strictures may be beneficial in highly select patients.
• Screening.
• Liver transplantation (85% 5-year survival; 20% will have recurrent disease).

Question 35

Fulminant Hepatic Failure.

Answer 35

1. Acute liver injury.
2. Hepatic encephalopathy.
3. Elevated PT/INR.

In persons without pre-existing liver disease.
Viral and drug-induced injury are the major causes.

Cerebral oedema common in hyperacute and acute disease. PT/INR the best lab to monitor status.
Early transplant evaluation.
? N-AC for all.

Question 36

King’s College Criteria for Liver Transplant Referral.

Answer 36

Acetaminophen-induced liver failure with:

a) Arterial pH <7.30 or
b) Grade 3 or 4 encephalopathy with PT >100s and Cr >340 mg/L.

Non-acetaminophen-induced liver failure with:

a) PT >100s or
b) Any three of:
- Age <10 or >40.
- Non-A and non-B viral hepatitis, idiosyncratic drug reaction, Wilson’s disease.
- Jaundice >7 days prior to encephalopathy.
- PT >50s.
- Br >180mg/L.

Question 37

Hepatitis B Serology Interpretation.

Answer 37

HBsAg -> hallmark of active infection.
(anti-HBsAb persists after -> recovery/immunity).
anti-HBcAb (IgM) -> acute infection.
anti-HBcAb (IgG) -> recovery/chronic.
HBeAg -> indicated replication/infectivity (~DNA).

Immune-tolerant phase (baby) -> living with virus.
- +ve HBeAg; +ve HBV DNA; ALT normal.

Immune-active phase: immune system turns on against HBV around 30 yrs of age.
- +ve/-ve HBeAg; reduced HBV DNA; elevated ALT.

Inactive chronic hep B phase: virus goes into hiding.
- -ve HBeAg; reduced HBV DNA; normal ALT.

Immune reactivation: virus attempts domination.
- -ve HBeAg; increased HBV DNA; increased ALT.

Question 38

Hepatitis B Treatment.

Answer 38

Indications:

1. Acute infection only if: fulminant hepatic failure, severe or protracted illness (>4 weeks).
2. Anyone with cirrhosis.
3. Immune active chronic HBV with:

a) HBeAg +ve (immune active) if >20,000 IU DNA and ALT >2x ULN.
b) HBeAg -ve if >2000 IU DNA, ALT >2x ULN. Consider liver biopsy if ALT <2x ULN and DNA >2000.
4. Presence of HCC.

Treatment NOT indicated in:

a) Immune-tolerant phase (HBeAg +ve; high DNA; normal ALT).
b) Inactive carrier phase (low or no DNA, normal transaminase).
c) Latent HBV infection (DNA without HBsAg).

Options:

• Interferon (young patients with well-compensated liver disease).
• Entecavir (rare resistance; can’t use if resistant to Lamivudine).
• Tenofovir.
• Lamivudine (safe in pregnancy; high resistance).
• Adefovir.
• Telbivudine.

Question 39

Extra-hepatic manifestations of HCV.

Answer 39

Lichen planus:

• 19% with lichen planus will have HCV.
• 6x risk for HCV in persons with lichen planus.

Porphyria cutanea tarda (50%).

Necrolytic acral erythema (erythematous papules most commonly on dorsal aspect of feet; all cases will have HCV).

Essential mixed cryoglobulinaemia.

• 50% will have cryoglobulins.
• arthralgias, MPGN, neurologic disease, peripheral neuropathy, leukocytoclastic vasculitis.

Lymphoma (10x increased risk).
Sjogren's syndrome/sicca syndrome.
ITP.
Diabetes.
Thyroid disease.
Autoantibodies - ANA, ASMA, RF in up to 65%.

Question 40

HCV Therapeutics.

Answer 40

NS3 (serine protease) -> “previrs”
NS5A (RNA binding site) -> “asvirs”
NS5B (RNA-dependent RNA polymerase) -> “buvirs”
Maviret (Gecaprevir/pibrentasvir)
- All genotypes.
- Expect a >90% SVR with current regimens.
- SVR at 12 weeks = cure.

Question 41

Alcoholic hepatitis.

Answer 41

Rule out HAV, HBV flair, acute HCV, biliary obstruction and Budd-Chiari.

Discriminant function: (4.6 x PT elevation) + Br (mg/dL)
If >32, high short-term mortality, consider steroids.

