NZ Gastro Flashcards
Pathophysiology of IBD
Multifactorial disease:
- Genetics: approx 200 susceptibility genes identified
- Identical twins: risk 30-35% - Environmental factors:
- Smoking (protective for UC, increased risk for CD)
- Appendicectomy (reduced risk of developing UC)
- Breast feeding - conflicting evidence
- NSAID use and infection - increases risk - Dysbiosis:
- Overactive immune response to normal gut flora
- Putative infectious agents: TB, listeria, shigella, yersinia, Bacteroides vulgatus, measles, E. coli subtypes
Incidence of IBD
Prevalence: 1 in 400 in general population with 20-25% in childhood
Current trend: earlier childhood presentation, CD more common in paediatric population
UC: M=F, CD: M>F
Early onset IBD (<5yo)
Need to rule out:
Immunodeficiency
- IL10 deficiency
- Chronic granulomatous disease
Ix:
- Neutrophil function
- Lymphocyte subset
- Immunoglobulin level
- Genetic panel for monogenic causes
Growth failure in IBD
Weight loss
27% Wt <3rd centile
13% Ht <3rd centile
Delayed puberty
Secondary to:
- Decreased oral intake (anorexia, pain, increased stooling)
- Chronic inflammatory state (catabolic)
- Malabsorption
Long term height outcomes in IBD
Mean 2.4cm deficit in adulthood
19% >8cm below expected from mid-parental height
Ht Z-score inversely proportional to delay in diagnosis
IBD-related arthropathy
- Peripheral arthropathy:
- Type 1: pauci-articular, large joints, asymmetrical, MIRRORS disease activity, HLA-B27, HLAB35 and HLA-DR related
- Type 2: polyarticular, small joints, INDEPENDENT of disease activity, may be associated with uveitis - Axial arthropathy:
- 5-10%, ankylosing spondylitis or sacroiliac joint arthritis, independent of gut disease activity
Faecal calprotectin
Neutrophil derived inflammatory marker
- 24kDa dimer of calcium binding proteins - present in cytoplasm of neutrophils
- Not degraded by intestinal enzymes or bacteria
Highly sensitive marker for inflammation, but nonspecific
Falsely elevated with NSAID use
IBD work up
- Inflammatory markers (ESR/CRP)
- FBC: thrombophilia, anaemia
- Albumin
- Faecal calprotectin
- TMPT genotype
- Measles and varicella serology
- Quantiferon Gold
- PORTO Criteria:
- -> Upper GI endoscopy, ileocolonoscopy, small bowel MRI
UC Histopathology
Loss of normal vascularity, erythema, ulceration, contact bleeding, friability, pseudopolyps (secondary to chronic inflammation), increased inflammatory cells in lamina propria, crypt abscesses, crypt irregularity
CD Histopathology
Non-necrotising granulomas, transmural inflammation, fissuring
Crohn’s: Induction therapy
- Enteral nutrition
- Enteral nutrition as effective as steroids in inducing remission (70% of cases)
- MOA: modulating gut microbiota in 8 weeks, prebiotic properties
- Benefits: improves growth delay and BMD, enables catch up vaccinations
- Progress: in responsive pts, will improve by ~14 days –> slow reduction in inflammatory process and weight gain
- Options: elemental vs polymeric
- Duration: exclusive enteral nutrition for 8 weeks (yuck)
Exclusive Enteral Nutrition in CD: Cochrane Review
- EEN remission rates from 20-84.2%
- Protein and fat source - no difference in outcome
- No significant difference between polymeric vs elemental
- Site of disease: not enough evidence to favour one particular site, may not respond as well if extensive colonic disease
Exclusive Enteral Nutrition in CD: In Practice
- 110 children treated so far with 8 weeks EEN
- Requires intensive dietetic support
- Clinical remission in 79.2%
- No clear phenotypic variation
- Significant improvement in ESR and CRP
- Mean weight gain of 7kg
- Wt improvement maintained to 6mth
EEN feed options
Elemental
- Amino acid-based feeds
- High osmolality
- Poor palatability
- 1kCal/mL (large volumes need to be consumed)
Polymeric
- Whole protein
- Less expensive
- Improved palatibility
- 1-1.5kCal/mL
TMPT deficiency and Azathioprine
1: 300 have TMPT deficiency (homozygotes)
- Shunts 6-MP to form more 6-TGN (thioguanine nucleotide)
- Significant bone marrow suppression
Homozygotes: consider alternative immunomodulator or significant dose adjustment
Heterozygotes: requires dose adjustment and close monitoring of FBC and 6-TGN levels
