Gastro Flashcards
1
Q
Faecal osmolar gap
A
= 310 (normal faecal omsolality, or use actual stool osm if known) - 2x (Faecal Na + K)
2
Q
Ix suggesting osmotic diarrhoea
A
Faecal osmolar gap >100
pH <5
Positive reducing substances
3
Q
Embryologically, when is the liver formed
A
4th week
4
Q
When does fetal biliary secretion start
A
12th week
5
Q
Carbohydrate metabolism in the late fetal/neonatal liver
A
Fetal glycogen stores accumulate rapidly near term
Immediately post birth infant is dependent on hepatic glycogenolysis and gluconeogenesis to maintain BSLs (milk high fat low carb)
Stores of hepatic glycogen deplete, reaccumulate by week 2
6
Q
Dominant fetal protein
A
aFP- synthesis of albumin increases in inverse from 7th/8th week gestation
7
Q
Which enzyme is low in the neonatal liver, contributing to jaundice
A
Uridine diphosphate glucoronosyltransferase - develops rapidly after birth regardless of gestational age
8
Q
Why are neonates particularly prone to TPN associated liver disease
A
Immaturity of the liver- reduced bile salt pool, hepatic glutathione depletion, deficient sulfation = production of toxic bile acids and cholestasis
Deficiencies of essential amino acids and excess lipid in TPN = hepatic steatosis
9
Q
Criteria for cyclical vomiting syndrome (5)
A
All of:
- 5 attacks in any interval, or 3 attacks in 6 months
- Recurrent episodes of nausea and vomiting lasting 1 hour to 10 days, occurring at least 1 week apart
- Stereotypical pattern and symptoms in the individual patient
- Return to baseline health between episodes
- Not attributed to another disorder
10
Q
Cyclical vomiting
- Age of onset
- Clinical features
- Associations
A
Onset 2-5 years old
Early morning or upon wakening
Prodrome similar to migraine
Assoc with epigastric pain, abdo pain, diarrhoea, fever
>80% have a first degree relative with migraine, may patients develop migraine in later life
11
Q
Normal infant stool volume
Diarrhoea stool volume
A
Normal infants 5mL/kg/day
Diarrhoea (infant) >10mL/kg/day
Diarrhoea (older children) >200g/24hrs
12
Q
Secretory diarrhoea
A
Examples: cholera, toxigenic E. coli, carcinoid, VIP, neuroblastoma, congenital chloride diarrhoea, C. diff, increased intraluminal bile salts
Watery stools with normal osmolality and stool ion gap <100
Diarrhoea persists during fasting
Stool WCC neg
13
Q
Osmotic diarrhoea
A
Examples: lactase deficiency, glucose-galactose malabsorption, laxative abuse
Watery stools, pH <5, osm gap >100, positive reducing substances, negative WCC
Stops with fasting
Positive breath hydrogen
14
Q
Diarrhoea due to increased motility
A
Eg. IBS, thyrotoxicosis
Loose-normal stool
Stimulated by gastrocolic reflex
15
Q
Diarrhoea due to bacterial overgrowth
A
Secondary to decreased motility
Loose-normal stool
16
Q
Diarrhoea secondary to decreased surface area
A
Combination osmotic and motility
Watery stool
Eg. Coeliac disease, short bowel syndrome, rotavirus
17
Q
Diarrhoea due to mucosal invasion
A
Blood and increased WCC in stool
Eg. salmonella, shigella, yersinia, campylobacter
18
Q
Causes of true constipation in neonate (3)
A
Hirschsprung
Intestinal pseudo-obstruction
Hypothyroidism
19
Q
Cleft lip associations vs cleft palate associations
A
Lip: Cranial facial anomalies
Palate: CNS anomalies
20
Q
Cleft palate sequelae
A
Recurrent OM
Malposition of the teeth
Hypernasal speech secondary to velopharyngeal dysfunction
21
Q
GORD onset/timing
A
Peaks at 4-5 months (2/3 babies), <5% by 12 months
22
Q
Barium swallow for Ix GORD