Prednisone 40mg daily for 28 days; 16 day taper.
Pentoxifylline 400mg tds as an alternative.
Discontinue non-selective beta blockers.

Question 42

Autoimmune hepatitis.

Answer 42

AST >10x or AST >5x with 2 x gamma globulin level.

Type 1 AIH:

• SMA and ANA.
• atypical p-ANCA (useful if other antibodies negative).
• anti-mitochondrial antibody.

Type 2 AIH:

• Anti-LKM1.
• Specificity 99%.

Liver biopsy.

Treatment not required in asymptomatic patients with normal or minimally elevated transaminases and gamma globulin levels and minimal necroinflammatory activity on biopsy.

Monotherapy -> prednisone 60, 40, 30, 30, 20, indefinitely.

Combination -> prednisone 30, 20, 15, 15, 10, 5…. azathioprine 50mg daily (or 1-2mg/kg/day).

Normalisation of labs and histology usually takes over 12 months.

Question 43

Haemochromatosis.

Answer 43

Most related to HFE gene mutations (C282Y or H63D).
Transferrin saturation >45%.
Ferritin >200 in men or >150 in women.
Liver biopsy is only needed in select cases.

Response to phlebotomy.

Extrahepatic manifestations:

• diabetes (50%).
• arthropathy.
• cardiomyopathy.
• hypogonadism (secondary).

Question 44

Wilson’s disease.

Answer 44

Autosomal recessive. >500 mutations found of ATP7B (ATPase).
Serum copper is typically low (decreased caeruloplasmin).

24-hour baseline urinary copper excretion (usually 2-3 x normal).
24-hour urine after 500mg D-penicillamine (>1600microgr copper diagnostic).

Manifestations:

a) Liver disease -> steatosis, fulminant hepatic failure with Coombs-negative haemolytic anaemia, cirrhosis. Only 50% have Kayser-Fleischer rings.
b) Neurologic disease -> behaviour deterioration, difficulty writing, tremor, speech change, Parkinsonism, dysarthria, dystonia. 98% will have Kayser-Fleischer rings. MR mays show basal ganglia hyperintensity on T2-weighted images.
c) Psychiatric - psychosis, depression, anxiety.

Treatment:
- copper removal.
Chelators - usually 6-12 months to remove excess copper.
D-penicillamine (30% cannot tolerate).
Trientine (expensive).
Tetrathiomolybdate (being studied).
- low copper diet.
- oral zinc -> interferes with copper absorption.

Question 45

Acute liver failure in Wilson’s Disease.

Answer 45

Clues: family history, AST/ALT >2.2, ALP/Br <4, low Hb, Copper >200 microgr/dL.

Early liver transplant evaluation.

Rapid removal of copper.

• Haemodialysis, peritoneal dialysis, haemofiltration.
• Plasmapheresis, plasma exchange.

Liver transplant is curative.

Question 46

Nonalcoholic fatty liver disease.

Answer 46

Hepatic steatosis in the absence of an identifiable cause.
Prevalence in the Asia-Pacific region is 5-30%.
NAFLD -> NAFL, NASH.
Associated with metabolic syndrome: obesity, hypertension, dyslipidaemia, insulin resistance or diabetes.
Transaminases may be normal or up to 5x ULN.
Liver biopsy only modality to distinguish NAFL from NASH and determine severity of disease.

Management:

• Weight loss/exercise.
• Vitamin E (antioxidant).
• Thiazolidinediones -> improve liver histology and labs; weight gain, swollen legs and heart failure.
• Vaccinate for HAV and HBV.

Question 47

Indications for Liver Transplantation.

Answer 47

Acute liver failure (Kings College criteria previous).
Cirrhosis with complications or MELD >/= 15.
Neoplasm involving the liver -> HCC single lesion = 5cm or three or less lesions = 3cm.
Liver-based metabolic disease.
Complications due to liver disease:
- Recurrent cholangitis in PSC.
- Intractable pruritis.
- Hepatopulmonary syndrome.
- Primary hyperoxaluria.
- Refractory ascites.
- Recurrent variceal bleeding.
- Refractory hepatic encephalopathy.

Question 48

Chronic Pancreatitis.

Answer 48

Progressive fibroinflammatory process resulting in permanent structural damage and impairment of exocrine and endocrine function.
Complications include pseudocysts (10%), bile duct or duodenal obstruction (5-10%), pancreatic ascites, splenic vein thrombosis and pseudoaneurysms.

