Gastroenterology Flashcards
1
Q
1st Line Treatment of Mild-Moderate Ulcerative Colitis
A
5ASA - Mesalazine or Sulfasalazine
(No role for methotrexate)
2
Q
Treatment of Severe UC
A
IV Steroid Induction + VTEp
3
Q
1st Line treatment Chrons Disease
A
no role for 5ASA
Steroid Induction
Maintain with methotrexate or azathioprine
4
Q
1st Line for Crohns disease with perianal fistula
A
Infliximab
5
Q
4 extra-intestinal manifestations that don’t correlate with disease activity in CD?
A
Uveitis, Pyoderma gangrenosum, PSC and small joint and axial arthritis
6
Q
EPCLUSA
A
Sofosbuvir (NS5B inhibitor)
Velpatasvir (NS5A inhibitor)
- 1 pill daily for 12 weeks
- Preferred in those with cirrhosis
- Unable to use in renal failure
7
Q
MAVYRET
A
Glecaprevir (NS3/4A)
Pibrentasvir (NS5A Inhibitor)
- 3 tabs daily for 8 weeks
- Ok for use in renal failure
8
Q
VOSEVI
A
Voxilaprevir (NS3/4A inhibitor)
Sofosbuvir (NS5B inhibitor)
Velpatasvir (NS5A inhibitor)
- For treatment failure.
9
Q
Ustekinumab
A
IL-12, IL23 inhibitor
Targets Th 17 T cell activity
Indicated for induction and maintenance crohns disease.
10
Q
Serology In Crohns Disease
A
Positive pANCA - UC
Positive ASCA - Crohns
11
Q
Sorafenib
A
Oral Multikinase inhibitor….
Prolongs disease free survival for 3 months in those with advanced HCC
12
Q
First Line H Pylori Eradication therapy
A
14 days - Clarithromycin + Amoxicillin + Esomeprazole
(if penicillin allergy, substitute with metronidazole)
13
Q
2nd Line H h pylori eradication therapy after failure
A
Quinolone based triple therapy - 10 days of Levofloxicin, amoxicillin + esomeprazole
14
Q
3rd and 4th line Line H h pylori eradication therapy after failure
A
Bismuth based quadruple therapy - 14 days Bismuth, teracycline, metronidazole, PPI
Rifabutin based triple therapy - Rifabutin + amoxicillin + PPI
15
Q
Hep C treatment in Cirrhosis
A
Compensated cirrhosis (Childs A) - as for no cirrhosis, Epclusa preferred.
Decompensated Cirrhosis (Childs B and C)
- Avoid use of NS3/4A inhibitors Glecaprevir, Voxilaprevir
- Epclusa + Ribavirin is recommended.
16
Q
Follow-up after Hep C Treatment:
A
12 weeks post completion of treatment perform HepC RNA PCR - negative PCR at 12 weeks = SVR and is highly predictive of successful treatment.
No followup needed unless:
- Cirrhosis - 6 monthly US for HCC surveillance, monitoring for varicies and osteoporosis.
- Ongoing exposure risk - annual RNA testing, harm reduction strategies.
17
Q
Vedolizumab
A
Alpha integrin (Gut selective) inhibitor used for induction and maintenance treatment of CD
(NATALIZUMAB = ALPHA INTEGRIN INHIBITOR, NOT GUT SELECTIVE)
18
Q
Cutaneous manifestations of IBD
A
Pyoderma gangrenosum - papule that elvoles into an ulcer with a violaceous boader.
Erythema nodosum - tender eyrthematous nodules on extensor surfaces of lower limbs
Both correspond to disease activity.
19
Q
Occular manifestations of IBD
A
Episcleritis - injection of the sclera and conjunctive. Corresponds to disease activity.
Uvetitis - headache, blurred vision, photophobia. Occular emergency requiring prompt referral. Does not correspond to disease activity.
20
Q
5-ASA’s (5 aminosalicylates)
A
Sulfaslazine, Mesalazine.
Sulfasalazine - rash, nausea, vomiting, headache.
First line for induction and maintenance in mild-moderate UC.
NO role in CD.
Combination of PO and Topical administration is more effective.
21
Q
Thiopurines (Azathioprine and 6-mercaptopurine)
A
Slow onset of action (2-3m) and need tapering steroid to bridge.
