Gastro Flashcards
1
Q
Sandifer syndrome - what is it and what is its presentation?
A
paroxysmal dystonic movement disorder occurring in association with gastro-oesophageal reflux, and, in some cases, hiatal hernia.
P/w food refusal and neck contortions/spasms/arching of back
Diagnosis: Improvement or disappearance of symptoms on a CMP-free diet adds substantial evidence to the diagnosis. If the reintroduction of CMP causes relapse of symptoms, the diagnosis seems established, because a challenge test is considered as the golden standard diagnostic test.
Also normal EEG
2
Q
What are reducing sugars? Provide examples (x4)
What about non-reducing sugars? 4x examples?
A
Reducing (FML-G)
Fructose
Maltose
Lactose
Glucose
Non-reducing (LMS-S)
Lactulose
Mannitol
Sorbitol
Sucrose
3
Q
How to calculate osmotic gap of stool?
How is this helpful?
A
Osmotic gap = subtracting the sum of the sodium and potassium concentration in stool multiplied by a factor of 2 from 290 mOsm/kg to account for unmeasured anions (ie, 290 - 2 ({Na+} + {K+})
- >100-125 mOsm/kg = osmotic diarrhea ie there is a low concentration of Na and K in the stool
- <50 mOsm/kg = secretory diarrhea ie there is a high concentration of Na and K in the stool driving the diarrhoea
4
Q
Perianal excoriation and gaseous abdominal distension - what does this indicate from a GI perspective?
A
CHO malabsorption
5
Q
Causes- Digital clubbing
A
3’Cs!
CF
Celiac disease
Chron’s disease
6
Q
What do you test before starting azathioprine?
A
TPMT - genotype that metabolises thiopurines (azathioprine)
- > 0.5% can’t metabolise it so should start it
- > 11% are poor metabolisers so need reduced dose
7
Q
Extraintestinal manifestations crohns
A
- Oral aphthous ulcers
- Peripheral arthritis = non-deforming
- Erythema nodosum
- Digital clubbing
- Episcleritis
- Renal stones (uric acid, oxalate)
- Gallstones
8
Q
Sucrase- isolmaltase deficiency
Inheritance?
Pathophys
Sx
Diagnosis
Treatment
A
- *Inheritance**
- Autosomal recessive disorder
- *Pathophys**
- Complete absence of sucrase and reduced maltase digestive activity
- Can’t break down sucrose (ie fruits) and maltose (ie grains) – disaccharides (Sucrose = glucose + fructose, maltose = 2 x glucose)
- Unable to hydrolyze specific carbohydrates, including sucrose, maltose, and starch, resulting in O_SMOTIC DIARRHOEA_
Sx
o Asymptomatic if diet contains only lactose (ie exclusively breastfed)
o Begin when the infant is exposed to sucrose or a glucose polymer diet
o This can occur with the ingestion of non-lactose based infant formula or on the introduction of pureed food, especially sweets and fruits.
o Diarrhoea, bloating, abdominal pain and poor growth are observed
Diagnosis
o Stool chromatogrpahy: positive for sucrose and isomaltase (note: these are NOT reducing substances -> reduing substances NEG)
o Hydrogen breath test positive after sucrose ingestion
o Direct enzyme assay of small bowel biopsy.
Treatment
o Dietary sucrose restriction
o Enzyme replacement with a purified yeast enzyme, sacrosidase (Sucraid), is a highly effective adjunct to dietary restriction.
9
Q
What tests would you perform to investigate the cause of fatty stool?
A
Stool Fat globules – impaired digestion (you cannot digest the globules so they pass right through into the poo)
ie Lipase deficiency (exocrine pancreatic dysfunction) or liver disease (reduced bile salts)
Stool Fat crystals – impaired absorption (capable of partial hydrolysis)
ie mucosal damage (coeliac disease, short bowel syndrome)
Fat soluble vitamins - Serum A, D, E, elevated prothrombin time/inr (marker of K)
10
Q
What does the α1-antitrypsin stool test help to identify?
A
o Useful screening test for protein-losing enteropathy.
o This serum protein has a molecular weight similar to albumin’s; however, unlike albumin it is resistant to digestion in the gastrointestinal (GI) tract. Excessive α1-antitrypsin excretion in the stool should prompt further investigations to identify the specific cause of gut or stomach (Menetrier disease) protein loss.
11
Q
What pathogen can mimic appendicitis?
- what are the sx of this and what is the underlying pathophys?
A
Yersinia Enterocolita (GNB) • Watery/bloody diarrhoea and fever resembling salmonella or shigella • Infection is sometimes followed with arthritis, erythema nodosum or reactive arthritis
Pathophys
• Usually acquired through undercooked pork or contaminated water, meat or milk.
• Mild-self-limiting enterocolitis or terminal ileitis
• Can cause pseudoappendicitis as in the terminal ileum it invades Peyer’s patches lymphadenopathy
12
Q
Fructose malabsorption VS heridary fructose intolerance
Causes
Presentatiom
Ix/treatment
A
MALABSORPTION
a. Caused by reduced abundance of GLUT-5 transporter on the surface of the intestinal brush border membrane, which occurs in 5% of the population
a. Children consuming a large quantity of juice rich in fructose, corn syrup or natural fructose can present with diarrhoea abdominal distension and slow weight gain
b. Restricting juice usually involves symptoms without need for investigation
c. Fructose H2 breath testing can help diagnosis
H.F. INTOLERANCE
- Metabolic condition caused by deficiency in fructose 1,6-bisphosphonatealdose (aldolase B)
- Rapid accumulation of frucose-1-phosphate in hepatocytes
- Presents w vomiting, lethargy, jaundice, hepatomeegaly, hypoglycaemia on introduction of frustose into diet (ie puree/fruit and veg etc)
- Definitive dx on liver bx -> enzyme analysis
- Mx - lifelong elimintation of fructose from diet
13
Q
How do Sucrase isomaltase deficiency and hereditary fructose intolerance differ?
A
Both due to enzyme deficiencies required for breakdown of product and present with abdo pain, bloating, chronic diarrhoea on introduction of solids/puree/fruit and veg
SID - chronic diarrhoea in toddlers
HFI - jaundice and hepatosplenomegaly with VOMITING and letahrgy; quicker onset presentation
14
Q
Glucose galactose malabsorption
What causes it
PResentation
Diagnostic ix
Treatment
A
Deficiency in intestinal sodium/glucose transporter – SGLT1 transporter (SLC5A1 gene)
Presentation
- Would expect to have malabsorption signs from day 1
- Severe life-threatening diarrhoea in neonatal period
- Symptoms (Diarrhoea nad malabsorption) with lactose and sucrose (made of glucose + galactose)
- Diarrhoea resolves when sugars eliminated, E.g. when giving water.
Diagnostic ix
- Metabolic acidosis and dehydration -> can lead to death
- Stool – osmotic, acidic, reducing substances present (CHO malabs)
- Glycosuria – same defect in kidney
- Positive glucose breath hydrogen test
- Normal intestinal biopsy
Treatment – fructose based formula and lifelong dietary restriction
15
Q
Short Bowel Syndrome
- Causes
- Complications
A
Loss of >50% bowel (often due to NEC/could be due to hirschsprungs) can result in symptoms of generalized malabsorption disorder or specific nutrient deficiency
Complications
- Watery diarrhoea
- Gastric hypersecretion
- Ulcers with frank bleeding
- Bacterial overgrowth. Occasionally → colitis
- Nutrient and vitamin deficiencies
- Enteric hyperoxaluiria (calcium binds to fat in setting of steatorrhoea)→kidney stones
- “feeding colitis”
- TPN complications (cholestatic liver disease secondary to TPN, catheter breakage and occlusion, central line sepsis)
16
Q
Hep B virus
What are the serological markers of active infection vs vaccination vs previous infection
A
- Vaccinated patients: Anti-HBs Ab positive (Hbs Ag NEG, no Hbc Ab)
- Previous infection: Anti-HBs Ab and anti-HBe Ab detected; anti-HBc IgG
- Active infection: HBs-Ag, HBe-Ag (indicates viral replication and infectivity), anti-Hbc IgM
17
Q
features of Alagile syndrome + inheritance pattern
pathophys?
A
Autosomal dominant inheritance; abnormal JAG-1 gene on chromosome 20p12
Characterised by paucity of interlobular bile ducts and the following features:
- Chronic cholestasis (91%) -> Prolonged conjugated jaundice
- Cardiac: _peripheral pulmonary stenosis (_85%)
- Butterfly vertebrae (87%)
- Posterior embrotoxon of eye (88%, req slit lamp)
- Renal: TIN
- Dysmorphic facies: broad nasal bridge, triangular facies, deep set eyes (95%)
- Fat malabsorption -> low Vit ADEK and Elevated cholesterol levels
18
Q
What is the enzyme that conjugates bilirubin in the liver and in what disorders does this process become disrupted?
A
Bilirubin-uridine diphosphoglucuronate glucuronosyltransferase (UDPGT).
Present w unconjugated jaundice due to defective conjugation enzyme
1) Gilbert syndrome - Polymorphism in UGT1A1 decreasing gene activity by 30%. Presents after puberty, with recurrent episodes of jaundice (in 4%) which may be triggered by, among other things, dehydration, fasting, intercurrent illness, menstruation and overexertion.
2) Crigler Najjar syndrome
Type 1: Complete absence of UDPGT. Severe unconjugated hyperbilirubinaemia in first 3 days of life with kernicterus (=death) and pale stools (low faecal urobilinogen). trace conj bilirubin in bile. Tx: ptx -> liver tx
Type 2: decreased UGT1A1 activity. Unconjugated hyperbilirubinemia usually occurs in the 1st 3 days of life; serum bilirubin concentrations can be in a range compatible with physiologic jaundice or can be at pathologic levels.
NOT assoc w kernicterus or pale stools.
Low conj bilirubin levels in bile.
tx: phenobarbital
19
Q
How does cows milk reduce iron absorption
A
- low iron content of CM, which makes it difficult for infants to obtain the amounts of iron needed for growth.
- occult intestinal blood loss associated with CM consumption during infancy, a condition that affects about 40% of otherwise healthy infants. Loss of iron in the form of blood diminishes with age and ceases after the age of 1 year.
- inhibition of non-heme iron absorption by calcium and casein, both of which are present in high amounts in CM.
20
Q
Gastrin
- Where is it released?
- What is its role?
- What stimulates its secretion?
