Gastro Flashcards
Classification of HCV
RNA enveloped virus
Flaviviridae
Characteristics of HCV acute phase
Increase in HCV RNA (first to increase)
Increase in HCV Ag (positive after 1 month)
Rise in Anti-HCV Ab (positive within 12 weeks and remains positive for life)
Definition of successful viral eradication in HCV
Eradication of HCV RNA 12 weeks after treatment
Examples of NS3/4A
All the ones that end with -previr
Glecaprevir
Simeprevir/Telaprevir
Boceprevir
Paritaprevir
Voxilaprevir
Examples of NS5A
All the ones that end with - svir
Velpatasvir
Pibrentasvir
Elbasvir
Daclatasvir
Lediapasvir
Omhitasvir
Examples of NS5B
All the ones that end with -buvir
Sofosbuvir
Dasabuvir
First line therapies for HCV
Sofosbuvir (NS5B) + Velpatasvir (NS5A)
Glecaprevir (NS3A/4A) + Pibrentasvir (NS5A)
Spontaneous clearance of HCV more likely in
Women, younger patients, and patients with symptoms, high ALT levels, or IL-28 CC genotype
Extrahepatic manifestations of HCV
B-NHL (primarily DLBCL)
Mixed cryoglobulinemic vasculitis
Sicca symptoms
Higher cardiovascular events
Vasculitis
Porphyria cutanea tarda
Lichen planus
Membrano-proliferative GN
High risk features of HBV requiring surveillance
Anyone with cirrhosis
Anyone with first degree relative
Asian men > 40 yrs
Asian women > 50 yrs
ATSI > 50 yrs
African men and women > 20 yrs
Classification of HBV
DNA virus – partially double stranded
Pathology of immune tolerant phase
High level HBV RNA
HbeAg positive
Normal LFTs
Pathology of immune clearance phase
High HBV DNA
Abnormal LFTs
HbeAg positive
High risk progression of HCC and cirrhosis
Pathology of immune control phase
Low HBV DNA
Normal LFTs
HbeAg negative
Anti-Hbe positive
Pathology of immune escape phase
Occurs due to mutation of virus
High HBV DNA
Abnormal LFTs
HbeAg negative
Anti-Hbe positive
Pathology of acute HBV
Positive HbsAg
Positive Anti-Hbc IgM
Positive HbeAg
HBV-DNA +++
Pathology of chronic HBV
Positive HbsAg
Could have positive or negative HbeAg
Positive Anti-Hbc
HBV-DNA +++
Generally Anti-Hbc IgM not positive
Pathology of vaccinated against HBV
Positive Anti-HbS
Otherwise everything else negative
Pathology of cleared HBV
Positive Anti-HBs
Positive Anti-HBc
Treatment of HBV
Entecavir
Tenofovir disoproxil fumarate
Peg-IFN alpha 2a
Tenofovir alafenamide - not listed for monotherapy but is PBS listed for co-infections
Difference between tenofovir disoproxil fumarate with alafenamide
Alafenamide has less issues with bone mineral density and renal disease
Entecavir vs tenofovir
Entecavir
- Preferred over tenofovir for patients with renal and bone disease
Tenofovir
- Preferred over entecavir for pregnant patients and those with prior exposure to nucleoside analogues i.e lamuvudine
Guidelines of treatment for HBV
- For patients HBeAg positive chronic hepatitis, anti-viral therapy indicated when HBV DNA > 20,000 IU/ml and ALT persistently elevated or evidence of fibrosis
- For patients HBeAg negative chronic hepatitis, anti-viral therapy indicated when HBV DNA > 2,000IU/mL and ALT persistently elevated, or evidence of fibrosis
- All patients with cirrhosis and any detectable HBV DNA, regardless of ALT levels
Treatment of acute hepatitis B
- Supportive care
- Antiviral therapy generally not indicated unless severe or fulminant disease (coagulopathy, marked protracted jaundice, acute liver failure etc.)
