Gastroenterology Flashcards
1
Q
Symptoms of Vitamin A deficiency
A
Night blindness, dry eyes (xerophthalmia), poor growth, impaired immunity (esp at mucosal surfaces)
2
Q
Symptoms of Vitamin D deficiency
A
Rickets, hypocalcaemia, hypophosphataemia
3
Q
Symptoms of Vitamin E deficiency
A
Ataxia, progressive sensory and motor neuropathy, retinitis pigmentosa, loss of vision, haemolytic anaemia
4
Q
Symptoms of Vitamin K deficiency
A
Bleeding, inc APTT and PT
5
Q
Describe the mechanism of a1aT deficiency due to the common genotype PiZZ
A
- Most common form of alpha1-antitrypsin deficiency is homozygous PiZZ
- mutation SERPINA1 gene
- Serum levels 2.5 – 7 µmol/L (10-15% of normal)
- The genetic defect alters the configuration of the alpha1-antitrypsin molecule and prevents its release from hepatocytes therefore decreased serum levels
- absence of functional α1-antitrypsin leads to unchecked leukocyte elastase function, resulting in destruction of the alveolar walls and eventual emphysema
- Accumulation of excess a1aT in hepatocytes leads to destruction of these cells and liver disease
- Morbidity/mortality only in 5%
6
Q
Describe the anatomy of the oesophagus
A
- Stratified squamous epithelium
- Outer longitudinal muscle, inner circular muscle
- Myenteric plexus located between
- Blood supply from aorta (thoracic) and gastric (abdominal)
7
Q
Describe the anatomy/function of the stomach
A
- Columnar epithelium
- Chief cells - produce pepsin
- Parietal cells - produce gastric acid and intrinsic factor
- Produced 3L/day of secretions - stimulated by gastrin, vagal stimulation, histamine via H2 receptors
- Supplied by the coeliac axis
8
Q
Describe the function and blood supply to the small intestine
A
- Ileum absorbs Vit B12 and bile salts
- Blood supply via SMA
9
Q
Describe the blood supply to the colon
A
- Supplied by SMA until the distal transverse colon, then the IMA
10
Q
Describe the function and blood supply to the pancreas
A
- Exocrine 98%, endocrine 2%
- Supplied by the coeliac axis
11
Q
Oligosaccharides and disaccharides are hydrolysed to monosaccharides and then absorbed. Describe the pairings
A
- Maltose and isomaltose -> glucose
- Sucrose -> glucose and fructose
- Lactose -> glucose and galactose
12
Q
Describe the exocrine function of the pancreas
A
- Produces trypsin, chymotrypsin and elastase
- These convert proteins into oligopeptides and amino acids in the duodenum
- These then enter the portal vein and are carried to the liver
13
Q
Gene mutations associated with pancreatitis?
A
- SPINK1 - AR pancreatitis, heterozygotes usually asymptomatic
- CFTR mutations may cause pancreatitis with or without other manifestations of cystic fibrosis, inherited in an AR manner or in conjunction with a SPINK1 mutation
- PRSS1 mutations are present in 80% of patients with autosomal dominant hereditary pancreatitis
14
Q
What is absorbed in the duodenum?
A
Iron
15
Q
What is absorbed in the jejunum?
A
CHO, proteins, fat, vitamins
16
Q
What is absorbed in the ileum?
A
Bile acids, vit B12
17
Q
What is the breath hydrogen test for?
A
Diagnosing lactose malabsorption, sucrase deficiency or small intestinal bacterial overgrowth.
18
Q
What is the gene associated with Hirschsprungs?
A
RET gene
19
Q
Pseudoappendicitis is caused by?
A
Yersinia enterocolitica
20
Q
Describe Progressive familial intrahepatic cholestasis (PFIC)
A
- 1/3rd of childhood cholestasis, usually presents weeks-months age
- PFIC1 and PFIC2 are characterised by a low-normal GGT (type 3 high GGT)
- Usually a maternal history of pregnancy-induced cholestasis
- Three subtypes (PFIC1, PFIC2, PFIC3), all of which are inherited in an autosomal recessive pattern
- PFIC2 is most common, most severe, onset in neonatal or early infantile period with jaundice and pruritus. Medical therapy with urso, but progress to liver failure and transplant
- Plumbing correct, but bile stuck in hepatocytes due to error in pumps
21
Q
What is the incubation period of Hep A?
A
3 weeks, spread via faecal-oral route
22
Q
What are the expected insensible water losses for a extreme preterm and a larger preterm on day 1 of life?
A
- Very immature preterm infants (<1kg): 2-3 mL/kg/hr (immature skin, lack of subcutaneous tissue, and a large exposed surface area)
- Larger premature infants (2-2.5kg) nursed in an incubator: 0.6-0.7 mL/kg/hr
23
Q
What is the role of glucokinase?
A
- Facilitates phosphorylation of glucose to glucose-6-phosphate. It occurs in cells in the liver, pancreas, gut, and brain
24
Q
Describe the passage of chylomicrons
A
Enter the lymphatic system, travel to the thoracic duct, then enter the bloodstream
25
What is the role of gastrin?
- Stimulated by vagal, and stomach distension
- Stimulates peptin, gastric acid and intrinsic factor
- Causes gastric emptying and pancreatic secretion
26
What is the role of secretin?
- Stimulated by intraluminal acid
- Stimulates pancreatic bicarb secretion
- Inhibits gastric acid and peptin secretion
- Delays gastric emptying
27
What is the role of cholecystokinin-pancreozymin?
- Stimulated by intraluminal food
- Stimulates pancreatic bicarb/enzyme secretion
- Causes gallbladder contraction, inhibits gastric emptying, and gut motility
28
Describe the process of bile flow and bile acid formation
- Bile is made in the liver and stored in the gallbladder, then secreted into the duodenum
- Bile acids are formed from cholesterol
- Primary acids are conjugated with amino acids which form secondary bile acids. These are then deconjugated in the intestine and reabsorbed from the terminal ileum. They are then transported back to the liver bound to albumin
29
What are the components of breast milk?
10% protein is secretory IgA. Also contains lymphocytes, macrophages, complement
30
What are the benefits of breast milk?
- Reduces risk of GI and resp infections, NEC, atopic eczema (only if born to atopic mother), diabetes
- Improved response to HiB vaccine
31
Discuss iron studies and iron deficiency
- Deficiency leads to microcytic hypochromic anaemia
- Decr Fe, inc transferrin = deficiency. Decr Fe, decr transferrin = chronic disease
- 5-10% of dietary iron is absorbed
- RF: excess cow's milk, tea, chronic blood loss, malnutrition, dietary deficiency
32
Discuss folate studies and folate deficiency
- Deficiency leads to megaloblastic anaemia, poor weight gain, thrombocytopenia, chronic diarrhoea
- Serum folate reflects recent changes, red-cell folate reflects total body stores
- Not an acute phase reactant
- RF: dietary deficiency, malabsorption (eg coeliac), incr requirement (pregnancy, infant), methotrexate, OCP, trimethoprim
33
Discuss B12 deficiency
- Deficiency leads to megaloblastic anaemia, inc methylmalonic acid + homocysteine in urine
- Anaemia, glossitis, peripheral neuropathy, optic atrophy, subacute combined degeneration of the cord
- RFs: pernicious anaemia (inc +ve gastric/parietal cell antibodies), vegan, malabsorption (short gut, loss of terminal ileum)
- Tx: IM B12 3-monthly
34
Discuss zinc deficiency
- Causes anaemia, growth retardation, peri-orofacial dermatitis, diarrhoea, immune deficiency
- Acute phase - decr zinc, decr metallothionein (zinc-binding protein)
- Not an acute phase reactant
- Can cause acrodermatitis enteropathica
35
Describe acrodermatitis enteropathica
- AR, impaired zinc absorption
- Perioral and anal skin rash, diarrhoea, recurrent infections, thrush, ocular changes, paronychia, alopecia and red-tinged hair
- Tx: PO zinc
36
What are the fat soluble vitamins?
A, D, E, K
37
Describe abetalipoproteinemia
- AR, failure of chylomicron formation, lack of fat malabsorption
- FTT, abdominal distension, foul-smelling bulky stools in early infancy, Vit E deficiency (ataxia, neuropathy)
- Decr cholesterol and triglycerides, absence of betalipoprotein
- Tx: medium chain triglycerides (absorbed cia portal vein, not via thoracic duct), Vit ADEK replacement
38
What is the difference between marasmus and kwashiorkor?