Measure thiopurine methyltransferase enzymes genotype or phenotype (preferred) to identify slow metabolises)
A/E:
- Myelosupression
- Hepatitis
- Pancreatitis
- Nausea/vomiting
Rare A/E: Hepatoslpenic T cell lymphoma
Non-melanoma skin cancer
22
Q
Role of methotrexate in IBD
A
Effective for induction and maintenance in CD but not UC.
A/E: hepatotoxicity, bone marrow suppression, interstitial pneumonitis.
23
Q
TNF inhibitors:
A
Intravenous:
- Infliximab
Subcutaneous:
- Adalimumab
- Certolizumab
24
Q
Definition of acute severe UC
A
6 or more bloody stools per day + one or more:
- Temp > 37.8
- HR >90
- Hb < 105
- ESR > 30
25
Initial Mx of acute severe UC
High dose steroids for 3-5 days and then PO
- 100mg IV Hydrocortisone 6 hourly
OR
- Methylprednisolone 60mg IV daily
26
Oxford Criteria
Used to assess the need for salvage therapy in acute severe UC.
Assessed on Day 3:
- 8 or more stools per day
- OR 3 or more stools per day with CRP > 45
Assessed on day 7:
- 3 or more stools per day with visible blood
If meets criteria, for salvage therapy
27
Salvage therapy for acute severe UC
1 -Intravenous Infliximab 5mg/kg
OR
2- Ciclosporin 2mg/kg IV
If perforation or megacolon --> surgery
28
Induction therapy for proctitis or distal colitis
Note enemas are useful until the splenic flexure.
Combination therapy most effective:
Rectal Mesalazine daily
AND Oral Mesalazine or Sulfasalazine.
If isolated proctitis -- use supposetry
If extending >20cm from anal verge - enema
Next step - add rectal corticosteroid (budesonide)
next step - 40mg prednisolone daily, until response, taper over 8 weeks. (consider budesonide if high risk of steroid induced adverse effects)
Next step - Tacrolimus
29
Maintenance therapy for UC
1 - PO and Rectal 5-ASA - Mesalazine
2 - If severe initial disease or frquent relapses, add Thiopurine to 5-ASA (Azathiopurine 2-2.5mg/kg daily)
30
Explain thiopurine shunting
Shunting occurs when thiopurines are preferentially metabolised to 6-methyl-mercaptopurine in preference to 6-thioguanine nucleotides.
High 6MMP can lead to nausea and hepatotoxicity,
6TGN is responsible for the theraputic effect, however high levels cause bone marrow supression.
Shunting can be reversed by co-administration of allopurinol 100mg daily.
31
Main differences in therapy for UC and Crohns
No role for 5-ASA or any rectal therapy in Crohns.
No role for methotrexate in UC.
32
Induction therapy in mild-mod Crohns
40mg Pred daily until response, taper for 8 weeks.
33
Induction therapy for Severe Crohns
High dose IV steroids for 3-7 days and then PO
34
Maintenance therapy for Crohns
- Thiopurines
- Methotrexate 10-25mg/week
- Biologics:
- TNF inhibitors (inflixmab)
- Ustekinumab (IL12/23)
- Vedolizumab (alpha integrin)
35
Perianal Fistula management
Long term antibiotic therapy (weeks to months)
Metronidazole 400mg 12 hourly (peripheral neuropathy) or Ciprofloxacin 500mg 12 hourly
TNF alpha inhibitor
36
Preventing recurrence of postoperative Crohns
After surgery CD will predictably recur at or proximal to the anastomosis.
Prevention:
- Metronidazole
AND
- Thiopurine, TNF inhibitor, or a combination of both.
37
Microscopic Colitis
Normal macroscopic appearance, however inflammation on biopsy - categorised into:
- Lymphocytic colitis
- collagenous colitis
Typically in older women with other autoimmune conditions.
Associated with medications - NSAIDS, SSRI, PPI
Mx: Stop offending medication. Supportive management with loperamide. Second line is PO budesonide.
38
Colorectal Ca screening in IBD
UC - Start 8 years after diagnosis and screen 3 yearly.
- If has PSC, risk is significantly increase. Screen from diagnosis and annually.
- Factors that increase risk a lead to annual screening:
- Active disease, PSC, FMHx <50 years, stricture, dysplasia.