Indications for treatment of chronic hepatitis B
- Cirrhosis or advanced fibrosis
- Acute liver failure
- Immune active phase – ALT >/ 2 ULN + significantly elevated HBV DNA level, with or without HBeAg
- Immunosuppression in HBV positive patients
- Coinfection with HCV or HIV
- Family history of HCC
Indication of HBV for pregnant women
Pregnant women with high viral load (>200,000) should be offered tenofovir from 28th week of pregnancy - reduces perinatal transmission of hepatitis B
Treatment of neonate with mothers positive for HBV
All infants should receive HBIg and hepatitis B vaccination as soon as possible after birth
Genotypes of HAV and HEV that affect humans
Genotypes 1-4
Transmission of HAV/HEV
HAV and HEV mostly spread via faecal-oral route
HEV genotype 3 and 4 are zoonotic viruses. Can be spread foodborne.
Prognosis for HAV and HEV
Both are self-limiting infections and do not require treatment
Risk of chronic HEV in immunosuppressed patients
Characteristics of HDV
Caused by small, defective RNA virus
Requires HBsAg for transmission
Co-infection of HBV and HDV associated with more severe acute hepatitis and higher mortality
- 50-70% of patients with chronic HBV/HDV co-infection develop cirrhosis
Treatment of HDV
Peginterferon alfa - at least 48 week course weekly SC injections
Bulevirtide 2mg SC/daily
Difference between all the stages of HBV infection
Immune tolerant
- Immune system does not recognise virus as foreign resulting in high levels of viral replication due to minimal immune pressure and no reaction
- High levels of virus
- Normal LFTs and minimal liver damage done at this stage
- E antigen positive
Immune clearance
- Immune pressure on HBV, causing decrease in viral loads and increase in ALT levels (due to immune reaction)
- Suppression of virus causing formation of e antibodies
- Tissue damage at this stage
Immune control
- Suppression of virus –> nil further replication and improvement in LFTs
Immune escape
- Due to mutations of virus, immune escape can occur
- Increase in viraemia and ALT
- E Antigen would be negative
- Tissue damage at this stage
Drugs that may induce autoimmune hepatitis
Minocycline
Nitrofurantion
Isoniazid
Prophylthiouracil
Methyldopa
Treatment for autoimmune hepatitis
1st line
- Budesonide + azathioprine
- Prednisone +/ azathioprine
Refractory disease
- High dose prednisone + azathioprine
- Calcineurin inhibitor
Azathioprine intolerance
- Mycophenolate mofetil
Diagnostic findings on primary biliary cholangitis
Increase IgM
Increase lipids
Positive AMA (in 95% of patients)
Positive ANA
If AMA negative, may have positive anti-GP210 or anti SP100
Nil need for liver biopsy if strong clinical suspicion
Management of PBC
Ursodeoxycholic acid - reduces rate of liver decompensation and transplantation
Management of pruritus with cholestyramine, antihistamines, rifampicin
Treatment other complications: OP, fat soluble vitamin deficiency, lipid issues, autoimmune conditions
Diagnosis of primary sclerosing cholangitis
Cholestatic LFT picture + MRCP findings (strictures of intra and extrahepatic bile ducts)
Management of PSC
Minimal therapies to improve long term effects
Ursodeoxycholic acid can improve LFTs, but nil effects on long term outcomes
Prognosis of PSC
Increased rate of bowel cancer and liver cancer
Requires annual assessment of liver with MRCP, liver US and colonoscopy
Histology findings on PSC
Bile duct inflammation and fibrosis
Histology findings on PBC
Bile duct damage
Granulomas within portal tract
Most frequent extra-pancreatic manifestation of type 1 AIP
IgG4 related AIP
IgG4 related sclerosing cholangitis is most frequent extrapancreatic manifestation
Presentation of IgG4 cholangitis
Cholestatic liver disease
Usually steroid responsive
Diagnosis of MAFLD