A
Used to exclude anatomical abnormalities eg. hiatal hernia
Can have false positives (test induces reflux) and false negatives (miss episodes) - neither sensitive nor specific for GORD
23
Q
pH study for Ix GORD
A
Need to correlate episodes of symptoms with pH readings
Will not detect non-acidic reflux, and will miss brief episodes
False positives if probe placed too low
Normal ranges: 4% pH <4 (older children), 6% infants
Need to stop PPI before test
24
Q
Endoscopy to Ix GORD
A
Only used if there is concern about reflux oesophagitis (eg. severe dyspepsia, unexplained anaemia, concern about strictures)
25
Intraluminal impedance to Ix GORD
Combination of pH probe and impedance electrodes- will detect acidic and non-acidic reflux
26
Eosinophillic oesophagitis
- Link with atopy
- Sex
- Diagnosis
- Scope findings
- Pathophysiology
>20% patients not atopic, >25% no FHx atopy
3:1 males
Mean age dx 7
Diagnosis: isolated (not rest of GI tract) osephageal eosinphilia >15/hpf
Linear furrows, white spots, trachealisation
Hypersensitivity reaction- combined immediate (Mast cells) and delayed (T cell)
Inhaled and ingested allergens
Can have elevated IgE and eosinophilia peripherally
27
Eosinphillic oesophagitis
- Treatment
- Prognosis
Can be responsive to PPI (PPI have antieosinophil effects)
Remove allergic stimulus- cow's milk in infants, 4 ot 6 food elimination diet in older children
Trial elemental formula (neoncate, elecare) for 6-8 weeks then reassess - if improvement can trial reintroduction
Topical steroids, short term systemic steroids
Very little evidence of leukotriene receptor antagonsit, monoclonal Ab
Chronic relapsing remitting condition
28
FPIES
T cell mediated hypersensitivity
>90% have negative SPT and RAST at diagnosis (positive predicts a protracted course)
Symptoms 1-3 hours post ingestion
Usually anaemia, neutrophilia, thrombocytosis and hypoalbuminaemia at time of diagnosis
Cow's milk FPIES have 60-90% resolution by 3 years
29
Wilson's disease
- Genetics
- Ix
```
AR- mutation in ATP7B gene
Most people are compound heterozygous
Ix
- Low caeruloplasmin
- Serum copper non-specific
- Elevated urinary copper (very high- can be slightly elevated in other forms of chronic liver disease)- higher post penecillamine challenge
- high AST:ALT 4:1
- Low ALP
- Elevated liver copper on biopsy
```
30
Wilsons disease clinical features
Usual onset adolescence, >6 years
KF rings- older children who have had the disease longer
Initial Sx ADHD, behavioural deterioration
31
Wilsons disease Mx
Penicillamine challenge, liver biopsy
Penicillamine is the firts line choice for chelation- causes B6 deficiency and parasthesias
Trientene is second line
Zinc can be used in mild cases eg. pre-symptomatic siblings (competes with a displaces copper)
Screen siblings with genetic studies
32
Alagille syndrome
| - Genetics
AD- JAG1, NOTCH2 <10%
33
Alagille syndrome
- Major features (5)
- Minor features (8)
R sided cardiac lesion 60-100% (peripheral pulmonary stenosis MC, ToF, PDA, septal defects)
Embryotoxon (thickened and centrally displaced anterior border ring of Schwalbe)
Vertebral anomalies - butterfly and hemi-vertebrae
Facial features 75% -Deep set eyes, broad forehead, prominent chin (stuck on)
Cholestasis with paucity of bile ducts (can look like biliary atresia on biopsy initially)
```
Short stature, FTT, IUGR
Delayed puberty
High pitched voice
Renal anomalies eg. renal dysplasia, RTA
Short radii
Hypercholesterolaemia
Vascular anomalies esp intracranial
