Gastro Flashcards
Where is GLP1 secreted from
L cells in the duodenum
Adverse effects of GLP1
Pancreatitis, nausea, tachycardia
Where is GIP secreted from
K cells of small intestine
Side effects of PPI
Cancer (due to hypergastrinaemia)
Pneumonia
Gastroenteritis (c.diff)
Osteoporosis
Hypomag
Interstitial nephritis
Microscopic colitis
Causes of hypergastrinaemia
PPI
Atrophic gastritis (pernicious anaemia, h.pylori)
Vagotomy/small bowel resection
Gastrinoma
Renal failure
Hypercalcaemia
Hyperlipidaemia (arterfact)
What is Zollinger-Ellison syndrome and how does it present. Associated syndrome
Gastrinoma usually in duodenum
Fasting gastrin >10,000
Gallium 68 dotatate PET
1/3 pt have MEN1 (A.D, chromosome 11q13)
Presents with abdominal pain, diarrhoea, heartburn
If MEN1 present, need subtotal parathyroidectomy prior to gastrectomy as normalising Ca2+ may result in normal gastrin levels and no need for gastrectomy
Gastropancreatic NETs
60% non-functioning
90% of pts with carcinoid syndrome have metastatic disease at diagnosis
Urinary 5HIAA (pineapples and avocado cause false positives)
IHC: chromogrannin A, synaptophysin
Ki67 index correlates with mitotic count
Which cells control peristalsis
Interstitial cells of Cajal = pacemaker cells
Acute pancreatitis causes
Gallstones 40%
Alcohol 30%
Triglycerides 2-5%
Drugs
AI
ERCP (5-10% of ERCP pts)
Trauma
infection
How many acute pancreatitis patients will have recurrent pancreatitis
1/3
further 1/3 will go on to develop chronic pancreatitis
Chronic pancreatitis presentation
Abdo pain (post-prandial)
Fat malabsorption –> steatorrhoea + decreased fat soluble vitamins and decreased B12
Glucose intolerance +/- diabetes
Diagnosis of malabsorption
72hr quantitative faecal fat
Faecal elastase
CT
MRCP
Types of inherited pancreatitis
Disorders associated with trypsin
-Hereditary pancreatitis: PRSS1 gene (trypsinogen)
-SPINK1 mutation - onset adolescence, normal trypsinogen
Pancreatic ductal secretion abnormalities
-CF gene mutations
-Varian common chymotrypsin C
Autoimmune pancreatitis
IgG4 pancreatitis presentation
Mild recurrent attacks
May present with a mass
Increased serum IgG4
Responds to steroids
ABCB4 Disease
Transmembrane floppase
Transports phosphatidylcholine into bile duct
Increased risk of DILI
3 factors that are looked at to determine if a pancreatic cyst could be malignant
Size >3cm
Main duct dilatation
Solid component
If 2/3 do endoscopic U/S + biopsy
What type of bacteria is H pylori
Gram negative spiral/rod
100% develop chronic infection from acute infection
Important virulence factor for H pylori
CAG A –> increased risk of cancer
Key cytokine in pathogenesis of immune response to H pylori
IL-8
When to test for H pylori clearance
4 weeks after therapy started (2 weeks after therapy finishes)
Type of T cell and key chemokine involved in eosinophilic oesophagitis
TH2 driven
Eotaxin-3 is key eosinophilic chemokine
Presentation of eosinophilic oesophagitis
Dysphagia + food impaction
Young males
Assoc. with atopic disorders
Assoc. with carbamazepine hypersensitivity syndrome
Diagnosis and management of eosinophilic oesophagitis
Endoscopy: rings and furrows
Biopsy: 15 eosinophils/hpf, basal zone hyperplasia
Management
PPI
Topical steroid - budesonide
Diet 6/4/2/1/ elimination diet
Dupilumab
Endoscopic dilatation for refractory symptoms
6 week elimination diet (cow’s milk protein is key)