- Marasmus - muscle wasting, low body fat stores
- Kwashiorkor - oedema, flaky/peeling skin, rash
- Usually a combination of both is seen
39
What are the causes of intestinal failure?
- Short bowel syndrome: NEC, atresia, volvulus, trauma, Crohn's, resections
- Motility disorders: chronic idiopathic pseudo-obstruction
- Mucosal disorders (present early with intractable diarrhoea) e.g. microvillus inclusion disease, tufting enteropathy, SCID, autoimmune enteropathy (usually TPN-dependent, may need SB transplant)
40
Stool fat globules vs fatty acid crystals vs reducing substances
- Fat globules = maldigestion, failure of enzyme process or bile to suspend fats
- Fatty acid crystals = malabsorption, mucosal/brush border issue (fatty acid not absorbed)
- Reducing substances suggests carbohydrate malabsorption.
41
Features of bacterial overgrowth
- Anaemia, fat malabsorption, steatorrhoea, decr fat-soluble vitamins
- Arthritis, nephritis, hepatitis, vesiculopustular rash
- Short stature, weight loss, abdo pain, night blindness, ataxia
- Risks: recurrent antibiotics, loss of ileocaecal valve, motility disorders, GI surgery, short gut
- Ix: faecal fat, breath test (indicates sugar malabsorption)
- Tx: treat underlying cause, metronidazole, probiotics
42
What faecal test can confirm that hypoalbuminaemia is related to gastrointestinal losses?
- Stool level of alpha-1 antitrypsin is an excellent screening test for protein losing enteropathy, as alpha-1 antitrypsin is a nondietary, serum protein synthesized in the liver. Its molecular weight is similar in size to albumin, and it is resistant to intestinal and proteolytic digestion distal to the stomach.
43
Describe Peutz-Jagher syndrome
- AD
- Hyperpigmented macules (especially lips and intraoral), and multiple GI hamartomas (small intestine, colon, stomach)
- Increased risk of intussusception and cancer (GI, breast, reproductive)
- Most due to a mutation in LKB1/STK11
44
In the presence of insulin, the liver converts glucose to which forms for storage?
Glycogen and triglycerides
45
Food poisoning caused by improperly stored rice or meats is caused by?
- Bacillus cereus
- Toxin-mediated cause of gastroenteritis, rapid onset of vomiting and/or watery diarrhoea
- It does not cause fevers or invasive disease in immunocompetent patients. Management is supportive.
46
Melanosis coli is associated with?
- Laxative abuse with anthraquinone-containing laxatives (e.g. senna)
- It appears as a dark brown discoloration of the colon with lymph follicles shining through as pale patches
47
Describe the different vitamin Bs and their deficiencies
Cobalamin - B12: macrocytic anaemia, elevated homocysteine, peripheral neuropathy
Folate - B9: macrocytic anaemia, elevated homocysteine
Niacin - B3: pellagra (diarrhoea, dementia, dermatitis), weakness, insomnia
Riboflavin - B2: ariboflavinosis (sensitivity to sunlight, angular cheilitis, glossitis, dermatitis or pseudo-syphilis, pharyngitis)
Thiamin - B1: beriberi (weight loss, emotional disturbances, Wernicke's encephalopathy, weakness and pain in the limbs, arrhythmias, and oedema)
48
Describe hereditary fructose intolerance
- Rare, AR
- Deficiency of fructose-1,6-bisphosphate aldolase in the liver, kidney, and intestine
- Appears with the ingestion of fructose-containing food
- Early clinical manifestations resemble galactosemia and include jaundice, hepatomegaly, vomiting, lethargy, irritability, and convulsions
49
Describe short bowel syndrome
- Caused by: NEC, atresia, volvulus, gastroschisis, trauma, surgical resection, radiation enteritis
- If <40cm bowel left in infancy often need long-term TPN support
- Ileum adapts better than jejunum
- Loss of ileocaecal valve = faster transit, bacterial overgrowth (backflow as no valve)
- Aim early introduction of enteral feeds
50
What are poor prognostic factors in short bowel syndrome?
Smaller length of colon, IFALD, not achieved full enteral feeds after 5 years of TPN
51
What are indications for bowel transplant in short bowel syndrome?
Irreversible intestinal failure, lack of venous access, liver disease with coagulopathy, ascites, encephalopathy, life-threatening catheter sepsis
52
Describe lactose deficiency
- Usually acquired, commonly post rotavirus infection
- Lactase deficiency means cannot hydrolyse lactose to glucose and galactose
- Loose, explosive stools. REducing substances positive in stool
- Tx: lactose-free formula, low lactose intake in child
53
Describe galactosemia (= galactose-1-Phosphate Uridyl Transferase Deficiency)
- Rare, AR
- Rapid onset watery diarrhoea from 1st week of life. Resolves with withholding feeds
- Lactose in breast milk and formula = glucose and galactose. Unable to metabolize galactose-1-phosphate, the accumulation of which results in injury to kidney, liver, and brain.
- Injury may begin prenatally
- Jaundice, hepatomegaly, vomiting, hypoglycemia, seizures, lethargy, irritability, FTT, aminoaciduria, splenomegaly
- Reducing substances positive in stool + urine. Normal biopsy. Galactosuria.
- Tx: non-lactose containing milk
54
Infants with galactosemia are at increased risk of which infection?
E.Coli sepsis
55
Describe glucose-galactose malabsorption
- Rare, AR
- Rapid onset watery diarrhoea from birth, settles with withholding feeds
- Reducing substances positive in stool. Normal biopsy.
- Error in sodium/glucose cotransporter protein called SGLT1
- Tx: use fructose as main carbohydrate source
56
Describe sucrase-isomaltase deficiency
- Defect in carbohydrate digestion, lack of enzyme for hydrolysis (sucrose-> fructose and glucose)
- Watery diarrhoea, FTT after introduction of sucrose or complex carbohydrates into diet (fruit, juice, grains). Can be mild
- Negative reducing substances in stool (non-reducing sugar)
- Tx: remove sucrose and complex carbs from diet
- Positive hydrogen breath test indicates carbohydrate malabsorption
57
Describe achalasia causes, symptoms, investigation, and treatment
- Failure of relaxation of the lower oesophageal sphincter
- Dysphagia, cough, regurgitation, chest discomfort
- Risk of oesophageal carcinoma if left untreated
- Dx: via barium swallow: fluid level and narrowing of distal oesophagus
- Tx: balloon dilation or Heller myotomy, botulinum toxin
58
Describe Zollinger-Ellison syndrome
- Gastrinoma (gastrin-producing tumour of the endocrine pancreas) leading to gastric acid hypersecretion and intractable peptic ulcer disease
- May be part of MEN1 syndrome (AD)
- Tx: ranitidine, omeprazole +/- surgery
59
Causes and red flags for chronic diarrhoea
- Persistent >2-3/52
- Post infectious, coeliac, food intolerance, short gut, pancreatic insufficiency, IBD, antibiotics, laxatives, immunodeficiency, abetalipoproteinemia
- If thriving: constipation with overflow, toddler's diarrhoea, carbohydrate intolerance, IBS
- Red flags: FTT, weight loss, blood, night stools, fever/rash/arthritis
60
Describe the gold standard investigation for reflux?
- pH study - gold standard if uncertainty, poor treatment response, uncontrolled respiratory disease, considering surgery, pot-surgery
- If pH< 4 7-10% of time = mild, 10-20% = mod, 20-30% = severe
- Cannot detect anatomical abnormality, aspiration, alkaline reflux.
- Severity doesn't correlate with symptoms or degree or oesophagitis
61
Barium swallow for reflux assessment
- Can overdiagnose physiological reflux, and miss reflux events
- Good for malrotation, anatomical abnormalities, duodenal webs
62
What is the use of esophageal impedance probes?
- Measures the resistance between electrodes on a catheter. Increased resistance indicates retrograde bolus/reflux
- Good for assessing temporal relationship with symptoms
63
What is manometry used for?
- Measures pressure
- Useful for achalasia and motor disorders
- Not good for reflux assessment
64
Management of gastroesophageal reflux?