A
Released from G cells in gastric antrum
ROLE
- Release of: gastric acid, pepsin, IF
- Gastric emptying
- Pancreatic bicarb secretion
Stimulated by
- vagal nerve stimulation (‘rest and digest’)
- gastric distension
- aa in stomach (ie food)
- gastric pH >1.5
21
Q
Where is pepsinogen secreted from and what is its role
A
Secreted from chief cells in stomach
Inactive; converted to active form, Pepsin, by stomach acid
22
Q
What is the role of pepsin
A
Formed from pepsinogen on activation by stomach acid
PROTEIN digestion - Breaks proteins into smaller peptides and aa
23
Q
what is the role of iF and where is it secreted frmo?
A
Secreted from parietal cels in stomach
Role is to bind to ingested B12, enabling the complex to later be absorbed in distal ileum
24
Q
What is pernicious anaemia
A
Megaloblastic anaemia secondary to malabsorption of vitamin B12 secondary to intrinsic factor deficiency
Causes
- Autoimmune gastris (affects fundus; anti-IF Ab or anti-parietal cell Ab)
- Coeliac disease (inflammation of ileum affects absorption of B12/IF complexes)
- Atrophic gastritis (prevention of secretion of IF)
25
Role of duodenum
Chemical digestion
A small amount of absorption
- \> fat soluble vitamins A/D/E/K
- \> Ca, Mg, PO4 (CMP)
- \> Iron, folate, thiamine, riboflavin, niacin
Brunners glands secrete bicarb -\> neutralise stomach acid
26
Role of pancreas
```
Exocrine organ (98%)
- production of enzymes, pro-enzymes (maltase, lipase, amylase, nuclease, trypsinogen, chymotrysinogen)
```
Endocrine organ
- production of hormones (insulin, glucagon, somatostatin)
27
Role of ileum
Function is FAT and VitB12 absorption
Fats - BILE SALTS and lipid/cholesterol
28
Role of jejunum
Absorption:
* carbs, protein, lipids
* H20
* water soluble vitamins (Vitamin B, C)
* zinc
Villi and microvilli form the 'brush border'
* enable passive transport of some carbohydrates
* active transport of amino acids, small peptides, vitamins, and most glucose
29
What is absorbed in stomach?
H20
Alchohol
30
What is function of the colon?
Absorption
- Water
- Na, Cl
- Short chain FA
Secretion
- Bicarb
- Mucous
- K
31
What is the enterohepatic circulation?
What increases/decreases this process?
Process whereby bile is made by liver -\> conjugated -\> stored in the gallbladder, and subsequently released into the small intestine, where they are deconjugated and then can be reabsorbed in terminal ileum via portal vein back into circulation and subsequently returned to the liver.
A small proportion (10-20%) of bile acids are NOT reabsorbed from ileum and are excreted in stool
**Increased by**
* PS stimulation
* Gastrin
* Secretin
**Decreased by**
* Symp stimulation
* Cholestyramine
32
What is the diagnosis and associated treatment?
9 month old boy was referred with a 2 months history of vomiting. 15 days ago before admitting to our hospital, he started to make bizarrre head and neck movements as told by his parents. The parents provided careful video recording of these movements. The most striking feature pronounced neck dystonia with repeated rotation of the neck and tilting of the head towards the left shoulder. These movements were observed during or just after the feeding. Sometimes upward deviation of the eyes and head nodding accompanied these movements. All of these movements stopped when he was asleep. The milestones of motor and mental development were normal. His physical and neurological examinations were normal.
The patient had undergone an extensive evaluation, including subspeciality consultations. Routine laboratory tests were normal. Orthopedic, otorhinolaryngologic and ophtal-mologic evaluations were also normal. Cranial and cervical magnetic resonance imaging was normal. The video electroencephalograms (EEG) of the patients which were taken during the routine, sleepless and paroxysmal behaviors were normal. Cow's milk specific IgE was negative and skin prick test was normal. He had a macroscopically negative upper gastro-intestinal endoscopy; but esophageal biopsy revealed reflux esophagitis, with no hiatal hernia. Esophageal pH monitoring for 24 hour confirmed gastroesophageal acid reflux.
Sandifers syndrome
- \> Rare pediatric manifestation of gastro-esophageal reflux (GER) disease characterized by abnormal and dystonic movements of the head, neck, eyes and trunk.
- \> Often assoc w CMPA
- \> Sx resolve with treatment of GORD and exclusion of CMP and reoccur with reintroduction of cows milk protein
33
Mx of GORD (and indications for mx)
Ix if failure to resolve with simple measures or if relfux is complicated (ie FTT, aspiration, haematemesis, recurrent chest infx, iron deficiency anaemia, neurological changes)
1. Nurse infants PRONE
2. Smaller, more frequent feeds
3. _Thickener_/thickened feed
4. Trial hydrolysed formulas/feed (_?CMPA_) - peptijunior, neocate
5. Drugs
- \> Antacid to neutralise stomach acid - Gaviscon
- \> H2 blocker (ranitidine)
- \> PPI - omeprazole
6. Surgery (fundoplication)
- Indications: no response to medical mgmt (at least 3 mo trial), neurological disease (aspiration risk), peptic strictures, Barrrets
34
stool ph\<5 = ?
Acidic stool has a pH level of less than 5.5.
This indicates **carbohydrate malabsorption**, even in the absence of reducing substances.
35
Stool +++ fat globules = ?
**Fat malabsorption**
Ex
* Coeliac
* Giardiasis
* Lymphangiectasia
* Abetalipoproteinaemia (specific fat malabsorption)
36
Stool faecal elastase LOW = ?
Pancreatic insufficiency (ex: CF or Shwachman-Diamond syndrome)
37
What is the screening test (and positive result) for protein losing enteropathy?
Stool alpha 1 antitrypsin HIGH
The presence of large serum proteins in the stool, such as a1 -antitrypsin, indicates leakage of serum protein and serves as a screening test for protein-losing enteropathy.
38
What is the dominant protein implicated in CMPI?
Casein majority; also whey
39
Pathophys and sx of CMPA
The significant cow's milk allergens belong to casein protein and whey proteins. Most individuals with cow's milk allergies have a sensitivity to both caseins and whey proteins.
A non-IgE mediated mechanism most frequently causes cow's milk allergy
* delayed reaction
* pruritis, erythema, _ATOPIC ECZEMA_
* _GORD, blood/mucus in stool_
* Abdo pain, diarrhoea or _constipation,_
* _FTT, pallor (fe def anaemia_
IgE mediated tends to last longer
* immediate reaction
* pruritis, erythema, _URTICARIA and ANGIOOEDEMA_
* v&d, abdo pain, nausea
* _resp sx_
* anaphylaxis
40
Prognosis for CMPA
50% of children recover by 1 year of age and most of rest by 2 years of age
Earlier tolerance of cmp in those children who are specific IgE negative (non-IgE mediated)
41
What is post gastroenteritis intolerance?
transient condition occurring after acute gastro resulting in persistent diarrhoea \> 14 days
Involves temporary intolerance to lactulose secondary to CMP sensitisation and villous damage -\> positive for reducing substances (clinitest) in stool but no glucose (clinistix)
Resolves after 2-3 d on lactose free diet
42
Presence of reducing substances in stool indicates what?
CARBOHYDRATE malabsorption
- Reducing substances are not normally present in urine and faeces. This test will detect the presence of reducing sugars, eg glucose, lactose, maltose, fructose and galactose.
43
Lactose intolerance
Sx
Causes
Stool Ix findings
Sx
* Explosive WATERY diarrhoea
* Abdo distension/bloating
* Flatulence
* Loud, audible bowel sounds
Causes
- Late-onset lactase deficiency (most common - 40% of 'orientals' have this, onset age 10-14)
- Secondary - Transient post-gastroenteritis, Coeliac, Chron's
- Primary lactase deficiency (extremely rare)
Ix
* Lactose hydrogen breath test +
* Acidic stool with presence of reducing substances and lactose; stool neg for glucose
44
Congenital lactose intolerance
Congenital lactase deficiency is a rare AR disorder that has been reported in only a few infants.
Affected newborn infants present with intractable diarrhea as soon as human milk or lactose-containing formula is introduced.
Ix - Small intestinal biopsies reveal normal histologic characteristics but low or completely absent lactase concentrations.
Prognosis - Unless this is recognized and treated quickly, the condition is life-threatening because of dehydration and electrolyte losses.
Treatment - is simply removal and substitution of lactose from the diet with a commercial lactose-free formula.
45
Sucrase isomaltase deficiency
Rare AR condition
Congenital deficiency of enzymes sucrase (sucrose) and isomaltase (isomaltase)
Sx - The usual presentation generally is at weaning from breast milk when infants are first exposed to the offending carbohydrates -\> get an watery/osmotic diarrhoea, bloating, FTT, hyperCa
Ix - can see sucrose and isomaltase in stool chromatography. NEG reducing sugars (as sucrose and isomaltase are not reducing sugars)
Sucrase and isomaltase deficiencies in enzyme assays
Hydrogen breath test POS after sucrose ingestion
Mx - dietary sucrose restriction
46
What are reducing sugars?
Glucose
Lactose
Maltose
Fructose
Galactose
47
Glucose-galactose malabsorption
AR congenital deficiency of glucose galactose TRANSPORT site (SGLT1 co-transporter)
Presentation - Severe diarrhoea and dehydration as early as the first day of life and can result in rapid death if lactose (milk sugar), sucrose (table sugar), glucose, and galactose are not removed from the diet.
Dx - stools are acidic (ph\<5) and + for reducing sugars
Mx - Fructose containing formula as fructose is the only sugar that can be handled
48
Coeliac disease
pathophys
genetic assocation
Diagnostic Ix
Mx
* Gliadin intolerance (part of gluten protein complex in wheat, barley, oats, rye)
* _T-cell mediated_ small bowel (jejunal) mucosal damage
* IFN gamma, cytotoxic T cells, fibroblasts and plasma cells which go on to produce more IgA and IgG Ab
Genetic association - 100% have HLA DQ2/DQ8
Ix
* Anti-TTG (tissue glutaminase Ab) and total IgA \*most specific\*
* Need to do total IgA level as 1/200 have low IgA therefore may produce false negs
* Anti-endomysial Ab (IgA) - 95% sensitivity and specificity
* deamidated gliadin peptide-IgG (DGP-IgG) - test if low IgA
* HLA DQ2, 8 - 100% positive in affected individuals however lots of false positives. Good screening test as if negative, unlikely to have coeliac disease.