Need to measure TPMT level and ascertain genotype at time of IBD diagnosis
- Lag period of 3 months before Aza becomes effective –> can commence Aza therapy whilst awaiting TMPT genotype
Side effects of azathioprine
- Myelosuppression - dose dependent
- Pancreatitis
- Infection risk: VZV, EBV
- Hepatitis
- Malignancy: 4-fold risk of lymphoma
- Susceptibility to sun-related skin damage
Therapeutic monitoring of azathioprine
- Safety: FBC, LFTs, amylase, 6TG, 6MMP
2. Efficacy: 6TG
Predicting need for azathioprine therapy in IBD
Following induction of remission, majority require immunosuppression to maintain remission
- 75% of CD and 50% of UC by 2yrs
- 85% CD by 5yo
CD: severe colitis, requirement of IV steroids, oesophageal disease
UC: requirement of IV steroids
Indication for methotrexate in IBD
Intolerance or unresponsive to thiopurines
TMPT heterozygotes
Malignancy risk associated with infliximab
Hepatosplenic T cell lymphoma
- 76 cases described
- All received concurrent Aza therapy
- High mortality
General complications of liver disease
- Ascending cholangitis
- Nutritional deficiency
- Fat soluble vitamin + zinc deficiency
- Portal hypertension
- Hypersplenism - thrombocytopenia
- Varices - Synthetic liver dysfunction
Management of hepatitis B to prevent neonatal acquisition
- Pretreat mother antenatally to reduce viral load (tenofovir)
- HBIG and vaccination at birth + vaccination at 6wk/3mo/5mo (97% protection)
- Vaccination at birth provides 65-95% protection - After 5mo vaccination, reassess infant: HBsAg and anti-HBs
2-3% acquire Hep B despite above measures
2-3% do not respond to vaccine
First line agent for hepatitis B
Entecavir:
- Oral agent
- Nucleotide analogue - effective at suppression of viral replication
- Well tolerated
- Cons: unresolved question about length of treatment
NAFLD - pathophysiology
Excessive caloric intake + insufficient energy expenditure
- Increased adiposity (increased fat deposition in liver)
- Hyperinsulinism –> need more insulin to get glucose into cells, lipogenesis
- Fat causes inflammation –> secondary to metabolic stress and mitochondrial dysfunction
KASAI procedure (hepatoportoenterostomy)
Palliative procedure
Success depends on:
1. Age at operation
- <30 days - best outcome, longer transplant free survival
2. Experience level of surgeon (>5 Kasai procedures/year)
Percentage requiring liver tranplantation in biliary atresia
80-90%
Approx 40% of these transplants are required in the first 2 years post-Kasai procedure
Contraindication to Kasai procedure
Frank liver failure
Complications of Kasai procedure
- Ascending cholangitis
- Liver and biliary flow directly exposed to intestine and its contents
- Associated with worse outcome - Portal hypertension
- Growth failure
- Hepatopulmonary syndrome
Familial adenomatosis polyposis - risk of malignancy
Average age of onset of polyps = 16yrs
100% develop malignancy
If no prophylactic colectomy, average age of onset of colorectal Ca is 39yrs
Fibrosing colonopathy - CF
Colonic strictures with mucosal and submucosal fibrosis, destruction of muscularis mucosa
Increased risk with high dose pancreatic enzyme replacement
Most common causes of pancreatic insufficiency
- Cystic fibrosis
- Syndromes
- Shwachman-Diamond Syndrome (acinar cell hypoplasia, intact ducts; skeletal abN)
- Pearson Syndrome (pancreatic cell atrophy w/ fibrosis –> reduced acinar and duct function)
- Johanson-Blizzard Syndrome (acinar cell hypoplasia, intact ducts; no bone marrow abN)
Shwachman-Diamond Syndrome increases risk of…
AML
Benefits of fish-oil based lipids
- Less inflammatory
- Increased antioxidant activity
- Decrease phytosterols
- Increase biliary flow
- Decrease de novo lipogenesis
RF for intestinal failure associated liver disease (IFALD)
- Prematurity and low birth wt
- Primary GI disease e.g. NEC
- Lack of enteral nutrition
- Catheter-related bloodstream infections
- Small bowel bacterial overgrowth
- Prolonged TPN
- Excessive IV glucose, amino acids or omega-6 fatty acids
Management of IFALD
- Cycling of TPN - introduce breaks between therapy if pt able to cope nutritionally (TPN wean is most important)
- Urso (increase enterohepatic circulation)
- Advancement of enteral feeding
- Prompt treatment of sepsis
- Ethanol and Ab line locks
