Gastroenterology Flashcards
UC management
Mild
(5ASA induction & maintainence)
Directly inflamed rectum: PR 5-ASA
Mild disease with pancolitis:
5-ASA PO
Moderate flare
Steroids
Severe flare
prednisolone +
- Immunomodulators: thioprine/azathioprine
- Biologics: infliximab, vedolizumab
- Consider colectomy
PUCAI >65 = severe flare
PUCAI 35-64 = moderate flare
PUCAI 10-34 = mild flare
Crohns management
Mild
- 5ASA
- EEN
- Steroids (short term)
- +/- antibiotics
Mod-severe
Induction:
- EEN
- IV methylpred
- Infliximab early use if severe/high risk for complicated disease (extensive SB, steroid unresponsive)
Maintainence:
- 5ASA
- Azathioprine: inhibit lymphocyte proliferation, but do not improve mucosal inflammation
- Methotrexate
- Infliximab
Symptoms of congenital chloride diarrhoea
AR chr7 gene
Defective Cl/HCO3 transport DI
- Polyhydramnios
- Watery diarrhoea at birth
- HypoK/cl, alkalosis
- Stools high K/Na
- Rx: IV fluid, slow reintroduction of PO fluids >1mo
Symptoms of glucose-galactose malabsorption?
> 30 mutations SGLT1, AR
Osmotic diarrhoea
- Diarrhoea, dehydration in neonatal period
- Follow ingestion of glucose, breast milk or traditional formulas
- Improves with removal of glucose/lactose/galactose
- +ve glucose breath test
Rx: fructose formula, lifelong glucose/galactose dietary restriction
Syndromes associated with Achalasia
Achalasia = lack of relaxation LES (RP >30mmHg), loss of peristalsis
Triple A syndrome
12q13 deletion
Achalasia
ACTH insensitivity- low BSL
Alacrima
Rozycki syndrome
AR
Deafness, short stature, muscle wasting, vitiligo
Intermittent dysphagia for solids + liquids, corkscrew pattern on barium swallow, Dx?
Diffuse Esophageal Spasm= Normal peristalsis interspersed with abnormal high pressure waves
Rx: CCB, nitrates, anticholinergics, surg- long myotomy
- no effective treatment
Mechanism of GERD, how is GERD defined?
Reflux plus one of
Histopathological changes of esophageal epithelial lining
Symptoms of reflux (eg. FTT, esophagitis, episodes of aspiration pneumonia)
Caused by transient relaxation of LES
Reduces LES pressure to 0-2 mm Hg lasting > 10 seconds
Regulated by vasovagal reflex, stimulated by – gastric distension
Indication for fundoplication in reflux?
Neurological disease
Not responding to medical therapy
Complications of esophagitis
Peptic strictures
Barrett’s esophagus
Gastrostomy feeds
Respiratory disease
Symptoms of GERD vs oesophagitis, definition of GERD?
Reflux plus one of
Histopathological changes of esophageal epithelial lining
Symptoms of reflux
GERD = vomiting/feed regurgitation, aspiration- cough/wheeze, OSA, FTT
Oesophagitis = irritability with feeds/back arching, feed refusal, LOW
- Chest pain/abdo pain in older children
- Sandifer syndrome: neck contortions/food refusal
Complications of reflux?
Eosophagitis/erosive oesophagitis- severe resporatory disease
Strictures - dysphagia
Barretts oesophagus (rare in children)- metaplastic transformation of squamous -> columnar epi
Aspiration pneumonitis/laryngitis
Interactions with asthma
Associated with BRUE
Dx eosinophilic oesophagitis & Rx?
> 15 Eo per HPF on Bx
Peripheral eosinophilia/raised IgE
SPT pos for allergen
Dysphagia in older kids, FTT, poor feeding/vomiting in younger
Rx:
Target elimination/6 food elimination diet (milk/wheat most common, then eggs/nuts/seafood)
PPI 40-50% effective
Topical fluticasone/budesonide
Anti IL5 (mepolizumab/relixumab)
Age range for FB ingestion, most common site of lodging?
Majority (80%) of FB occur in children 6 month to 3 years
Most lodge at the level of the cricopharyngeus (UES), the aortic arch, or just superior to the gastroesophageal junction (LES)
FBs requiring removal vs watch & wait
Sharp objects (above duodenum), disc button batteries or those associated with respiratory symptoms 🡪 urgent ETT and endoscopy
Asymptomatic blunt objects and coins can be observed for 24 hours to see if they passage into the stomach
Meat impactions can be observed for 12 hours
Mx caustic ingestion?