* Jejunal biopsy is gold standard
* FBE - anaemia (iron and foalte def)
* Hypoalbuminaemia
Mx
- lifetime gluten free doet
49
1. Conditions and syndromes assoc w coeliac disease
2. Complications associated with coeliac disease down the track
Dermatitis herpetiformis (intensely itchy autoimmune blistering rash; all chidlren with this rash have coeliac disease)
IgA deficiency
Autoimmune disease - thyroid, Addisons, T1DM, Sjogren, alopecia etc
Syndromes
* T21
* Williams syndrome
* Turners syndrome
Down the track....
- Malignancy - NHL, T cell lymphoma, bowel carcinoma
- Osteoporosis
- Decr fertility
- Epilepsy w occipital calcifications
50
Biopsy findings of coeliac disease
Jejunum
- Partial to total villous atrophy
- Crypt hyperplasia/elongation
- Loss of brush border
- Incr intraepithelial lymphocytes
- Abnormal flattened epithelial cells
51
What is intestinal lymphangectasia
What is it?
Causes?
Clinical features
Ix
Mx
Dilatation of intestinal lymphatic vessels with leak of lymph (rich in protein, lipid, lymphocytes) into intestine and peritoneal cavity -\> results in **protein losing enteropathy**
Causes
- Congenital: noonans, turners, coeliac disease
- Acquired: obstruction from abdo or thoracic surgery, malrotation, malignancy etc
Presentation usually \<3yo
- diarrhoea steatthorea from fat malabsorption
- protein losing enteropathy (oedmea, lymphodema, effusions, chylous ascites)
Ix
- small bowel biopsy
- **elevated faecal alpha1 antitrpsin** (sec to protein losing enteropathy)
- hypoalbuminaemia, hypogammaglobulinaemia (low IgG, IgA and IgM levels or lymphocytopenia)
Mx
- High protein, **low LONG chain FA and high MED chain TGL die**t (ex - monogen formula if infant)
52
What condition features the following?
What is the underlying pathophys?
Whats the clinical progression
1. Severe isolated fat malabsorption from birth -\> featuring FTT, steatorrhoea, abdominal distension
**Abetalipoproteinaemia = Bassen Kornsweig syndrome (AR inherited)**
_Severe fat malabsorption_ *from birth* with progression to _neuropathy secondary to vitamin E deficiency_
Pathophys
* microsomal triglyceride transfer protein deficiency in small bowel -\> congenital fat malabsorption
Progression
* Progressive neuropathy from ~10years of age secondary to vitamin E deficiency
- ataxia
- loss of proprioception and vibration sense
- _peripheral neuropathy_
- _retinitis pigmentosa_
* May develop _RICKETS_ (reduced vit D, Ca absorption)
Leads to
* decr serum levels of cholesterol, triglycerides and vitamin A/D/E/K
* jejunal bx : fat accumulation in intestinal cells
* acanthocytes in blood (spikey red cells)
Mx
- Diet high in MCT
- Supplement w fat soluble vitamins (A, D, E, K)
53
Shwachman-Diamond Syndrome
Inheritance
Key features
Mx
Prognosis/main future risk
Inherited AR condition (mutation SBDS gene on chrom 7q11)
Features
1. **Pancreatic exocrine insufficiency** -\> fat malabsorption from birth
2. **Bone marrow failure** -\> (pancytopaenia) -\> thrombocytopaenia, anaemia and _cyclical neutropaenia_**.** HIGH HbF
3. **Skeletal abnormalities** - _short stature_, metaphyseal dysostosis, faltering growth, dental abnormalities and poor oral health
Mx
- pancreatic enzyme replacement tx
- steroids or androgens
+/- GCSF (stim bone marrow -\> neuts)
+/- HSCT
Prognosis
- Incr risk of MDS and leukaemic transformation
- Ave survival is 35years
54
1. Pancreatic exocrine insufficiency -\> fat malabsorption from birth
2. Bone marrow failure -\> thrombocytopaenia, anaemia and cyclical neutropaenia. HIGH HbF
3. Skeletal abnormalities -
= What condition?
Shwachman-Diamond Syndrome
55
Osmotic diarrhoea vs secretory diarrhoea
- distinguishing features
Osmotic (Driven by high osmotic load = intraluminal contents)
- Osmotic gap \> 125mOsml/kg
- Stops when feeding discontinued
- _Reducing substances present_ in stool
- Reduced stool electrolytes (na low)
Secretory (driven by active Cl secretion)
- Osmotic gap \<50
- Continues when feeding discontinued
- Very watery, severe diarrhoea
- Incr stool electrolytes (Na high)
- NOT assoc w rectal bleeding
56
Causes of osmotic diarrhoea
- Lactase deficiency/primary lactose intolerance
- Disaccharidase enzyme deficiencies
- Infectious enteritis
- Maldigestion (Chrones, coeliac disease, short gut)
- Exocrine pancreatic insufficiency (Cystic fibrosis)
- Fatty acid/bile salt malabsorption
- Transport mechanism disorder (glucose-galactose malabsorption)
- Bacterial overgrowth
57
Causes of secretory diarrhoea
Infx Gastroenteritis - Cholera, ETEC (toxigenic e coli)
Neural crest tumours/hormonal gut tumours (carcinoid, VIP)
Autoimmune enteropathy, microvillous inclusion
Congenital chloride diarrhoea
58
What is toddler's diarrhoea
what is it due to
Mx and prognosis
* Chronic diarrhoea up to 4-5 years of age with loose stools and incr freq (3-6x/day) but normal growth and examination
* IE is a diagnosis of exclusion (exclude malabsorption, CF, infection, coeliac, obstruction, neural crest tumours)
* Thought to be sec to decr gut transit time
* Mx - incr fat, decr fibre, decr juice -\> to incr gut transit time
* Normally spontaneously resolves w time
59
Red flags for chronic abdo pain
Pain localised away from umbilicus, waking child at night, radiating to back, legs, shoulders
Change in bowels
rectal bleeding or mucous
Dysuria
Unwell child - fevers, LOW, FTT
60
Indications for H pylori treatment in children
What is tx?
*\*Don't treat everyone with H pylori (common commensal in 25% in australia) as treatment course carries risk and also has been shown to der risk of atopy*
Indications for tx:
H pylori positive with:
1. PUD
2. First degree relative with gastric Ca (as H pylori chronic infection carries incr risk of ulceration, gastric carcinoma and gastric MALT lymphoma)
3. Refractory iron deficiency anaemia
Tx
- PPI, and 2 of :amoxicilin, clarythromycin and metronidazole
- Duration: 2 weeks
- Check 13C urea breath test after tx to ensure eradication (serology cannot confirm eradication)
61
Clinical features of peptic ulcers
Intermittent abdo pain, worse at night and soon after eating
Early satiety, fullness, bloating
Nausea, vomiting
Iron def anaemia
GI bleeding
62
What is main causes of ulcers in children?
What ix to confirm?
Mx?
H pylori
Ix
1. 13c urea breath test (as H pylori makes urease)
2. gastroscopy with biopsy -\> see gram negative spiral rods in surface layer of gastric antrum and erythematous lumpy/bumpy (Nodular) appearance of gastric mucosa
3. FBE, iron studies; may have assoc iron def anaemia
Mx
- H pylori eradication triple therapy: omeprazole + combination of 2 of amox, clarith or metronidazole
63
What part of bowel does crohn's typically affect
* Can affect any part from **mouth to anus** but _classically the ILEUM_ and spares the rectum
* '**Skip lesions**' - _patchy_ areas of inflammation w some normal areas of bowel inbtween (vs UC which is continuous)
* **Transmural** inflammation
64
Clinical features of Chron's disease
GI:
- Abdo pain (LRQ)
- Dairrhoea (bleeding not common)
- Anorexia
- Ulceration
- Abdo mass
- Perianal lesions - tags, abscess, fistulae, strictures
Extra-intestinal:
- Erythema nodosum
- Peripheral arthritis
- Apthous ulcers
- Clubbing
- Episcleritis
- _Renal stones (oxalate, urate)_
- _Gallstones_
- Cirrhosis
- uveitis, conjuctivities
- Fatty liver
- Cholangiocarcinoma
Systemic:
- FEver, malaise, LOW
- Growth retardation
- Nutritional deficiencies
- Anaemia
65
Clinical features of UC
GI
- diarrhoea w blood or mucous
- Abdo pain (LLQ)
Extra intestinal
- Pyoderma gangrenosum
- Ankylosing spondylitis
- Sclerosing cholangitis
- Chronic active hepatitis
- Cirrhosis
- uveitis, conjuctivities
- Fatty liver
- Cholangiocarcinoma
Systemic:
- Anaemia
- Growth retardation (malabsorption rare)
66
What is this condition?
Ulcerative colitis (UC)
* yellow arrow = lead pipe sign of the distal transverse colon (chronic UC)
* red arrow = thumbprinting of the proximal transverse colon (more acute sign, also present in Crohn disease)
67
Characteristic finding on barium swallow of crohns
Features on barium small bowel follow-through include:
* can affect anywhere from mouth to anus
* mucosal ulcers
* aphthous ulcers initially
* deep ulcers (\>3 mm depth)
* **longitudinal fissures**
* **transverse stripes**
* when severe leads to **cobblestone appearance**
* may lead to sinus tracts and fistulae
* widely separated loops of bowel due to fibrofatty proliferation (creeping fat) 2
* **thickened folds** due to oedema
* pseudodiverticula/pseudosacculation formation: due to contraction at the site of ulcer with ballooning of the opposite (usually antimesenteric) side
* **string sign: tubular narrowing due to spasm or stricture** depending on the chronicity
* partial obstruction
* on control films presence of gallstones, renal oxalate stones, and sacroiliac joint or lumbosacral spine changes should be sought
68
Histopth of Crohns lesions
Most common cause of IBD
Can affect whole GIT, mouth to anus
* Non caseating **granulomas**
* Transmural inflammation
* Patchy involvement
69
Indicaitons for surgery in chrons disease
1. Complications (more frequent than in UC) - Abscess, perforation, obstruction, bleeding
2. Disease unresponsive to medical tx -\> wide resection with R subtotal hemicolectomy
BUT _HIGH recurrence_ risk so **resection is NOT a cure.**
70
Management of Crohns disease
_Induction_
- **Enteral polymeric elemental diet** - 'Modulin IBD' oral/NGT for 8 weeks as initial tx
- OR Steroids - high dose IV or oral for 3-4 weeks then wean as tolerated
Maintenance
- Thiopurines (**Azathioprine** or 6MP) or **Methotrexate**
_For perianal disease or fistulae_
Induction with anti-TNF monoclonak Ab (infliximab)
+/- Metronidazole or ciprofloxacin as adjunct
OR Tacrolimus (calcineurin inhibitor) if above failed
7. Ca, vit D supps
+/- TPN
+/- Surgery
71
What part of bowel does UC typically affect
* Colon/Large intestine ONLY (Distal -\> prox large bowel classically)
* Startes with rectum, moves upwards
* Continuous (vs crohns which is patchy, skip lesions)
* Mucosa and submucosa ONLY (vs crohns which is transmural)
72
Significance of faecal calprotectin in diagnosis and monitoring of IBD
Is a Ca binding protein secreted by neutrophil
Is increased in infectious and inflammatory conditions (IBD, polyps, coeliac, NSAIDs) -\> therefore is NON-SPECIFIC
Has good negative predictive value in RULING OUT IBD (?functional abdo pain)
In the case of IBD, _levels correlate with endoscopic and histophatic severity of IBD (but not symptomatic severity)_
-\> can indicate activity level _(relapse) if level increasing_
73
Primary sclerosing cholangitis
What is the significance of this in IBD?