```
34
A1AT deficiency
| - Genetics
AR- SERPINA1 gene mutation
Most common allele of the protease inhibitor (Pi) system is M, Z predisposes to clinical deficiency
- Normal phenotype PiMM
- Liver disease PiZZ
- PiZ-, PiSZ, PiZI = predisposition to liver disease eg. NASH, rapid progression with Hep C
35
A1AT clinical features
Liver disease- can manifest of neonatal cholestasis or later-onset childhood cirrhosis
Jaundice, acholic stools and hepatomegaly present from 1st week - jaundice clears by month 2-4
Can have complete resolution, persistent liver disease or develop cirrhosis
Lung disease in 3rd or 4th decade
36
Hepatic hemangioma
MC benign liver tumour in childhood
Often assoc with hypothyroidism - receptors on tumour inactivates T4, resolved with tumour involution
Can have skin hemangiomas
Complications- high output cardiac failure, consumptive coagulopathy
37
Acute liver failure
MC cause non A-E hepatitis (seronegative viral infection)
| INR best indicator of need for transplant
38
Biliary atresia workup
US to exclude other anatomical issues eg. choledochal cyst (normal does not exclude BA)- gallbladder may be absent or small, triangular cord sign
Isotope excretion scan eg. HIDA- sensitive but not specific for BA
Liver biopsy- if suggestive of BA continue on to intra-op cholagiogram +/- Kasai (much higher success rate of performed in first 8 weeks of life)
39
Heterotaxy
Biliary atresia, abdominal situs inversus, polysplenia (functional asplenia), portal vein anomalies, intestinal malformation, congenital heart disease
40
Primary sclerosing cholangitis
```
High AST/ALT, high IgG, positive autoantibodies and inflammation on liver biopsy
Type 1: ANA/SMA positive
Type 2: LKM positive
Rare type: SLA positive
Dx by MRCP
Assoc with UC
```
41
Disaccharides (3)
```
Sucrose = Glucose + fructose
Lactose = Glucose + galactose
Maltose = glucose + glucose
```
42
Monosaccharides (3)
Glucose, galactose, fructose
43
Primary adult-type hypolactasia
Physiological decline in lactase after weaning - after age 3
| 15% white, 40% asian, 85% black
44
Secondary lactose intolerance
Following small bowel mucosal damage eg. coeliac disease, rotavirus
Transient, improves with mucosal healing
45
Fructose malabsorption
Children with diet high in fructose (eg. juice, corn syrup) can present with diarrhoea, abdo distension, slow weight gain
Due to abundance of GLUT-5 transporters on the brush border membrane (5% of the population)
46
Glucose-galactose malabsorption
Na/glucose cotransporter gene- SGLT-1
Usually AR
Presents with large volume watery diarrhoea following ingestion of glucose, breast milk or lactose-containing formulas
Initially can only have fructose, later in life limited amounts of glucose may be tolerated
Diarrhoea ceases once intake is ceased
47
Short gut syndrome- definition
Loss of >50% small or large bowel
| - Potential to wean TPN if >20cm bowel (>15cm if ileocaecal valve present)
48
Things absorbed in the duodenum and proximal jejunum (5)
```
Carbohydrates
Protein
Iron
Water-soluble vitamins eg. folate
CMP
```
49
Things absorbed in the distal ileum (2)
B12
| Bile salts
50
Things absorbed over the whole of the small intestine (2)
Mologlycerides and fatty acids
| MCTs
51
Things absorbed in the colon (2)
Water
| Electrolytes
52
Implications of resection of
- Jejunum
- Ileum
Jejunal resection better tolerated- ileum absorbs more Na and water, and can adapt to absorb other nutrients