Hepatic steatosis with overweight/obesity + T2DM –> MAFLD
Hepatic steatosis with lean/normal weight + at least 2 metabolic risk abnormalities –> MAFLD
Metabolic risk abnormalities associated with MAFLD
Waist circumference >102/88 in Caucasian men and women (or >90/80 in Asian men and women)
Blood pressure >130/85mmHg or treatment
Plasma triglycerides >/ 1.70 or treatment
Plasma HDL < 1.0 mmol/L for men or 1.3mmol/L for women
Prediabetes
Homeostasis model assessment of insulin resistance score >/ 2.5
Plasma high sensitivity CRP > 2
Management of MAFLD
Weight loss
Evidence of Mediterranean diet
Pharmacology TBD - some vidence with pioglitazone, obeticholic acid, GLP1 analogues
High risk patients of HCC requiring surveillance
Non-cirrhotic HBV
- Asian men > 40 yrs
- Asian women > 50 yrs
- Sub-saharian > 20 yrs
- Indigenous and Torres Strait > 50 yrs
All cirrhosis pts
Requirements for surveillance of HCC
6 monthly US +/- AFP
Evaluation of HCC
If < 10mm lesion –> repeat liver US +/- AFP in 3 months
If > 10mm lesion –> evaluate lesion with multiphase CT or MRI
Liver biopsy/alternative imaging/repeat imaging if indeterminate findings
Management of HCC
If solitary nodule </ 2cm –> Ablation or resection
If solitary nodule > 2cm or 2-3 nodules –> resection/transplant/ablation
If multiple nodules –> chemoembolisation
If metastatic disease –> systemic therapy
If non-transplant candidate –> supportive care
Transplant criteria for HCC
Single lesion </ 50-65mm
2-3 tumours, all </ 30mm/45mm
No macrovascular invasion, no regional nodal disease, no distant metastases
First line immunotherapy for HCC
Atezolizumab (PDL-1 inhibitor)
Bevacizumab (VEGF inhibitor)
Side effects of atezolizumab and bevacizumab
Atezolizumab –> AI related problems
Bevacizumab –> bleeding and thrombosis
Gene associated with alcoholic cirrhosis
PNPLA3 gene
Located on chromosome 12
Mechanism of hepatic fibrosis in alcoholic liver disease
Hepatic degradation of ethanol to acetyl-CoA by alcohol dehydrogenase results in NADH excess → ↑ NADH drives the formation of glycerol 3-phosphate (G3P) from dihydroxyacetone phosphate (DHAP) → ↑ in both G3P and fatty acids causes increased triglyceride synthesis in the liver and accompanying inflammation → steatohepatitis → chronic inflammation leads to hepatic fibrosis and sclerosis → portal hypertension and eventually cirrhosis
Histology of alcoholic hepatitis
Steatosis and degeneration of cells
Mallory’s hyaline cells ceens
Management of alcoholic hepatitis
Alcohol cessation
Prednisone may be used in subset of pts
Risk factors for paracetamol toxicity
- Prolonged fasting or dehydration
- Chronic under nutrition
- Chronic, excessive alcohol use
- Severe hepatic impairment
Paracetamol toxicity management
NAC infusion until
- ALT or AST decreasing
- INR < 2.0
- Pt clinically well
FFP if active bleeding
Considerations of liver transplant
INR > 3 at 48 hours, or >4.5
Oliguria or Cr > 200
Persistent acidosis or lactate > 3
Systolic hypotension despite resuscitation
Hypoglycaemia, severe thrombocytopenia or encephalopathy
Any alteration of consciousness
Immunotherapy with highest rates of side effects
Anti- PD-1/PDL-1 - pembrolizumab, nivolimuab, atezolizumab, avelumab
Anti-CTLA4 - ipilimumab
Treatment of immunotherapy hepatotoxicity
Grade >/ 2 (AST and/or ALT >3-5x ULN or bili >1.5-3x ULN)
- Corticosteroid
- withhold immunotherapy
- monitor changes in liver function
Grade 3 (AST and/or ALT >5x ULN or bili > 3x ULN)
- Corticosteroid
- Permanent discontinuation
Role of FIB-4
Identifies risk of liver disease
Low risk (<1.3) –> follow up in GP
High risk –> follow up with specialist, consider fibroscan, liver biopsy
Definition of portal HNT
Portal hypertension is defined as a hepatic venous pressure gradient (HVPG) of ≥ 6 mm Hg.