If asymptomatic – observe, trial of oral intake at 4 hours after exposure, earlier if low suspicion or likely benign ingestion after discussion with Poisons Information Centre
If any symptoms admit for oesophagoscopy (within 24 hours)
Keep NBM
Commence intravenous PPI
Can try milk/water dilution
Neutralization, induced emesis and gastric lavage are contraindicated
Strictures may require dilatation
Dx globus?
Persistent/intermittent sensation of lump in throat
- between meals
- no dysphagia, odynophagia, GERD symptoms, other more likely Dx
- >3mo of above criteria, sx >6mo
Features of Zollinger Ellison
Rare neuroendocrine tumor
Refractory PUD + diarrrhoea
Autonomous gastrin secretion
98% elevated gastrin levels
Assoc: MEN1, NF, TS
Tests for active H.Pylori infection?
H pylori stool antigen
Urea breath test (false neg due to PPI)
Endoscopy (invasive)
50% FP on serology with active infection
Tests for active H.Pylori infection?
H pylori stool antigen
Urea breath test (false neg due to PPI)
Endoscopy (invasive)
50% FP on serology with active infection
Indications for H.Pylori Rx?
Children with ulcers + proven infection
Children with histologically proven infection w/ gastro symptoms
Children with gastric lymphoma + proven infection
Children with atrophic gastritis w/ intestinal metaplasia + proven infection
Children with refractory IDA + proven infection
Causes of gastroparesis & Mx?
Gastric dysrhythmia and gastroparesis:
Severe gastric myoelectrical disorder
Rx – N+V, prokinetic therapy, gastro/jejunostomy, TPN ,
gastric electrical stimulation, pacemaker
Normal gastric rhythm and gastroparesis
Due to pylorospasm/ obstruction at pylorus/ duodenum with electrocontractile dissociation
Rx – botox/ balloon dilatation, surgical relief of obstruction, prokinetics and antinausea
Gastric dysrhythmia and normal emptying
Gastric myoelectric disorder
Rx – N+V, prokinetic therapy
Normal gastric rhythm and normal emptying
Visceral hypersensitivity/ nongastric causes
Rx – N+V, antidepressant therapy, drugs for fundic/ antral relaxation. Further Ix for other causes
Severe watery diarrhoea at birth , FTT +/- dysmorphic features
Congenital malabsorption syndromes
Mucosal
- Microvillous inclusion disease: most severe- +/- polyhydramnios, microvilli with involutions on Bx
- Tufting enteropathy - epithelial tufts involving 90% on Bx
- Enteric anendocrinosis: NEUROG3 gene- hyperchloraemic acidosis, absence of neuroendocrine cells
(all need lifelong PN/transplant)
Proprotein convertase 1/3 deficiency- PCSK1 gene, AR, watery diarrhoea, hyperinsulinism, hypogonadism/adrenalism
CHO deficient glycoprotein syndrome/enterocyte heparan sulfate def
- Genetic disorder of N-glycan assembly
Trichohepenteric syndrome: villous atrophy, trichorrhexis, dysmorphic- broad forehead/hypertelorism, cafe au lait, cardiac/liver Dx, defective Ab responses, poor prog 2-5 yrs
Autoimmune enteropathy = Sx AFTER 6mo age, introduction of diet/cease breastfeeding- villous atrophy/crypt hyperplasia, anti-enterocyte ABs, other autoimmune Dx, no response to elimination diets
eg. IPEX = chronic diarrhoea, dermatitis, autoimmune endocrinopathy (diabetes, thyroiditis)
APS1
Bile acid malabsorption (SCL10A2 mutation)- steatorrhoea, reduced chol, reduced bile acid reabs
Abetalipoproteinemia
- Defect in chylomicron formation
- Steatorrhoea, ADEK def- PN/ ataxia/retinitis
- Low chol, trigs, LDL
- Acanthocytes and fat inclusions on smear
- Homozygous hypobetalipoproteinemia- AD, Dx on Bx
Predisposing factors for SIBO?
