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
Positive ABs to ANA, ASMA, anti-actin +/- ANCA
Type 1 autoimmune hepatitis
Positive ABs to Anti-LKM-1, anti-liver cytosol
Autoimmune hepatitis type 2
Elevated serum IgM and cholesterol, ALP rise, Anti-mitochondrial Ab +ve
PBC
- Anti-mitochondrial Ab 95% sensitive, 98% specific
Effects of chronic cholestasis
Fat soluble vitamin deficiency (ADEK)
- Progressive areflexia, cerebellar ataxia, ophthalmoplegia, and decreased vibratory sensation
- Lesions found in the CNS, peripheral nerves and muscles
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
Intrahepatic cholestasis associated with lymphoedema of the lower extremities, intermittently elevated ALT/AST. Asymptomatic in between episodes
Aagenaes syndrome
- 50% normal life span
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
Jaundiced child with new Dx HCC- normal GGT, conjugated hyperbilirubinemia- TJP2 gene positive
PFIC 4
- Bile transporter disease
Asymptomatic/well child with conjugated hyperbilirubinemia- MRP2 gene found
Dubin-Johnson
- Bile transporter disease
Bx findings for Alagille syndrome
Bile duct paucity
Eye abnormalities in Alagille syndrome
Posterior embryotoxon
Other = microcornea, optic disc drusen, shallow anterior chamber
CV abnormalities in Alagille syndrome
Peripheral pulmonic stenosis
Other = Tetralogy of Fallot, pulmonary atresia, VSD, ASD, aortic coarctation
Rx Alagille syndrome
MDT management
Ursodeoxycholic acid
Other medications for pruritis – cholestyramine, rifampicin
Distinguish between biliary atresia and neonatal hepatitis
Neonatal hepatitis
- FHx incidence 20%
- More common in SGA/prem
- Likely to have intermittent pigmented/acholic stools
- Bilious fluid duodenal intubation
Biliary atresia
- Sporadic
- Persistent acholic stools
- Abnormal size/consistency of liver in BA
- May also have other abnormalities- heterotaxia, malrotation, vascular malformation
Bx shows bile ductular proliferation, the presence of bile plugs, and portal or perilobular edema and fibrosis, with the basic hepatic lobular architecture intact
What condition?
Biliary atresia
Bx shows severe, diffuse hepatocellular disease, with distortion of the lobular architecture, marked infiltration with inflammatory cells, + focal hepatocellular necrosis; the bile ductules unchanged
What condition?
Neonatal hepatitis
Bx shows PAS positive diastase resistant granules
What condition?
A1AT
Ix findings in biliary atresia
Conjugated hyperbilirubinemia
Triangular cord sign on USS
Failure of tracer excretion on HIDA scan
Bile duct proliferation- plugs & fibrosis on Bx
Best outcome for timing of surgery in BA?
Kasai <30 days of age has BEST outcome
Success rate for establishing good flow is much higher (90%) if performed before the 8th week of life
Will require liver Tx if failing Kasai
Conditions with decreased BUGT and proportion
Crigler Najar <20%
- Type 1 = complete (AR)
- Type 2 = partial (AR)
Gilberts- 5-50%
Treatment for Crigler Najar
Risk = kernicterus
Phototherapy
Exchange transfusion
Oral calcium phosphate supplementation = phototherapy more effective as it forms complexes with bilirubin in the gut
Phenobarbital therapy (CYP450 enzyme induction)
Cholestyramine + agar
Orlistat (irreversible inhibitor of intestinal lipase) increases faecal fat excretion and decreases plasma unconjugated bilirubin concentration
Transplant
How to determine difference between CN1/CN2
Phenobarbital therapy (CYP450 enzyme induction) = can be considered to determine responsiveness and differentiate between type I and II 🡪 NO response in type I
Differentiating Dubin Johnson & Rotor (both bilirubin uptake transport disorders)- Rotor = SLCO1B1/3 gene
Normal GB & liver
total urinary coproporphyrin excretion is elevated, with relative increase in the amount of coproporphyrin I isomer
Enzyme deficiency in galactosemia
Galactose-1-phosphate uridyl transferase (GALT) deficiency
- Classic galactosaemia (most common/severe)
Galactokinase (GALK) deficiency
Uridine diphosphate (UDP) galactose-4-epimerase (GALE) deficiency
Infant with mixed hyperbilirubinemia after introduction of feeds, e.coli sepsis, hepatomegaly and poor growth.