Ileal resection- malabsorption and Na and water + malabsorption of bile salts causes further osmotic colon secretion of fluids and electrolytes = profound issues with fluid and electrolyte managemnt
53
Medications/dietary supplements used in short gut syndrome
PN
Trophic feeds with extensively hydrolysed and MCT-enriched formula/BM
Soluble fibre and antidiarrhoeals if large bowel output (although can increase risk of bacterial overgrowth)
Cholestyramine if distal ileal resection
Empirical treatment of batcerial overgrowth with metronidazole
54
Short gut syndrome complications (8)
TPN= line infection/thrombosis, hepatic cholestasis, cirrhoesis, gallstones
Obstruction
Infection
Bacterial overgrowth
Carbohydrate malabsorption
B12 deficiency- occurs 1-2 years after PN withdrawal
Renal stones secondaty to hyperoxaluria secondaty to steatorrhoea (Ca binds excess fat rather than oxalate)
Feeding colitis- bloody diarrhoea secondary to mild patchy colitis with progression of enteral feeds- Rx with hypoallergenic diet and mesalamine
55
Short gut syndrome prognosis
50% acheive enteral autonomy within 5 years fo resection
| May need intermittent TPN
56
Cryptosporidium
Leading protozoal cause of diarrhoea in children, esp immunocompromised
Obtained by ingestion of oocytes - person-person, animal-person, water
Incubation 2-14 days
Profuse, watery, nonbloody diarrhoea
Systemic features
Fever 30-50%
Self limiting 5-10 days if immunocompetent
57
Coeliac disease aetiology
Immune mediated systemic disorder elicited by gluten (or related prolamine from rye, barley, oats) in genetically susceptible individuals
Causative factors:
- HLA gene (COELIAC1), DQ2 in 90%, DQ8 in the remainder
- Non HLA genes COELIAC2-4
- Drugs eg. inteferon alfa
Monozygotic twins have 100% concordance
Risk factors:
- Frequent rotavirus = increased risk
- Delayed introduction of gluten, BF, early introduction of gluten = no change to risk in high risk individual
58
Coeliac disease pathophysiology
T cell mediated chronic inflammation
59
Coeliac disease clinical features
Intestinal symptoms (usually presents < 2 years of age)
- FTT, chronic diarrhoea, vomiting, abdo distension, muscle wasting, anorexia, irritability
- Constipation, rectal prolapse, intussusception
Extra-intestinal features
- Apthous stomatitis, anaemia unresponsive to iron replacement
- Rickets, OP, enamel hypoplasia of the teeth (Ca and vit D malabsorption)
- Muscular atrophy (malnutrition)
- Peripheral neuropathy, epilepsy, irritability, cerebral calcifications, cerebellar ataxia (thiamine/B12 deficiency)
- Short stature, late puberty, secondary hyperparathyroidism
- Dermatitis herpetiformis, alopecia areata, erythema nodosum (autoimmunity)
- Idiopathic pulmonary haemosiderosis
60
Risk factor to develop coeliac:
- 1st degree relative FHx
- Autoimmune thyroiditis, T1DM, autoimmune liver disease, autoimmune endocrinopathies, alopecia
- Down, William, Turner syndromes
- Selective IgA deficiency
61
Types of coeliac disease
Clinical coeliac disease
Silent coeliac disease- asymptomatic 1st degree relative with small bowel mucosal damage on biopsy
Potential coeliac disease- positive Abs without small bowel changes
Latent coeliac disease- prev gluten-dependent enteropathy with normal histology
62
Coeliac disease prognosis
Main cause of death is Non-Hodgkin Lymphoma
63
Diagnosis of coeliac disease
1. Screening with anti-TTG IgA + total IgA
- Negative with normal total IgA = coeliac disease unlikely
2a. TTG <10x upper limit => endoscopy with biopsy