HVPG > 10 mm Hg is clinically significant and > 12 mm Hg is associated with complications.
Aetiology of portal HTN
Prehepatic
- Portal vein thrombosis
- Splenic vein thrombosis
Intrahepatic
- Cirrhosis including fibrous proliferation (most common cause of portal hypertension in the US)
- Hepatosplenic schistosomiasis
- Massive hepatic metastases
- Hepatic sinusoidal obstruction syndrome (SOS; previously called hepatic veno-occlusive disease)
Posthepatic
- Budd-Chiari syndrome
- Right-sided heart failure
- Constrictive pericarditis
Management of portal HTN
Non-selective B blocker - carvedilol is choice
Portal systemic shunts:
Transjugular intrahepatic portosystemic shunt (TIPS or TIPSS) for
- Persistent, recurring, or treatment-resistant upper gastrointestinal bleeding resulting from portal hypertension, e.g., from esophageal varices
- Refractory ascites
- Acute thrombosis of portal vein
- Patients with hepatorenal syndrome who are not eligible for or are awaiting liver transplantation
Total portosystemic shunts
Selective portosystemic shunts
Principles of acute liver failure
Hypothermia
Hypernatraemia
Hypocapniea
Haemofiltration
Pathophysiology of hepatic encephalopathy
Cirrhosis → ↓ hepatic metabolism and portosystemic shunt → accumulation of neurotoxic metabolites, including ammonia (NH3) → excess glutamine and swelling produced by astrocytes → cerebral edema and ↑ intracranial pressure → neurological deterioration
Metabolic effects:
Hypokalemia → shift of K+ ions out of the cells → shift of H+ ions into the cells to maintain electroneutrality → intracellular acidosis → tubular cells produce more ammonia → neurological deterioration
Metabolic alkalosis → decreased H+ ion availability → decreased conversion of ammonia to ammonium (NH4+) → increased levels of ammonia → diffuses freely through the blood-brain barrier → neurological deterioration
Management of hepatic encephalopathy
Lactulose - a synthetic disaccharide laxative
- First-line treatment for hepatic encephalopathy
- Improves symptoms of hepatic encephalopathy by decreasing the absorption of ammonia in the bowel
Rifaximin: a broad-spectrum, nonabsorbable oral antibiotic (off-label)
- Reduces the number of ammonia-producing intestinal bacteria
May be added to lactulose if recurrent episodes occur
MOA of lactulose for HE
Lactulose is converted to lactic acid by intestinal flora → acidification in the gut → conversion of ammonia (NH3) to ammonium (NH4+) → ammonium is excreted in the feces → decreased blood ammonia concentration
Pregnancy related liver disease
- Severe preeclampsia and eclampsia
- HELLP syndrome
- Acute fatty liver of pregnancy
Features of severe pre-eclampsia and eclampsia
Occurs after gestational week 22
High BP
Proteinuria
Oedema
Seizure
Renal failure
Pulmonary oedema
Features of HELLP syndrome
Late second trimester to early postpartum
Abdominal pain
Nausea/vomiting
Haemolysis
Elevated liver enzymes
Low platelet
Features of acute fatty liver of pregnancy
Third trimester
Abdominal pain
Nausea/vomiting
Jaundice
Hypoglycaemia
Hepatic failure
Definition of haemochromatosis
Iron overload of genetic origin and related to relative hepciden deficiency
Pathophysiology of haemochromatosis
HFE gene defect (homozygous) → defective binding of transferrin to its receptor → ↓ hepcidin synthesis by the liver → unregulated ferroportin activity in enterocytes → ↑ intestinal iron absorption → iron accumulation throughout the body → damage to the affected organs
Aetiology of haemochromatosis
Primary (hereditary) haemochromotosis -
- Classical and most frequent form: adult hemochromatosis type I
- Homozygous or heterozygous for the HFE gene defect
- Located on chromosome 6
- Most commonly affects C282Y and H63D
- Associated with HLA-A3 genotype
- Inheritance: autosomal recessive with incomplete penetrance
Further forms: Hemochromatosis types II–IV are also hereditary, but significantly less frequent.