Galactosemia
Ix findings in galactosemia
Increased plasma glucose/RBC galactose 1P
Signs of liver dysfunction
- Mixed hyperbilirubinemia
- Elevated AST/ALT
- Coagulopathy
- Reducing substances + evidence of proximal RTA in urine
Rx elimination of galactose from diet
Sx of tyrosinemia
Deficiency of fumarylacetoacetate hydrolase
Results in buildup of FAA causing oxidative cell damage
Progressive liver disease- cholestasis, coagulopathy & RTA
Increased succinylacetone in urine
Increased blood tyrosine concentration
Ingestion, transport of copper
2-5mg absorbed in duodenum 40-60%
Transported via caeruloplasmin in liver
Excreted via bile
Total 50-150mg
Features of wilsons disease
Asymptomatic hepatomegaly +/- hepatitis/liver failure- cryptogenic cirrhosis
Tremor/dysarthria/Parkinsonism
Personality change, psychosis
Haemolytic anemia
Ix findings for wilsons disease
Low ceruloplasmin
High urinary copper +/- serum
KF rings
Liver Bx shows accumulation of copper
Ix findings for wilsons disease
Low ceruloplasmin
High urinary copper +/- serum
KF rings
Liver Bx shows accumulation of copper
Rx Wilsons disease
Dietary restriction- fish, nuts, chocolate
Meds:
- Penicillamine (10-15% can have worsening neuro Sx)
- Triethylene tetramine dihydrochloride (Trientine)
- Ammonium tetrhiomolybdate
- Zinc- impairs Cu uptake in gut
Liver transplant
Genetic findings for patient with A1AT with liver disease (no other risk factors)
Patients with liver disease usually PiZZ homozygotes and have alpha1 antitrypsin levels <10-20% of normal (<2 mg/ml)
- Polymers accumulate in liver and cause disease
- Children do not usually develop emphysema but are at increased risk for asthma
What does citrin deficiency cause?
Intrahepatic cholestasis
- identified from newborn metabolic screen with hypergalactosaemia, hypermethioninemia, and hyperphenylalanaemia
- More prevalent in East Asian
Cause of neonatal haemachromatosis
Alloimmune disorder with maternal antibodies directed against the fetal liver
- High rate of familial recurrence
- IgG maternal activates MAC complex
Dx neonatal haemachromatosis
High ferritin >2-3000
Liver Bx immuno-staining with anti-human C5b-9 complex
Buccal/parotic Bx shows mucosal glands laden with iron
Sx neonatal haemachromotosis
Severe liver failure including coagulopathy, ascites, hypoalbuminaemia, mixed hyperbilirubinaemia and cirrhosis
Rapid progression to multi-organ failure and death
Rx neonatal haemachromotosis
Iron chelating agents
Exchange transfusion
Poor prognosis
90% recurrence rate in future pregnancies
Most common bugs implicated in liver abscess, most common type?
Bacterial = Staphylococcus aureus, Streptococcus, E coli, Klebsiella pneumoniae, Salmonella
Amoebic disease = Entamoeba histolytica
Solitary 70%
Transmission for Hep A/E
Faecal-oral route
Transmission for Hep B,C,D
Parenteral, intrapartum, sexual
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
Most common viral hepatitis?
Hep A
Rx Hep A
Vaccine/ IG (unvaccinated with exp <2wks)
Cholestyramine for pruritis
Rx Hep A
Vaccine/ IG (unvaccinated with exp <2wks)
Cholestyramine for pruritis
Phases of Hep B virus
Immune tolerant- high HBV-DNA >20,000 & HbeAG, normal ALT/AST (most children for mo-yrs)
Immune clearance- falling HBV-DNA, HbeAg+ve, ALT/AST high (immune mediated liver injury)
Immune control- low HBV DNA, HBeAg-ve, anti Hbe +ve. ALT/AST normal
Immune escape- elevated HBV-DNA >2,000 (virus mutates), ALT/AST high, Hbe-ve, increasing liver fibrosis
Rx Hep B
Pegylated interferon
Weekly S/C injection for 48 weeks
- SFx: myalgia, lethargy, cytopenias
NRTI: entecavir + tenofovir
Cx Hep B
Fulminant liver failure- 1/3rd children
Cirrhosis 20% (RFs: age, co-infection (hep C, A, HIV), high levels of HBV DNA, alcohol intake )
HCC- 1/3rd children
Hep B associated GN
How common is intrapartum transmission Hep C?