Aetiology:

• Alcohol abuse.
• Genetic - CFTR, SPINK 1.
• Ductal obstruction.
• Autoimmune pancreatitis.
• Systemic diseases -> SLE, hyperparathyroidism.

Main problems:

• Abdominal pain.
• Pancreatic insufficiency (exocrine insufficiency in >90% loss of pancreas).

MRI is best imaging modality.
Dx. is strongly suggested by pancreatic calcification, steatorrhoea, diabetes mellitus.

Faecal elastase is the most sensitive and specific lab test.

Correction of pancreatic insufficiency:

• low fat diet.
• pancreatic enzyme supplements.
• medium chain triglycerides.

Question 49

Bacterial virulence factors H. pylori

Answer 49

cagA gene - increased neutrophil recruitment and associated greater inflammatory activity.

Question 50

Timeframe for resuming warfarin post-endoscopy for GIB.

Answer 50

7-14 days.

Question 51

Coeliac Disease Histology

Answer 51

Crypt hyperplasia
Villous atrophy
Increased intra-epithelial lymphocytes

Question 52

Coeliac Disease Associations

Answer 52

Test in all 1st degree relatives
CD more common in T1DM.
More common in thyroid and other auto-immune diseases (only test if symptoms).
Down syndrome (x5)
Peripheral neuropathy or ataxia.
Persistently deranged LFTs.
Pancreatitis (3x risk).
IDA.
B12 deficiency.
Fat soluble vitamins - ADEK.
Copper deficiency.
Bone disease - vitamin D deficiency, DEXA at 1-year.

Question 53

SB biopsy shows PAS-positive macrophages in sub-mucosa.

Answer 53

Whipple’s disease

Question 54

CMV and HSV oesophagitis

Answer 54

HSV - small discrete ulcers

CMV - giant ulcers

Question 55

Consider perforation if 2 out of 3 present (ascitic fluid)

Answer 55

Total protein >10
Glucose <2.8
LDH > serum ULN

Question 56

Isolated bilirubin elevation

Answer 56

Gilbert syndrome
Crigler-Najjar syndrome (unconjugated)
Haemolysis (unconjugated)

Question 57

Isolated ALP (non-hepatic)

Answer 57

Bone disease (fracture, Paget's, hyperparathyroidism, osteolamalacia, tumour).
Pregnancy

Question 58

Viral Hepatitis A

Answer 58

Humans only reservoir.
Faecal-oral route, 28-day incubation.
Vaccinate high-risk groups.
Vaccinate up to day of departure in young (<40), 2-weeks prior in older, immunocompromised or with liver disease.
Post-exposure prophylaxis with single dose vaccine within 2 weeks if healthy persons 1-40 years.
Vaccine and IG in <1, >40 and immunocompromised or liver disease.

Question 59

Specific therapeutics for drug induced liver disease.

• Paracetamol
• Valproic acid

Answer 59

Paracetamol - N-acetylcysteine

Valproic acid - L-carnitine

Question 60

Low/absent 6-TGN

Low/absent 6-MMP

Answer 60

Non-adherence.

Education.

Question 61

Low 6-TGN

Low 6-MMP

Answer 61

Under-dosing.

Increase dose and monitor levels.

Question 62

High 6-TGN

High 6-MMP

Answer 62

Thiopurine-refractory.

Another drug: MTX, anti-TNF.

Question 63

Low 6-TGN

High 6-MMP

Answer 63

Thiopurine resistance.

Add allopurinol and reduce thiopurine dose.

Question 64

Barret’s oesophagus timing for repeat endoscopy.

Answer 64

No dysplasia: 3–5 years
Low-grade dysplasia: 6–12 months
High-grade dysplasia in the absence of eradication therapy: 3 months.

Question 65

Modified Child Pugh Score

Answer 65

Remember the ABCDE of Cirrhosis. (Modified Child-Pugh score)
A for Albumin
B for Bilirubin
C for Coagulation (PT/INR)
D for Drain the Ascites
E for Encephalopathy

Question 66

MELD Score

Answer 66

The MELD score is based on objective measures (serum bilirubin, creatinine, and PTT) and the Child-Pugh class is based on both objective and subjective measures (ABCDE as above).