- Reassurance, adjusting volume of feed and position
- Trial dairy free/ hydrolysed formula
- Antacids (gaviscon), thickeners
- H2 receptor blockers - ranitidine
- PPI - omeprazole (increases pH, good for erosive oesophagitis)
- Pro-kinetic drugs - metoclopramide, domperidone, erythromycin
- Nissen's fundoplication +/- pyloroplasty (if delayed gastric emptying) +/- PEG: if no response to medical treatment, aspiration, chest pain, strictures
65
Differential diagnosis for gastroesophageal reflux?
Eosinophilic oesophagitis, candida oesophagitis, cow's milk allergy oesophagitis, achalasia, Crohn's disease
66
Describe eosinophilic oesophagitis
- Chronic allergic inflammation of the oesophagus
- Fails to respond to regular reflux treatment
- Dysphagia, food impaction, FTT, vomiting, heartburn
- More common with personal and FHx atopy
- Ix: endoscopy/histology - eosinophils >20/hpf, furrowed and ringed oesophagus.
67
What is the treatment for eosinophilic oesophagitis?
- Dietary elimination (wheat, cow/soy, fish, egg), topical fluticasone/budesonide, high dose PPI
- Likely relapsing course
68
What are the causes of congenital diarrhoea?
- Congenital microvillus/inclusion disease
- Tufting enteropathy
- Congenital chloride diarrhoea
- Autoimmune enteropathy
- Usually from birth, >4 diarrhoea per day, FTT
69
Describe congenital microvillus/inclusion disease
- Poor tolerance of even minimal enteral intake, TPN-dependant
- Poor survival rate, may be cured with transplant
70
Describe tufting enteropathy
- Epithelial dysplasia with tufts of epithelial cells on biopsy
- May be able to tolerate enteral feeds with age
- Associated with choanal atresia, imperforate anus, short stature, delayed bone age
71
Describe congenital chloride diarrhoea
- Usually polyhydramnios
- Severe watery secretory diarrhoea from birth, failure or chloride reabsorption
- Does not resolve with cessation of enteral feeds
- Hyponatremic, hypochloremic, metabolic alkalosis
- Raised stool pH and chloride
- Tx: Na and KCl supplements
72
What are the causes and treatment of exocrine pancreatic insufficiency?
- Chronic diarrhoea due to fat malabsorption
- Steatorrhoea, faecal elastase <150ug/g (can have false +ve in watery stools)
- Causes: CF, hereditary pancreatitis, Shwachman-Diamond syndrome, acute pancreatitis, coeliac disease, Crohn's disease, SLE
- Tx: pancreatic enzyme replacement (Creon)
73
Describe intestinal lymphangiectasia
- Dilatation of the intestinal lymphatics, loss of lymph fluid into the gut, leads to protein-losing enteropathy and fat malabsorption
- Primary (congenital) or acquired (pancreatitis, pericarditis, malignancy, post-Fontan)
- Hypoalbumina, lymphopenia, hypogammaglobn
- Dilated lymphatics on biopsy. Elevated faecal a1aT level (measure of protein-leakage)
- Tx: medium chain triglycerides (absorbed directly into portal vein)
74
Describe features of protein-losing enteropathy
- Hypoalbuminaemia, oedema, low IgG, low lymphocytes
- Increased risk of infections
- Nutritional supplements required
75
What human leukocyte antigen complex is associated with coeliac disease?
HLA-DQ2 and HLA-DQ8 (98% of those with coeliac are positive for these, but so are most of the population. However, if your patient is negative for these then they don't have coeliac)
30-40% general population +ve HLA DQ2/8
50% family members of coeliac pt +ve
Useful for negative predictive value
76
What are the non-GI manifestations of coeliac disease?
Dermatitis herpetiformis (itchy papules and vesicles), iron-deficiency anaemia, osteoporosis, Rickets, fatigue/lethargy, short stature, delayed puberty, stomatitis, infertility
77
What is the risk of a 1st degree relative having coeliac disease?
10%
78
Who should be screened for coeliac disease?
1st degree relatives (10% risk) - 4-8% relatives have no symptoms
T21 (10%)
T1DM (high false +ve rate from TTG, so if symptoms, need scope) 5-10%
autoimmune thyroiditis (7%)
IgA deficiency (7%)
Williams and Turner's syndrome
Autoimmune liver disease
79
What are the gold standard investigations for coeliac disease?
TTG-IgA (high sensitivity and specificity) and IgA - may have false -ve if IgA deficiency
- If above positive, then lab runs EMA
- If low IgA - lab runs DGP IgG (deamidated gliadin peptide) assay
• TTG abs usually disappear on treatment after 6‐12 months ; titre correlates with degree of mucosal damage
• false +ve TTG IDDM , chronic liver disease, psoriatic/ rheumatoid arthritis and heart failure
• sensitivity of transglutaminase (TTG) abs is > 90%
- Small bowel biopsy (subtotal villous atrophy, crypt hypertrophy, plasma cell infiltrate, intraepithelial lymphocytosis)
```
ESPHAGAN non biopsy diagnosis
• Compatible history
• TTg >10 ULN + Endomyseal Ab +ve
• Second, separate TTg +ve
• Clinical response to Gluten elimination
```
80
What syndromes are associated with Hirschsprungs?
T21, MEN2A+B, central hypoventilation syndrome, Bardet-Biedl, Smith-Lemli-Opitz
81
Describe choledochal cysts?
- Congenital dilatations of the CBD. Can cause biliary obstruction and cirrhosis.
- In infants: cholestatic jaundice, ascites and coagulopathy
- In older child: abdo pain, jaundice, and mass occurs (33%)
- Acute cholangitis (fever, RUQ pain, jaundice, leukocytosis) may be present
- Dx: cysts seen on USS
- Tx: primary excision of the cyst and a Roux-en-Y choledochojejunostomy. Can get recurrent cholangitis or stricture at the anastomotic site
82
What are the red flags in abdominal pain?
Age < 5 years, fever, weight loss, skin rashes/joint symptoms, vomiting, waking from sleep, referred to back/shoulders, urinary symptoms, FHx IBD/peptic ulcer, perianal disease, blood in stools
83
List some function GI disorders
Cyclical vomiting, functional dyspepsia, IBS, abdominal migraine, childhood functional abdominal pain +/- syndrome (inc. loss of functioning, headache, limb pain, poor sleep).
84
What factors and symptoms are associated with functional GI disorders?
Anxiety, over-achievers, stress, school refusal, parental discord, recent viral illness, food intolerance, constipation, illness in family members
85
What are the treatments for functional GI disorders?
- Avoidance of over-investigating
- Reassurance, acknowledgement that the pain is real, lifestyle modifications (diet, exercise, regular school attendance)
- Ranitidine (dyspepsia), pizotifen (migraine), simple analgesia, antiemetics, anti-spasmodics
86
Crohn's disease vs. ulcerative colitis
- CD: panenteric, skip lesions, granulomas/strictures/fissures, transmural inflammation, raised inflamm markers >UC, perianal disease, arthritis more common than in UC, M>F
- UC: distal bowel/colon, diffuse disease, can be pancolitis up to 60%, extra-intestinal manifestations, toxic megacolon, mucosal + submucosal inflammation (can be transmural in severe), can get backwash ileitis into terminal ileum
87
Describe the endoscopy/biopsy results in chron's disease
- Focal lesions with transmural inflammation
- Granulomas in 40-60%
- Strictures, fissures
- Small bowel + perianal disease (can image with MRI)
88
Describe the endoscopy/biopsy results in ulcerative colitis
- Mucosal and submucosal inflammation
- Goblet-cell depletion
- Cryptitis and crypt abscesses
- NO granulomas
89
What are the extra-intestinal manifestations of ulcerative colitis?
- Arthropathy (ankylosing spondylitis)
- Erythema nodosum
- Iritis/uveitis
- Liver disease (autoimmune hepatitis, sclerosing cholangitis)
90
What is the most appropriate test to investigate hereditary fructose intolerance?
Serum aldose B enzyme measurement
91
pANCA and ASCA markers in IBD
ASCA +ve in 50-60% of CD
| pANCA +ve in 70% of UC
92
What is the treatment of crohn's disease?
- Exclusive enteral nutrition (induces remission in 70-80%), 6-8/52 duration. Elemental (peptide chains/AA) or polymeric (whole protein)
- Steroids if severe/ no remission after EEN
- Maintenance: Pentasa/mesalazine/5-ASA or azathioprine, methotrexate, infliximab
- 90% relapse in first 12 months
- ABs eg metronidazole for 6/52 for perianal disease
- Azathioprine or 6-MP induce remission in 60-80%. Risks BM suppression, hepatitis, pancreatitis, rash. Check TMPT level
- Infliximab if severe - 0,2,6 weeks then Q8weekly
- Surgery if failed/isolated ileocecal disease/strictures or fistulas . 70-80% require surgery across lifetime
93
What is the treatment of ulcerative colitis?