2b. TTG >10x upper limit => HLA and EMA antibodies
- If positive diagnosis made
- If negative for biopsy
Asymptomatic patient at high risk- diagnosis is by biopsy
64
How much gluten per day is ok for coeliac disease
<20 ppm gluten = <50mg/day
65
Intestinal lymphangiectasia
Obstruction of the lymphatic drainage in the intestine- congential defect or secondary (eg. constrictive pericarditis, CCF, retroperiotneal fibrosis, abdominal TB, retroperitoneal malignancies)
Assoc: Noonan, Turner, Klippel-Treunaunay
Lymphopenia, hypoalbuminaemia, hypogammaglobulinaemia, oedema, elevated stool A1AT, steatorrhoea, chylous ascites
Scope: uniform symmetric thickening of the mucosal folds throughout the small intestine
Rx: low LCT, formula containing protein and MCTs, supplement low fat diet with MCT oil`
66
Congenital chloride diarrhoea
```
Polyhydramnios
Secretory watery diarrhoea
Metabolic alkalosis
Hypochloraemia and hyponatremia
Elevated stool chloride >90
```
67
Antibodies in coeliac disease
IgA more sensitive, only use IgG in IgA deficiency
TTG- sensitivity 93%, specificity 98%
EM- 99% specific, 70% sensitive
DPG (gliadin) less specific and sensitive
68
IBD onset + classification
MC onset preadolescent - young adult
Bimodal- 10-20 years and 50-80 years
Paediatric <17 years
Early onset <10 years- more likely to have colonic involvement
Infant/toddler onset < 2 years
Neonatal onset- more likely to be monogenetic
69
Risk factors for IBD (4)
Ethnicity- caucasian
FHx
- Both parents >35%
- 36% monozygotic twin concordance for CD, 16% UC
Syndromes- Turner, Hermasky-Pudlack, glycogen storage disease 1b, immunodeficiencies
Environmental- western diet, ABs at a young age, vaccination, smoking (CD)
70
Antibodies positive in IBD
p-ANCA 70% UC, <20% CD
| anti-saccharomyches cerevisiae 55% CD
71
Clinical features IBD rectal bleeding, diarrhoea, mucous, pus
Common UC
72
Clinical features IBD- abdo pain
Common CD
73
Clinical features IBD- abdo mass
Common in CD, not present in UC
74
Clinical features IBD- perianal disease
Common CD, rare UC
75
Clinical features IBD- pyoderma gangrenosum
Rare CD, present UC
76
Clinical features IBD- erythema nodosum
Common CD
77
Clinical features IBD- mouth ulceration
Common CD, rare UC
78
Clinical features IBD- Thrombosis
UC
79
Clinical features IBD- strictures, fissues, fistulas
Common CD, rare UC
80
Clinical features IBD- toxic megacolon
Present in UC, not in CD
81
Clinical features IBD- sclerosing cholangitis
Present in UC, less common CD
82
Clinical features IBD- cancer risk
Increased CD, greatly increased UC
83
Clinical features IBD- growth retardation
15-40% CD patients short stature at diagnosis, 90% overall
84
Associated features of IBD which correlate with severity of bowel disease (3)
Peripheral arthritis
Erythema nodosum
Anaemia
85
Associated features of IBD which do not correlate with severity of bowel disease (3)
Sclerosing cholangitis, ankylosing spondylitis, sacroilitiis
86
UC fulminant colitis
Fever, severe anaemia, hypoalbuminaemia, leucocytosis, >5 bloody stools per day
87
UC prognosis
After initial treatment, 5% will have prolonged remission (>3 years)
25% presenting with severe disease will require colectomy within 5 years
Risk of colon cancer begins to increased 8-10 years post diagnosis (no increased risk if proctitis alone)
88
AXR findings toxic megacolon
Colon >6cm
89
UC treatment
Proctitis alone: 5-ASA enema/supp
Mild-mod: sulfasalazine/mesalamine (5-ASA)- continue in remission. Alt extended release budesonide.