- Rotating Ab prophylaxis for SBBOG
GLP-2 analogue: Teduglutide
Trophic hormone secrted by enteroendocrine L cells (ileum and R colon) - increases villous height and serum citrulline levels
Result: reduces TPN requirements in pts with short gut syndrome
Clinical trials in paediatrics underway
Intestinal failure definition
Anatomical loss of >75% of expected small bowel length for gestational age
OR
TPN dependence >42 days
Reduction in gut function, such that IV supplementation is required to maintain health and/or growth
Aetiology of intestinal failure
- Critical reduction in intestinal mass:
- Short bowel syndrome - Poor tolerance of feeds
- Motility disorders: gastroschisis, chronic intestinal pseudo-obstruction, long-segment Hirschprung Disease - Abnormal enterocyte function
- Microvillus inclusion disease, tufting enteropathy - Multisystem disease
- IPEX, mitochondrial disorders, congenital glycosylation defects
Hereditary disorders causing pancreatitis
Candidate gene and genetic linkage studies have identified polymorphisms in:
- Cationic trypsinogen gene (PRSS1)
- Serine protease inhibitor kazal type 1 (SPINK1)
- CFTR
- Chymotrypsinogen C (CTRC)
- Cathepsin B (CTSB)
- Calcium sensing receptor (CASR)
Treatment for Ascariasis lumbricoides
4 drugs recommended by WHO: 1. Albendazole 2. Levamisole 3. Mebendazole 4. Pyrantel embonate All 4 have a cure rate of >90% in pts with ascariasis
Mycophenolate Mofetil: MOA and SE
Inhibits synthesis of guanosine monophosphate nucleotides, blocks purine synthesis preventing proliferation of T and B cells
SE: diarrhoea, cytopenias, N&V, thrombosis/thrombophebitis in IV formulation
KCal in CHO, protein and fat
4-4-9 rule
CHO: 4cal/gram
Protein: 4cal/gram
Fats: 9cal/gram
Management of DIOS
- Hydration
- Laxatives
- Bowel washout
- Prokinetics
- +/- Surgery
Intestinal adaptation in short bowel syndrome
Structural: hyperplasia, angiogenesis, bowel dilatation and elongation
Functional: increase transporters, accelerated crypt cell differentiation, slowing transit time, increased nutrient and fluid absorption
Factors that promote enteral autonomy in short bowel syndrome
- Residual small bowel length
- Intact ileocaecal valve
- Primary diagnosis of NEC
- > 50% residual colon
- No small bowel ostomy
- Decreased serum conjugated bilirubin at referral
- Care and follow up at same centre specialising in intestinal rehabilitation
Preventative treatment option for pre-symptomatic siblings with Wilson’s disease (identified on genetic testing)
Zinc supplementation
- Competitive inhibitor of copper, helps displace copper from tissue and increase excretion in urine
- Zn alone is insufficient to treat symptomatic Wilson’s disease
Wilson Disease Treatment
- Penicillamine +/- pyridoxine (Pen causes Vit B6 def)
- Trientene as an alternative if Pen not tolerated
- Zinc supp and low copper diet
- If fulminant liver failure or decomp cirrhosis, liver transplant is necessary
- -> May not ameliorate neurological Sx as Cu deposits in basal ganglia
Splenomegaly with thrombocytopenia can be a manifestation of…
Portal hypertension
Some quirks in investigation result of different liver diseases…
- Wilson disease: low ALP (Cu displaces Zn)
- Autoimmune hepatitis: high total protein due to hypergammaglobulinemia
Antibodies associated with autoimmune hepatitis
Liver: - Type 1: ANA +/- SMA - Type 2: LKM (2a: no hep C, 2b: yes hep C) - Type 3: soluble liver antigen Biliary tree (sclerosing cholangitis) - ANA, SMA, ANCA
Liver conditions that can recur despite liver transplantation
Autoimmune hepatitis
Poor prognostic indicators of autoimmune hepatitis
- Type II disease
- Younger age at presentation
- Coagulopathy
- Jaundice at presentation
- Severe biopsy findings
Associations with secondary sclerosing cholangitis
- Cystic disease (Carolis disease)
- Chemical cholangitis (CFLD)
- Choledocholithiasis (Haemolytic anaemias - pigment stones)
- Previous hepatobiliary surgery
- Immunodeficiencies
- -> X-linked hyper-IgM syndrome assoc. with cryptosporidium
2 main causes of echogenic liver
- Fat storage within the liver - fatty liver disease
2. Glycogen storage within liver - GSD
Factors predicting mortality after liver transplantation
- Encephalopathy
- Male gender