CD - if >1/3 of bowel involved then screen for CRC as per UC. Some increase in small bowel Ca risk but very rare so not screened.
39
Adverse Effects of Anti-TNF
Infection
Melanoma risk if doubles
Drug induced lupus
40
High risk features in CD
Age <40
Perianal disease
High titre ASCA
NOD 2 mutation - associated with fibrostenotic complications.
Smoking, deep ulcers, strictures
41
High risk features in UC
< 40 years
Extensive disease
PSC
Deep ulcers
High titre pANCA
42
Anti-TNF
Infliximab, Adalinumab, Golimumab
- Work better in CD than UC
43
Adhesion molecule inhibitor for IBD
Vedolizumab
Works better for UC than CD
Gut specific and very little systemic immunosuppression, therefore good for people with issues with infection.
44
Anti-IL 12/23
Ustekinumab
ONLY for CD
45
Vaccination and immunosuppression
Don't give live vaccines 3 weeks prior to, or for 3 months after immunosuppression.
Live vaccines: VZV, MMRV, Japanese E, Yellow Fever.
45
Vaccination and immunosuppression
Don't give live vaccines 3 weeks prior to, or for 3 months after immunosuppression.
Live vaccines: VZV, MMRV, Japanese E, Yellow Fever.
46
Most common gene mutation in Lynch Syndrome (HNPCC)
Autosomal dominant Inherited mutation of DNA mismatch repair genes.
Most common mutation MSH2 60%, MLH1 (30%).
47
Testing for HNPCC?
Gene testing is expensive.
Test for micro-satellite instability which is a surrogate marker for DNA mismatch repair gene dysfunction.
48
Risk of Cancer in HNPCC?
80% lifetime risk for colon cancer (2/3 in proximal colon)
In women, 80% risk of endometrial ca.
Also increased risk of:
- ovarian
- Stomach
- small intestine
- hepatobiliary tract
- upper urinary tract
- brain
- skin
49
Cetuximab
Cetuximab is a EGFR inhibitor that inhibits activation of wild type K ras.
Primary used for treatment of colorectal ca.
50
Gastrin:
- Where is it released from? What is its role?
Released from G cells in the ANTRUM of the stomach.
Released in response to stomach distension and extrinsic nerves. Inhibited by low pH and somatostatin.
Effects:
- Secretion of HCL, pepsinogen and intrinsic factor
- increased gastric motility
- stimulated growth of gastric mucosa
51
CCK
- Where is it from? What does it do?
From I cells in the upper small intestine
Released due to presence of protein and fat
Effects:
- Stimulates pancreas to release pancreatic enzymes
- Contraction of gallbladder and relaxation of sphincter of oddi
- Decreases gastric emptying
52
Somatostatin
- where is it from ? what does it do?
Released from D cells in the pancreas and stomach
Released due to presence of fat, bile salts and glucose in the intestinal lumen.
Effects:
- DECREASES acid and pepsin production, gastrin
secretion, insulin and glucagon secretion
53
Lynch Syndrome
Accounts for 2-3% of CRC
Autosomal dominant, high penetrance
Defect in DNA MMR genes - most common are MSH2, MLH1.
Germline mutation in one allele causes microsatelite instability. Somatic inactivation in second allele in CRC (second hit)
Mostly right sided/proximal
54
Amsterdam Criteria for HNPCC
Used to detect patients for testing
3-2-1 rule:
- 3 relatives with lynch associated ca (CRC, endometrial, SB, upper tract TCC)
- 2 generations
- 1 diagnosis before age 50
55
Explain Microsatellite Instability
Microsatellites are specific sequences of DNA bases made up of mono, di, tri or tetra tandem repeats.
DNA MMR is essential for maintaining genomic integrity by correcting small errors during DNA replication.
Characteristic feature of loss of MMR is expansion of contraction of micro-satellite regions in tumour compared with normal tissue.
Epigenetic silcencing of MLH-1 gene is associated with BRAF V6000E mutation - this generally rules of Lynch syndrome.
56
How to test for microsatellite Instability
PCR to amplify sequences - expensive.
IHC to detect loss of staining of MSH2, MLH1, MSH6, PMS 2 - cheaper and easier. This is done.
57
How to test for microsatellite Instability
PCR to amplify sequences - expensive.
IHC to detect loss of staining of MSH2, MLH1, MSH6, PMS 2 - cheaper and easier. This is done.