- If severe, urgent IV steroids
- Mild or L-sided: pentasa or steroids
- Mod-severe: 2-4/52 pred, then wean over 4-8/52
- Maintenance: pentasa or sulfasalazine, 2nd line azathioprine or 6-MP (if relapse within 6 months, or steroid dependant). 5-ASA continued for anti-cancer effect.
- Surgery can be curative for UC, 25% by 10y age. Subtotal colectomy + ileostomy
94
What are the complications of ulcerative colitis?
Toxic megacolon, growth failure and osteoporosis (steroids), cholangitis, thrombosis, colon cancer (depending on disease severity and duration)
95
What is the treatment of toxic megacolon?
IV steroids, hospital admission, may require ciclosporin, infliximab, colectomy
96
Describe FPIES
- Profuse vomiting, floppy, pallor, shock, dehydration, acidosis and occ diarrhoea. 2-4 hours post ingestion
- Most common triggers rice, cow's milk, soy, but can be any food
- Non IgE-mediated, RAST/SPT negative, no urticaria
- Ix: acidotic, respond quickly to fluid resus
- Avoid offending antigen, eHF (peptijunior) or AAF (neocate)
- Oral food challenge in hospital after 2-3 years
97
Describe pseudomembranous colitis
- C.diff infection, usually due to antibiotics disrupting intestinal flora
- Pathogenesis due to toxin production
- Can be asymptomatic to life-threatening
- Tx: vanc (PO) + metronidazole (IV or PO) +/- probiotics. Relapse 15-20%
- Usually due to amox, cephalosporins, clindamycin
- Can lead to toxic megacolon and perforation
98
Osmotic vs secretory diarrhoea
- Stool osmolarity - (Na + K) x 2
- Osmotic diarrhoea: osmotic gap >50, improves with fasting, stool volume moderately increased
- Secretory diarrhoea: osmotic gap <50, continues despite fasting, stool volume very large
99
Describe osmotic diarrhoea
- Osmotic gap >50, acidic stool <5.5
- Improves with fasting
- Unable to absorb solutes e.g. unabsorbed carbs
- Causes: infectious enteritis, disaccharide deficiency, laxative abuse, bacterial overgrowth, impaired absorptive states (coeliac, pancreatic ti insuff, short gut), steatorrhea
100
Desribe secretory diarrhoea
- Osmotic gap <50, neutral stool
- Continues despite fasting
- Losing electrolytes, hyper-permeable gut
- Causes: toxogenic E.Coli, cholera, gut hormone tumours, intractable diarrhoea states (microvillous inclusion, autoimmune enteropathy)
101
What are the causes of GI bleeding in a neonate?
- UGI: VKDN, maternal blood, coagulopathy
| - LGI: anal fissure, maternal, volvilis, NEC
102
What are the causes of GI bleeding in an infant?
- UGI: mallory weiss, oesophagitis, pulm hemosiderosis
| - LGI: fissure, CMPI, intussusception, infective colitis
103
What are the causes of GI bleeding in a child/adolescent?
- UGI: mallory weiss, gastritis, varices, ulcer
| - LGI: fissure, IBD, infectious, meckels, HUS, HSP
104
What is the mechanism of the pro-kinetic effect of erythromycin?
Motilin receptor agonist
105
In very early onset IBD mutations in the gene for which receptor are commonly found?
IL-10
106
Describe intussusception
- Peak 6-9m, M>F x 4, usually ileocaecal
- Spasmodic pain, pallor, irritability, vomiting can become bilious, blood-stained stools/redcurrant jelly, abdominal mass
- Can be secondary to Meckel's, polyps, LNs, lymphosarcoma, HSP
- Tx: air enema or laparotomy
107
Describe Meckel's diverticulum
- Remnant of vitellointestinal duct, 50% contain ectopic gastric, pancreatic, or colonic tissue
- 2% of children, M:F 2:1, 2 foot from ileocaecal valve, 2 inches long
- Intermittent painless bleeding. Can present with intussusception, peritonitis, perforation
- Technetium scan shows ectopic gastric mucosa. Tx via resection
108
Describe Hirschprungs
- Absence of ganglion cells in myenteric plexus of distal bowel
- M>F, failure to pass meconium >48 hours, associated with T21, CHOVS. May present as constipation when older
- RET gene on Ch 10
- Enterocolitis can occur pre or post-op
- Explosion faeces/air after DRE
- Dx via suction rectal biopsy
- Tx: excision, temporary colostomy with subsequent pull through
109
Describe juvenile polyposis
- 85% of polyps, present age 2-6yrs, painless PR bleeding
- Usually <30cm from anus
- Not pre-malignant if solitary (can be pre-malignant if multiple)
110
Describe Peutz-Jeghers syndrome
- AD, STK11 gene
- Diffuse GI hamartomatous polyps (usually jejunum + ileum), hyperpigmentation of buccal mucosa and lips
- Pre-malignant
- Endoscopic screening and imaging from age 8
- Pain, bleed, intussusception, anaemia
111
Describe familial adenomatous polyposis
- AD, mutation in APC gene (tumour suppressor gene) on Ch5q21
- Numerous polyps throughout colon. Can be asymptomatic, or rectal bleeding, cramping, diarrhoea
- Epidermoid cysts, osteomas, fibromas, and lipomas
- 100% risk colonic carcinoma, need screening + prophylactic colectomy in 20s
- Inc risk hepatoblastoma when young
112
Describe Gardener syndrome
- FAP (familial adenomatous polyposis) with desmoid tumors, fibromas, osteomas (typically mandibular), epidermoid cysts, and lipomas.
113
What percentage of neonates have jaundice and prolonged jaundice?
30-50% have jaundice, 15% have prolonged jaundice. 1:2500 have conjugated jaundice
114
What are the signs of kernicterus?
- Irritability, seizures, opisthotonos, fever, hypertonia
| - Late complications: athetoid cerebral palsy, hearing loss, paralysis of upward gaze
115
What is the cause of breast-milk jaundice?
- Substances in maternal milk (B-glucuronidase and non-esterified FA) may inhibit normal bilirubin metabolism
- SBR rapidly drops if BF stopped for 48 hours
116
Describe Gilbert Syndrome
- Decreased in UGT activity (but normal total amounts), leading to reduced bilirubin conjugation. Unconjugated bilirubinemia
- Inc incidence neonatal and BM jaundice
- Up to 40% have reduced RBC lifespan, therefore correlation with SBR and enzyme activity unreliable
- Often presents after puberty with inc bilirubin or jaundice post fasting or illness
- M>F. No treatment required. Occ phenobarbital. AR
- Inc risk of jaundice with chemo exposure
117
What is tocilizumab?
- Recombinant humanized anti-human monoclonal antibody directed against the IL6 receptor
- Used for refractory systemic and polyarticular JIA
- Active TB infection is an absolute contraindication
- IL6 (Tocilizumab) and IL1 (anakinra, canakinumab and rilonocept) inhibitors are all more effective that TNFa inhibitors (infliximab) in treating systemic JIA. TNF alpha inhibitors are more effective at treating other categories of JIA.
118
Describe the function and structure of the pancreas
- 95% exocrine - elastase (carbohydrate), lipase (fats), chymotrypsin and trypsin (protein)
- 5% endocrine - Langerhan's cells. Beta cell - insulin, alpha cells - glucagon, delta cells - somatostatin, gamma - polypeptide, epsilon - ghrelin
119
Describe Crigler-Najjar syndrome
- AR. Unconjugated bilirubinemia due to defect in conjugation
- Type 1: severe deficiency of UGT1A1 activity, high risk of kernicterus. Requires phototherapy life-long, and repeat exchange transfusions. No response to phenobarbital. Require liver transplant. Pale stools.
- Type 1: moderate deficiency, may require phototherapy, responds to phenobarbital. Kernicterus unusual. Normal LFTs and stool
120
What are the main causes of conjugated jaundice?