Dysmotility – short bowel syndrome (due to adaptive changes in SI), pseudo-obstruction, malnutrition
Biliary obstruction – cirrhosis
Pancreatic insufficiency – chronic pancreatitis
Absent ileocaecal valve / communication – intestinal fistula, bowel strictures, short bowl
Other – diabetes, prematurity
Syndromic causes of pancreatic insufficiency?
Cystic fibrosis – most common congenital disorder associated with exocrine pancreatic deficiency
Shwachman-Diamond syndrome – second most common congenital disorder
Rare disorders – Johanson-Blizzard syndrome (severe steatorrhoea, aplasia of alae nais, deafness, hypothyroidism, scalp defects(, Pearson bone marrow syndrome (sideroblastic anaemia, variable neutropenia, thrombocytopaenia), and isolated pancreatic enzyme deficiency
Autoimmune polyendocrinopathy syndrome type 1 – rare autosomal recessive disorder caused by a mutation in AIRE
Chronic mucocutaneous candidiasis is associated with failure of the parathyroid gland, adrenal cortex, pancreatic beta cells, gonads, gastric parietal cells and thyroid gland
Pancreatic insufficiency and steatorrhoea are common
Signs of congenital lactase deficiency?
AR condition
Features
Diarrhoea from birth
Hypercalcaemia and nephrocalcinosis
Clinical symptoms occur 30mins to 2 hours after consumption
Abdominal pain, bloating, flatulence, diarrhea & vomiting
Dx: Lactose intolerance test/breath test
Acidic stool pH <7.5 & positive reducing substances >0.25% suggestive
Cause of hepatic cholestasis and cirrhosis w short bowel sx on PN?
Hepatic cholestasis and cirrhosis – causes multifactorial:
Toxic defects of TPN on hepatocytes
Disruption of bile flow and bile acid metabolism
Frequent occurrence of bacterial translocation and sepsis with endotoxin release in portal circulation
Allograft rejection rates in intestinal transplant?
Acute rejection rates for intestinal allograft are significantly higher than with any other organ – range of 80 to 90%
Severe rejection may require treatment of anti-lymphocyte antibody rejection; as high as 30%
Vascular rejection uncommon, chronic rejection 15%
GVHD is infrequent but life threatening (80% mortality)
What findings on blood tests indicate what malabsorption?
Stool tests
Microscopy/Culture 🡪 RBC/WBC associated with inflammatory conditions
Microscopy for ova/cysts/parasites 🡪 Giardia
Antibody tests for parasites
pH and reducing substrates 🡪 CHO malabsorption
Quantitative stool fat 🡪 identify fat malabsorption
Alpha-1 antitrypsin 🡪 protein malabsorption
Elastase 🡪 exocrine pancreatic insufficiency
Calprotectin 🡪 IBD
Blood tests
FBE + film
Microcytic anaemia 🡪 Fe deficiency
Lymphopenia 🡪 Lymphangiectasia
Neutropenia 🡪 Shwachman syndrome
Acanthocytosis 🡪 Abetalipoproteinaemia
Serum IgA and tTG antibodies 🡪 celiac disease
What criteria do children have to meet for Dx coeliac without biopsy?
Characteristic symptoms of coeliac disease
tTG-IgA levels >10× upper limit of normal
A positive endomysial antibody (EMA) on a different blood sample
Positive HLA susceptibility for coeliac disease
Coeliac disease patients are at risk of which cancers?
20X RR for small bowel lymphoma (EATL)
30x RR for small bowel adenocarcinoma (uncommon generally, one of few conditions which causes)
2-4X RR for esophageal cancer
Epidemiology of IBD? Which is more common in paediatrics, what is the trend in prevalence?
0.5-8/100,000
Higher incidence of CD vs. UC in paediatrics
Incidence of paediatric IBD (and IBD in general) has been increasing over the last 30-40 years (15x CD, 11x UC)
Theories for increase
- Increased awareness
- Westernisation, hygiene hypothesis
- Change in microbiota/decreased helminth infections
Evidence between IBD and residence in or immigration to industrialized nations, Western diet, use of antibiotics at a younger age, vaccination, less exposure to microbes at a young age
Genes associated with IBD?
First IBD gene identified NOD2 (CARD15) – identified in 2001
- Genetic influence higher in CD than UC
- Concordance rates in twins is higher in CD (35-50%) than in UC (16%)
Pathology findings suggestive of IBD?