Question 67

Hepcidin and ferroportin

Answer 67

Ferroportin stimulates iron release from enterocyte into the bloodstream

Hepcidin inhibits iron release from enterocyte into bloodstream.

Question 68

Extraintestinal manifestations of IBD that are associated with active GI disease includes:

Answer 68

Oral ulcers
Erythema nodosum
Large joint arthritis
Episcleritis.

Question 69

Extraintestinal manisfestations of IBD that are independent of GI disease includes:

Answer 69

Primary sclerosing cholangitis
Ankylosing spondylitis
Uveitis
Pyoderma gangrenosum
Kidney stones
Gallstones.

Question 70

** variants are associated with early initial surgery due to stenosis and withsurgical recurrence in Crohn’s disease. Patients with these variants could benefit frompreventive and/or early therapeutic strategies.

Answer 70

Nod2/CARD15

Question 71

Ustekinumab mechanism

Answer 71

Ustekinumab is a human monoclonal antibody against the p40 subunit of IL-12 and IL-23

Question 72

IBD subtypes and pANCA + ASCA

Answer 72

Positive pANCA + Negative ASCA = UC (97% specific)

Positive ASCA + Negative pANCA = Crohns (97% specific)

Question 73

Hormones that stimulate appetite

Answer 73

Ghrelin, AgRP, NPY.

Question 74

Discriminant Function

Answer 74

Used in alcoholic hepatitis.
DF = (4.6 x PT elevation) x Br
>/=32 indicates high short-term mortality, consider steroids

Question 75

MELD score components

Answer 75

Dialysis at least twice in last week.
Cr
Bilirubin
INR
Sodium

Question 76

IBD genetic risk

Answer 76

NOD2/CARD15/IBD1 - 40-fold risk.

Question 77

Crohn’s Disease Management

Answer 77

Mild (OPD) - Oral 5-ASA (Pentasa)
Mod
- oral steroids (40mg/d for 2 weeks, then taper 5mg/week).
- if no response over 2 weeks, to hospital for IV methylprednisolone for 3-5 days.
Severe
- hospital for IV steroids.

Remission
* Use steroid-sparing agent.
Azathioprine, 6-MP, MTX
Oral T-ASA
Biologicals

Question 78

Ulcerative Colitis Management

Answer 78

Distal Colitis

• 5-ASA (supp)
• 5-ASA (enema)
• Steroid (foam)
• Oral 5-ASA
• Oral/IV steroids

Pancolitis

• Oral 5-ASA
• Oral steroids
• IV steroids
• Biologicals

Remission
- Oral 5-ASA/Azathioprine

Complications

• IV Cyclosporin
• Biologicals
• Surgery

Question 79

Thiopurine AEs

Answer 79

Idiosyncratic
- Allergy, pancreatitis

Dose-dependent
- hepatic toxicity, myelosuppression

Question 80

Infliximab MOA + Indication

Answer 80

Infliximab is a IgG1κ monoclonal antibody that binds to soluble and transmembrane forms of TNF-α with high affinity to disrupt the pro-inflammatory cascade signalling. Binding of the antibody to TNF-α prevents TNF-α from interacting with its receptors.

Indications: moderately severe, steroid-refractory (ACT 1) or on mesalamine (ACT II).

Question 81

Choice of 2nd line agents for IBD

Answer 81

Anti TNF agents
- Infliximab, Adalimumab, Certolizumab, Golimumab

Anti-integrin
- Natalizumab, Vedolizumab

Anti IL-12/23
- Ustekinumab

JAK inhibition
- Tofacitinib

Question 82

Anti IL-12/23

Answer 82

Ustekinumab

Question 83

Live vaccines and IBD

Answer 83

Live vaccines 3-6 months after stopping immunomodulator therapy.
Wait at least 3 weeks from the last immunisation with a live vaccine before starting immunomodulator treatment.

Question 84

Extraintestinal Manifestations of UC

Answer 84

Peripheral oligoarthritis (HLA-B27 in 26%)
Erythema nodosum, pyoderma gangrenosum
Aphthous stomatitis
Iritis/uveitis

Question 85

Risk Factors for SIBO

Answer 85

Anatomical - strictures, diverticula, fistula.
Motility - diabetic gastroparesis, pseudo-obstruction, scleroderma, slow transit, post-radiation enteropathy, parkinson’s, IBD.
Others - age, narcotics, IBD, gastrectomy.