Achalasia presentation and pathogenesis
Dysphagia to solids and liquids
Age 30-60
Loss of intrinsic oesophagus innervation leading to incomplete relaxation of the lower oesophageal sphincter
Likely viral cause
Secondary cause is chugs disease (parasite trypanosoma Cruzi)
Diagnosis of achalasia
Endoscopy
Barium swallow: Bird’s beak + holdup in dilated oesophagus
Manometry is most sensitive - increased resting pressure in distal oesophagus
Management of achalasia
Botox
Balloon dilatation (risk of rupture though)
Surgery
-Laparoscopic cardiomyotomy
-POEM procedure
PEG
Oesophagectomy if:
-Megaoesophagus
-Malignancy
What cancer needs to be monitored for in achalasia
SCC
Disease associations of coeliac disease
Dermatitis herpetiformis
AI conditions: T1DM, hypothyroidism, IgA deficiency
Downs and Turner syndrome
Liver disease
Osteoporosis (complication)
Coeliac disease serology and HLA
- IgA tissue transglutaminase Ab with total IgA level
- If IgA def, test for anti-deaminated gliadin peptide IgG antibodies or tissue translutaminase IgG
HLADQ2 and HLA DQ8
-Good NPV but poor PPV
ALL POSITIVE SEROLOGY REQUIRES AN ENDOSCOPY AND BIOPSY OF THE DUODENUM TO CONFIRM DISEASE
Coeliac disease biopsy findings
Villous atrophy
Crypt hyperplasia
Raised intra-epithelial cell lymphocytosis
MARSH staging 0 –> 3
Pathophysiology of GORD and negative/positive risk factors
Transient relaxation of LES
H pylori is protective
When to do endoscopy in GORD
Only if poor response to PPI or red flag symptoms
Barrett’s oesophagus histology and risk factors
Change from squamous to columnar
RFs
-Reflux symptoms >5 years
-Male
-Smoking
-Central obesity
-Caucasian
Frequency of endoscopic surveillance in Barrett’s
No dysplasia = 3-5 years
Low-grade = 6-12 months +/- ablation
High-grade = endoscopic resection
Early cancer = endoscopic resection + PET/CT
Mutations in Crohns
NOD2
Associated with increased fibrostenotic complications and increased surgery prates
RFs for cancer in U.C/Crohns
Duration of disease
Extent of disease
PSC (high risk, can occur early, start screening at diagnosis, consider urso or surgery)
FHx of CRC
Disease activity
Surveillance colonoscopy in IBD
8 years from diagnosis in UC extending above the rectum and CD with more than 1/3 of colon involved
Then:
Annually if active disease/PSC/FHx of CRC in 1st deg relative <50yo/colonic stricture/previous dyplasia
3 yearly if inactive UC/CD/IBD and FHx of CRC in 1st deg family member >50yo
5 yearly if 2 previously normal scopes
Predictors at diagnosis for severe Crohn’s
Steroids required at diagnosis
Age <40
Peri-anal disease
UC Therapy
5 ASAs oral and rectal 4.8g/d response limit
Steroids if inadequate response
Thiopurines if needing 2 or more steroid courses a year
Anti-TNFs
Vedolizumab
JAK inhibitors
Difference between UC therapy and CD therapy
More aggressive in CD
Rapid step up approach
Introduce TNF-a early and if complicated disease
Stop smoking!!!!!!!!!!!!!An
TNF-a side effects
TB, invasive fungal infection, viral
Lymphoma (DLBCL assoc with EBV)
Melanoma risk doubled
Demyelinating disorders
Drug induced lupus
CHF
Abnormal LFTs
Derm - psoriaform reactions
Vedolizumab target
Blocks AbB7-MAdCAM interaction thereby blocking lymphocyte trafficking
Ustekinumab target
IL12/23
Moderate potency
Good if psoriasis present
Tofacitinib and upadacitinib targets
Tofacitinib Jak 1 AND 3
Upadacitinib Jak 1
Low TPMT level and NUDT15 mutation with thiopurines