58
FAP screening
Screen with sigmoidoscopy from 10-15 years olds
AFAP (attenuated FAP, <100 polyps) - screen with colonoscopy from 45 years.
59
FAP Colectomy Indications
Suspected CRC
High grade dysplasia
Significant symptoms - bleeding
Marked increase in polyp numbers
Inability to survey colon
60
NBCSP Screening Criteria
Overall population - 2 yearly FOBT from age 50-74
Patients at increased risk:
Category 1 = 1 relative diagnosed with CRC aged 55 or older. Lifetime risk approx 2 x general population. Start screening program at age 45.
Category 2 = risk is 3-6 times. 1 1st degree relative <55. 2 1st degree relatives of any age. 1 1st deg relative and 2 second degree relatives.
- FOBT 2 yearly from age 40-50, and colonoscopy every 5 years from 50-74.
Category 3 = risk is 7-10x. 3 first or second degree relatives with CRC, at least 1 diagnosed <55. or 3 1st deg relatives at any age.
- FOBT 2 yearly from 35 to 45, 5 yearly colonoscopy from 45-74
7% positivity rate for FOBT
1/30 will have cancer
61
Lynch Syndrome screening
1-2 yearly colonoscopy from age 25 or 5 years younger than youngest effected case.
62
FAP screening
Screening sigmoidoscopy from age 10-15 years,
Once adenoma detected then annual colonoscopy until colectomy and ileorectal anastomosis (then annual rectal/ileal pouch scope)
63
A/E of EGFR MoAbs in CRC
Cetuximab and Panitumumab
- Acneform rash
ONLY used in RAS wild type tumours
64
BRAF inhibitor in CRC
Encorafenib
65
VEGF inhibitor in CRC
Bevacizumab
A/E: hypertension, delayed wound healing
66
A/E Entecavir
Lactic acidosis (decompensated cirrhosis)
High risk of resistance if patient previously used lamivudine (therefore use tenofovir)
67
A/E Tenofovir
Neuropathy
Fanconi Syndrome
Reduced BMD
Lactic acidosis
68
Choosing between entecavir and tenofovir
Entecavir is first line. But dont use if:
- Prior exposure to nucleoside analogues (lamivudine) as high risk of resistance.
- Pregnancy
- Ok in cirrhosis, but risk of lactic acidosis
Tenofovir mainly used if previous exposure to lamivudine, pregnancy, or co-infection with HIV.
Dont use tenofovir if:
- Renal impairment (eGFR < 60)
- Risk of osteoporosis
69
When to treat Hep B ?
HepB eAg positive:
- ALT >2x ULN (ULN = 19 in females, 30 in males)
- DNA >20 000
- evidence of fibrosis
HepB eAg negative:
- ALT >2 x ULN
- DNA > 2000
- Evidence of fibrosis
All patients with cirrhosis and any detectable HBV DNA should be treated.
70
Monitoring of HBV treatment:
Measure HBV DNA every 12 weeks after starting treatment.
<60 IU/ml = complete response
60-2000 = Adequate response
>2000 IU/ml = sub-optimal response, consider add on therapy.
71
When to treat HBsAg but cAb positive patients during immunosuppression?
Only with very high risk treatment:
- Stem cell transplant
- B cell depleting therapy
- Acute leukaemia and high grade lymphoma treatment
Otherwise don't need to treat these patients as risk of reactivation is very low. ("cleared hep B")
72
Treatment of Hep B in Pregnancy:
If high viral load > 200 000 IU/ml -!!! treat with TENOFOVIR from 28 weeks. If Viral Load <200 000, then dont need to give antiviral.
No need to change method of delivery.
All infants should receive HBV Ig and Vaccination within 4 hours of birth.
No risk of transmission to vaccinated infant. Breastfeeding is encouraged.
Tenofovir ok for breast feeding.
73
Hep D virus treatment:
Hep D is small defective RNA virus that requires HBsAg for transmission and packaging.
Co-infection confers high risk of advanced disease.
Hep B DNA often low as is suppressed by Hep D
Treatment: PegInterferon alpha for 48 weeks. New treatment is Bulevirtide.
74
Hep E Virus facts
HEV virus is RNA virus
4 different genotypes:
- Genotype 1 and 2 - fecal oral route, in low income countries. Pregnant women have high mortality.