- Assisted ventilation prior to transplant
- Seizures post-transplant
Liver biopsy findings on biliary atresia
- Bile ductular proliferation
- Intracanalicular bile plugs
- Giant cells
+/- fibrosis
Good prognostic indicators for biliary atresia
- Kasai procedure within 30 days of life (very few can have transplant-free survival)
- Performed at a centre that does >5 kasai/year
- Re-establishment of bile flow and resolving jaundice
- -> Cirrhosis develops more slowly
Bad prognostic indicators for biliary atresia
- Presenting in frank liver failure
- Failure to re-establish bile flow post-kasai
- Persistent jaundice despite kasai
- Ascending cholangitis
DDx for biliary atresia
- Alagille syndrome (AD)
- A1AT (co-dom)
- CMV infection
- Progressive familial intrahepatic cholestasis (AR)
- Galactosemia
Hepatosplenomegaly in biliary atresia
- An indication of progressive cirrhosis with portal hypertension
Aim of Kasai procedure
- Resume bile flow (bile duct microchannels >150mirom have greater chance of success), decompress the liver, delay onset of cirrhosis and sustain growth before planning for liver transplant (almost inevitable)
Risk factors for hepatocellular carcinoma
- Viral hepatitis (C)
- Glycogen storage disorder
- Tyrosinemia
- PFIC type 2
- Cirrhosis (secondary to other disease)
Management of pancreatitis
- IV fluids
- Parenteral analgesia
- NBM
- Commence low-fat feeds when pt improving and wishes to eat
- No antibiotics
- Severe pancreatitis: transpyloric tube feeding wiht semi-elemental formula recommended very early in course of therapy
RF for portal vein thrombosis
- Umbilical catheterisation in neonates
- Protein C, Protein S and antithrombin III deficiencies
- Anticardiolipin Abs
- Pancreatitis
Aims of treatment of Hepatitis B
- Control viral response
- E Ag negative state
- sAb positivity
Chronic hepatitis B/carrier - serology
- Chronic active HBV: positive HBsAg, Anti-HBc +/- HBeAg
- Chronic carrier (inactive): positive HBsAg, Anti-HBc
Remote/past hepatitis B - serology
- Positive Anti-HBsAg, anti-HBcAg
Active hepatitis B/window period - serology
- Active: Positive HBsAg (early), HBeAg, HBc IgM (window)
- Window: positive HBc IgM
Hepatitis B treatment: Entecavir
- Oral agent
- Nucleotide analogue - effective at suppressing virus
- Well tolerated, but unclear duration of therapy
Hepatitis B treatment: Interferon
- 58% response
- Weekly subcut injections
- Pros: more durable response, fixed duration of treatment, lack of resistant strains
- Cons: subcut, expensive, SE (flu-like Sx, BM suppression, anorexia depression)
Hepatitis B treatment: Lamivudine
- 23% response in children c.f. 15% in placebo
- Pros: oral, cheap, well tolerated
- Cons: increased risk of drug resistance - 70% by 5yrs, less durable response
Paracetamol dose threshold for hepatic injury
- Acute single: >200mg/kg or 10g (whichever less) over period of <8hrs
- Repeated ingestions:
- -> >200mg or 10g over 24hr period
- -> >150mg or 6g over 24hr period for preceding 48hrs
- -> >100mg or 4g/day in pts with predisposing factors (prolonged fasting, dehydration, other enzyme-inducing drugs)
Paracetamol kinetics in liver
- 20% of paracetamol metabolised by small intestines, 80% metabolised by liver
- Liver: 90% metabolised to inactive sulphate + glucuronide conjugates –> excreted in urine. Remainder metabolised by cytochrome P450 (2E1, 3A4) to form highly toxic NAPQI
- NAPQI usually mopped up by glutathione –> excretes into urine –> does not cause hepatic injury
Pathophysiology of paracetamol OD
- Supratherapeutic doses cause +++NAPQI –> saturates glutathione stores by 70-80%
- NAQI disrupts oxidative phosphorylation –> reduced ATP, lactic acidosis and release of Ca from mitochondrial stores –> apoptosis and necrosis of hepatocytes
- Superoxide anion form’n –> oxidative damage
- NAC infusion: converted to glutathione to mop up NAPQI, cysteine (midproduct) supplies sulphate to convert paracetamol for urinary excretion
Risk of requiring liver transplant in paracetamol OD
- Repeated supratherapeutic doses over prolonged period
RF of severe liver damage and death
- Extent of delay beyond 8hrs before commencement of NAC infusion
Is it beneficial to start NAC infusion in a pt in fulminant liver failure beyond 8hr window?