Predisposes to leukopenia
Risks of thiopurines
Lymphoma (young EBV seronegative males)
Non-melanoma skin cancers
Ozanimod MOA
S1P modulator
-Traps lymphocytes within the lymphatic tissue
Combination Immunomodulator and TNFa
Increases trough TNF
Increased toxicity - opportunistic infections and hepatosplenic T-cell lymphoma
Increased efficacy
Management of acute severe UC
IV hydrocortisone 100mg QID + IV fluids + aim Hb >100
Flexi sig to exclude CMV
At D3-5 assess for clinical response
-3-8 BM + CRP >45 or >8BM = 85% will get colectomy
If no clinical response salvage therapy with cyclosporin or infliximab or surgery
Immunomodulator effective for pouchitis
Vedolizumab effective
Pregnancy and IBD
Being in remission at time of conception is key
MTX not safe
C-section only if active perianal disease,, otherwise mode of delivery determined by obstetric indications
Timing of live vaccines in IBD
Not within 3 weeks prior to IM/TNFa and 3 months after cessation
IBD histology
Basal lymphoplasmacytosis
Crypt architecture disruption
Granulomas (CD not UC)
Paneth cell metaplasia
Extra-intestinal manifestations of Crohn’s
Skin:
-Erythema nodosum (correlates with disease activity)
-Pyoderma gangrenosum
-Sweet syndrome (HLAB54) tx with steroids
Joint:
-Peripheral arthritis
-Axial arthritis - rule out ank spond
Eye
-Episcleritis/scleritis/ant.uveitis
Extra-intestinal manifestations that do not get better if Crohn’s gets better
Pyodgerma gangrenosum
PSC
Small joint and axial arthritis
IBD ANCA and ASCA serology
+ p-ANCA - ASCA = UC
- p-ANCA + ASCA = CD
SIBO diagnosis and management
> 10*5 colony forming units/ml of jejunal aspirate
Glucose and lactulose breath tests good specificity but low sensitivity
Treat with abx (tetracyclines)
Highest RF for Hep C
IVDU
Factors that predict spontaneous clearance of Hep C
Fmelae
young
MHC genes, IL28B
Extra-hepatic manifestations of Hep C
Membranoproliferative GN
Prophyria cutanea tarda
Cryoglobulinaemia
T2DM
B-NHL (mostly DLBCL)
Sicca symptoms
Cardiovascular events
Lichen planus
Percentage of Hep C infections that become chronic and factors that increase this
70%
NASH and alcoholic liver disease increase risk
DAA classes and drug interactions
NS3/4A - end in EVIR (3=E)
NS5A - end in SVIR
NS5B - end in UVIR
Carbemazepine
Amiodarone - bradycardia
Rosuvastatin and atorvastatin –> rhabdo
PPIs –> decreased DAA efficacy
Hep C genotype 3 in cirrhotics
Poorest response to DAAs
Clinically significant genetic polymorphism that causes resistance to NS3 protease inhibitor or NS5A inhibitor, and how to treat these patients
Y93H
Treat with VOSEVI (Voxilaprevir + ledipasvir + sofosbuvir)
Checking for SVR in Hep C
PCR at 12 weeks
Can be done at 4 weeks if at risk of losing pt to follow-up
No further follow-up if LFTs normal and SVR
If ongoing risk behaviour, screen annually
Highest risk of chronic hep B
Vertical transmission mother to child
Mum HbEAg+ve highest risk
Number 1 cause of all primary liver cancers
Hep B
Factors associated with rapid disease progression in Hep B
Older age
Alcohol
Hep C/Hep D/ HIV
Smoking
Male
FHx HCC
Hx of reversion from Anti HbE to HbAg
Cirrhosis
HBV genotype C
Core promoter mutation
Hepatitis B genotype with the poorest prognosis
Genotype C
Treatment options for Hep B
Entecavir
-Can cause lactic acidosis
Tenofovir
-Use if previous lamivudine exposure
Side effects of entecavir, TAF and TDF
Entecavir: lactic acidosis