Diagonsis of PSC
Serum markers?
Tx
NOTE- PSC is a complication of UC \>\> Chrohns
-\> Incr risk of cholangiocarcinoma and colonic malignancy
Diagnosis of PSC req 2/3 of the following:
1. serum alkaline phosphatase _(ALP) \> 1.5x the upper limit of normal_ for longer than 6 months
2. _cholangiography_ demonstrating _biliary strictures or irregularity_ consistent with PSC
3. _liver biopsy_ consistent with PSC (if available)
Autoantibodies (non-specific): 80% have p-ANCA, 20-50% have ANA, anti-smooth muscle Ab and _anti mitocondrial Ab (AMA)_
Tx: trial of urso -\> transplant
Prognostic marker = anti-GP2 IgA (poor prognosis)
74
pANCA in UC vs CD
**70% positive in UC**
20% positive in CD
75
What is this a comlication of?
Toxic megacolon - complication of UC
* Radiololical diagnosis, colon width \>2.5 vertebrae
76
Classic histology findings of UC w biopsy
* Mucosal involvement only (rather than transmural in CD)
* Continous damage (rather than skip lesions in CD)
* Gland destruction
* Crypt abscesses
* Decr globlet cells
* Pseudo-polyps
* Friability
* Ulceration
77
Management of UC
1. Induce remission (at diagnosis or for
a subsequent flare)
- **First line is 5-aminosalicylic acid** (5-ASA) agents (sulfazalazine, mesalazine, olsalazine) - oral or topical enemas/suppositories
- Steroids
- Biologics (thiopurines -azathioprie, 6MP ; mtx)
2. Long-term maintenance of remission
- 5-ASA agents
- Thiopurines.
78
Prevention of coeliac disease
Delayed introduction of gluten does not help, neither does early introduction (same incidence)
79
Atypical presentations of coeliac disease
Vitamin D, E, K, b12, folate and iron deficiency
Refractory constipation
Dental enamel erosion
Abnormal liver enzymes
Peripheral neuropathy (related to B12 def)
80
Role of DQ2/8 typing in coeliac disease
Useful for screening family members
- if NEGATIVE, highly unlikely to develop or have coeliac disease
- if positive, not very useful (should have endoscopy if equivocal TTg or EMA)
81
What rash is associated with coeliac disease?
Dermatitis herpetiformis
-\> intensely itchy blisters filled with a watery fluid
82
How to assess gluten free diet compliance/whether tx is working in coeliac disease
anti-TTG Abs usually disappear on treatment after 6-12 months
_Titre of TTG correlates w degree of mucosal damage_
Note: exceptions are in type 1DM, CLD, psoriatic or rheumatoid arthritis, heart failure (get false + TTG)
83
Kwashiorkor vs marasmus malnutrition
Kwashiorkor:
* Insufficient PROTEIN intake +/- calories
* Thin hair, skin
* Soft pitting painless **oedema** usually involving _feet and legs_
Marasmus:
* CALORIE malnutrition
* 'wizened old man'; hungry, emanciated child
* Hypothermic, bradycardia, hypotensive -\> skin and bones, muscle atrophy and very little subcut fat
84
When would you expect reflux to be at its worst?
4 months of age (due to large feed vols relative to size and lying down most of the time) then should gradually improve over next 12-18mo
85
GOR mechanism
transient inappropriate relaxation of lower oesophageal sphincter
86
Adverse effects of PPIs
Incr risk of
- Acute gastroenteritis
- CAP
- Candida
- Interstitial nephritis
- Fundal Polyps
- Liver enzyme derangement
87
Duration of tx with PPI for GORD
4 week trial period to see if any benefit
takes 4 days to reach therapeutic levels
88
Eosinophilic oesopagitis
1% of oesphagitis
Atopy in 80%
Peripheral eosinophilia in 50%
Sx- dysphagia, vomiting, heart burn, abdo pain, food impaction, FTT
-\> failure to respond to PPI
Diagnosed on endoscope - lots of eosinophils on bx
```
Tx - Topical fluticasone/budesonide is effective (asthma puffer WITHOUT use of space; spray and swallow then brush teeth after and don't eat for 30min
Elimination diet (assoc food injury; often cow milk 60% efficacy)
Note- systemic steroid SE profile not ideal for use.
```
89
Eosinophilic oesopagitis
Sx
Diagnosis
Treatment
1% of oesphagitis
Atopy in 80%
Peripheral eosinophilia in 50%
Sx- poor feeding -\> vomiting -\> abdo pain -\> dysphagia -\> food impaction; FTT
-\> failure to respond to PPI
Diagnosed on endoscope - lots of eosinophils on bx
No diagnostic blood tests
```
Tx - Topical fluticasone/budesonide is effective (asthma puffer WITHOUT use of space; spray and swallow then brush teeth after and don't eat for 30min
Elimination diet (assoc food injury; often cow milk 60% efficacy)
10% respond to high dose PPI
Note- systemic steroid SE profile not ideal for use in kids.
```
90
Bleach ingestion (alkaline agent) management
Ingestion can cause full thickness burn
If symptomatic (drooling, dysphagia and abdo pain) - need urgent referral to surgeons
If asymptomatic - can give clear fluids and admit for observation
If clear history, need scope
Do NOT induce emesis (causes further oesophageal damage)
91
Pill induced oesophagitis
Commonly caused by doxy/tetracycline
NSAIDs, aspirin
Potassium
Due to local pill adherence to oesophageal wall (when tablets taken dry without water and get 'stuck')
92
What is h pylori and what is its pathophys?
Curved gram SPIRAL negative rod -\> found in gastric antrum
common precursor of gastritis and peptic ulcers
PAthophys: synthesise _urease_ which produces ammonia that damages the gastric mucosa. Ammonia also neutralises stomach acid which allows H pylori to live in the stomach
Virulence factor: Cytotoxin-assoc Gene A product (CAGA) -\> implicated in malignancy
Ulceration occurs 90% in duodenum
93
how is h pylori transmitted?
faecal oral route
94
Which form of IBD is assoc w strictures, fistulas and perianal disease?
Crohns (complications less common in UC)
95
Indications for surgery in crohn's vs UC
Crohn's - complications only (fistulas, strictures, perianal disease); high rate of disease recurrance and affects much larger portion of GIT
UC - for cure (disease refractory to medical mx); requires colonic resection
96
Mainstays of tx for IBD
* **Enteral** **polymeric** elemental diet (**crohns**)
* **5-asa** (**UC)**
* Steroids
* Azathioprine/Mtx
* Abx (**crohns** - metronidazole or cipro)
* Infliximab (Anti-TNF monoclonal Ab)
* Tacrolimus (anti calcineurin)
97
At what age does cancer surveillance begin in UC patients?
10 years of age
98
What GI condition does smoking protect you against?
Ulcerative colitis
(Note - smoking is a RF for crohns)
99
Chrons vs UC - major differences
**Crohns**
* Pain **LRQ**
* Bleeding not common during bowel movements
* **Mouth -\> anus**
* Inflammation in one or more **patches**, **skip-lesions**
* Colon has **cobblestone** appearance and thickened wall
* **Granulomas** often present
* **Transmural** inflammation
* only 20% p-anca +
* Complications more frequent
* Smoking can worsen condition
* **Polymeric enteral diet** first line
* Surgery only for complications (not curative)
* erythema nodosum, apthous ulcers, clubbing, episcleritis, renal stones (oxalate, uric acid), gallstones
**UC**
* Pain **_LLQ_**
* _**Bleeding** common_ during bowel movements
* Inflammation **colon only**
* **Continuous** inflammation, not patchy
* Colon wall thinned
* Granulomas not present
* Shallow ulcers **(mucosa, submucosa)**
* **70% + p-anca**
* Complications less frequent
* Smoking is protective
* **5-ASA** or 6MP first line
* Surgery/resection is curative (colectomy if unresponsive to medical tx or ongoing \>10yrs)
* cx: PSC, chronic hepatitis and cirrhosis, ank spondylitis, pyoderma gangrenosum
100
Azathioprine SE/adverse effects
MOA: inhibits purine synthesis (required for DNA and RNA synthesis).
SE
* Bone marrow suppression, hepatotoxicity, diarrhoea
* Pancreatitis
* Immune suppression
* Infection
* Malignancy
* Immune dysregulation
101
MOA infliximab
Indication in IBD
anti-TNF alpha monoclonal Ab
Used for crohn's disease, fistulating disease/resistance to other medical tx
102
which form of IBD is more common in children?
CD \> UC
103
What genetic mutation is liked to Crohn's disease and what does it place patients at increased risk of?
NOD2 (=CARD15)
Incr risk of:
* disease onset at younger age
* Stricturing phenotype
* Ileal disease
104
what condition is the mutation JAG1 assoc with?
Alagille syndrome
105
changes to gut microbiome in IBD
reduced bacterial biodiversity, incr bad bacteria ( e co) and candida
106
What is this condition?
Ulcerative colitis
* Continuous _without skip lesions_,or carpeting of the whole colon is classic for ulcerative colitis.