- Genotype 3 and 4 - zoonotic infections (pigs) found in higher income countries. Usually older males. Chronic infection only reported in types 3 and 4 and can occur in immunosuppressed patients.
Acquired through fecal oral route
Causes an acute viral hepatitis
Diagnosis is with HEV IgM or RNA
Recovery usually within 4-6 weeks
Treatment is supportive.
75
Hep A virus Facts
Hep A is an RNA virus
Fecal oral transmission
Incubation 15-50 days
Causes an acute hepatitis
Treatment is supportive with 90% recovery in 3-6 MONTHS.
76
Other viruses that may cause hepatitis:
EBV
CMV
HSV
VZV
Parvovirus
77
Autoimmune hepatitis diagnosis
Positive ANA
Positive Anti-Smooth Muscle Ab
Anti-Liver Kidney Microsome (LKM) Ab
Elevated IgG Levels
Anti-Soluble Liver Ag/Liver Pancreas Ab
Liver Histology:
- Interface hepatitis, lymphocytic/lypmhoplasmacytic infiltrate in the portal tracts extending into the lobule.
78
Drugs associated with autoimmune hepatitis
Minocycline
Nitrofurantoin
Isoniazid
Propylthiouracil
Methyldopa
79
Definition of Primary Biliary Cholangitis
Autoimmune disease effecting the small and medium bile ducts, presenting with fatigue and pruritis.
Female to male 9:1
80
Diagnosis of PBC
If ALP is >1.5 ULN and Positive Anti-Mitochondrial Ab - no biopsy needed.
If negative mitochondrial Ab, requires liver biopsy. May be positive for Anti GP120 or Anti SP 100
Look for other autoimmune disease.
81
Treatment of PBC
Ursodeoxycholic acid
Manage pruritis: Cholestyramine, Antihistamines, rifampicin
Transplantation
81
Treatment of PBC
Ursodeoxycholic acid - this leads to histologic improvement, better survival, and less need for liver transplant.
Manage pruritis: Cholestyramine, Antihistamines, rifampicin
Transplantation
82
PSC Definition
Autoimmune fibro-inflammatory disease of the LARGE bile ducts (but can also affect the small ducts in small duct PSC).
More common in men than women.
83
PSC-IBD Phenotype
85% of PSC cases have UC.
- rectal sparing, mild pancolitis with backwash ileitis
- high risk of CRC, more intensive screening from diagnosis
84
Diagnosis of PSC
Diagnosis can be made non-invasively with MRCP:
- multifocal intra- and extra-hepatic bile duct stricturing with upstream bile duct dilation.
ERCP should be considered in patients with jaundice, worsening pruritis, bacterial cholangitis or a dominant stricture of bile duct mass on MRCP.
Biopsy is not needed (except for small duct PSC)
85
Treatment of PSC
Liver transplantation. Median transplant free survival is 12 years.
- indications are decompensated cirrhosis, recurrent bacterial cholangitis, hilar cholangiocarcinoma.
No current medical therapy.
ERCP to dilate strictures.
15% lifetime risk of cholangiocarcinoma.
- Screen with yearly MRCP and Ca 19-9 level
85
Treatment of PSC
ERCP should be considered in patients with jaundice, worsening pruritis, bacterial cholangitis or a dominant stricture of bile duct mass on MRCP.
Biopsy is not needed (except for small duct PSC)
86
HCC surveillance guidelines:
6 monthly liver USS and serum AFP:
- Any patient with cirrhosis
- Non-cirrhotic patients with Hep B AND increased background risk (asian men >40, asian women >50, Subsaharan africans >20, ATSI >50)
If new lesion <1cm - repeat in 3 months
If new lesion >1cm proceed to further evaluation with quad phase CT or MRI
87
Diagnosis of HCC
Can be diagnosed based on classical imaging with quad phase CT:
- non-rim arterial phase hyper-enhancement
- port venous delayed washout
88
Staging of HCC
Staging is via Barcelona Clinic Liver Cancer staging system (BCLC)
- Stage 0 - single lesion less than 2cm - curative intent resection or ablation
- Stage A - Single lesion >2cm or 3 less than 3cm - curative intent resection or if unable than transplant.
..... From stage B onwards, non-curative therapy
- Stage B - >3 lesions or any lesions >3cm. Transarterial chemo-embolisation.