TAF: lactic acidosis
TDF: Nephropathy, Fanconi syndrome, decreased BMD, lactic acidosis
Populations that benefit from entecavir over tenofovir
Presence of CKD, bone disease or chronic steroid use
When to treat Hep B
Not routinely recommended if E Ag positive but normal ALT
Treat if:
E Ag+ with DNA>20,000 and ALT/fibrosis
E Ag- with DNA >2,000 and ALT/fibrosis
Treat all with cirrhosis and any DNA level regardless of ALT levels
Monitoring response to Hep B treatment
Check response at 12 weeks, 24, 36, 48
If DNA <60 - continue treatment
If DNA 60 - 2,000 - continue treatment, monitor DNA 3/12
If DNA >2,000 - add on/switch therapy, monitor DNA 3/2
Swapping Hep B therapy
If on adenovirus - swap to entecavir
If on anything else - swap to tenofovir
Treatment of HIV/Hep B co-infection
Treat with HBV active ART regardless of HBV disease phase
TAF preferred
TDF if pregnant (data lacking on TAF)
When to treat HbsAg negative, core Ab positive
If going to receive high-risk chemo:
-SCT
-B-cell depleting/Anti-CD20
-Acute leukaemia or high-grade lymphoma therapy
Everything else = low risk - don’t need to treat
HBV treatment in pregnancy
All should have antenatal screening
Pregnant and high viral load (200,000) = tenofovir at week 28
All infants born to HbsAg positive mum = HbIg and vaccine ASAP (within 4 hours) after birth. Routine vaccine at 2, 4, 6 months. Test 3 months after last vaccine
Can breastfeed on tenofovir
No need to change mode of delivery
What does the Hb E Ag do
Present early in disease, indicates high viral load
Defects the immune system to allow chronic infection to develop
HBV and HDV co-infection (5% of Hep B patients)
Have more severe hepatitis and mortality
Treat with peg-interferon
Hep D is a defective virus requiring Hep B co-infection to express its pathogenicity + for transmission and packaging
Send Hep D S Ag + viral load in anyone Ab positive
HBV DNA level in HBV/HDV co-infection
Usually low or negative in Chronic HDV infection because HDV suppresses HBV viral replication
Hep E
Food borne
Genotype 3 most common in Aus
Zoonotic reservoirs
Pig meat major source in industrialised countries
Drugs precipitating auto-immune hepatitis
Minocycline
Nitrofurantoin
Isoniazid
PTU
Methyldopa
Autoantibodies in autoimmune hepatitis
Anti-SMA (AHI-1)
Anti LKM1 (AHI-2)
Anti LKM3
ANA
PBC presentation and associated conditions
Fatigue and pruritus
Sjogrens, thyroid disease, scleroderma, RA
Marker in AMA-ve PBC
Anti-GP210 and/or anti-SP100
Serology in PBC
Increased IgM
Increased lipids
AMA +ve (95%)
ANA +ve (30%)
PBC treatment
Ursodeoxycholic acid
For itch: cholestyramine, antihistamines, rifampin
Consider liver transplant
PBC complications
Osteoporosis
Fat soluble vitamin deficiency
Lipid issues
Other autoimmune disease (thyroid)
PBC histology
Bile duct damage
Granulomas
PSC pathology
Destruction of intra and extra-hepatic bile ducts, commonly leading to multi-focal strictures and eventually cirrhosis
PSC presentation
Abdo pain, fatigue, pruritus
Diagnosis of PSC
Increased ALP
Multi-focal biliary stricture
Exclusion of secondary sclerosing cholangitis
Liver biopsy when small duct PSC or PSC-AIH
PSC and U.C
70% of PSC have colitis (mainly U.C)
IBD presents at a younger age in PSC patients than in those without
If Crohn’s disease phenotype, milder PSC outcomes
Cancer risk in PSC
Increased CRC and hepato-biliary Ca risk
Screen with colonoscopies yearly