- Idiopathic neonatal hepatitis (40%)
- Extrahepatic biliary atresia (25-30%)
- Intrahepatic cholestasis syndromes (20%) eg Alagille
- Alpha1 antitrypsin deficiency (7-10%)
121
Describe idiopathic neonatal hepatitis
- Diagnosis of exclusion
- Inc risk with LBW or prematurity
- Histology: hepatocellular swelling/ballooning, focal hepatic necrosis, multinucleated giant cells
- RFs for poor prognosis: severe jaundice >6m age, acholic stools, FHx, persistent hepatosplenomegaly
- 90% do well with no long term liver disease
122
What are the investigations for biliary atresia?
- USS (fasting) - often absent gallbladder
- HIDA - no excretion
- Biopsy - expanded portal tracts, bile duct proliferation, bile plugs and fibrosis
- Exploratory and operative cholangiography
123
What is the treatment for biliary atresia?
- Kasai procedure (portoenterostomy) unless decompensated failure.
- Best results if <8 weeks age
- High risk ascending bacterial cholangitis (from SB conduit) 45-50%
- 80% need liver transplant by age 20. 50% jaundice-free post op. Progressive disease
- Need vitamin A, D, E, K replacement.
- Role of urso/steroid/phenobarb unclear
124
Describe biliary atresia
- T1 - obliteration CBD, T2 - common and hepatic ducts, T3 - obliteration entire extrahepatic tree (most common form)
- Conjugated bilirubinemia, may have pale or normal stools
- Usually well-grown (c.f. IUGR in Alagille's)
- 25% associated with other congenital abnormalities
125
Describe syndromic biliary atresia
- Abdominal situs inversus, multiple spleens, portal vein anomalies, malrotation, congenital heart disease
126
Describe Alagille syndrome
- AD, defect in JAG1 gene on Ch20p12
- Other gene defect (NOTCH2 gene)
- Intrahepatic biliary hypoplasia (can initially get bile duct proliferation, but develop paucity with time)
- Peripheral pulmonary stenosis, ToF
- Abnormal facies: broad forehead, deep set eyes, triangular face, hypertelorism, narrow nose, butterfly vertebra, posterior embryotoxon
- IUGR/FTT
- Short stature, delayed puberty, high pitched voice, ICH secondary to circle of willis abnormalities
- Severe cases require transplant. Urso can help improve bie drainage
```
MAJOR FEATURES
MINOR FEATURES
Right sided cardiac lesions (22%)
Embryotoxin
Vertebral anomalies – butterfly & hemi-vertebrae
Facial features (around 3⁄4)
Cholestasis with paucity of bile ducts
```
```
MINOR FEATURES
Short stature
Delayed puberty
High pitched voice
Renal anomalies
Short radii
Hypercholesterolaemia
Vascular anomalies especially intra-cranial
```
127
Describe progressive familial intrahepatic cholestasis (PFIC)
- May present as neonatal hepatitis, cholestasis, FTT, pruritus, progressive liver disease requiring transplant in first few years of life
- Type 1-3 (type 1+2 normal GGT, type 3 high GGT)
- T1 chloride sweat test +ve
128
What is the most common inherited cause of conjugated jaundice?
Alpha1 antitrypsin deficiency
129
Describe Alpha1 antitrypsin deficiency
- AR. Mutation at protease inhibitor locus on Ch14
- ZZ abnormal, MM normal. Do genotype rather than measure a1aT levels (is an acute phase reactant)
- Liver and lung disease
- Associated IUGR, hepatomegaly, may have acholic stools
- 2% present with Vit K-responsive coagulopathy
- 50% with neonatal hepatitis develop chronic liver disease, and 50% require transplant by age 10
- Replacement a1aT not helpful because abnormal protein still accumulating in hepatocytes
130
What are the causes of unconjugated hyperbilirubinemia?
- Infections: bacterial, TORCH
- Metabolic: carbohydrate (GSD, galactosemia), protein (tyrosinemia, UCD), lipid, bile acid (Zellweger - peroxisomal)
- Endocrine: hypothyroid, hypopituitarism
- Chromosomal: T21, Patau
- CF, TPN, haemochromatosis, histiocytosis, neonatal SLE
131
What are the symptoms and causes of acute hepatitis?
- Malaise, anorexia, N+V, fever, tender hepatosplenomegaly, lymphadenopathy, rash, jaundice
- Viral most common. Hep A worldwide. Seronegative-non A-E most common in NZ
- Also caused by paracetamol toxicity, isoniazid, phenytoin, cotrimoxazole, methotrexate
132
Describe the transmission and infectivity of Hep A
- 20-25% of hepatitis worldwide
- Faecal-oral route
- RNA virus
- Incubation 2-6 weeks, shedding up to 3 months
- < 5% people symptomatic
133
Outcome of Hep A infection
- Mortality increases if <5yo
| - RFs: fulminant hepatic failure, prolonged cholestasis, recurrent, neuro/renal/pancreas involvement
134
Symptoms, bloods, treatment of Hep A
- Flu-like or asymptomatic
- Can develop abdo pain, malaise, jaundice, fever, nausea
- Inc conj bilirubin and ALT/AST. If inc bili but falling LFTs then indicates hepatocyte death
- Dx: Anti HAV IgM (acute) + IgG (persists)
- Tx: supportive, immunisation, immunoglobulin
135
What are the causes of acute liver failure?
- Infants: haemochromatosis, disseminated HSV, histiocytosis, metabolic (galactosemia, tyrosinemia)
- Older: viral hepatitis, metabolic, paracetamol, Wilson's, idiopathic, autoimmune
136
Which carbohydrates are absorbed by the intestinal sodium-glucose transporter 1 (SGLT-1)?
Glucose and galactose
137
What investigation results would you expect in acute liver failure?
- Raised AST and ALT
- Raised PT/INR due to low Vit K
- Raised direct and indirect bilirubin
- Increased ammonia
138
What are the complications of acute liver failure?
- Encephalopathy - secondary to ammonia
- Renal failure - due to hepatorenal syndrome, ATN, direct kidney toxicity. 50% require dialysis
- Coagulopathy - Vit K def, thrombocytopenia
- Cardiovascular - hyperdynamic, circulatory failure
- Pulmonary - aspiration shunting, infection, oedema
- Metabolic - hypoglycemia, metabolic alk/acidosis, electrolyte abnormalities
139
What is the treatment of acute liver failure?
- Ventilation if resp failure
- Avoid correcting INR unless active bleeding (INR is an indicator of progress)
- Fluid support, dialysis
- FFP if bleeding, aim plts >50, plt transfusion, Vit K if needed
- Ranitidine/omeprazole, IV AB/fungal prophylaxis
- TPN rarely indicated
- NAC if overdose
- May require emergency liver transplant
140
At what dose is paracetamol likely to cause significant hepatotoxicity?
>200mg/kg (or 150mg/kg over 24 hours)
141
What are indicators of poor prognosis in paracetamol overdose?
pH< 7.3, PT >100, INR >6.6, creat >300, grade 3-5 encephalopathy
142
What is the treatment for paracetamol overdose?
- Depends on timing, dose. If >8hrs since overdose then always start NAC while awaiting bloods
- NAC 300mg/kg/day until INR <1.5 + ALT <50, paracetamol <66.
143
What are associated risk factors in paracetamol overdose?
- Pt on phenobarbitone or carbamazepine (p450 inducers)
- Malnourished
- Chronic illness
- Gilbert/Crigler-Najjar syndrome
144
What happens in a paracetamol overdose?
- With overdose, glutathione is depleted and NAPQI is not detoxified
- This impairs mitochondrial and nuclear function, leading to cell death
145
What are the laboratory findings in Wilson's disease?
- High AST:ALT ratio > 4:1 (characteristic for Wilsons)
- Raised liver and urinary copper, serum copper may be low or normal
- Decreased free ceruloplasmin (copper carrying protein)
- Low ALP common
- Raised urinary copper after penicillamine challenge
- 30% have coombs +ve anaemia
- May have increased ANA
146
What is the treatment of Wilson's disease?
- PO Zinc can prevent copper accumulation in asymptomatic siblings
- Penicillamine (can cause Vit B6 def and paresthesia) or trientine (less used in NZ as expensive)
- Liver transplant if failure
147
Desribe the genetics and presentation of Wilson disease
- AR, mutation of ATP7B gene on Ch 13. Most are compound heterozygotes, useful for sibling screening
- Present age 5-12y: jaundice, abnormal LFTs, hepatitis, acute or chronic LF, cirrhosis, portal hypertension, Kayser-Fleischer rings on slit lamp (may be absent < 3y age), tubular nephropathy
- Neurological (2nd decade): low mood and behaviour, decr school progress, incoordination, tremor, dysphagia and dysarthria
148
What are the complications of chronic liver disease?