- Stage C - Vascular invasion or metastatic - treat with systemic therapy
- Stage D - Childs-Pugh C, ECOG >2, for supportive management.
89
Transplant Criteria for HCC
Milan Criteria:
- 1 less than 5cm
- 3 less than 3 cm
No macrovascular invasion, no nodal disease, no mets.
90
Systemic therapy for Stage C (advanced stage) HCC
Atezolizumab and bevacizumab shown to be suprior in recent RCT
Previous first line was -
- Sorafenib
- Lenvatinib
Atezolizumab and bevacizumab
91
Acute management of paracetamol overdose
<2 hours - give charcoal
2-8 hours - measure paracetamol level and ALT at 4-8 hours and be guided by nomogram.
>8 hours - start NAC (acetylcysteine infusion)
If MR paracetamol >10g or 200mg/kg should be given charcoal up to 4 hours.
92
Paracetamol toxic dose
>10g or 200mg/kg
93
Acetylcysteine regimen:
Standard 2 bag regimen:
- 200mg/kg in 500ml over 4hours
- 100mg/kg in 1000ml over 16 hours
Double the second bag to 200mg/kg if:
- massive overdose, double the nomogram line
94
Criteria for ceasing NAC infusion:
Give for 20 hours.
2 hours before completion check the ALT and Paracetamol level.
Cease if:
- ALT decreasing
- INR <2
- patient clinically well.
and
For MR paracetamol and patients with initial paracetamol conc greater than double the nomogram line, paracetamol <10mg/L
95
Kings College Criteria for Transplant in Paracetamol Toxicity
pH <7.3
Or all of the following criteria:
- INR >6.5
- Creatinine >300
Encephalopathy grade 3/4
96
Criteria for consulting liver transplant unit:
Any of the following:
INR > 3.0 at 48 hours or greater than 4.5 at any time
Oliguria or Cr > 200
Persistent acidosis or lactate >3
Systolic hypotension <80
Hypoglycaemia
Severe thrombocytopenia
Encephalopathy of any degree
Any alteration in consciousness.
97
Management of immune checkpoint hepatitis
Grade 1 = AST/ALT 1-3 x ULN or Bili 1-1.5 x ULN. Continue treatment and monitor weekly.
Grade 2 = AST/ALT 3--5 x ULN or Bilirubin 1.5-3 x ULN. Withold ICI (do not restart until grade 1), start steroids at 0.5 - 1 mg/kg/day. Monitor.
Grade 3 = AST/ALT >5 x ULN or Bilirubin >3 x ULN. Institute corticosteroids 1-2mg/kg and permanently discontinue ICI.
98
Management of varices
No varicies - repeat endoscopy in 2-3 years.
Small <5mm
99
4 H's of acute liver failure
Treatment goals in acute liver failure:
Hypothermia
Hypernatraemia 145-150
Hypocapnia 30-45
Haemofiltration - renal replacement therapy.
100
Pregnancy related liver disease:
Pre-eclampsia: late in pregnancy, other features of HELP
Acute fatty liver of pregnancy:
- 3rd trimester
- jaundice, AST/ALT 300-1000, high bilirubin, Synthetic liver dysfunction with hypoalbuminaemia, hyperammonaemia, coagulopathy
- Clinical: Polyurin and polydipsia
101
Haemochromatosis pathogenesis
Autosomal recessive, mutation in HFE Gene (C828Y/C828Y most common)
Leads to deficiency of hepcidin
Ferroportin constantly active and absorbing iron.
Iron deposits in liver, pancreas, heart, pituitary
102
Diagnosis
Iron studies - high transferrin sats, high ferritin
If confounding factors for high ferritin
MRI-T2 showing "black liver and white spleen"
Genetic testing for HFE C282Y mutation. If not homozygous, refer for further genetic testing of less common mutations.
103
Haemochromotosis Management
Phebotomy:
- Aiming for serum ferritin 50ng/ml and transferrin sats of 50% (50/50)
Iron chelation with deferoxamine is rarely used.
Family genetic counselling.
104
Wilsons Disease pathogenesis
Autosomal recessive, mutations in ATP7B gene.
ATP7B is a copper transporting transmembrane protein, which mediates excretion of copper into the bile and incorporates copper into ceruloplasmin (copper transport protein).