* Mucosal inflammation causes a _granular appearance_ to the surface of the bowel. As inflammation increases, the bowel wall and haustra thicken. Mucosal ulcers are undermined (button-shaped ulcers). When most of the mucosa has been lost, islands of mucosa remain giving it a pseudo-polyp appearance.
107
which form of IBD is primary sclerosing cholangitis associated with?
UC \>CD
108
porto criteria for IBD diagnosis
upper GI endoscopy
ileocolonoscopy
Small bowel imaging (MRI)
109
Granulomata on endoscopy favours a diagnosis of which form of IBD?
Crohns disease
- collections of histiocytes
110
What infective organism can mimic IBD presentation?
C diff - infection and colonisation is also higher in individuals with IBD
111
early onset IBD is assoc with mutations in which receptor?
IL10
112
What do u have to think about in a young BOY with newly diagnosed IBD
Very early onset IBD (\<6yo) is assoc w Chronic granulomatous disease (disorder of neutrophil function) - esp in boys
113
Rapid step up (biologics) in mgmt of IBD is indicated for?
Severe disease
Perianal disease
Fistulising disease
Steroid dependent disease
114
Induction of remission for chrohn disease
Exclusive enteral nutrition (for 6 - 8 weeks then gradual reintroduction of normal diet)
steroids if EN failed
If failed steroids and EN then consider infliximab early on
115
Inducing remission for UC
Steroids
If steroids failed, need biologics (cyclosporin, infliximab)
116
Toxic megacolon is assoc with which GI condition?
UC \>CD
C diff colitis
117
Kayser-Fleischer rings are a feature of what condition?
how do u diagnose this condition
what is the f**irst line treatment of choice**?
Wilson's disease
(but note- not always present in Wilson's disease and usually seen in children age 3 onwards)
gold standard diagnosis - liver bx with copper estimation
* Also: increased 24 hr urinary Cu extrection (even more elevated after pencillamine given)
* low serum caeruloplasmin
treatment -
* copper chelation tx (PO penicillamine)
* reduce dietary intake of copper
* liver transplant if fulminant liver disese
118
Copper studies in wilson disease
* *Urinary copper is high +**
* *Liver copper high** (gold standard)
serum copper - highly variable, low, high or normal
**Serum caeruloplasmin - LOW**
119
What liver enzyme changes are characteristic of Wilsons disease
AST:ALT ratio ~ 4:1
Low ALP
120
What is the most likely diagnosis for this condition?
Infant with conjugated bilirubinaemia
Ejection systolic murmur
family history of severe intracranial bleeding
Alagille syndrome
121
what is pruritis in jaundiced infants due to?
retained bile acids in skin
122
How is Alagille syndrome inherited?
Autosomal dominant
123
What is the typical cardiac lesion seen in alagille syndroem
Peripheral pulmonary stenosis
124
Typical liver histology/bx findings in Alagille syndrome.
What is a ddx?
Bile duct paucity
DDX - biliary atresia
125
Typical liver histology/bx findings in Alagille syndrome.
What is a ddx?
Bile duct paucity
DDX - biliary atresia
126
Alagille syndrome diagnostic features
Major
- R sided cardiac lesions (specifically peripheral pulmonary stenosis)
- embryotoxin
- vertebral anomalies (butterfly vertebrae most common)
- facial features ( triangular facies with broad, prominent forehead and small, pointed chin, hypertelorism, deep-set eyes)
- chronic cholestasis w paucity of bile ducts
Minor features
- short stature
- delayed puberty
- renal anomalies
- short radii
- high cholesterol
127
Infant with massive hepatomegaly - what are your top ddx?
Glycogen storage disorder
Liver tumour
128
what are the most common liver tumours in children (benign vs malignant, 1 each)
Benign - Hepatic haemangioma
Malignant
- Hepatoblastoma
129
What is the most common cause of acute liver failure in NZ and Australia?
other causes if acute liver failure?
Seronegative viral infection (ie no pathogen identified)
other causes
* seropos viral infections (HSV, enterovirus, echovirus, adenovirus)
* Hep B \> hep C
* drugs (paracetamol, Na valproate)
* haemochromatosis
* Wilson's disease
* metabolic
* galactosaeamia
* tyrosinaemia
* zellweger syndrome (peroxisomal)
* mitochondrial disorders
130
Indications for correcting INR in ALF
Transport stability
Procedure
Bleeding
131
what anomalies are associated with 50% of OA cases
CHARGE syndrome - colomba, heart, atresia choanae, restricted growth, genital, ear anomalies
VACTERAL association
Trisomy 18 or 21
132
what is the commonest form of OA?
Type C (84%) which is blind ending proximal oesophagus with trachea-(distal) oesophageal fistula
133
Drooling, resp distress, feeding problems and unable to pass NGT
PHx polyhydramnios
what is the diagnosis? What would CXR show?
Oesophageal atresia
CXR - NGT curled in upper pouch of OA
Diagnose with contrast study (NOTE water-soluble contrast as barium/gastrograffin is erosive)
+/- bronchoscopy/gastroscopy looking for fistula opening
Also need to consider echo, limb/spine X-rays, renal USS and thorough exam of anus and genitalia for associated anomalies (VACTERL, CHARGE)
134
when would delayed operative repair in OA be indicated?
Long-gap (wait 2-9mo)
or VLBW \<1500g)
135
What is the highest risk surgical complications post OA repair?
Oesophageal/anastamotic stricture formation (35%)
Leak or recurrence of fistula are next most common
136
Where does duodenal atresia/stenosis generally occur in duodenum
distal to ampulla of vater (outflow tract of pancreatic and bile duct)
137
Bilious vomiting in first 48-36 hrs of life following first feed
Progressive worsening
May be projectile
Abdo distension +/- absent bowel movements
Blood gas - hyperkalaemic, hyperchloraemic metabolic alkalosis or paradoxical acidosis (especially
What is this condition?
What ix would you do to confirm this?
Duodenal Atresia
```
Double bubble on AXR
Contrast study (helps to distinguish from midgut volvulus)
```
138
Cx post duodenal atresia repair (medical and surgical)
Anastamotic leak
Megaduodeum
Impaired duodenal motility
Cholecystitis
Pancreatitis
Eosophagitis, PUD, GORD
139
Gastroschisis
1. what is it?
2. diagnosis
3. Mgmt
Paraumbilical abdo wall defect
Evisceration of bowel NOT covered by membrane.
75% 'simple'
25% 'complex', associated w atresia/stenosis, perforation, necrosis, malrotation, volvulus
Antenatally diagnosed (20 week morph scan)
- elevate dAFP
- IUGR 60%
Deliver ~36weeks neonatal tertiary center
- \> NVD unless very large herniation/incl liver
- \> SFB
- \> place bowel in transparent bag
- \> NGT decompression
- \> surgical repair without compromising abdo organs
140
Bilious vomiting and abdo distension within first 1st month of life but CAN present older with recurrent reflux or episodic vomiting (often non-bilious) or abdo pain
What is the diagnosis and what investigations would you perform?
Malrotation (midgut volvulus)
30% present in the first month of life and 75% in the first 5 years of life
AXR may show proximal air in stomach and prox duodenum with no gas beyond that (double bubble) however CAN BE NORMAL
UGI contrast study is diagnostic
-\> bird beak appearance if complete obstruction, otherwise corkscrew/spiral appearance
141
Ladds procedure is used to treat what condition?
What is the pathophys of this condition?
**Intestinal malrotation +/- volvulus**
_Embryology_
Between the 4th to 8th weeks of development expansion of the GI tract causes the primary intestinal loop to buckle into the area of the yolk stalk.
As the primary intestinal loop buckles it *twists 90 degrees counterclockwise.*
The primary loop returns to the abdomen during the _8th to 10th week_ of gestation with an *additional 180 degrees counterclockwise rotation* _(TOTAL of 270-degree counter-clockwise rotation)_
The proximal portion of the bowel is fixed to the retroperitoneum early in gestation, at the _ligament of Treitz_, whereas fixation of the colon is gradual and usually completed near term.
**Pathophysiology**
Malrotation refers to *impaired rotational process of the midgut as it returns from outside* of the abdominal cavity (extracoelomic phase of development) to the abdominal cavity.
The impaired rotational process *could be non-rotation or partial rotation* and/or combination of both which results in abnormal fixation of the cecum to the right abdominal wall and obstruction of duodenum by bands of peritoneum called Ladd bands.
142
Hirschsprungs disease (HD)
Pathophys
Presentation
Daignosis
Mx
Pathophys
* failure of neural crest cells to migrate and form enteric nervous system
* aganglionic distal bowel (occurs from rectum upwards) - absence of PS ganglia =\> unopposed sympathetic acrivity and hypertonus of affected bowel segment
Main presenting sx is **delayed passage of meconium** (difficult in premature babies as delayed passage is normal)
+/- abdo distension, reduced stool output, vomiting, diarrhoea
- older kids: refractory constipation
- abdo distention and growth failure
Diagnosis
- rectal suction biopsy is definitive
- AXR may jsut show constipation
- fluoroscopy may show narrow aganglionic segment and dilated proximal segment
Mx is surgical:
- definitive repair (direct resection and anastamosis or endorectal pull through)
- ultra short segment: anal dilatation and partial sphincterotomy
143
A child with HD presents unwell with vomiting, explosive watery (+/- blood stained) diarrhoea and is febrile - what is the main concerning diagnosis and mgmt?
Hirschsprung's **Enterocolitis** - can be fatal
A high index of clinical suspicion is required to make the diagnosis. Abdominal x-ray is helpful and usually shows significantly dilated bowel loops and air-fluid levels.
HAEC is an emergency. Prompt treatment is required with IV antibiotics, (e.g metronidazole, gentamicin, amoxicillin) fluid resuscitation and surgical evaluation, which may include rectal washouts or an emergency colostomy.
144
What is the main gene associated with HD ?
What syndromes are assoc w HD?
Gene: RET oncogene (also implicated in MEN1A, MEN2A)
Syndromes assoc:
* Down syndrome (t21)
* Waardenburg syndrome (SNHL, depigmentation of hair, eyes, hidely set facial features)
* Biedl Bardet syndrome (obesity, atypical retinitis pigmentosa, mental deficiency, genital dystrophy, polydactylism and familial occurrence)
145
What prenatal markers are associated with anorectal malformations?