Secondary haemochromatosis -
- Caused by iron overload
- Transfusion-related (e.g., in individuals with beta-thalassemia major or other forms of chronic anemia requiring chronic transfusion)
- Ineffective erythropoiesis
- Thalassemia
- Sickle-cell anemia
- Sideroblastic anemia (e.g., hereditary sideroblastic anemia; anemia of chronic disease)
- Excessive alcohol consumption
Clinical findings of haemochromatosis
Fatigue/impotence
Arthropathy
Bronze skin
Liver disease
Signs of DM
Management of haemochromatosis
Phlebotomy - aiming serum ferritin < 50
Iron chelation
Dietary changes
PPIs
Family screening
Liver transplantation indicated if:
- Decompensated cirrhosis
- Hepatocellular carcinoma
Presentation of Wilson’s disease
Young patient
Kayser Fleischer rings
Moderately elevated ALT
High bili:ALP ratio
Coombs negative haemolytic anaemia and encephalopathy
Panda sign on MRI
Low ceroplasmin
Elevated 24 hr urine copper
Genetic mutations of Wilson’s disease
Autosomal recessive disorder
Caused by mutations in ATP7B gene
ATP7B is coppy transporting transmembrane protein
Management of Wilson’s disease
Chelating agents (D-penicillamine)
Zinc agents
Liver transplant if acute liver failure
Use of Maddrey’s DF
Determine prognosis and use of steroid in alcohol hepatitis
Maddrey’s DF > 32 - poor prognosis, should have corticosteroids
Montreal classification of Crohn’s disease
Age, disease location, disease behaviour
Montreal classification of UC
Age and extent
Histology of IBD
Crypt architectural distortion and lymphoplasmic infiltrate within lamina propria
Genetic factors of IBD
NOD2 gene
HLA B27 association
Relevance of NOD2 in CD
Associated with fibrostenotic complications and increased surgery rates in CD
Environmental exposures and IBD
Smoking associated with CD but protective for UC
High fat/proteun diet
Poor hygiene
Antibiotics
Classification of UC
Proctitis - E1
Left sided - E2
Pancolitis - E3
Risk factors for colon cancer in UC
- Increased duration and extent of disease
- Primary sclerosing cholangitis
- Co-existent FHx
- Disease activity
Surveillance guidelines for IBD
Annual
- Active disease
- PSC
- FHx of colorectal cancer in first degree relative < 50 yrs
- Colonic stricture, multiple pseudopolyps
- Previous dysplasia
3 yearly
- Inactive UC
- Crohn’s colitis
IBX and FHx of CRC in first degree relative > 50y/o
5 yearly
- Two previous normal colonoscopies
Risk factors for severe CD
- Steroids at diagnosis
- Age < 40 yrs
- Perianal disease
- Smoking
- Strictures
- Upper GI disease
- Deep ulcers in colon
- High titre ASCA
- NOD2, ATG16L1, MDR1 genes
Treatment targets for IBD
Therapeutic drug levels
Mucosal healing
Normal calprotectin
Risk factors for severe UC
Age < 40 yrs
Extensive disease
Primary sclerosing cholangitis
Deep ulcers
High titre pANCA
Approach to UC therapy
Treatment according to disease extent and severity
- 5-ASAs oral and rectal
- Steroids if inadequate control with 5 ASA but taper
- Thiopurines - if requiring steroids > x1/year
- Anti-TNFs - infliximab > adalimumab, golimumab
- Vedolizumab
- JAK inhibitors - tofacitinib
Approach to CD therapy
Symptoms dependent on location and phenotype
Step up vs top down approach
Stop smoking
Indications for rapid step up therapy
Active disease
Extensive disease