Mod-severe: Prednisolone (may req IV), surgery if unresponsive to IV, inflizimab
Frequent relapses: azathioprine or 6-MP (steroid sparing)
Meds to maintain remission: probiotics (also reduce pouchitis), 5-ASA
Surgery: colectomy with J-pouch
90
Side effects 5-ASA
Rash, fever, bloody diarrhoea (can be difficult to distingush side effects of 5-ASA from UC flare)
91
Side effects of infliximab in UC
Increased risk of infection and malignancy
92
Side effects of azathioprine in UC
Lymphoproliferative disorders
93
Complications of colectomy/J-pouch in UC
Pouchitis 30-40%
| Increased stool frequency once ileostomy reversed
94
Rx which have no evidence in UC
TPN
| Continuous enteral elemental nutrition
95
Endoscopy features CD
Skip lesions, transmural inflamamtion
96
Clincal manifestations CD
Obstruction - RLQ pain
Colonic inflammation- diarrhoea, bleeding, cramping
Systemic- fever, malaise, fatigue, growth delay, pubertal delay
Gastric/duodenal- epigastric pain and vomiting
Fistula formation- malabsorption, bacterial overgrowth
97
CD Rx
5-ASA- mild disease
Metronidazole- 1st line for perianal disease
Steroids- exacerbations (do not continue once well, steroids do not promote mucosal healing)
Azathioprine/6-MP
MTX- improves height velocity
Infliximab- induction and maintenance of remission and mucosal healing
Enteral nutritional therapy (as effective as steroids in improving Sx and better for mucosal healing)
98
No evidence for CD
Probiotics
99
Hirschsprung disease epidemiology
1:5000 live births, 4:1 males short segment, 2:1 males total colonic agangliosis
100
Risk factors for Hirschsprung disease
```
Familial (long segment)
T21
Joubert syndrome
Smith-Lemli-Opitz
Shah-Waardenburg syndrome
MEN2
Neurofibromatosis
Neuroblastoma
Congenital hypoventilation
```
101
Hirschsprung genetics
Usually sporadic- AR or AD
| Many genes involved including RET signalling pathway
102
Duodenal obstruction
```
Usually atresia
50% of patients prem
Associated with:
- Congenital heart disease 30%
- Malrotation 20-30%
- Annular pancreas 30%
- Renal abnormalities
- ToF
- Skeletal abnormalities
- Anorectal abnormalities
- 50% have chromosomal abnormalities eg. T21
- Polyhydramnios 50%
Double bubble on AXR
```
103
Pyloric stenosis
1-3/1000 babies
RF:
- White>Black>Asian
- Males esp first born 4-6x more likely than females
- Mother with PS- 20% of male offspring, 10% of female offspring
- B and O blood groups
- Erythromycin in first 14 days
- Female infants of mothers treated with macrolides
- Apert syndrome, Zellweger syndrome, T18, Smith-Lemli-Opitz, Cornelia de Lange
104
Meckel diverticulum
- MC congenital anomaly of GIT
- Caused by incomplete obliteration of the omphalomesenteric duct during 7th week gestation
- 3-6cm outpouching of the ileum, usually 50-75cm from the ileocaecal valve (2 inches, 2 feet)
- 2% of the population
- 2 types of ectopic tissue- pancreatic or gastric
- Generally present before the age of 2, 50% of all lower GI bleeds in <2 year olds
- 2x more common in females
- Acid-secreting mucosa causes intermittent painless rectal bleeding
- Can be frank or melaena
- Diverticulitis average age 8- similar to appendicitis
Meckel scan
- IV infusion of technetium-99m pertechnetate => ectopic gastric mucosa take this up
- False negative in anaemic patients
105
Functional abdominal pain types
Functional dyspepsia
IBS
Abdominal migraine
Functional abdominal pain syndrome
106
Functional dyspepsia
functional abdominal pain or discomfort in the upper abdomen
107
IBS- criteria
Functional abdominal pain associated with alteration in bowel movements
All of the following:
- Abdo pain/discomfort associated with 2 or more of the following at least 25% of the time:
• Improvement with defaecation
• Onset associated with a change in frequency of stool
• Onset associated with a change in form of stool
- No evidence of other pathology
Can have PR mucous
Low FODMAP diet may help
108
Abdominal migraine
Functional abdominal pain with features of migraine (paroxysmal abdo pain with anorexia, nausea, vomiting or pallor + FHX migraine)