Intrapelvic or abdominal cysts
Hydronephrosis
Single kidney
Markers of VACTERL
146
Postnatal mgmt of anorectal malformations
IV fluids
Abx
NG decompression
Inspect perineum at 24 hrs (?mec on perineum vs urine vs no passage)
Surgical referral
Evaluate for assoc defects (cardiac, oa, renal, spinal and lumbar anomalies)
147
What inflammatory cell is implicated in Eosinophilic oesophagitis?
TH2 assoc inflammatory disease
IL 5 IL13
148
Pathogenesis of Eosinophilic eosophagitis
Eosinophilic dysmotility and histological eosinophilia
Pathogenesis
- disuption of mucosal barrier which allows presentation of Ag to T cells -\> inflammatory response by TH2 and IL 13. IL15 and eotaxin 3 in mucosal recruit eosinophils from bone marrow.
Eosinophils and mast cells secrete proteases, cytokines and histamine to promote inflammation and tissue remodelling.
149
EoE
What is it?
Presentation
Ix
Cx
Tx
Eosinophilic dysmotility and histological eosinophilia
```
Younger children (\<12yo): regurgitation and feed intolerance, vomiting.
Older children \>12yo: food obstruction, dysphagia, abdo pain
```
Ix
- Endoscopic assessment: rings, oedema, exudate, furrows, strictures
Treatment
- Food elimination diet (dairy and wheat initially, then can add egg and soy; 59% remission rate)
- PPI (resolution of sx w PPI alone in 1/3 of children)
- Steroids are first line for adults eg budesonide (not approved for children but some trials running/can be used off label -\> 67% remission with monotherapy)
- biologics are in trial (dupilumab)
150
What condition?
EoE
Scope features
- rings
- furrows
- exudates
- oedema
- strictures
151
Alpha 1 antitrypsin deficiency - what is the pathophys?
Genetics
* AD
* COmmon in Northern europeans
Pathophys
* Alpha 1 antitrypsin is a protease inhibitor that is made by the liver
* Usually helps to INACTIVATE the proteolytic enzymes release from dead bacteria/leuks in lungs and liver
* Deficency -\> accumulation of proteolytic enzymes -\> AUTOPHAGY (self-tissue destruction)
Clinical manifestations
* Childhood onset LIVER DISEASE
* Neonatal cholestasis and transient jaundice in first few months
* Hepatomegaly
* Childhood cirrhosis
* ADult onset LUNG DISEASE (Age 20-40)
* Emphysema
* Skin: angiooedema, cold-contact urticaria
152
Alpha 1 antirrypsin deficiency: **IX and MX**
**_Alpha antitrypsin phenotyping_** = Protease inhibitor phenotype (**PiZZ** = disease)
- \> note that *PiMM is normal* phenotype.
- \> **Homozygotes PIZZ** **(also PISZ)** is **grossly abnormal** and will develop **clinically significant liver disease**
* *-\> Pi-null** =NO AAT protein =\> no liver disease but SEVERE adult onset _emphysema_
- \> other variants (PIMZ, PISS, might give you an extra risk of liver disease, but won't cause it itself)
**_Low Alpha 1 antitrypsin serum levels_**
**_Liver biopsy_** should be diagnostic in children but not necessarily in neonates.
Mx
- liver transplant if severe liver disease
- lung disease: danazol (incr alpha1 antitrypsin), enzyme replacement therapy
153
Neonatal cholestasis +/- pale stools
Jaundice
What are the ddx?
THIS is CONJUGATED JAUNDICE - always pathological
**main ones to think about**
* **Alpha 1 antitrypsin deficiency**
* **Biliary atresia** (extraheptic duct obstruction)
* Alagille syndrome (intrahepatic duct paucity/hypoplasia -\> obstruction)
* Caroli disease (Intrahepatic duct dilation -\> obstruction)
* Metabolic disease
* CF
Differentiate between alpha 1 antitrypsin and biliary atresia via
* **Cholangiogram**
* Protease inhibitor phenotype
* alpha 1 antitrypsin serum level
154
Complications/chronic outcomes of alpha antitrypsin deficiency
25% Early liver failure
25% Cirrhosis -\> +/- HCC
50% clinically well with Chronic hepatitis
155
Management of alpha 1 antitrypsin deficiency
Liver
- supportive treatment for chronic liver disease
- Liver transplant if liver failure (also helps to prevent progression of lung disease)
156
How does alpha 1 antitrypsin deficiency present?
11% neonatal presentation:jaudnice, cholestasis +/- echoic stools (mimics biliary atresia)
- \> early liver failure
- \> cirrhosis
- \> chronic hepatitis
6-10% present with liver disease later in life (childhood)
- \> portal hypertension, hepatosplenomegaly
- \> chronic hepatitis
- \> cirrhosis
- \> HCC
157
Wilson's disease what is the responsible gene mutation, inheritance pattern and pathophys?
AR condition, gene is **ATP7B (**protein responsible for copper transport in hepatocytes and excretion via biliary system and also makes caeruloplasmin)
**Copper transport defect**
* Essentially Cu is unable to be incorperated to make caerolplasmin and cannot be excreted via biliary system
* Results in copper accumulation in liver cells which then spills out into circulation and into other organs (brain, kidneys, eye, kidneys, joints)
* Also have low caeroloplasmin levels
* Can result in multi-organ disease in school aged children
158
What do you investigate for diagnosis of Wilson's disease
Liver disease and any 2 of the following:
- Liver disease (LFTs)
* *- Reduced level of serum caeruloplasmin**
- Liver Bx -\> *Elevated liver copper* _(not specific)_
- Opthal review for Kayser-Fleischer rings
* *- Elevated 24 hours urinary copper excretion**
- Coombs negative haemolytic anaemia
159
Manifestations of Wilsons disease
Possible liver manifestations
**NOT IN NEONATES**. SCHOOL AGED CHILDREN (\>5yo) AND UP.
* **Chronic hepatitis in 40%** - note closely resembles autoimmune hepatitis
* Hepatosplenomegaly
* Liver failure
* Cirrhosis
* Portal HTN
* **Asymptomatic LFT abnormalities** (ensure you follow this up to ensure normalisation)
* Acute liver failure with associated **haemolytic anaemia** (in older children)
* CNS effect (\>10yo) - due to Cu deposition in basal ganglia
* Intention tremor
* Dysarthria
* Choreoathetosis
* Dystonia
* Behaviour change
* Deterioration in school performance
* Renal:
* Proximal RTA (Fanconi syndrome)
* Kayser-Fleisher rings - pathopnomonic
* HYPOparathyroidism
* Arthritis
Eyes - Kayser-Fleischer rings
Neurological - can get bradykinesia, rigidity, ataxia, tremor, dyskinesia, dysarthria (PD like presentation)
Pure psychiatric - psychosis. Or more subtle such as poor school performance.
160
Management of Wilson's disease
Cu chelator
- Trientine
- OR D-penicillamine
+/- Zinc acetate - reduces absorption of Cu in gut
+/- low Cu diet
+/- liver transplant (corrects the defect but comes with life long immunosuppression)
Genetic counselling/family screening (AR condition - there will be an asymptomatic carrier in the family)
161
NAFLD - pathophys
Fatty/unhealthy diet, sedentary lifestyle, genetics
- \> hyperinsulinaemia
- \> steatosis (ALT rise) -\> inflammation and fibrosis -\> irreversible cirrhosis
162
Presentation of NAFLD
RF for NAFLD
Isolated hepatomegaly, raised ALT/AST or chronic liver disease
RF
- obesity
- acanthusis nigricans - T1 or T2 DM (marker of insulin resistance)
- OSA
163
How to diagnose NAFLD
Is a diagnosis of exclusion!
So need to exclude alpha 1 antitrypsin deficiency and Wilsons disease
LFTs
Coags
Fasting BSL, insulin, cortison
Lipids
HBA1c
Liver US - will see fatty liver on US
Liver Bx (rarely)
164
Management of NAFLD
Weight loss #1 - resensitises insulin
Metformin - incr insulin sensitivity
Vitamin E - normalises ALT
Orlistat - lipase inhibitor; reduces fat absorption
Carnitine - normalises ALT
165
Liver failure in a neonate
- what diagnoses are most likely?
Metabolic
* galactosaemia (carb metabolism disorder)
* tyronsinaemia (aa metabolism disorder)
166
Recurrent encephalopathy with _hyperammoninaemia_
What differentials?
METABOLIC! Not liver aetiology.
Fatty acid oxidation disorders
Urea cycle defects
Organic academia and resp chain disorders
167
chronic cholestasis - differentials?
alpha 1 AT deficiency
Neonatal haemochromatosis
Metabolic stuff
- inborn errors of bile synthesis
- inborn errors of peroxisomal function
- congenital disorders of glycosylation
168
Hepatomegaly - what can cause this?
Liver
* Wilson disease
* Haemochromatosis
* Alpha1 antitrypsin deficiency
* infectious hepatitis
* autoimmune
* neoplasm
* primary liver (HB, HCC, haemangioma)
* secondary deposits - leukaemia, lymphoma, NB, LCH)
* Budd-chiari syndrome
Cardiac failure
Haem
* haemolysis - sickle cell, thalassaemia, hereditary spherocytosis
Metabolic
* Glycogen storage disorders (1, 3, 6)
* Lysosomal storage disorders
* Gaucher disease
* neimann pick disease
* wolman disease
169
Factors
170
Phases of digestion
Mostly occurs in SI due to large SA
1. Luminal phase: breakdown of protein, carbs and fats by digestive enzymes and bile
2. Mucosal digestion: hydrolysis of carbs and peptides by brush border enzymes
3. Mucosal absorption: transepithelial transport of broken down compounds into blood vessels via enterocytes
171
Causes of impaired digestion/absorption
Maldigestion
- enterokinase and trypsinogen deficiency
- deconjugation of bile salts
- motor and anatomical causes -\> stasis of contents
- bacterial overgrowth (decr luminal availability of substrates)
Mural causes
- impaired brush border integrity
- -\> lactose or sucrose isomaltase deficiency
- -\> Coeliac, IBD = damaged surface
Microbial causes
172
Where is iron absorbed?
Duodenum
173
Where is vitamin B12 absorbed?
Terminal ileum
174
Where are bile acids absorbed?
Terminal ileum
175
Where are electrolytes absorbed?
Colon
176
Where are fat soluble vitamins absorbed?
Terminal ileum
177
Where is mg absorbed?
Jejunum
178
Where are peptides absorbed?