Annual U/S
Annual MRCP + Ca19-9
Most frequent extra-hepatic manifestation of Type 1 AIH (IgG4 related)
IgG4 related sclerosing cholangitis
-Usually cholestatic liver disease
-Usually steroid responsive
Immunotherapy for HCC
Lenvatinib/sorefanib - hand-feet syndrome
Atezolizumab/bevacizumab (PDL1 + VEGF) - risk of vatical bleeding, need endoscopy prior
What is the anti-LKM1 antibody directed at and clinical relevance
CYP2D6 is the antigen
Anti-LKM1 (type 2 AIH) is associated with poor response to therapy and poor outcomes
Alcoholic hepatitis management
Prognosticate into low and high risk (Maddrey’s + Glasgow score)
If high risk, do biopsy to look for ASH
-If ASH - give pred 40mg + NAC
-At D7 assess response with Lille score
If <0.56 continue pred for 4 weeks total
If >0.56 cease pred
Paracetamol metabolism
90% metabolised to inactive sulphate + glucoronide conjugates
Remainder is metabolised by CP450 to highly reactive intermediary NAPQI
In normal conditions, NAPQI is bound by intracellular glutathiones and eliminated in the urine as mercapturic adducts
Risk factors for paracetamol toxicity
Prolonged fasting or dehydration
Chronic under-nutrition
Chronic excessive alcohol use
Severe hepatic impairment
Activated charcoal timing for paracetamol overdose IR and MR formulations
Within 2 hours for IR
Within 4 hours for MR
Indications for liver transplant in paracetamol overdose
INR >3.0 at 48 hours
INR >4.5 at anytime
Oliguria or creat >200
Persistent acidosis <7.3 or arterial lactate >3
BP <80 despite resuscitation
Hypoglycaemia, severe thrombocytopenia, or encephalopathy
GCS <15 not associated with co-ingestion product
Hepatotoxicity with checkpoint inhibitors
6-12 weeks after starting treatment
Histologically looks like classical AIH
Treatment of hepatotoxicity with checkpoint inhibitors
Corticosteroids
Hold drug if Grade 2, restart when Grade 1 or baseline
Cease drug if Grade 3
Carvedilol in cirrhosis
Decreases HVPG
Prevents decompensation
Mortality benefit
Prevents oesophageal variceal but not gastric variceal bleeds
Severe pre-eclampsia and eclampsia
After week 22
Prevalence increases in multiple gestations
Pres: Increased BP, proteinuria, oedema, seizure, renal failure, pulmonary oedema
Diagnosis: PLT >70,000, urine protein >5g in 24 hours, abnormal LFTs (10%)
Tx: BP control (bb, methyldopa), Mg sulfate, early delivery
1% maternal death
HELLP Syndrome
Late 2nd trimester to early post-partum
Pres: Abdo pain, N/V, low platelets, hemolytis, LFT derangement, normal PT + fibrinogen
Prompt delivery
5% maternal death
1% hepatic rupture
1-30% foetal death
Acute fatty liver of pregnancy
Third trimester
Prevalence increases with male foetuses, multiple gestations, primiparous
Pres: Abdo pain, N/V, jaundice, hypoglycaemia, hepatic failure
Platelets <100,000, AST and ALT 300-1000, low antithrombin III, high pT, low fibrinogen, high bilirubin, DIC
Prompt delivery, liver transplant
less than or equal to 10% maternal death up to 45% foetal death
Haemochromatosis pathophysiology, inheritance and genetics
Autosomal recessive
Iron overload related to relative hepcidin deficiency with regard to iron status, or rarely, to hepcidin resistance
HFE gene
-C828Y/C282Y (high prevalence) = hepcidin deficiency
-SCL40A1 (ferroportin) - hepcidin resistance (loss of hepcidin receptor function)
Haemochromatosis presentation and target organs
Adult >30 (after menopause in females)