- Malnutrition
- Portal hypertension
- Ascites
- Coagulopathy
- Hepatorenal syndrome
- Hepatopulmonary syndrome
- Portopulmonary syndrome
149
What are the types of chronic liver disease
- Compensated - may be asymptomatic
- Decompensated - liver synthetic failure
- End-stage - persistent inc bilirubin, INR >1.3, alb <35, FTT, chronic hepatic encephalopathy, ascites, variceal bleeding
150
What is the treatment of malnutrition associated with chronic liver failure?
- Special formula (low Na, has MCFA)
- Vit A,D,E,K replacement
- High calorie intake, NGT feeds
151
Management and complications of ascites associated with chronic liver failure?
- 50% die within 2 years of ascites. Risk of bacterial peritonitis
- Na and fluid restriction, spironolactone/thiazide/frusemide diuretics
152
What are the causes of chronic liver disease?
- Infancy: biliary atresia, Alagille, storage/metabolic (GSD, galactosemia, UCD, Zellweger, PFIC), CF-related liver disease, neonatal hepatitis, LCH
- Childhood: autoimmune hepatitis, sclerosing cholangitis, drugs/toxins, Budd-Chiari (occlusion hepatic vein), hepatic vein thrombosis
153
Describe the process and treatment of portal hypertension
- Major cause morbidity and mortality (30-50%)
- Due to chronic liver disease or PV occlusion (thrombophilia)
- PV pressure >5mmHg or PV-HV gradient >10mmHg
- Splenomegaly, oesophageal/gastric/rectal varices, ascites, encephalopathy, porto-systemic collaterals, GI bleed
- Tx varices: sclerotherapy, ligation, propranolol, portosystemic shunt
- May require liver transplant
154
Describe hepatorenal syndrome
- Oliguria <1ml/kg/day, FeNa <1%, urine:plasma creat ratio <10, low gFr, inc creatinine, not hypovolaemic
- T1 - rapidly progressive, poor prognosis. T2 - less precipitous
- Mortality >90% with severe liver disease
- Can be reversed with liver transplant
155
Hepatopulmonary syndrome vs. portopulmonary syndrome
- Hepatopulmonary: intrapulmonary vasodilation, alveolar-arterial gradient >20mmHg. Can be reversed with transplant. Pulm artery histology normal.
- Portopulmonary: intrapulmonary vasoconstriction, normal alveolar-arterial gradient. Not usually reversible with transplant, can trial vasodilators. Raised PA pressure, pulm artery histology abnormal with concentric medial hypertrophy
156
What is the triad of hepatopulmonary syndrome?
- Liver dysfunction, intrapulmonary AV shunt, arterial hypoxaemia (alveolar-arterial gradient >20mmHg).
- T1 functional, T2 anatomical
- SOB, cyanosis, clubbing, SOB improves with lying down as shunting occurs in bases of lungs
- Trial 100% O2
157
What disorder is associated with autoimmune hepatitis?
Ulcerative colitis, primary sclerosing cholangitis
158
Describe the types of autoimmune hepatitis
- Type 1: more common, ANA+ve, anti SMA +ve
| - Type 2: harder to treat, anti-LKM1 +ve, but up to 20% may not have antibodies detected at presentation
159
What is the presentation and treatment of autoimmune hepatitis?
- Can present as acute hepatitis, insidious onset, or portal hypertension
- Inc ALT/AST, serum IgG >1.5 x normal
- Tx: corticosteroids, azathioprine, mycophenolate, liver transplant
- Relapse common (40%). IgG levels and autoantibody titres correlate with disease activity
- Can cause primary sclerosing cholangitis
160
Describe primary sclerosing cholangitis
- Progressive inflammation or intra or extrahepatic bile ducts. Can cause ascending cholangitis, portal HTN.
- Dx via ERCP, risk cholangiocarcinoma
- Inc pANCA. Associated with UC.
- Pain, pruritus, jaundice, raised LFTs
- 30% require transplant (but can recur in transplant)
- Tx: urso, vancomycin
161
How does infliximab work?
- Infliximab is a monoclonal antibody against tumour necrosis factor alpha (TNF-α)
- It works by binding to TNF-α, and therefore inhibits the binding of TNF-α to its receptor cells.
162
How is Hep B transmitted?
- Vertical/perinatal transmission - 70-90% risk if mother HbeAg +ve. If vertical transmission then 90% risk of chronic carrier (CLD, HCC).
- Horizontal - parenteral, sexual, environmental
163
Describe acute vs chronic hepatitis B
- Symptomatic acute hepatitis - complete resolution in 90%, lifelong immunity
- Asymptomatic chronic infection - HbSAg +ve for >6/12 - 90% develop chronic liver disease. Can lead to cirrhosis and hepatocellular carcinoma
164
What is the treatment of hepatitis B?
- Interferon a, pegylated interferon.
- Antivirals: entecavir, tenofovir - cause viral suppression but doesn't cause viral clearance
- 50% seroconvert with therapy
- May require transplant if cirrhosis
- If SAg+ve, require hep B immunoglobulin and vaccination at birth (+ vaccine 6w, 3m, 5m). But if E antibody +ve just give vaccination
165
What is the worldwide prevalence of Hep B and Hep C?
Hep B 5% (chronic carriers) and Hep C 3%
166
What is the transmission mode of Hep C?
Via blood. Vertical is rare
167
What are the symptoms of Hep C?
Usually asymptomatic. Leads to cirrhosis over years.
| 20% clear infection, 50% chronic asymptomatic, 30% chronic active infection.
168
What is the testing and treatment for Hep C?
- Serology: anti-HCV antibody positive, HCV RNA+ve in 2 consecutive samples
- Tx: interferon alpha and ribovarin, sofosbavir and ledipasvir, new agent = glecaprevir and pibrentasvir (cures Hep C in most). 70% adults seroconvert with therapy. Most common indication for adult liver transplant (cirrhosis, HCC)
169
Describe non-alcoholic fatty liver disease
- Most common cause of paediatric liver disease, up to 50% in obese children (but can occur in non-obese)
- Spectrum of steatosis to steatohepatitis to fibrosis and cirrhosis
- Asymptomatic, or abdo pain, hepatomegaly, acanthosis nigricans, insulin resistance
- Inc ALT. USS - enlarged, echogenic liver. Biopsy is gold standard, but not often performed
- Tx: lifestyle, tx diabetes/cholesterol, antioxidants
170
What are the differences between type 1 (adult pattern) and type 2 (more common) NASH?k
- Type 1: steatosis, ballooning degeneration, perisinusoidal fibrosis
- Type 2: steatosis, portal inflammation and fibrosis, no ballooning
171
What are the contraindications to liver transplant?
Severe sepsis, severe irreversible extra-hepatic disease, mitochondrial cytopathies with multi-system involvement, giant cell hepatitis with DAT+ve haemolytic syndrome
172
What is the immunosuppression after liver transplant?
Lifelong immunosuppression with either cyclosporine or tacrolimus (or sirolimus or mycophenolate if renal impairment), steroids
173
What are the complications post liver transplant?
- Early: graft failure, PV or HA thrombosis, med SEs (ARF, HTN, high BSL), hemorrhage
- >1/52: rejection, sepsis, biliary leak or strictures
- Late: EBV, lymphoproliferative disease (B-cell proliferation), infection, immunosuppression side effects, strictures/thrombosis, disease recurrence (tumour, HBV), new autoimmune hepatitis
- 75% survival at 10 years
174
What does the failure of INR to normalise after a Vit K dose indicate?
Liver failure
175
What changes do you see with albumin in liver disease?
- Has a long half life, therefore no change in acute
| - If <35 in CLD then decompensated liver failure
176
Is ALT or AST more liver-specific?
- ALT is more liver specific as only found in liver and muscle
- AST found in liver, heart, muscle, kidney, pancreas, RBC
- Therefore if isolated AST or ALT rise then check CK to rule out muscle pathology
177
AST:ALT ratio >4:1 suggests?
Wilson's disease
178
What is the difference between ALP and GGT?