FBE- anemia & thrombocytosis
Raised ESR/CRP
Hypoalbuminemia (malabsorption)
Raised ALT/GGT
Raised stool calprotectin
May have +ve ABs- CD- ASCA, UC- pANCA- low sensitivity
Causes of VEOIBD and Hx suggestive?
Onset <6
Immunodeficiencies: IL-10 mutation, atypical SCID, CVID, CGD, neutrophil defects, Wiskott-Aldrich syndrome, agammaglobulinaemia, hypergammaglobulinemia M syndrome, familial HLH, IPEX
Hx suggestive: young age, FHx immunodeficiency/IBD- males/consanguinous, recurrent infections, resistance to conventional IBD therapies, skin/nail/hair lesions, tumors, HLH
Relationship of growth to IBD? What is the most sensitive parameter to monitor?
High rates growth failure with CD 60-85%, UC 6-12%
Height velocity is most sensitive parameter to recognize impaired linear growth
Decreased growth velocity may precede abdo Sx 50% of patients
- exacerbated by steroids
Most common congenital GI anomaly?
Meckels diverticulum
2-3% of infants, appears as a 3-6cm outpouching of the ileum
Most common congenital GI anomaly?
Meckels diverticulum
2-3% of infants, appears as a 3-6cm outpouching of the ileum
Embryology/pathogenesis of Meckels & rule of 2s?
Diverticulum = remnant of the embryonic yolk-sac connection to the gut (vitelline or omphalomesenteric duct), produced by failure of involution during gestation
Rule of 2s:
- 2% population
- First 2 yrs of life
- M:F 2:1 (very few female predominant GI conditions!)
- 2ft of ileocecal valve
- 2inches length
Most common GI tumor?
Juvenile colonic polyp
1-3% of population <21ys
Peak 2-10yrs
Usually rectosigmoid region, solitary common
Bright red painless bleeding post defecation +/- prolapse of polyp
Histopathology post rotavirus infection?
Jejunal and duodenal mucosa- shortening and blunting of the villi, WBC infiltrate
Invades SI villi and leads to:
- loss of enzymes
- decreased absorption
- villous atrophy
- secretory/osmotic diarrhoea
Pathology on this scope?
Ulcerative colitis
- Mucosal ulcertion, erythema, granularity/friability
Histo: mucosal inflamm, crypt abscesses/inflammatory infiltrate, mucous depletion
Findings in Transcobalamin II deficiency?
Inhereted defect in transport protein of B12 (takes from GI/liver to storage sites)
Sx: severe megaloblastic anemia, FTT, neurological sx, glossitis, diarrhoea, vomiting
Normal serum B12 as TC1,2 proteins intact, transport protein defective
Biopsy findings for
Alagile
Biliary atresia
PFIC
NASH/NAFLD
Crigler Najjar
Alagile- paucity of interlobular bile ducts
Biliary atresia- biliary fibrosis/duct proliferation with bile duct plugs
PFIC- cannalicular cholestasis (1), + fibrosis/giant cells, decreased BSEP Abs (2)
NASH: Steatosis/ballooning degeneration/pericellular fibrosis
NAFLD: Steatosis and inflammation, no fibrosis
Crigler Najjar: Normal structures +/- bile plugs, decreased UDP-glucuronosyltransferase level on tissue enzyme assay of liver tissue
Biopsy findings for
Alagile
Biliary atresia
PFIC
NASH/NAFLD
Crigler Najjar
Alagile- paucity of interlobular bile ducts
Biliary atresia- biliary fibrosis/duct proliferation with bile duct plugs
PFIC- cannalicular cholestasis (1), + fibrosis/giant cells, decreased BSEP Abs (2)
NASH: Steatosis/ballooning degeneration/pericellular fibrosis
NAFLD: Steatosis and inflammation, no fibrosis
Crigler Najjar: Normal structures +/- bile plugs, decreased UDP-glucuronosyltransferase level on liver tissue enzyme assay
Diagnosis? Associated disease & Rx?