Defecting ATP7B stops ceruloplasmin formation and excretion of copper. Excess copper accumulates in the liver and the brain.
105
Natural history of Wilsons Disease
18 years - Symptomatic liver disease
24 years - neuropsychiatric disease (tremor, rigidity, dystonia, psychiatric)
Classic patient is young patient <40 years, moderately elevated ALT and a high bili:ALP ration.
Look for haemolytic anaemia and encephalopathy with KF rings.
106
Diagnosis of Wilsons Disease
Can present as any form of liver disease from acute liver failure to decompensated cirrhosis.
Low Ceruloplasmin
Copper content in biopsy elevated
Elevated 24 hour urine copper
Kayser-Fleischer rings - golden/brown rings in the membrane of the cornea .
MRI-B - Panda Sign, T2 shows Cu deposit in basal ganglia.
107
Treatment of Wilsons Disease
Cu Chelators - D-penicillamine
Zinc supplementation inhibits the intestinal uptake of copper
Liver transplant is advanced disease.
108
Alpha1 anti trypsin deficiency pathogenesis
Mutation in the SERPINA1 gene which encodes AAT.
Mis-folding and accumulation in liver (inclusion bodies) leads to toxicity and eventually cirrhosis.
Loss of function leads to lack of inhibition of proteases and proteolytic destruction causing pan-lobular emphysema.
Z allele (Glu342Lys)
S allele (Glu264Val)
M allele = wildtype
PiZZ (homozygosity for Z allelle) causes neonatal hepatitis, cirrhosis in adult, and lung disease.
PiSZ
PiMZ is a "contributor" which increased risk of COAD and liver disease in the presence of other risk factors.
109
Type of renal stones in Crohns Disease?
Calcilum oxalate stone. Common complication of Crohns disease after bowel resection.
Decrease in bile acid absoprtion leads to fat malabsorption which binds to calcium. This leads to increased oxalate absorption, which is deposited in kidney.
110
Indication for TIPs in Cirrhosis:
Refractory ascites defined as >4 LVP within 6 months.
111
Most common indication for liver transplantin Aus?
Hepatitis C Cirrhosis with or without HCC (28%)
Others:
HCC 14%
Alcoholic Liver disease 13%
NASH 6%
Hepatitis B 3%
112
Classic presentation of Chronic mesenteric ischaemia
Post-prandial abdominal pain, fear of eating, weight loss.
Older adult with cardiovascular risk factors.
113
Definition of liver steatosis
>5% hepatocytes loaded with fatty vacuoles or >5% of liver weight.
114
Paracetamol metabolism
90% metabolised via glucuronosyltransferase and sulfotransferase into glucorinide and sulfate conjugates which are excreted in urine.
5% excreted unchanged in urine.
5% metabolised via CYP 2E1 into NAPQI, which binds glutathione and is excreted in urine.
Therefore increased risk of toxicity if:
- Fasting
- Alcohol intake - induces CYP2E1 expression
- CYP2EI inducing drugs
NAPQI is highly hepatotoxic
115
Tacrolimus Side Effects
Diabetes
Nephrotoxicity - renal afferent artery constriction.
Electrolyte: hyperkalaemia, hypophosphataemia, hypomagnesiaemia, metabolic acidosis.
Hypertension
Hyperlipidaemia
Increased risk of infection
Neurotoxicity: tremor, insomnia, paresthesia. Rare serious neurotoxicity includes seizures, cortical blindness, encaphalopathy and central pontine myelinolysis.
116
Mechanism of Terlipressin
Binds to V1a receptors on splanchnic vascular smooth muscle causing vasoconstriction --> reduced portal pressures, increased renal blood flow.
However also binds to V2 receptors in renal collecting duct - therefore can cause hyponatraemia.
117
Contraindications to terlipressin
Unstable coronary artery disease, pregnancy. Caution in asthma and COPD.
118
Portal Vein thrombosis
Thrombosis of the PORTAL VEINS (ie Inflow). Usually NOT due to hypercoaguable state.
Common in patients with cirrhosis.
Chronic thrombosis is usually asymptomatic and does not need anticoagulation.
Acute thrombosis can be symptomatic with development of ascites and or variceal haemorrhage. Anticoagulation can be considered if there is concern that thrombosis has extended into the superior mesenteric vessels.
119
Budd-Chiari Syndrome
Thrombosis is u