Caucasion
Fatigue/impotence
Arthropathy
Bronzed skin
Liver disease
Diabetes mellitus
Males more likely to develop severe iron overload and present younger
Organs: Liver, pancreas, heart, pituitary
Diagnosis of haemochromatosis
Increased transferrin saturation
Increased ferritin
then genetic testing
Iron overload management
- Phlebotomy
-Aim ferritin 50 (key) and tsat 50% - oral iron chelation (rarely used)
Indications for phlebotomy in haemochromatosis and prognosis
- Ferritin 400-1000
- Evidence of tissue injury (ALT/AST, decreased EF)
- increased tissue iron by MRI or tissue biopsy
Survival is normal if ferritin <1000 at diagnosis
Wilson’s disease inheritance, mutation and function of the protein involved
Autosomal recessive
Mutation in ATP7B gene
ATP7B protein is a copper transporting transmembrane protein which mediates excess copper secretion into bile and incorporation of Cu into ceruloplasmin
Presentation of Wilsons disease
Wide range of liver disease
Non-autoimmune haemolysis
Neuropsychiatric disease
Kayser-Fleischer ring (90% of neuro, 40% of hepatic)
Panda sign of basal ganglia on T2-weighted MRI
Young 5-40yo
Increased ALT and Increased bilirubin:ALP ratio
Diagnosis of Wilsons disease
Decreased ceruloplasmin
Increased copper content on liver biopsy >5 UNL
Increased 24 hour urine copper
Kayser-Fleischer rings
Demonstration of Cu based changes in basal ganglia
Treatment of Wilson’s disease
- Chelators
-D-penicillamine of Tridentine (binds Cu and increases excretion) - Zinc - inhibits intestinal uptake of Cu
- Tetrathiomolybolate
-Increases biliary excretion - Liver transplant if acute liver failure or decompensated cirrhosis
SAAG results
> 1.1 is suggestive of portal hypertension with 97% accuracy
Toal protein <15 is considered high risk for SBP
SBP diagnosis and management
> 250 polys in ascitic fluid
3rd gen ceph or pip taz + albumin for first 3 days
Check efficacy with repeat ascitic fluid at 48 hours
-Drop in PMN count by 25% predicts success
Primary and secondary prophylaxis of SBP
Primary: If protein is <10
Secondary: norflox or bactrim. Decreases recurrence rate from 70 - 20%
Acute management of variceal bleeding
Aim Hb 70-90
Octreotide/terlipressin
Scope with banding
Ceftriaxone for 5 days
TIPS if ongoing bleeding despite above
How does terlipressin work
Long-acting vasopressin analogue
-Mediates vasoconstriction via V1 receptors - preferentially expressed in vascular smooth muscle cells in sphlancnic bed
-Reverses splanchnic vasodilation occurring in portal hypertension improving renal perfusion
Hepatic encephalopathy presentation
Altered sleep-wake cycle
Acute confusion
Coma
How does lactulose work in HE
Acidifies colon leading to NH3 –> NH4 (non-absorbable) and increases intestinal transit –> decreased ammonia absorption
How does rifaximin work in HE
Non-absorbable antibiotic
Decreases ammonia production via decreased ammonia producing bacteria
Add on therapy to lactulose if recurrence
Relevance of AFP level in HCC when considering transplant
AFP level >1000 is a contraindication - indicates microvascular invasion
Presentation of veno-occlusive idsease and management
Triad of
-Weight gain
-Jaundice
-Hepatomegaly
Treat with defibrotide
Zidovudine side effects
Bone marrow suppression
Efavirenz side effects
Neuropsychiatric
Hepatitis
Atazanavir side effects
Crystalluria
Urolithiasis
Benign unconjugated hyperbilirubinaemia