- ALP found in liver, kidney, bone, placenta, intestine. Reflects biliary epithelial damage, Low ALP in zinc deficiency
- GGT found in biliary, liver, kidney, pancreas, brain, breast, intestine. Age-related, much high until 9m age. Most sensitive for hepatobiliary disease, but cannot differentiate between intra and extra-hepatic disease
179
What are the causes of acute pancreatitis?
- Structural (15%), idiopathic (25%), familial, trauma (23%), drugs (10%)
- DKA, hypercalcaemia, CF, medications, trauma, viral, gallstones, systemic illnesses
180
What are the symptoms and treatments for acute pancreatitis?
- Sudden onset abdo pain with raised amylase or lipase 3 x ULN
- Epigastric or back pain, N+V, fever, tachycardia, occ jaundice
- Tx: analgesia, IVF, pancreatic rest
- Enteral feeds better than TPN (decr morbidity and mortality)
- Antibiotics only if severe pancreatic necrosis
- Can use octreotide infusion to reduce pancreatic secretions
181
What are complications of pancreatitis?
Oedema, necrosis, abscess, shock, bacteraemia, renal failure, pleural effusions
182
Which factors increase the risk in pancreatitis?
Younger, raised WCC on admission, low calcium or albumin, inc urea
183
Describe chronic pancreatitis
- Acute pancreatitis progressing to end stage fibrosis
- Usually associated with CF, hereditary pancreatitis or idiopathic
- CF most important cause in children
- Faecal elastase <100 is suggestive of severe exocrine insufficiency
- X-ray/USS - calcifications in pancreas, likely chronic pancreatitis
- Tx: supportive, CREON replacement, management of diabetes
184
Which immunological mechanism is the major cause of the destruction of the small intestinal villous architecture in coeliac disease?
Activation of T lymphocytes
185
Describe the APC gene and its associations
- APC = adenomatous polyposis coli gene
- Tumour suppressor gene
- Mutations lead to polyposis syndromes
- FAP (polyps from age 16, 100% risk malignancy), hepatoblastoma (associated with FAP)
- Gardiner syndrome (AD, colonic polyps and osteomas, epidermal cysts, thyroid cancer)
- Turcot syndrome (AR, colonic polyps that become malignant, CNS tumours GBM and medullo)
186
What might you use a hydrogen breath test for?
- Lactose and fructose malabsorption (peak 2-4 hrs)
- Bacterial overgrowth (faster peak)
- Functional bowel disorders (eg IBS), fast transit time (faster peak)
- Difficult to perform in children, gold standard for overgrowth is culture of aspirates from small bowel
187
Describe calprotectin
- ESR/CRP of the gut
- Present in the cytoplasm of neutrophils, therefore increased in disorders where there are increased gut neutrophils
- Not degraded by intestinal enzymes or bacteria
- Good screening test, but non-specific
- Can be elevated with NSAIDs
188
Describe DIOS
- Distal intestinal obstruction syndrome
- GI manifestation of CF (uncommon < 10yrs age)
- 45% of patients have history of meconium ileus
- Cramping RLQ pain, palpable mass, reduced stool frequency
- More common with pancreatic insufficiency (despite adequate enzyme replacement)
- Tx: hydrate, laxatives, bowel washout, prokinetics
189
What are the GI manifestations of CF?
- Meconium ileus (10-15% pt with CF ; 80-90% pt with men ileus have CF)
- DIOS (15% PT CF) - RLQ pain, mass, constipation
- Pancreatic insufficiency (reduced faecal elastase)
- CFRD
- Rectal prolapse (20%)
- Increased risk of GI tract tumours
- Fibrosing colonopathy (strictures and fibrosis, inc risk with high dose CREON, needs surgical resection)
- CF associated liver disease with biliary cirrhosis and portal hypertension, HCC
190
Describe CF-associated liver disease
- Most common non respiratory cause of CF mortality
- Spectrum of disease: transaminitis to multilobular cirrhosis:
Hepatic steatosis (30-70%) ;Focal biliary cirrhosis (10-70%) --> multilobar biliary cirrhosis (5-10%)
- RFs: male, pancreatic insuff, a1aT heterozygosity, severe genotype
- Develops before puberty, slow progression, portal hypertension(secondary to biliary cirrhosis) - can cause further Resp compromise if ++HSM and ascites, need ADEK replacement
synthetic destruction is rare and late
median survival after onset cirrhosis 4.5years
- Can have liver transplant if good respiratory function
191
What are the causes of exocrine pancreatic insufficiency?
- Cystic fibrosis
- Shwachman-Diamond syndrome
- Pearson syndrome
- Johanson-Blizzard syndrome
192
How do you test for pancreatic insufficiency?
- Steatocrit/ 24 hour faecal fat
- Faecal elastase or chymotrypsin
- False +ve with diarrhoea (enzyme diluted by stool)
193
Describe Pearson syndrome
- Pancreatic insufficiency
- Pancreatic fibrosis
- Vacuolated erythropoietic precursors (microcytic anaemia and low platelets)
- No skeletal abnormalities (c.f. S-D syndrome)
194
Describe Shwachman-Diamond syndrome
- AR ; SBDS gene on Ch7
- Pancreatic insufficiency - agenesis of pancreatic acinar cells, replaced by fatty tissue
- Bone marrow dysfunction - neutropenia 98%, anaemia 40%, thrombocytopenia 30%, pancytopenia 20%
- Skeletal abnormalities - dysplasia, osteoporosis
195
Describe Johanson-Blizzard syndrome
- Pancreatic insufficiency
- Hypoplasia of nasal alae
- Devel delay, short stature, urogenital/anogenital malformation
196
SMOF vs omevagan
- SMOF = fish and other
| - Omegavan = only fish, used for IFALD
197
Management of IFALD?
- Early addition of SMOF (omega-3 fatty acids)
- Cycling of TPN
- Urso
- Advancement of enteral feeding
198
How does urso work?
The drug reduces cholesterol absorption and is used to dissolve (cholesterol) gallstones
199
What are GLP-2 analogues used for (e.g. teduglutide)?
- Increase villous height in short bowel syndrome patients and increase serum citrulline levels
- Reduces TPN requirements
200
Fructose malabsorption is due to errors in which transporters?
GLUT 2 and GLUT 5
201
Discuss calcineurin inhibitors
- Inhibit activation of T cells
| - Cyclosporine and tacrolimus
202
What is the mechanism of action and side effects of mycophenolate?
- Blocks purine synthesis, prevents proliferation of B and T cells
- Inhibits synthesis of guanine monophosphate nucleotides
- SEs: diarrhoea, cytopenia, N+V, thrombosis
203
How do sirolimus and everolimus work?
m-TOR inhibitors
204
How does azathioprine work?
Acts on cell cycle, impedes DNA synthesis, inhibits proliferation of cells esp. lymphocytes, down-regulation of immune response
205
What are massive hepatic haemangiomas associated with?
Hypothyroidism (cause increased inactivation of T3 and T4)
206
What GI issue can develop post Fontan procedure?
Protein losing enteropathy (? elevated central venous pressure, low vascular compliance, elevated serum hepatocyte growth factor)
207
What are the main causes of protein losing enteropathy?
- Lymphatic obstruction (lymphangiectasia, constrictive pericarditis)
- Mucosal erosion or ulceration (infection, inflamm)
- Epithelial cell dysfunction (congenital glycosylation defects)
- PLE is a symptom, not a disease. Need to treat underlying condition
208
Treatment of protein losing enteropathy
- Difficult to treat
- Low fat diet
- Oral budesonide (steroid)
- Octreotide (decr GI secretions)
209
Why would we test for citrulline levels?
- Marker of small bowel mass and function
- Amino acid produced by small bowel enterocytes
- Low citrulline = low functional enterocytes e.g. short-gut, villous atrophy
- Levels can be elevated in renal impairment
210
What gene is associated with A1AT deficiency?
Serpina1 gene
211
PiZZ phenotype of A1AT is associated with?
Liver disease
212
What are the side effects of tacrolimus?
Nephrotoxicity (better than cyclosporine), hypertension, low magnesium, neurotoxicity
213
What are the side effects of cyclosporine?
Renal impairment (worse than tac), gingival hypertrophy, hirsutism
214
Describe very early onset IBD
- Often significant perianal disease. <6y/o
- Disorders of regulatory T cell and IL10 functioning
- BMT curative for some (not all)
- Increasing incidence
- Often present with different phenotype and more severe disease
- High incidence monogenic causes - CGD, Wiskott Aldrich, hyper IgM, agammaglobulinemia
215
What is A.lumbricoides?