Pyoderma gangrenosum
UC (5%) > Crohns (2%)
Liver complications of ARPKD
PKHD1 gene
Initially hepatic fibrosis (fibrocystin accumulates in bile duct cells)
Hepatomegaly & portal hypertension develop over time
Later = Caroli disease (multifocal, segmental dilatation of large intrahepatic bile ducts)- RUQ pain, cholelithiasis/ cholangitis
Normal stool pattern in children
Breastfed babies- 10x per day - 1x every 10d
12mo 2-3 stools per day
2-3 - 1-2per day
Absorption of water/solutes from large intestine
Na+ coupled transport: glucose, galactose, AAs/oligopeptides
(Na+ pumped out of cell, osmotic gradient between cells- water follows)
Na/H+ exchange- electrolytes
Paracellular transport- passive, via tight junctions
Stool sodium in secretory diarrhoea
Secretory diarrhoea (enterotoxin e.g. cholera, E. coli, Salmonella, Shigella, pancreatic islet cell tumour, cathartics) result in liquid faeces with high sodium levels, usually 55-100mmol/L
Patho/Sx of Gilberts Disease?
Common disorder of bili metabolism
5-15% - AR defect in TATAA promoter sequence
- Leads to deficiency in diphosphogluconate-glucuronyltransferase 1A1 (conjugates bili)
- Unconjugated hyperbili
- Triggered by fasting/dehy/illness
Most common extra-intestinal manifestations of UC?
Arthritis 21%
Stomatitis/PSC 4%
Uveitis 4%
EN 3%
Ank spond/PG 2%
Psoriasis 1%
IBD extraintestinal manifestations and genes assoc?
Raised Cytokeratin 18- disease marker of?
Chronic liver disease
- Cleaved during cell death & released into blood
Causes of elevated ALP?
Dx this rash
Pellagra (isn’t niace)
- Niacin deficiency (B3)
3 D’s of B3
- dermatitis, diarrhoea, dementia
Dx this rash
Acrodermatitis enteropathica
- AR GI defect in zinc absorption
- Presents later than acquired
- Breast mild protective
Acquired
- Prem, low maternal BM zinc, malabsorption
Check ALT, breask milk, zinc not a good measure of levels
Rx: elemental zinc
Effects of heat, strenuous exercise, reduced salt intake in CF patient?
Hypochloraemic, hyponatraemic dehydration,
metabolic alkalosis and hypokalaemia.
Sodium/Chloride depletion = ECF volume contraction
- increased aldosterone = sodium exchanged
for H + ions in kidney = alkalosis
Conditions associated with increased risk of coeliac disease?
Family history, Down syndrome, Turner syndrome, IgA deficiency, T1DM, autoimmune thyroid disease and dermatitis herpetiformis.
Management of NASH
Lifestyle changes
Meds:
- Statins
- Metformin, SGLT2/GLP1 inhibitors, thiazolidinediones
- Vitsamin E, omega 3 FAs
- PPAR agonist
- Caspase inhibitors
H.Pylori linked to what GI cancer?
H. pylori have an increased risk of gastric mucosa-associated lymphoid tissue (MALT) lymphoma, a rare cancer of the stomach
Ix findings in hereditary haemochromatosis
Fe studies (Fe saturation > 55%, ferritin > 200-300)
Genetic testing for C282Y and H63D mutations
Broad forehead, hepatomegaly, hypotonia and impaired neuro function with psychomotor retardation. Liver cells on Bx show absence of peroxisomes
Zellweger (cerebrohepatorenal syndrome)
- AR
- Fatal by 6-12mo
Jaundiced child with cholestasis, Low GGT, steatorrhoea, pruritis & Vit D deficient Ricketts - mutation F1C1 on 18q21
PFIC1
- Severe form of intra-hepatic cholestasis
- Bile transporter disease
Middle eastern child with cholestasis, worsening LFTs, low GGT, BSEP gene positive
PFIC 2
- Bile transporter disease
Teenager with conjugated hyperbilirubinemia - HIGH GGT, portal HTN, gall stones & MDR3 gene mutation
PFIC 3
- Bile transporter disease
Asymptomatic/well child with conjugated hyperbilirubinemia- MRP2 gene found
Dubin-Johnson
- Bile transporter disease
Stages/presentations of of hep A
- Prodromal- viremia, non specific symptoms
- Icteric 1-2wks post
- Initial improvement then relapse- 6-10wks
- Cholestatic
- Fulminant 1-5%
Can get arthritis, vasculitis, myocarditis, AKI
Infant presents with cholestatic jaundice, severe liver dysfunction including ascites and coagulopathy, +/- mass
Dx?
Choledochal cyst
- USS/MRCP diagnostic
- Rx roux-en-y choledochojejunostomy (prevents risk of cholangiocarcinoma)