Question 86

FAP

Answer 86

Autosomal dominant

APC gene - chromosome 5

• tumour-suppressor gene
• multiple mutations

100s-1000s colonic adenomas
100% penetrance
- adenoma mean age 16
- carcinoma mean age 39

Clinical Syndromes:

• Gardner’s syndrome: osteomas, odontomas, epidermoid cysts, desmoid tumours.
• Turcot’s syndrome: CNS malignancies
• Attenuated FAP: less polyps, presents later in life.

Question 87

MYH-associated polyposis

Answer 87

Autosomal recessive

MutY human homolog
- encodes base excision proteins MYH, OGG1, MTH1

80% penetrance

Clinical:

• multiple >15 adenomas
• < age 50
• accounts for >40% attenuated FAP without APC mutation

Question 88

HNPCC

Answer 88

3-2-1 rule
3 (or more) relatives with HNPCC-related cancer, one of whom is a FDR of the other two.
At least 2 successive affected generations
One (or more) diagnosed under the age of 50.
FAP excluded.
Tumours verified by pathology.

Autosomal dominant.
5 mismatch repair genes
MLH1 and MSH2 - >95%
Protein product involved in repair of DNA mismatches
Microsatellite instability (MSI)
- close to 100% HNPCC
- <15% sporadic CRC
Multiple mutations
80% penetrance

Clinical
Single, mainly right-sided tumours
Earlier than sporadic, but generally after age 50
Usually <10 adenomas
Rapid progression, but prognosis > sporadic CRC
Extraintestinal tumours: endometrial, ovarian, gastric.

Question 89

Screening based on hereditary CRC syndrome

Answer 89

FAP

• Sigmoidoscopy annually until 35 then 3 yearly beginning age 12-15.
• Gastroscopy 1-3 yearly starting age 30-35.
• Colonoscopy if attenuated FAP, continue until 65

HNPCC

• Colonoscopy biannually beginning age 25 or 5 years earlier than the youngest cancer in family, annually in mutation carriers.
• Pelvic exam/TVUS 1-yearly beginning age 25-35.
• Gastroscopy every 2 years in mutation carriers.

Question 90

Peutz-Jegher Syndrome

Answer 90

Peutz-Jeghers syndrome (PJS) is a rare inherited disease that is characterised by gastrointestinal polyps in association with pigmentation affecting skin and mucous membranes.

Peutz-Jeghers syndrome is due to germ line mutations in the Serine Threonine Kinase tumor-suppressor gene found on chromosome 19p13.3 (also called STK11/LKB1). The gene abnormality may be inherited or arise sporadically (35%). The key factor may be reduced apoptosis, or programmed cell death, in the affected cells.

PJS has autosomal dominant inheritance. This means that offspring of affected individuals have a 50% chance of inheriting the disease.

Question 91

FAP Extracolonic

Answer 91

Duodenal/ampullary, pancreas, thyroid, gastric.

Question 92

HNPCC Extracolonic

Answer 92

Endometrial, renal, ureteric, small bowel

Question 93

UC V Crohn’s

Answer 93

Crohn's
Any part, usually terminal ileum
Skip lesions
Transmural
Crypt abscesses, granuloma

UC
Continuous
Rectum extending proximally
Mucosa + submucosa
Inflammatory infiltrate

Question 94

Vedolizumab MOA

Answer 94

Vedolizumab is a humanized monoclonal antibody that binds to integrin α4β7 on the surface of the T-lymphocyte and by blocking the α4β7 integrin, this results in gutselective anti-inflammatory activity (inhibits trafficking of leucocytes to the site of inflammation). And because it is gut selective the drug does interfere with the CNS.

Question 95

Hep B therapy and pregnancy

Answer 95

Women with mild liver disease and low viremia should commence treatment only after becoming pregnant.
Women with moderate liver disease but no cirrhosis should be treated before pregnancy and if responds to treatment, this could be stopped before pregnancy.
Women with advanced liver disease should be treated before and during pregnancy and continue treatment after delivery.
Women with mild liver disease but with very high viremia should be treated in the last trimester with a ‘B’ category drug such as Tenofovir but discontinue this after delivery (post-partum).

Question 96

SAAG

Answer 96

SAAG = serum albumin - ascitic fluid albumin
High (>1.1g/dL) indicated portal hypertension.
- Ascitic protein >2.5g/dL
– Heart failure, pericardial disease, early Budd-Chiari.
- Ascitic protein <2.5g/dL
– Cirrhosis, late Budd-Chiari
Low (<1.1g/dL) indicated normal portal pressure.
– malignancy, tuberculosis, nephrotic syndrome, protein-losing enteropathy.