Most common worm infection
216
What is the treatment of worms?
Albendazole, mebendazole
217
Describe IPEX syndrome
- Immunodysregulation polyendocrinopathy enteropathy X-linked syndrome
- Early onset T1DM
- Severe watery diarrhoea (+FTT) 1st week life
- Dermatitis/ erythroderma
- Hypothyroidism
- Allergies
- Cytopenias
- Mutations in FOXP3 gene, abnormal activation of effector T cells
- Inc immunoglobulins and IgE
- Die before age 2 if untreated
- HSCT only curative option
218
What is the risk of IBD if a first degree relative have IBD?
8-10% (30% in identical twins)
219
What is the contribution of smoking in IBD?
- Increased risk of CD
| - Decreased risk of UC
220
What are the orofacial manifestations of IBD?
Aphthous ulcers, angular cheilitis, cobblestoning mucosa (CD)
221
What are the skin manifestations of IBD?
Erythema nodosum (symmetrical, mirrors bowel activity)
Pyoderma gangrenosum
Cutaneous crohn's - indurated, swollen skin
222
Joint involvement in IBD?
- Type 1 - asymmetrical large jointm mirrors disease activity
- Type 2 - polyarticular, small joints independent of gut disease
- Axial arthropathy e.g. ankylosing spondylitis or sacroiliac joint arthritis, independent of gut disease
223
Describe TPMT deficiency
- 10% heterozygous, 0.3% homozygous
- Leads to shunting and increased 6TGN which causes increased bone marrow suppression
- Reduce azathioprine dose by 50% if hetero, avoid if homozygous
224
Side effects of azathioprine?
- Bone marrow suppresion (assoc increased 6TGN ; risk with TPMT deficiency)
- Liver toxicity (Assoc with increased 6MMP)
- Pancreatitis
- Infection risk - EBV, VZV. Make sure immunised prior to starting
- Malignancy- 4 x inc risk lymphoma (however malignant potential of untreated IBD)
- Monitoring: FBC, LFTs weekly and then 3-monthly, 6TG level, 6MMP
Allopurinol (XO inhibitor) worsens toxic effects of Aza on BM suppression ; (XO important for inactivating 6Mp)
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What is the mechanism of action of methotrexate?
- Anti-folate and anti-metabolite
- Use in CD when thiopurine intolerance or unresponsiveness
- No data for use in UC
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Side effects of methotrexate?
- Nausea
- Liver toxicity
- Bone marrow suppression
- Infections
- Lung fibrosis
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Risk factors for coeliac disease
- 1st degree relative - 10%
- T1DM 8%
- T21 10%
- Autoimmune thyroid disease 7%
- Turners, Williams
- IgA deficiency
- Autoimmune liver disease 12%
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Describe neonatal haemochromatosis = gestational alloimmune liver disease
- Alloimmune liver disease, maternal antibodies to hepatocytes which cross placenta and damages liver in utero
- Elevated ferritin - inc iron on liver biopsy
- Systemically unwell with hypotension, coagulopathy, cytopenia
- Parotid/pancreas iron accumulation
- High recurrence rates in subsequent pregnancies - maternal IVIG from 20/40
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Acrodermatitis Enteropathica
Zinc deficiency from impaired absorption of zinc in the gut
Autosomal recessive
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Skin rash around mouth and perianal
Chronic diarrhoea when weaning breast milk
Reddish tint to hair
Alopecia
Superinfection with Canadia
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Note : serum zinc low in acute inflammation
White-cell zinc more accurate
Low ALP associated with zinc deficiency
Treat with oral zinc
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H Pylori
investigation
treatment
H.Pylori infection is common in childhood but most infected children are asymptomatic and do not require investigation or treatment.
Primary infection usually occurs early in childhood through the faecal- oral route. Once infected, spontaneous resolution is rare.
In adults and occasionally in children, H.pylori may cause gastric and duodenal ulcer disease and confers a minor malignancy risk. Functional abdominal pain is common in paediatrics and may co-exist with asymptomatic H.pylori carriage. Treatment of H.pylori carriage does not improve functional abdominal pain in children.
The carriage of H.pylori may reduce the incidence of autoimmune conditions later in life
Investigation and subsequent treatment should be limited to patients with a high level of suspicion of peptic ulcer disease.
1. Peptic ulcer disease typically causes left upper quadrant pain, alters with eating and may be nocturnal. Proton pump inhibition will reduce the symptoms and these will reoccur on cessation of treatment.
2. Patients with iron deficiency that responds to supplementation and then re-occurs on an iron replete diet may be referred for endoscopy if there is no other source of blood loss evident.
H.pylori should be diagnosed endoscopically with two biopsies for histology from the gastric fundus and body. A urease based test (i.e. CloTest) should be performed.
A biopsy for culture should be taken if there is any concern about antibiotic resistance.
Non-invasive testing (stool, blood, breath hydrogen) should not be used to diagnose H.pylori in children but may be used to document successful eradication.
In children without symptoms consistent with H.pylori, a positive blood or stool screening test for H.pylori does not require further investigation. A positive test is unlikely to be reassuring to patients and carers.
Treatment
Omeprazole + amoxicillin + clarithromycin for 14 days.
Second line treatment or penicillin allergy : Omeprazole + clarithromycin + metronidazole
At a minimum of four weeks after conclusion of triple therapy a stool or blood antigen test should be done.
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Portal hypertension causes
Pre-hepatic: Portal vein thrombosis
Hepatic: Idiopathic, cirrhosis
Post hepatic: Budd chiari, constrictive pericarditis, VOD
Varices, splenomegaly and hyperspenism, ascites, distended abdo veins
10% hepatopulmonary disease (hypoxia)
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Abdominal rotation in utero
Malrotation is incomplete rotation of the intestine during foetal development.
The gut starts as a straight tube from stomach to rectum. The mid bowel (distal duodenum to mid-transverse colon) begins to elongate and progressively protrudes into the umbilical cord until it lies totally outside the confines of the abdominal cavity. The bowel rotates around the superior mesenteric artery, which supplies blood to this section of gut, acts as an axis. The duodenojejunal loop begins superior to the SMA, and the cecocolic loop begins inferior to the SMA. Both rotate 270 degrees in a counter clockwise direction.
The duodenum and the colon that follows is directed to the left upper quadrant. The cecum subsequently rotates counterclockwise within the abdominal cavity and comes to lie in the right lower quadrant. The duodenum becomes fixed to the posterior abdominal wall before the colon is completely rotated. After rotation, the right and left colon and the mesenteric root become fixed to the posterior abdomen, providing support to the mesentery and the superior mesenteric artery, thus preventing twisting of the mesenteric root and kinking of the vascular supply.
Abdominal rotation and attachment are completed by 3 months of gestation.
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Fructose absorption via which mechanism
Fructose is a simple monosaccharide found in many plants, where it is often bonded to glucose to form the disaccharide sucrose.
Free fructose is absorbed directly by the intestine. When fructose is consumed in the form of sucrose, it is digested and then absorbed as free fructose.
As sucrose comes into contact with the membrane of the small intestine, the enzyme sucrase catalyses the cleavage of sucrose to yield one glucose unit and one fructose unit, which are then each absorbed.
After absorption, it enters the hepatic portal vein and is directed toward the liver.
Fructose absorption occurs on the mucosal membrane via facilitated transport involving GLUT5 transport proteins.
Fructose enters via Na+ independent facilitated diffusion - it enters the cell via GLUT5, and exits via GLUT2.
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Patients with crohns at risk of what type renal stone
calcium oxalate
If ileal disease, can't reabsorb bile
Fat malabsorption have unabsorbed LCFA which binds calcium in lumen (oxalate bound to calcium) ; oxalate absorbed in colon(patient with ileostomies don't get calcium oxalate stones - may get uric acid stones)
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Superior mesenteric artery syndrome
occurs when the duodenum) is compressed between two arteries (the aorta and the superior mesenteric artery). This compression causes partial or complete blockage of the duodenum.
SMAS typically is due to loss of the mesenteric fat pad (fatty tissue that surrounds the superior mesenteric artery). The most common cause is significant weight loss caused by medical disorders, psychological disorders, or surgery.
In younger patients, it most commonly occurs after corrective spinal surgery for scoliosis.