Complicated disease (if fistula –> use TNF inhibitor)
Not reaching treatment target
Biologics used in IBD
Anti-TNFs - Infliximab, adalimumab, golimumab
(works better in CD > UC)
Anti-integrin - Vedolizumab
(works better in UC > CD)
Anti-IL12/23 - Ustekinumab
Use of steroids in IBD
Effective as induction but not maintenance agents
Budesonide used in mild ileocolonic CD or UC
MOA of azathioprine
Azathioprine > non-enzymatic conversion to 6-MP > 6-TIMP > 6-MMPR (mercaptopurine) and 6-TGN (thioguanine)
6-MMPR > hepatotoxicity
6-TGN > T cell apoptosis
Measuring thiopurine metabolites
Low/absent 6-TGN + Low/absent 6-MMP –> Non compliance
Low 6-TGN/Low 6-MMP –> underdosing
Low 6-TGN/High 6-MMP –> Thiopurine resistance
High 6-TGN/High 6-MMP –> Thiopurine refractory
Adverse events of azathioprine
Myelosuppression
Hepatitis
Pancreatitis
Nausea/vomiting
Flu-like symptoms
Hypersensitivity syndrome
Infection
Lymphoma
Non-melanoma skin cancer
Anti-TNFa agent classification
Chimeric - Infliximab
Human - Adalimumab
Humanised Fab’ PEG - certolizumab
Human recombinant receptor/Fc fusion - Etanercept
Adverse effects of Anti-TNF
Infection - Tuberculosis, invasive fungal infections, viral infections, bacterial sepsis
Lymphoma
Melanoma risk doubled
Demyelinating disorders
Drug-induced lupus like syndrome
Congestive heart failure
Abnormal LFTs
MOA of vedolizumab
Gut specific
Blocks a4B7-MAdCAM –> T cell adhesion –> causes T cell migration –> inflammatory cytokines (IL-17, IFN-y) produced by T cells
MOA of ustekinumab
Blocks IL-12/23 via p40 subunit
Effective for moderate disease but not severe
Use of JAK inhibitors in IBD
Highly effective however significant toxicity
Used for UC, but not available for CD
MOA of Tofacitinib
JAK 1/3 inhibitors
MOA of upadacitinib
Blocks JAK1 predominantly
MOA of ozanimod
S1P modulator
Traps lymphocytes within lymphatic tissues
Reduces lymphocytes in circulation
Side effects of ozanimod
Bradycardia and cardiac conduction delays
Macular oedema
Management of acute severe UC
IV hydrocortisone
Flexible sigmoidoscopy and biopsy
Salvage therapy vs Surgery
Management of fistula
Antibiotics
Surgery
Anti TNF
IBD medications contraindicated in pregnancy
MTX
Thalidomide
Inadequate data for
- Allopurinol
- Tofacitinib
- Upadacitinib
- Ozanimod
Role of parietal cell
Releases H+ acid
Activated by Ach (released from distension of stomach) and H2
Inhibited by SSR (from paracrine, D cell) and CCK (gastrin)
Role of ECL cell
Releases Histamine –> H2
Activated by ACh and M3 (from enteric nervous system), and somatostatin (from D cell)
Role of D cell
Releases somatostatin and SSR
Activated by ACh and M3
Role of G cell
Releases gastrin
Activated by vagus nerve (via gastrin-releasing peptide and GRP released from presynaptic terminals of postganglionic fibers), amino acids and peptides,
Decreased acidity and distention of the stomach
Inhibited by somatostatin
Role of D cells
Releases somatostatin
Inhibits gastrointestinal secretions
↓ Gastric acid
↓ Gastrin
↓ Pepsinogen
↓ Cholecystokinin
↓ Secretin
↓ Pancreatic secretions (VIP, glucagon, insulin)
↓ Gastric inhibitory polypeptide
- Inhibits gall bladder contraction
- Decreases motility of the stomach and intestine
- Causes splanchnic vasoconstriction