109
Functional abdominal pain syndrome - criteria
Functional abdominal pain without the characteristics of functional dyspepsia, abdominal migraine or IBS
25% of the time have at least one of the following:
- Some loss of daily functioning
- Additional somatic Sx such as headache, limb pain or difficulty sleeping
110
Rome III criteria for childhood functional abdominal pain
All of:
o Episodic or continuous abdominal pain
o Insufficient criteria for other functional gastrointestinal disorders
o No evidence of an organic process that explains symptoms
111
Evidence for Rx in functional abdominal pain
CBT- beneficial
Acid suppression for dyspepsia
Low dose amitriptyline, anti-diarrhoeal and non-stimulating laxative for IBS (inconsistent)
Famotidine- inconclusive
Peppermint oil in IBS- likely to be beneficial
Lactobacillus- unlikely to be beneficial
Lactose-restricted diet or fibre supplements- no evidence
112
Achalasia
Incomplete relaxation of the lower oesophageal sphincter and lack of normal peristalsis
Clinical features- dysphagia, regurgitation, recurrent pneumonia, weight loss, chest discomfort
Autoimmune (Abs to auerback plexus)
Congenital (infancy or early childhood eg. Allgove syndrome - achalasia, alacrima, adrenal deficiency
Degenerative
Infection eg. Chagas disease
Barium fluroscopy- bird's beak
113
Oesophageal atresia/TOF
1/4000
90% blind upper oesophageal pouch with lower segment TOF
1/3 assoc with VACTERL
114
Pregestemil
MCT formula
115
Amino acid formulas
Elecare
Neocate
Alfamino
116
Extensively hydrolysed formulas
Alfare
Pepti Jnr
Allerpro
Novolac
117
Hep B antigens
HBsAg
HBcAg
HBeAg- marker of active viral replication, usually correlated with HBV DNA levels
118
Hep B serology
Infection:
HBsAg positive ~4 weeks after infection- coincides with onset of symptoms
HBeAg + HBV DNA positive ~4 weeks after exposure
Elevated ALT ~8 weeks after exposure, peak 12 weeks
Later anti-HBc IgM positive
Anti-HBs may be negative during acute infection
Recovered past infection:
Anti-HBs positive
Anti-HBc IgG positive
```
Chronic infection:
Anti-HBc IgG positive
HBsAg positive
Anti-HBs negative
Viral PCR may be negative or positive
```
Vaccination:
Only positive anti-HBs, negative anti-HBc
119
Hep A clinical features
Gastro-like illness +/- jaundice
Duration 1-2 weeks
Incubation period 3 weeks- viral shedding in faeces maximal just prior to onset of symptoms
ALF < 1%
120
Extrahepatic manifestations hep c
Small vessel vasculitis
Membranoproliferative glomerulonephritis
Nephrotic syndrome
121
Hep C treatment
Peginterferon, ribavirin (esp in genotype 2 or 3)
- Anaemia, neutropenia
Newer treatments available- lacking evidence in paediatric patients
122
Hep C treatment
Peginterferon, ribavirin (esp in genotype 2 or 3)
- Anaemia, neutropenia
Newer treatments available- lacking evidence in paediatric patients
123
Genetic disorders of UDP-glucoronulslytransferase + their clinical features
Crigler-Najjar type 1 and 2
Gilbert syndrome
Defect in UGT1A1 gene
Congenitally non-obstruction, nonhaemolytic unconjugated hyperbilirubinaemia
124
Gilbert syndrome
Common plymorphism- TA insertion in the promoter region of UGT1A1
Occurs after puberty
5-10% of caucasian population
Not associated with chronic liver disease
125
Crigler-Najjar syndrome type 1
AKA Glucuronyl transferase deficiency
AR- abolish UGT1A1 activity
Severe unconjugated hyperpilirubinaemia in the first 3 days of life
Kernicterus universal without treatment
Dx by liver biopsy/genetic studies
No response to phenobarbital treatment (there is a response in CNII)
Often need ongoing phototherapy through the early years of life
Cure- liver transplant
126
Crigler-Najjar II
AKA partial glucuronyl transferase deficiency
AR, missense mutaton UGT1A1 gene
Responds to phenobarbital
Jaundice in the first 3 days, persisting >3 weeks of age
Kernicterus is unusual
127
Crigler-Najjar II
AKA partial glucuronyl transferase deficiency