Question 97

Barrett’s oesophagus

Answer 97

Barrett’s esophagus: – After initial diagnosis, repeat scope in 12 months to ensure no dysplasia. – If no dysplasia on biopsy on 2 scopes- do 3 year follow up gastroscopy. – If no dysplasia, treat with high dose PPI long term. Consider antireflux surgery. – If low grade dysplasia: repeat scope within 1 year follow up until no dysplasia. – If High grade dysplasia: surgical resection if medically fit.If not, then consider 3 monthly close endoscopic surveillance or endoscopic ablative therapy.

Question 98

Presbyoesophagus

Answer 98

Presbyoesophagus is a term that has been traditionally used to describe the manifestations of degenerating motor function in the aging esophagus.

Various mechanisms have been proposed: interruption of the reflex arc, perhaps from a central cause (e.g. ischemic stroke) decreased sensitivity to distension and reduced secondary peristalsis

Typical findings on fluroscopy:

• decreased frequency of normal peristalsis
• tertiary contractions (ranging from minor to severe)
• esophageal dilatation
• impaired lower esophageal sphincter relaxation

Question 99

Achalasia Pathophysiology

Answer 99

Achalasia results from progressive degeneration of ganglion cells in the myenteric plexus in the esophageal wall, leading to failure of relaxation of the lower esophageal sphincter (LES), accompanied by a loss of peristalsis in the distal oesophagus.

Question 100

Primary Biliary Cirrhosis

Answer 100

Primary biliary cirrhosis is a chronic progressive cholestatic liver disease of unknown cause. It is an autoimmune disorder that occurs predominantly in women (80% to 90% of cases) between 40 and 60 years of age. The diagnostic triad associated with primary biliary cirrhosis includes a cholestatic liver profile, positive antimitochondrial antibody titers, and compatible histologic findings on liver biopsy. Serum alkaline phosphatase level is usually elevated ten times or more above normal.

Question 101

Primary Sclerosing Cholangitis

Answer 101

Primary sclerosing cholangitis is a chronic cholestatic liver disease of unknown cause that is characterized by progressive bile duct destruction and may lead to secondary biliary cirrhosis. Laboratory findings include a cholestatic liver profile, with serum alkaline phosphatase levels three to five times greater than normal and mild hyperbilirubinemia.

Question 102

Autoimmune Hepatitis

Answer 102

In type I there is an association with other autoimmune diseases (e.g. pernicious anaemia, thyroiditis, coeliac disease and Coombs-positive haemolytic anaemia), – Pathogenesis is unknown but probably a viral attack that causes a sequence of T cell mediated events against liver antigens, producing a progressive necroinflammatory process which results in fibrosis and cirrhosis. – In the teens and early twenties the disease (often type II) presents as an acute hepatitis with jaundice and very high aminotransferases, which do not improve with time. – Patient may range from being asymptomatic to presenting with fatigue and findings of cirrhosis with hepatosplenomegaly, cutaneous striae, acne, hirsuties, bruises and, sometimes, ascites. Lab findings: – High serum aminotransferases – Lesser elevations in the ALP and bilirubin. – High serum gammaglobulins particularly the IgG. – High prothrombin time. – Mild normochromic normocytic anemia – Thrombocytopenia – Leucopenia Type I: (a) anti-nuclear (ANA) (b) anti-smooth muscle (anti-actin) (c) soluble liver antigen (anti SLA/LP) – 10-30% cases. This occurs most frequently in girls and young women. Type II: anti-liver/kidney microsomal (anti-LKM1). The main target is cytochrome P4502D6 (CYP2D6) on liver cell plasma membranes. Treatment: – Prednisone as induction and Azathioprine as maintenance – Mycophenolate, ciclosporin and tacrolimus(resistant cases) – Treatment is lifelong – Consider liver transplant if treatment fails.

Question 103

Gastro - incubation periods

Answer 103

Incubation period:
1-6 hrs: Staphylococcus aureus, Bacillus cereus
12-48 hrs: Salmonella, E. coli
48-72 hrs: Shigella, Campylobacter
>7d: Giardiasis, Amoebiasis

Question 104

IBD (pANCA / ASCA)

Answer 104

Positive pANCA + Negative ASCA = UC (97% specific) Positive ASCA + Negative pANCA = Crohns (97% specific)

Question 105

Most common mutation seen in HNPCC?