- Decreases growth hormone and TSH secretion
Activated by postprandial - gastric acid, fatty acids, and amino acids entering the duodenum
Inhibited by vagus nerve (ACh)
Role of GLP1
Secreted by L cells in duodenum and colon
Proglucagon cleavage product
Short acting effects - slows gastric emptying
Long acting effects - increase insulin, reduces glucagon
Adverse effects - pancreatitis, nausea, tachycardia
Role of GIP
Released by K cells in small intenstine
Glucose dependent insulin secretion
Side effects of PPI
Hypergastrinaemia
- Prolonged acid inhibition
- Atrophic gastritis –> pernicious anaemia, H pylori
- Gastrin secreting tumours
- Renal failure
- Hypercalcaemia
Pneumonia
Gastroenteritis
Osteoporosis
Hypomagnesaemia
Interstitial nephritis
Microscopic colitis
Features of MEN1
Hyperparathyroidism
Pituitary and pancreatic cancer
1/3rd pts present with Zollinger Ellison syndrome
Autosomal dominant
Diagnosis of gastropancreatic neuroendocrine tumours
Urinary 5HIAA - 90% sensitivity
Ki-67 index to review severity
Motility disorders associated with loss of interstitial cells of Cajal
Slow transit constipation
Chronic idiopathic constipation
Achalasia
Gastroparesis
Afferent loop syndrome
Megacolon and megaduodenum
Paraneoplastic dysmotility
Crohn’s disease
Chaga’s disease
Chronic pancreatitis definition
Permanent structural damage and impaired exocrine + endocrine function
Leading to malabsorption and malnutrition
Presentation of chronic pancreatitis
Abdominal pain, worse post-prandially
Pancreatic insufficiency
- Fat malabsorption –> steatorrhoea, B12 deficiency
- glucose intolerance/overt diabetes
Complications of chronic pancreatitis
Pseudocysts
Bile duct/duodenal obstruction - from fibrosis of pancreatic head or compressive effects of pseudocyst
Pancreatic ascites/pleural effusions
Diagnosis of chronic pancreatitis
72 hour quantitative faecal fat –> diagnostic for malabsorption
Faecal elastase
Abdominal XR - review for calcification of pancreatic duct
CT Abdomen - review for pancreatic atrophy, duct dilatation, parenchymal and intraductal calcifications
MRCP
Management of chronic pancreatitis
Pancreatic enzyme supplementation
Fat soluble vitamin supplementation
Restrict fat intake
Lipase supplementation
Inherited causes of pancreatitis
Disorders with trypsin:
- PRSS gene - trypsinogen
- SPINK1 mutation
Pancreatic ductal secretion abnormalities:
- CF gene mutations
- viarant common chymotrypsin C
Features and management of IgG4 AI pancreatitis
Mild recurrent attacks
Raised serum IgG4
Very responsive to steroids
Management of fluid collections
If acute fluid/necrotic collection –> delay
If pseudocyst –> drain
If walled off necrosis –> debridement
Definition of ABCB4
Transmembrane fioppase protein
Transports phosphatidylcholine into bile duct
ABCB4 disease
Heterozygous disease
Causes
Intrahepatic cholestasis of pregnancy
Isuses with gallstones
Can be treated with ursodeoxycholic acid
Homozygous disease causes neonatal cholestasis
Features of serous cystadenoma
Located at head of pancreas
Imaging - Honeycombed, microcystic
Central stellate scar with calcification
Histology - glycogen-rich cuboidal cells
Generally not premalignant
Features of IPMN
Located at head of pancreas
Imaging - Dilated main or branch duct
Histology - columnar mucin-producing cells