- Yes
- It can still reduce mortality
- Reduces risk of cerebral oedema, inotrope requirements and increases survival rates by 30%
Timeline of events in paracetamol overdose
- Usually asymptomatic over first 24hrs
- 24-72hrs: RUQ pain, LFT derangement, prolongation of INR and PT
- 72-96hrs: fulminant liver failure, coagulopathy, multisystem organ failure
- 96hrs-14 days: die or survive + recover
Best marker for potential for injury after paracetamol OD
- Timed serum paracetamol level plotted on nomogram
Other markers of IBD
- Gene associated w/ IBD: NOD2 - regulates monocyte response to antigens
- p-ANCA positive in 70% with UC
- Anti-Saccharomyces cerevisiae Ab found in 55% with CD
Crohn’s disease presentation
- Transmural inflammation with skip lesions from mouth to anus, includes perianal disease
- Fistulising, stricturing disease with granulomas
- PC: abdo pain with RIF mass (consider perforation), perianal diz with fissures, fistulas, abscesses which can cause stenosis; orofacial granulomatoses, aphthous ulcers, angular cheilitis, erythema nodosum and pyoderma gangrenosum
Indicators of bleeding (colitis) in IBD
- Low Hb
- Low albumin (also might indicate small bowel involvement in CD)
MOA of azathioprine
- Active metabolite 6MP further metabolised to 6-MMPR which inhibits de novo purine synth and thioguanine nucleotide which incorporates into DNA –> inhibits proliferation of lymphocytes, causes apoptosis
- TPMT enzyme facilitates 6MP down 2 different pathways –> it inactivates it (controls amount of drug) and also converts it to 6-MMPR
SE of azathioprine
- Myelosuppression (6TG - dose dependent)
- -> Mild lymphopenia is acceptable
- Idiosyncratic reaction (pancreatitis)
- Infection risk
- Hepatitis (6-MMP)
- Malignancy - 4-fold increased risk of lymphoma
TNF-a
- Pro-inflammatory cytokine, particularly damaging in Crohn’s disease
- TNF-a inhibits insulin-like growth factor and downregulates growth hormone receptor
Manifestations which correlate with disease activity in IBD
- Erythema nodosum
- Anaemia
- Type 1 Peripheral Arthropathy (oligoarticular)
Formula for daily kcal requirement under basal conditions
100kcal/kg for first 10kg
50kcal/kg for next 10kg
20kcal/kg for rest of wt
(Like maintenance fluids)
Associations with infectious diarrhoea
- Recent travel: toxigenic E. coli, Giardia
- Fever with high WBC: shigella
- HUS: E. coli 0157:57
- Swimming in lakes or drinking well water: Giardia
- Consumption of pork/intestines: Yersinia
DDx for refractory constipation
- Hypothyroidism
- Hypocalcemia
- Coeliac disease
- Spinal dysraphism
- Hirschprung’s disease (empty rectum)
- Fanconi Syndrome/other causes of significant electrolyte disturbances
Most common type of TOF
Upper oesophageal atresia with distal tracheo-oesophageal fistula
VACTERL association
Vertebral anomalies
Anal atresia
Cardiac - PDA, VSD, ASD
TOF
Renal - urethral atresia with hydronephrosis
Limb anomalies - humeral hypoplasia, radial aplasia, hexadctyly, proximally placed thumb
Ingestion of toxic products: alkali agents
- Liquefactive necrosis with intense infalmmation
- PC: drooling, dysphagia, abdominal discomfort, airway Sx e.g. stridor, retractions
Most common sites for foreign body lodgement in the oesophagus
- Thoracic inlet (60-80%)
- Gastro-oesophageal junction (10-20%)
- Level of aortic arch 5-20%
Conditions associated with intestinal malrotation
Asplenia/polysplenia/heterotaxy syndrome Atrial isomerism Congenital diaphragmatic hernia Duodenal/jejunoileal atresia Oesophageal atresia/TOF Gastroschisis/omphalocoele Hirschsprung disease, intestinal pseudo-obstruction Intussusception
Gardner Syndrome
- Mutation on APC gene