Proximal SI (duodenum and jejunum)
179
Where is zinc absorbed?
causes of zinc deficiency
features of zinc deficiency
Absorbed in duodenum
Causes
* Inherited form - inability to absorb zinc from duodenum (develops when weaned from breast)
* Maternal zinc deficinecy in Breast fed infants
* Prolongued TPN in prem babies
* Malabsorption (CF)
Sx of acrodermatitis entropathica = zinc deficiency
* Well demarcated rash (face, flextures, perineum)
* Glossitis, stomatitis
* FTT/short stature
* Chronic diarrhoea
* Delayed wound healing
* Recurrent bacterial and candida infections
* Eyes - photophobia, conjunctivitis, blepharitis
180
Where is Mg absorbed?
Jejunum
181
Where are CHO absorbed?
Duodenum
182
Where are Ca and Ph absorbed?
Prox SI (duodenum and Jejunum)
183
Where are lipids absorbed?
Prox SI (jej and duodenum)
184
Sx of malabsorption
Diarrhoa
Steatorreat
Abdo pain
Iron deficiency
LOW
Malnutrition
185
Osmotic vs secretory diarrhoea
1. Stop feeding patient - if diarrhoea settles, it is OSMOTIC.
High stool volumes is suggestive of secretory diarrhoea.
2. Calculate stool osmotic gap: 290mosm/kg - 2(stool Na + K)
- \> Normal gap = 50-100
- \> High \>100 = osmotic diarrhoea (something in stool driving diarrhoea OTHER THAN K and Na)
- \> Low \<50 = secretory (hyper permeable digestive tract, losing electrolytes. have high stool volume of Na and K)
Note that both types of diarrhoea have normal stool osmolarity (290mOsm)
186
Causes osmotic diarrhoea
- Carbohydrate malabsorption (lactose or sucrose intolerance, lactase deficiency )
- coeliac disease (poor integrity of SI brush border)
- abx (altered microbiome reducing carb metabolism by bacteria)
- lactulose/osmotic laxative abuse
- short bowel syndrome
187
Causes of secretory diarrhoea
Infective
- Bacteria (cholera, ETEC, staph, salmonella, shigella)
- Rotavirus and HIV
- Parasites (cryptosporidium and giardia)
Drugs/hormones
- Carcinoid tumour (neuroblastoma VIP), gastronoma (zollinger-Ellison syndrome), HIV protease inhibitors and chemo agents
Congenital disease
Ileal resection
Inflammation (ex IBD or in response to pathogens ex C diffO
188
Alpha1 antitrypsin level - what does this indicate?
If elevated in stool , Used to diagnose protein losing enteropathy
SI pathology
189
Stool elastase - what does it indicate?
If low, can indicate fat malabsorption secondary to pancreatic insufficiency
190
Reducing substances in stool - what does this indicate?
CHO intolerance
191
Elevated fat globules in stools - what does it indicate?
Indicates fat malabsorption
192
Elevated fatty acid crystals in stools - what does it indicate?
Indicates that pancreas is intact as TGL have been digested to glycerol and FFA
193
What is dermatitis herptiformis associated with
Coeliac disease
194
What genes are associated with CD
HLADQ2 95% of patients with CD (2 copies of DQ2.5 have highest overall risk)
- note that not everyone with this gene will develop Coeliac disease
HLADQ8 only accounts for 5%
195
RF for developing coeliac disease
Relatives of patients with coeliac disease
Type 1 diabetes
IgA deficiency
Autoimmune thyroid disease (Graves, Hashimoto)
Downs syndrome
Turners syndrome
Williams Syndrome
196
Ix for coeliac disease
1. IgA anti-TTG Ab
- \> need to also order Total IgA (note - if this is low then you know that IgA anti-TTG Ab cannot be reliably interpreted, often under 2yo as immune system not fully developed yet)
2. igA endomysial Ab (EMA)
3. IgA and IgG deaminated gliadin peptide antibody
Note NOT anti-gliadin Ab
Note these tests rely on patients taking in enough gluten for at least 2 weeks prior to testing
4. HLADQ2/8 gene testing can be used to RULE OUT coeliac disease
5. Duodenal scope
197
What is the no biopsy approach to coeliac disease investigation?
Initially test _AntiTTG and total IgA_
If antiTTG \>10x ULN and repeat blood test is positive for EMA-Iga, then don't need a biopsy
198
Bacteria causing inflammatory diarrhoea/dyssentery
Shigella
ETEC, EHEC
Salmonella
C diff
Campylobacter
199
What is postenteritis syndrome? treatment
State of temporary villous atrophy secondary to mucosal injury
- Loss of brush border enzymes and zinc deficiency
Treatment: normal diet! TPN makes brush border atrophy worse
200
Bacteria causing non-inflammatory watery diarrhoea
Cholera
E coli
Staph aureus
Giardia
Rotavirus
Also clostridium perfringens and b cereus
201
Bacteria that cause enteric fever
Salmonella typhi
Yersinia enterocolitica
202
Mechanism of action of cholera toxin
The A subunit of the cholera toxin (has A and B subunits) activates the G protein stimulating 'adenylate cyclase' -\> produced cAMP -\> activates CFTR Cl channel -\> massive Cl secretion along with Na and K into intestinal lumen -\> get huge losses of Na, Cl and K in stool = secretory diarrhoea with low osmotic gap
203
SGLT1
Deficiency of this = ? condition
Sodium-dependent glucose transporter
Located in the small intestine and the epithelial cells of the kidney tubules of the nephron
deficiency of this = glucose-galactose malabsorption syndrome
204
What emerging evidence is there for tests for diagnosis of CD in patients already on gluten free diets?
T cells sensitised to HLA-DQ gluten tetramer
Flow cytometry -\> frequent of specific T cells to total CD4 T cell populations
CD patients on GFD-\> 97% sensitivity and 95% specificity
and for CD patients on gluten, 100% sensitivity and 90% specificity
205
infectious Causes of gastro
Bact
* staph
* Watery: ETEC, cholera
* Bloody: EIEC, EHEC, shigella, campylobacter, salmoenella, yersinia
Viral
* rotovirus (60% in \<2yr olds in winter)
* adenovirus
Protozoal
* giardia
* crytosporidium
206
MOA of ORS (oral rehydration solution)
contains glucose and Na
absorbed across even a damage mucosa via Na/glucose cotransporter (SGLT1 is an active pump)
Water follows via osmosis down concentration gradient
207
What electrolyte/blood gas changes might you see in SEVERE dehyration
Acidosis
HypoNa OR HyperNa (rare)
HypoK
HypoCa
Hypoglycaemia
208
What do you suspect in a patient with these + diarrhoea + LOW and iron deficiency?
Erythema nodosum
Feature of **Chron's disease**
209
What do you suspect in a patient with these + diarrhoea + LOW and iron deficiency?
pyoderma gangrenosum
= ulcerative colitis
210
What do you suspect in a patient with these + diarrhoea + LOW and iron deficiency?
Apthous ulcer
Feature of **chron's disease**
211
Causes of pancreatitis
Remember: 'I get smashed'
* I: idiopathic
* G: _gallstones_, genetic - _cystic fibrosis_
* E: ethanol (alcohol)
* T: trauma, _TPN_
* S: steroids
* M: mumps/measles, malignancy (and other _infections_: EBV, varicella, coxsackie)
* A: autoimmune
* S: scorpion stings/spider bites
* H: hyperlipidaemia/_hypercalcaemia/hyperparathyroidism_ (metabolic disorders)
* E: ERCP
* D: drugs (tetracyclines, furosemide, _asparaginase,_ _azathioprine_, _sodium valproate,_ thiazides and many others)
212
Blood findings in pancreatitis
Elevated serum lipase
Elevation in LFTs
Leukocytosis
Hyperglycaemia
HYPOCalcaemia (correlates w severity of disease)
USS- ?pancreatic abscess or pseudocyst req surgical drainage
213
Clinical signs of acute haemmhoragic pancreatitis
Grey turner sign - bruising to flanks
Cullen sign - bruising to periumbilical region (C around the belly button)
214
Causes of chronic pancreatitis
Hereditary
* PRSS1 (AD, 80% penetrance) - most common
* SPINK1
* CFTR
Cystic Fibrosis
Wilson's disease
Autoimmune pancreatitis
Metabolic disease
* isovaleric acidaemia
* cystinosis
* cystinuria
* hyperPTH
215
Familial adenomatous polyposis
Genetics
* AD
* **APC gene** mutation
features
* Onset \<10yo
* Pre-malignant **adenomatous colon polyps (need at least 100** for diagnosis) 100-1000 in distal bowel
* -\> colorectal cancer if undiagnosed/untreated
Mx
* Need annual colonoscopy after age 10
* Pan-colectomy in late teens or early 20s
216
What is the condition?
WHat is the gene mutation/inheritance pattern and what are the main features/risks/cx with this disease?
**Peutz-Jegher syndrome**
AD, 50% sporadic mutations
Mutation in **STK11** gene
1. **Melanocytic freckles**/pigmentation to **lips, gums** (often present before age 5, can fade w time)
2. **Benign Small bowel haematomatous polps** (rarely become cacnerous but do often present ages 6-18yo w SBO or intussception or iron def anaemia from bleeding)
3. Predisposition to malignant tumours
* GI (lifetime risk of 39 percent)
* Pancreatic
* Breast cancer
* Uterine, ovarian cancer
* Lung cancer
217
Carcinoid syndrome
What is it caused by?
Sx?
Diagnosis
Mx
* Secretion of METASTATIC (all have liver mets) neuroendocrine tumours secreting Serotonin (5-HT)
* often located in GIT
* Sx
* Facial flushing and telangiectasia
* Watery diarrhoea, abdo pain
* Bronchoconstriction
* CV:
* Diagnosis: elevated urine 5HIAA (5HT metabolite) and serum 5HT
* Mx: octreotide (inhibits release of gut hormones) and resection of primary tumour
218
Features of vitamin C defiency/scurvy
Caused by lack of fruit and vegetable intake (citrus
Involved in collagen intake
Sx
* swollen, bleeding gums
* easy bruising and bleeding
* delayed wound healing
* irritability
* muscle and joint weakness
219
PEllagra
what is it?
presentation?