Premalignant
Features of MCN
Affects mostly women
Located at body, tail of pancreas
Imaging - septated cyst, calcification in cyst wall
Histology - ovarian like stroma
Premalignanct
High risk features of pancreatic findings
Size > 3cm
Main duct dilatation
Solid component
Risk factors for pancreatic cancer
Smoking
Chronic pancreatitis
Cystic fibrosis
BRCA1, BRCA2
Lynch syndrome
FAMMM
Hereditary pancreatitis
Peutz-Jeghers syndrome
Indications for testing in H pylori
Active peptic ulcer disease or history of PUD
Low grade gastric mucosa-associated lymphoid tissue lymphoma or history of endoscopic resection
Uninvestigated dyspepsia
Long term aspirin use
Long term NSAID use
Unexplained IDA
ITP in adults
Completion of H. pylori treatment
H pylori treatment
2 week course of
Amoxicillin/Tetracycline/Bismuth
Otherwise levofloxacin/moxifloxacin
Symptoms of eosinophilic oesophagitis
Dysphagia
Food impaction
Chest pain
Heart burn
Abdominal pain
Refractory “GORD”
Diagnostic findings of eosinophilic oesophagitis
Scope - multiple ridges down oesophagus
Histology - esophageal oesinophilia, basal zone hyperplasia, dilated intercellular spaces
Management of eosinophilic oesophagitis
PPIs
Topical steroids (fluticasone, budesonide, ciclosonide)
Elimination and elemental diets
Dilation
Antihistamines, immunosuppressants, immunomodulators
Features of achalasia
Inadequate relaxation of the lower esophageal sphincter (LES) and nonperistaltic contractions in the distal two-thirds of the esophagus due to the degeneration of inhibitory neuron
Management of achalasia
Low surgical risk -
Pneumatic dilation
- The success rate at one month is ∼ 85%; perforation risk is ∼ 2%.
LES myotomy (Heller myotomy): a surgical procedure in which the lower esophageal sphincter is incised longitudinally to re-enable passage of food or liquids to the stomach.
Peroral endoscopic myotomy: An endoscopy-guided myotomy of the inner circular muscular layer of the lower esophageal sphincter (the longitudinal muscle layer is preserved)
- May be considered in other esophageal motility disorders (e.g., diffuse esophageal spasm) as well, in which case the myotomy incision may need to be extended into the esophageal body
High surgical risk:
Botulinum toxin injection in the LES
- A good choice for patients who are poor surgical candidates
- More than 50% of patients require treatment again within 6–12 months.
If other measures are unsuccessful: nitrates or calcium channel blockers
Vitamin B12 deficiency causes
Diet
Atrophic gastritis: H pylori, pernicious anaemia
Gastrectomy
Bacterial overgrowth
Pancreatic insufficiency
Crohn’s disease
Blocking agents (i.e. neomycin)
Drugs - PPI, metformin, colchicine
Histology of coeliac disease
Villous atrophy
Lymphocytosis
Disease associations with coeliac disease
Dermatitis herpetiformis
Autoimmune conditions
- IDDM
- Hypothyroidism
- IgA deficiency
Down syndrome
Turner syndrome
Liver disease
Investigations for coeliac disease
TTG Antibody + IgA
Serology
Biopsy
Definition of Barrett’s oesophagus
> 1cm of columnar metaplasia in distal oesophagus
Risk factors for Barrett’s oesophagus
Reflux symptoms > 5yrs
Male gender
Tobacco smoking
Central obesity
Caucasian
Risk of cancer for Barrett’s oesophagitis
Low risk