Answer 105

The frequency of mutations caused by MSH2 in HNPCC families is approximately 60%. MLH1 is 30%.

Question 106

This extra-colonic malignancy is most strongly associated with HNPCC

Answer 106

Endometrial cancer

Question 107

Gastrointestinal Hormones

Answer 107

Gastrin from G cells = ” G for Gastrin”
CCK from I cells = ” I love hot ChiCKs”
Secretin from S cells = ” Secret Secretary” Somatostatin from D cells= “I’m So Drunk”

Question 108

In the treatment of chronic hepatitis C infection, which of the following is the most common side effect of ribavirin treatment?

Answer 108

Haemolytic anaemia

Question 109

MELD score based on

Answer 109

The MELD score is based on objective measures (serum bilirubin, creatinine, and PTT) and the Child-Pugh class is based on both objective and subjective measures (serum albumin, PT, serum bilirubin, degree of ascites, and encephalopathy).

Question 110

Causes of hypergastrinaemia

Answer 110

1) Prolonged acid inhibition- proton pump inhibitors,H2-receptor antagonist.
2) Atrophic gastritis- pernicious anemia, H.pylori.
3) Vagotomy or small bowel resection
4) Gastrin secreting tumor (ZES)
5) Renal failure
6) Hypercalcemia
7) Hyperlipidemia (artefactual)

Question 111

What is the most useful serological test to diagnose autoimmune pancreatitis?

Answer 111

Autoimmune pancreatitis: – very rare disorder – associated with Sjogren’s, PBC and RA – Raised serum IgG4 – Responds to steroids

Question 112

The Cag A negative H. pylori is mostly associated with which condition?

Answer 112

Gastric ulcer -CAG A neGative DuOdenal ulcer- CAG A pOsitive

Question 113

Coeliac disease is associated with HLA

Answer 113

HLA-DQ2 or DQ8 is associated in 99.6% of patients with coeliac disease.

Question 114

Causes of low resting lower esophageal sphincter:

Answer 114

Fat CCK
alcohol
smoking
caffeine
gastric distention

Question 115

The following Hepatitis B genotype carries the worse outcome:

Answer 115

The correct answer is Genotype C.

Genotype A and B is most responsive to Interferon.

Question 116

What defines chronicity in hepatitis B infection?

Answer 116

Hepatitis surface antigen positivity beyond 6 months.

Question 117

Predictors of poor response in paracetamol overdose

Answer 117

Predictors of poor outcome in paracetamol includes:

Metabolic acidosis
Coagulopathy
Encephalopathy
Renal failure
A liver transplant unit should be consulted if any of the following criteria are met:

INR >3.0 at 48 hours or >4.5 at any time;
Oliguria or creatinine >200 μmol/L;
Persistent acidosis (pH < 7.3) or arterial lactate >3 mmol/L;
Systolic hypotension with blood pressure less than 80 mmHg, despite resuscitation;
Hypoglycaemia;
Severe thrombocytopenia;
Encephalopathy of any degree, or any alteration of consciousness (Glasgow coma scale <15) not associated with co-ingestion of sedatives.

Question 118

PBC

Answer 118

Primary biliary cirrhosis: – Mostly women age over 45. – Anti-mitochondrial antibody is positive in 95% of cases. – An immune attack on the small bile ducts (only) – Progression of the disease can be slowed by therapy with ursodiol (ursodeoxycholic acid). – Patient may have osteomalacia that can be corrected with 25-hydroxyvitamin D. – Transplantation is an effective treatment for those patients who develop end-stage liver disease with PBC. (Bilirubin >100 is an indication for transplant) PBC vs PSC? In Primary Sclerosing Cholangitis: – there is fibrosis of the larger bile ducts – PSC is strongly associated with Ulcerative colitis (80%). – onion skinning fibrosis around bile ducts. – disease complicated by cholangiocarcinoma in 10%. – Urso is not useful.

Question 119

A 35-year-old woman presents with jaundice and lethargy. Her blood tests are shown below: Serum Br 110 (2-24), ALP 650 (30-110), AST 240 (<45). Anti-mitochondrial antibody is positive.

Answer 119

Primary biliary cirrhosis (PBC).