<5%
More commonly perinatal
- 20% will clear
- 30% chronic active
- 50% chronic asymptomatic
More common than Hep B
Relevance of IL-8 /IL28B genotype in HCV
IL-8 genotype = may suggest response to therapy (NEW TEST)
Rx Hep C
PEG IFN
Ribavirin
New drugs **
Nucleotide analogue + NS5B inhibitor:
Sofosbuvir plus velpatasvir and glecaprevir plus pibrentasvir
Cx Hep C
5-10% cirrhosis + hepatoma
Rheum- Sjogrens, myalgia, arthritis
Porphyria/lichen planus
Cryoglobulinemia
MPGN
Keratoconjunctivitis, Mooren ulcer
Causes of liver failure
Viral - Hep B, C if co-infection
Autoimmune 5%
HLH
40-50% idiopathic
Metabolic diseases (wilsons, galactosemia, FFAO defects, haemachromatosis, fructose intolerance, lysosomal)
Meds-
Vascular- Budd-Chiari, stroke, cardiomyopathy, ischaemia
Diseases that are a contraindication to liver Tx
Mitochondrial disorders
Niemann-Pick C
HPS (HLH)
Leukaemia 4%
How to treat high ammonia in liver failure
Protein restriction
Sodium benzoate
Gut purging with enemas/lactulose
Rifaximin or neomycin – can reduce enteric bacteria responsible for ammonia
What is quad H therapy and how does it improve cerebral oedema in hepatic encephalopathy?
Hyperventilation – lower PaCO2
Hypernatraemia aim 148-152, fluid restriction n2/3 maintenance
Hypothermia
Haemofiltration – to reduce ammonia
Most common cause of death in hepatic failure?
brainstem herniation (commonest cause of death)
What veins form portal vein?
Splenic vein & SMA
- 2/3rds of hepatic blood flow
- <50% of total liver O2 supply
Rx portal HTN
Meds:
Fluid resus- crystalloids, blood
Octreotide/somatostatin analogues
Vasopressin - splanchnic vasoconstriction
GTN
Surgical
- endoscopic variceal sclerosis
- Sengstaken-Blackmore tube
- Portocaval shunt (risk of thrombosis)- preferred in patients with good liver function
- Rex shunt
- Transjugular IH shunt
- Liver Tx
Indications for liver Tx
Obstructive disease
- Biliary atresia failing Kasai, PSC
Metabolic
- Alagile, PFIC, neonatal hepatitis
- A1AT, tyrosenemia, GSD, Wilsons, haemachromatosis, urea cycle defects
Hepatitis
Liver tumors
GVHD/haemophilia
Complications of liver transplant
Thrombosis- hepatic artery (freq/early), portal vein (5-10%, later, with BA)
Bile
- Strictures most common 10-30%
- Leak also common
Rejection - first 2wks 20-50%, requires Bx confirmation, Banff severity classification
- Chronic less common 5-10%
Diseases that recur post liver Tx
Hepatitis B + C viral infection
Primary biliary cirrhosis/sclerosing cholangitis
Autoimmune hepatitis
NAFLD/Alcohol associated liver disease
Haemochromatosis
Hepatocellular carcinoma
Diseases that do not recur post liver Tx
Congenital anatomical anomalies
-Biliary atresia
-Polycystic liver
-Caroli disease
-Alagille syndrome
-Congenital hepatic fibrosis
Metabolic disease
-Wilsons disease
-Alpha-1 antitrypsin deficiency
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)
What is caroli disease/caroli syndrome
Caroli disease = bile ductal ectasia without other hepatic abnormalities
Caroli syndrome = bile duct dilatation associated with congenital hepatic fibrosis
- AR
- Choledochal cysts also often common
- Associated with ARPKD
- Can lead to cholangitis/sepsis/cirrhosis
Associations PKD & liver disease
ARPKD
- Hepatic fibrosis & bile duct ectasia
- Presenting Sx in 25%
ADPKD
- Dilated non-communicating liver cysts 50%
- Increase in size with age
Caroli Disease
Congenital hepatic fibrosis
Features of ascending cholangitis & Rx
Charcot’s triad of RUQ pain, fever and jaundice – 50-75%
Reynold’s pentad – RUQ pain, fever, jaundice, hypotension & confusion
Rx taz/cef & met
ERCP + stent
Cholecystectomy
CCK-diisoproyl iminodiacetic acid scan demonstrating GB ejection fraction of <35% - Dx?