- Supranumery teeth, GI polyps (hundreds of adenomatous polyps) and osteomas
- Soft tissue tumours inc desmoid, sebaceous and epidermoid cysts, lipomas
- Osteomas of skull, maxilla and mandible
- Congenital hypertrophy of retinal pigment epithelium
Hirschprung Disease - extent of involvement
- 75% begin at the anus and extend proximally to sigmoid
- 8% have entire colonic involvement
- Even small number involve small intestines
Risk of an affected sibling with Hirschprung Disease inheriting the disease
7%
Associations with HD
Down syndrome Laurence-Moon-Bardet-Biedl syndrome Smith-Lemi-Opitz syndrome Waardenberg Syndrome CCHS
Genes/factors that affect migration of neural crest cells to distal intestines
Hox and Sox homeobox genes
Glial-derived enurotrophic factor and endothelin receptor B/endothlin 3
Diagnosis of HD
- Suction rectal biopsy
- Absence of any ganglion cells in a bx containing adequate mucosa
- -> Absence of submucosal (Meissner) and myenteric (Auerbach) plexuses and hypertrophied nerve bundles with high concentrations of acetylcholinesterases between muscular layer and submucosa
Microvillus Inclusion Disease
- Severe intractable secretory diarrhoea from birth
- MYOB5 gene mutation in some with early onset MVID
- Villous hypoplasia and diffuse thinning of mucosa with no inflammatory cells
- PC: polyhydramnios, severe secretory diarrhoea >200ml/kg/day with electrolyte imbalances, dehydration and FTT
- Mx: TPN, intestinal transplantation
Tufting enteropathy
- EPCAM gene mutation - abnormality in integrin protein disrupting cell-cell and cell-cell matrix signalling
- Intestinal mucosal dysplasia focal epithelial tufts, which may not be present from birth (often misdiagnosed as autoimmune)
- PC: severe intractable diarrhoea in the first few weeks of life
- Mx: TPN and intestinal transplant
Congenital chloride diarrhoea
- SLC26A3 gene - Na independent Cl/HCO3 exchanger within apical membrane of ileal and colon
- Presents with severe secretory diarrhoea in first few weeks of life
- Metabolic alkalosis, hypochloremia, hypokalemia, hyponatremia
Effects of intestinal lymphatic obstruction (e.g. due to ectasia)
- Lymphatic loss into gut or peritoneal cavity –> loss of protein, fat, fat-sol vitamins and lymphocytes
- Impairs lymph flow –> increased P in intestinal lymphatics leads to leakage of lymph into intestinal lumen, reduced recirculation of intestinal lymphocytes into peripheral circulation and decreased absorption of fat-soluble vitamins
- Oedema, growth failure, steatorrhea, immune def
- HypoCa and hypoMg as cations complex with unabsorbed fatty acids in gut –> pass in poo
Stool test results in intestinal lymphatic obstruction
- Positive A1AT
- Positive for both fat globules and crystals
Coeliac disease and HLA
HLADQ2 and HLADQ8
Coeliac disease histology
- Intraepithelial lymphocytes
- Villous atropy/loss
- Crypt elongation
- Loss of brush border, abnormal flattening of epithelial cells
Atypical presentation for coeliac disease
Psychiatric symptoms: common in females
- Anxiety, depression
- Anger, moodiness, impatience
Coeliac disease diagnosis
- Anti-TTG IgA x10 ULN
(in pts with normal IgA levels) - Anti-endomysium Ab + (on separate collect)
- Small intestinal biopsy (not required in some places if above are positive)
Indications for repeat scope/formal challenge
- If Dx made at <2yo
- If initial biopsy was inadequate/Bx not taken
- Clinical response is equivocal
- Screened pts i.e. no symptoms
Anti-TTG monitoring of disease activity
- Normalise on treatment after 6-12mths
- Monitoring of compliance after 1yr
- CLINICAL improvement occurs in 3wks
Complications of coeliac disease
- Bone disease: osteopenia