AR, missense mutaton UGT1A1 gene
Responds to phenobarbital
Jaundice in the first 3 days, persisting >3 weeks of age
Kernicterus is unusual
128
Portal hypertension definition
Portal pressure >10-12 mmHg
| normal ~7mmHg
129
Clinical features of portal HTN
MC- varices
Splenomegaly
Hepatopulmonary syndrome >10%- arterial oxygenation defect due to intrapulmonary microvadcular dilation from release of endogenous vasoactive molecules in to the circulation eg. NO
130
Treatment variceal bleeding
Fluid/blood resus
Vitamin K/FFP/platelets if port HTN is secondary to liver disease or other coagulopathy present
PPI infusion/H2-blocker infusion
Vasopressin infusion- increases splanchnic vascular tone and therefore decreases portal blood flow, alternatively octreotide
Endoscopic sclerosis or band ligation
131
Chronic treatment varices
B-blockers eg. propanolol- lowers cardiac output and portal perfusion
132
Chronic treatment varices
B-blockers eg. propanolol- lowers cardiac output and portal perfusion
133
Liver transplant complications
Primary graft failure
Hepatic artery thrombosis 5-10%- early vascular complication
Portal vein/hepatic vein strictures -later
Biliary strictures MC- 30% post liver transplant
Rejection usually occurs within 1st 2 weeks-3 months
- Abnormal LFTs
MC infections CMV and EBV
EBV induced post-transplant lymphoproliferative disease
134
Liver transplant complications (7)
Primary graft failure (rare in paediatric pop)
Hepatic artery thrombosis 5-10%- early vascular complication
Portal vein/hepatic vein strictures -later
Biliary strictures MC- 30% post liver transplant
Rejection usually occurs within 1st 2 weeks-3 months
- Abnormal LFTs
MC infections CMV and EBV
EBV induced post-transplant lymphoproliferative disease
135
Causes of acute pancreatitis
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Blunt abdominal injuries
Systemic diseases eg. HUS, IBD
Biliary stones
Drugs- valproate, L-aspariginase, 6-MP, azathioprine
Infection
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136
Acute pancreatitis pathology
Insult --> premature activation of trypsinogen to trypsin within the acinar cells --> trypsin actives other pancreative proenzymes --> autodigestion
137
Diagnosis of pancreatitis in children
2 of the following:
Abdominal pain
Serum amylase and/or lipase activity >3x upper limit normal
Imaging findings compatible with acute pancreatitis
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Genetic mutations leading to chronic/recurrent pancreatitis (4)
PRSS1- AD, recurrent attacks of pancreatitis
SPINK1- recurrent or chronic pancreatitis
CFTR- chronic pancreatitis from ductal obstruction
CTRC- recurrent pancreatitis
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GLUT transporters
SLC2A family
GLUT1- BBB + all cells
GLUT2- bidirectional transport of monosaccharides, renal tubular cells/liver cells/pancreatic b cells
GLUT3- neurons and placenta
GLUT4- adipose tissue, skeletal muscle, cardiac muscle
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Familial adenomatous polyposis
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MC genetic polyposis syndrome
APC gene mutation, 30% de novo
- Colonic polyps - late in the first decade, >= 5 at time of diagnosis
- Colon cancer 100% by 50 years
- GI adenomas (eg. stomach, duodenum)
- Hepatoblastoma (1.6% by age 5)
- Extraintestinal: desmoid tumors, epidermoid cysts, osteomas, fibromas, and lipomas
Related syndromes- Gardner, Turcot
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141
Sensitivity and specificity of 99m technetium scan
Sens 85%, spec 95%
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PFIC (progressive familial intrahepatic cholestasis)
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Defective secretion of bile acids
Type 1, 2, 3
1 and 2 associated with life0threatening cholestasis, but no elevation in GGT
Assoc with HCC
2 Rx by liver transplant (but can recur)
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Rx: urso, liver transplant