Biliary dyskinesia
Most common cause of cholecystitis in children
Acalculous > calculous
- Strep/GN/parasites
- Post trauma
Conditions predisposing to cholelithiasis?
biliary dyskinesia, chronic haemolytic disease, ileal resection or disease, CF, cirrhosis, cholestasis, Crohn’s, obesity, prolonged TPN, prematurity, prolonged fasting, treatment of childhood cancer, abdo surgery pregnancy, sepsis
Phases of liver drug processing
Phase 1: Activation
Enzymatic activation of substrate to reactive intermediates
- CYP system
Phase 2: Conjugation
Conjugation with glucuronic acid, sulfate, acetate, glycine, glutathione
- Can be overwhelmed if too much toxic metabolite
Phase 3: Excretion
Excretion of drug metabolites by transporters – eg multiple drug resistant protein 1 (MDR-1)
CYP inducers/inhibitors
Inducers: phenytoin, phenobarbital, rifampin, CBZ, St Johns Wort, glucocorticooids, HIV antivirals
Inhibitors: erythromycin/clarithromycin, cimetidine, zoles, antivirals (protease inhibitors), grape juice, ciclosporin, amiodarone, sertraline
Relationship UC/PSC
2-8% of patients of UC
Of those with PSC, 70-90% have UC
pANCA or anti—SMA antibodies +ve- what complication of IBD?
PSC
Associations with PSC and malignancy?
Strongly associated with hepatobiliary malignancies = cholangiocarcinoma, HCC, gall bladder carcinoma
Incidence of 9-14%
What condition is Focal biliary cirrhosis pathognomic for?
CF
Risk factors = male gender, increasing age, pancreatic insufficiency, possible meconium ileus
Causes of MASSIVE hepatomegaly
Malaria
Leishmaniasis
Myelofibrosis
CML/CLL
Gauchers
Tryptase activity in stool?
Excludes exocrine pancratic disease
Severe diarrhoea, dehydration and metabolic acidosis in breast fed baby. Renal stones seen on abdo US?
Glucose-galactose malabsorption (AR)
6mo baby with severe vomiting, hypoglycemia. Jaundice & hepatomegaly on exam. Noted to have high uric acid on bloods. Recently introduced solids (fruit puree)
Hereditray fructose intolerance
- deficiency of fructose-1,6-bisphosphate aldolase in liver, kidney and intestine
- rapid accumulation of fructose-1-phosphate & toxicity
6mo infant, poor feeding, watery diarrhoea, bloating & poor growth. Formula fed, introducing solids. Stool negative for reducing substances/H+ breath test positive.
Sucrase-isomaltase deficiency (AR)
- Disaccharide deficiency (lack sucrase/isomaltase, have lactase & maltase)
Severe watery diarrhoea in infant either breast feeding or formula fed. RTA/amino-aciduria, reducing substance +ve in stool. Worse in infancy/older childhood
Primary lactose intolerance (rare)
- congenital (no lactase)
- familial (reduced lactase)
NASH biopsy findings?
Non-alcoholic steatohepatitis biopsy shows: Steatosis with ballooning degeneration, mallory hyaline, lobular inflammation or pericellular fibrosis.
NASH is worse than NAFLD
= NASH = smashed
NAFLD biopsy findings?
Non-alcoholic fatty liver disease biopsy shows: Moderate steatosis with mild inflammation but without ballooning injury or fibrosis
NAFLD = baffled
PFIC biopsy findings?
PFIC 1 biopsy shows: Cannalicular cholestasis.
PFIC 2 biopsy shows: Cannalicular cholestasis with fibrosis and giant cell hepatitis. Absent or decreased expression of BSEP (bile salt export pump) antibodies on immunohistochemistry staining.
Crigler Najar biopsy shows?
Crigler Najjar biopsy shows: Occasional bile plus within cannaliculi following cholestasis. Otherwise normal. Decreased (or absent) UDP-glucuronosyltransferase level on tissue enzyme assay of liver tissue.
What hormone does this cell secrete? MOA of that hormone?
D cell
Somatostatin
- Inhibits acid secretion
What hormone does this cell secrete? MOA of that hormone?
Chief cell
Pepsinogen
Pepsin (active form) = proteolytic
What hormone does this cell secrete? MOA of that hormone?
G cell
Gastrin
Symptoms of excess vitamin A?
N&V
Raised ICP & cerebral oedema
Headache
Irritability, drowsiness, skin peeling/discolouration if chronic