- Malignancy risk: lymphoma»_space; oropharyngeal, oesophageal, liver
- Decreased fertility
These risks are reduced when gluten free diet is introduced
Oesophagus muscle structure
- Upper 1/3 = striated muscle (excitatory neurons)
- Lower 2/3 = smooth muscle (inhibitory neurons)
- Stratified squamous epithelium (non-keratinised)
Achalasia and viral association
Can be secondary to autoimmune process with latent infection of HSV1 in genetically susceptible individuals
Consequences of GORD
- Oesophagitis: dysphagia
- Irritability and excessive crying
- Malnutrition
- Haematemesis
- Recurrent aspiration –> pneumonia
- Other associated respiratory events
Eosinophilic oesophagitis
- Atopy occurs in 80%
- Peripheral eosinophilia in 50%
- Endoscopy: radial furrowing with longitudinal tram tracking, >20 eosinophils/hpf
- PC: food bolus that is episodic (often occurs at transition of striated to smooth muscle)
Management of eosinophilic oesophagitis
- Food elimination diets: elim of 4 or 6 food groups causes dramatic improvements in eosinophils –> worse again on challenge
- -> Wheat, cow’s milk, soy milk, nut, fish, egg
- High dose PPI effective in 10%
- Steroid therapy
- -> Fluticasone or budesonide - need to swallow
- Leukotriene receptor modifiers are meh
Cells and hormones of the stomach
- Parietal cells: release H+ via H/K-ATPase
- Chief cells: release gastric lipase, pepsinogen –> pepsin in acidic environment
- G cells: secrete gastrin
- D cells: secrete somatostatin
- Mucous neck cells: secrete mucus to protect gastric lining from acid and pepsin
Control of the parietal cell
- Under control of the vagus nerve –> ACh
- ACh stimulates parietal cells directly - M3 receptor
- ACh stimulates G cells and endochromaffin-like (ECL) cells –> gastrin binding to CCK-b receptor, histamine binding to H2-receptor respectively
- ACh, gastrin and histamine promote H+ secretion
- D cells release somatostatin - inhibits H+ secretion with prostaglandins
Cell signalling pathways involved in parietal cell control
- Gastrin and ACh act via IP3 signalling pathway
- Histamine increases cAMP and somatostatin + prostaglandins decrease cAMP
Malignancies associated with H. pylori infection
Gastric MALT lymphoma
Gastric adenocarcinoma
Pathophysiology of H. pylori infection
- H. pylori ingestion (cagA and vacA+) –> gastric antral colonisation - initially decreases acid secretion (low Cl-)
- Active gastritis mediated by macrophages –> loss of normal inhibition control of acid secretion
- Chronic superficial gastritis secondary to hypergastrinemia and reduced D cell population and/OR
- Duodnenal gastric metaplasia –> hypergastrinemia
- Can lead to gastric or duodenal ulceration, atrophic gastritis
- Atrophic gastritis –> intestinal metaplasia –> possible malignancy
Most common trigger of FPIES
Cow’s milk and soy (can cross-react)
Major milk allergen in cow’s milk
B-lactoglobulin
Caseins
Most common solid food trigger of FPIES (and related consequences)
Grains (esp. rice)
Solid food induced FPIES is more likely to have protracted course, children are more likely to require IV fluid resuscitation
Occurs in older infants 4-7mths when solids are introduced
Acute management of FPIES
- IV fluid resuscitation
- IV methyprednisolone
+/- IV ondansetron has shown to be effective in small #
Best non-invasive predictors of portal HTN
Platelet count
Spleen length
Serum albumin
Pharmacological therapy to decrease portal pressure during haemorrhage
- IV vasopression - increases splanchnic vascular tone and decreases portal vein flow
- Nitroglycerin patch - decreases portal pressure
- Octreotide - somatostatin analogue which decreases splanchnic blood flow with fewer side effects