= Niacin deficiency (from animal products - fish, meat, milk, eggs)
Features - 3 Ds
1. Dermatitis - erythema to sun exposed areas; red tongue, angular stomatitis
2. Dementia - depression, encephalopathy, psychosis
3. Diarrhoea (also constipation)
220
Causes and Presentation of vitamin A deficiency
**Sources** - milk, eggs, liver, green veg
**Causes**
* fat malabsorption
* liver disease (where fat soluble vitamins are stored)
* dietary deficiency is RARE
Symptpms
* Eyes: dry eyes/no tears, night blindness, photophobia, conjunctivities and 'bidot's spots' (see photo)
* Poor growth/FTT
* Dev delay
* Dry scaly skin
221
THiamine deficiency
* Sources
* Causes
* Symptoms
=Vitamin B1
Sources
* most foods esp legumes contain thiamine
Causes
* deficiency can develop _quickly (2-3 weeks)_
* dietary defiency (rice-only diet; alcoholics; BF babies to deficient mothers)
Symptoms = beriberi
* _Wet = cardiac_
* Dilated heart w cardiac failure and oedema
* tachycardia, tachypnoea, hepatomegaly
* QT prolongation
* _Dry = neuro_
* Lower limbs - loss of reflexes, loss of vibration, paraesthesias
* **Wernicke-korsakoff syndrome**
* _Eyes_: nystagmus, papilloedema, LR palsies, fixed pupils etc
* Ataxia/_cerebellar_ signs
* Confusion, irritability -\> _coma_
222
Definition of acute liver failure
1. Acute liver injury
2. Hepatic encephalopathy
3. Elevated prothrombin time/international normalized ratio (INR) - represents impaired synthetic function (vitK)
223
Cx/features of chronic liver disease
* Hepatomegaly/normal liver/small liver (cirrhosis=shrunken)
* Jaundice and pruritis (also for acute)
* Palmar erythema
* Spider nicae
* Clubbing
* Signs of portal HTN: caput medusae, varices, splenomegaly
* Ascites (hypoalbuminaemia)
* Hepatic encephalopathy: drowsiness, foetor herpaticus, hepatic flap
* Gynaecomastia, testicular atrophy
* Hepatorenal syndrome (2ndary renal impairment)
* Coagulation dysfunction from prolongued INR (decr vit K synthesis) -\> easy bleeding, bruising, purpura, telangiectasia etc
224
what causes hepatic encephalopathy?
Build up of ammonia levels -\> toxic to CNS -\> causes oedema nad neuronal death
This is beacuse ammonia is normally metabolised in liver to urea (krebs/urea cycle, occurs in hepatocytes) which is water soluble and can then be excreted in urine
225
What blood changes would you expect ot see in fulminant liver failure?
Coags: elevated PT/INR
LFTs: elevated
Low albumin
Elevated ammonia
Hypoglycaemia
UEC: Low K, low Na
Hyperbilirubinaemia
226
LFTs for intra vs extrahepatic jaundice
227
Long term effects of kernicteris
* SNHL
* learning difficulities
* CP (choreoathetoid)
228
Biliary Atresia
Progressive obliteration of all or part of extrahepatic bile ducts
Leads to chronic liver dailure and death
Presentation
* Prolongued jaundice and pale stools in neonatal period (25%)
* hepatosplenomegaly
* progressive liver disease
* can be associated with situs invertus
Diagnosis
* Liver biopsy is diagnostic
* TOBIDA radioisotope scan: absent excretion of isotope into intestine (but preserved uptake into liver)
Mx
* Kasai procedure
* liver transplant at later date
229
Cx of kasai procedure
* cholangitis
* fat malabsorption
* cirrhosis
* portal HTN
230
Features of vitamin E deficiency
* Peripheral neuropathy
* Cerebellar ataxia
231
Caroli Disease vs sydnrome
What is it
PResentation
AR condition
Disease: isolated congenital cystic dilation of hepatic ducts -\> obstruction
Syndrome: Also has congenital hepatic fibrosis and ARPCKD
PResentation
* Recurrent episodes of acute cholangitis and biliary lithiasis
* incr risk of cholangiocarcinoma
232
Dubin Johnson syndrome
Inheritance pattern
PAthophys
Presentation
AR condition
Pathophys: Impaired biliary excretion of bilirubin glucuronides
PResentation: usually asymptomatic
* Featuring mild CONJUATED hyperbilirubinaemia (benign condition)
* A darkly pigmented liver (found on autopsy) is due to polymerized epinephrine metabolites, not bilirubin
No treatment needed
233
Haemochromatosis
- What is it?
- Cause/genetics
- Clinical manigestations
- Ix
- Mx
Disease of excess IRON deposition and absorption due to hepcidin deficiency
* hepcidin is mater iron regulator; normally plays role in negative feedback when iron levels are high
* deficiency results in no inhibition of iron absorption or release from storage -\> excess iron which gets deposited in tissues
Genetics
* AD
* HFE gene mutation
Clinical manifestations
* Bronze skin
* Liver: fibrosis, cirrhosis, 30% risk of HCC
* Pancreas: IDDM
* Heart: cardiomyopathy, arrhythmias
* Endocrine: hypopituitarism, growth failure, hypothyroid, hypoparathyroid, testicular atrophy
* Also deposits in joints
Ix
* Elevated ferritin, iron
* Total (transferrin) iron binding capacity - saturated
* Liver and BM biopsy
Mx
* Iron chelation with **desferrioxamine**
* Venepuncture rarely done these days
234
What disease is associated with childhood use of aspirin?
Reye Syndrome
Associated with aspirin use, some viral infections (influenza B, varicella)
Usual age group: 4-12yo
* Acute encephalopathy
* Fatty degeneration of liver
High mortality (40%)
Presentation
* Viral prodrome (URTI or chicken pox)
* 4-7 days later: intially vomiting ++++
* Encephalopathy (lethargy -\> confusion, delirium -\> coma, seizures -\> death)
* Hepatomegaly (no jaundice or icterus)
* May be hyupoglycaemic
Ix
* Elevated ammonia
* Elevated AST, ALT
* Elevated LDH
* Elevated CK
* Elevated INR/PT - bleeding risk
* Hypoglycaemia
* CSF: normal analysis but raised ICP
* Liver bx: fatty infiltration
Tx
* Supportive
235
Causes of gallstones in children
Uncommon
- pigment type 70%
- cholesterol stones 20%
Causes (note fat soluble vitamins absorbed in ileum)
- Chronic haemolysis (sickle cell, spherocytosis)
- Crohn disease
- Ileal resection
- CF
- Chronic TPN
- Obesity
236
RF and pathophys of TPN assoc liver disease in neonates
RF for development
* LBW
* Incr duration of TPN (25% if \> 2wks)
* Lack of enteral feed
* Sepsis
Pathophys
* TPN causes steatosis (fatty infiltration of liver cells) -\> cholestasis -\> fibrosis -\> cirrhosis
237
Progressive familial intraheptic cholestasis
Sx/presentation
Types 1-3 (distinugishing features)
```
Familial conditions (AR) caused by defects in biliary transporters
Sx: cholestasis, jaundice, and failure to thrive, intensise pruritis, steatorrhoea due to fat malabsorption and fat soluble vitamin deficiencies (vit E neuropathy, osteopaenia)
```
PFIC-1 earliest onset. assoc **watery diarrhoea.**
PFIC-2 assoc w marked **giant cell hepatitis** on liver biopsy.
PFIC-3 is associated with a markedly **elevated GGT.**
Liver bx: cholestasis, duct hypoplasia, hepatocellular injury, and fibrosis. Giant cell change T2\>T1 and 3
Tx: need liver transplant
238
Abdo distension from birth and Bilious vomiting several hours after in neonate
What is this?
What condition is it associated with?
How do you treat it?
**Mec ileus** (retention of thick tenacious meconium in the bowel (ileum, jejunum or colon), which results in bowel obstruction)
* 85% have CF
* Contrast enema demonstrates a microcolon
Tx
* Uncomplicated meconium - **(Gastrografin) enema** + IV fluids. The hypertonicity of the radiopaque agent (1,900 mOsm per L) draws fluid into the bowel to facilitate passage and expulsion of the tenacious meconium.21
* When a Gastrografin enema is unsuccessful, **laparotomy** is indicated to evacuate the obstructing meconium by enterotomy irrigation
239
**Autoimmune enteropathy**
- Presentation
- Bloods and bx findings for diagnosis
- tx
- assoc conditions
**Pathophys** - CD4 T cell mediated
**Presentation :** Refractory diarrhea and malnutrition. It is seen primarily in infants \<6mo.
* Suspect AIE in an individual who is thought to have celiac disease but who fails to response to dietary manipulation with a strict gluten free diet
**Bloods:** anti-enterocyte (AE) or anti-goblet cell (AG) antibodies
**Biopsy**: small bowel villous changes including blunting and atrophy, usually most prominent in the proximal small bowel
**Tx** - nutritional support (often need PN) and immunosuppression
Assoc - autoimmune and endocrine conditions (thyroid) ; IgA immunodeficiency
240
Autoimmune hepatitis
- presentation
- serum markers/dioagnosis
- associated conditions
- treatment
Occurs late teens or early 20s and between the ages of 40 and 50
Women \> men
**Presentation:** may bne aymptomatic or present w cirrhosis or fulminant liver failure.
Other sx: fatigue, general ill health, lethargy, weight loss, mild right upper quadrant abdominal pain, malaise, anorexia, itching, nausea, jaundice or joint pain especially affecting the small joints.
Diagnosis
* Elevated AST, ALT
* NORMAL ALP and bilirubin
* Auto-antibodies
* Elevated ANA
* anti-smooth muscle antibody (SMA) = type1
* anti-liver kidney microsomal antibodies = type 2 (more severe but more rare)
* anti soluble liver antigen (SLA)
* liver–pancreas antigen (LP)
* Elevated IgG
* Liver bx diagnostic
Associated with other conditions such as _arthritis_, _ulcerative colitis_ and _sclerosing cholangitis_
Treatment: steroids -\> azathioprine/biologics/immunosuppressants
241
Cholestyramine MOA
Bile acid sequestrant
-\> Binds bile in the gastrointestinal tract to prevent its reabsorption.
242
Choledochal cyst
What is it
PResentation
Cx
Ix
Mx
Rare congenital dilations (enlargements) of the bile ducts, a network of long tube-like structures that carry bile from the liver to small intestine for digestion
Most present within 1 year of life
Classic triad (often only 2/3): jaundice, right upper quadrant mass, and abdominal pain
Cx: cystolithiasis, cholangitis, pancreatitis and malignancy
Ix: USS: cystic or fusiform dilatation of common hepatic duct or the intrahepatic ducts w distal tapering
Mx: surgical removal of cyst and reconstruction via roux-en-y
