Gastro Flashcards
Sandifer syndrome - what is it and what is its presentation?
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
What are reducing sugars? Provide examples (x4)
What about non-reducing sugars? 4x examples?
Reducing (FML-G)
Fructose
Maltose
Lactose
Glucose
Non-reducing (LMS-S)
Lactulose
Mannitol
Sorbitol
Sucrose
How to calculate osmotic gap of stool?
How is this helpful?
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
Perianal excoriation and gaseous abdominal distension - what does this indicate from a GI perspective?
CHO malabsorption
Causes- Digital clubbing
3’Cs!
CF
Celiac disease
Chron’s disease
What do you test before starting azathioprine?
TPMT - genotype that metabolises thiopurines (azathioprine)
- > 0.5% can’t metabolise it so should start it
- > 11% are poor metabolisers so need reduced dose
Extraintestinal manifestations crohns
- Oral aphthous ulcers
- Peripheral arthritis = non-deforming
- Erythema nodosum
- Digital clubbing
- Episcleritis
- Renal stones (uric acid, oxalate)
- Gallstones
Sucrase- isolmaltase deficiency
Inheritance?
Pathophys
Sx
Diagnosis
Treatment
- *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.
What tests would you perform to investigate the cause of fatty stool?
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)
What does the α1-antitrypsin stool test help to identify?
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.
What pathogen can mimic appendicitis?
- what are the sx of this and what is the underlying pathophys?
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
Fructose malabsorption VS heridary fructose intolerance
Causes
Presentatiom
Ix/treatment
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
How do Sucrase isomaltase deficiency and hereditary fructose intolerance differ?
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
Glucose galactose malabsorption
What causes it
PResentation
Diagnostic ix
Treatment
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
Short Bowel Syndrome
- Causes
- Complications
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)
Hep B virus
What are the serological markers of active infection vs vaccination vs previous infection
- 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
features of Alagile syndrome + inheritance pattern
pathophys?
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
What is the enzyme that conjugates bilirubin in the liver and in what disorders does this process become disrupted?
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
How does cows milk reduce iron absorption
- 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.
Gastrin
- Where is it released?
- What is its role?
- What stimulates its secretion?
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
Where is pepsinogen secreted from and what is its role
Secreted from chief cells in stomach
Inactive; converted to active form, Pepsin, by stomach acid
What is the role of pepsin
Formed from pepsinogen on activation by stomach acid
PROTEIN digestion - Breaks proteins into smaller peptides and aa
what is the role of iF and where is it secreted frmo?
Secreted from parietal cels in stomach
Role is to bind to ingested B12, enabling the complex to later be absorbed in distal ileum
What is pernicious anaemia
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)
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
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)
Role of ileum
Function is FAT and VitB12 absorption
Fats - BILE SALTS and lipid/cholesterol
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
What is absorbed in stomach?
H20
Alchohol
What is function of the colon?
Absorption
- Water
- Na, Cl
- Short chain FA
Secretion
- Bicarb
- Mucous
- K
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
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
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)
- Nurse infants PRONE
- Smaller, more frequent feeds
- Thickener/thickened feed
- Trial hydrolysed formulas/feed (?CMPA) - peptijunior, neocate
- Drugs
- > Antacid to neutralise stomach acid - Gaviscon
- > H2 blocker (ranitidine)
- > PPI - omeprazole - Surgery (fundoplication)
- Indications: no response to medical mgmt (at least 3 mo trial), neurological disease (aspiration risk), peptic strictures, Barrrets
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.
Stool +++ fat globules = ?
Fat malabsorption
Ex
- Coeliac
- Giardiasis
- Lymphangiectasia
- Abetalipoproteinaemia (specific fat malabsorption)
Stool faecal elastase LOW = ?
Pancreatic insufficiency (ex: CF or Shwachman-Diamond syndrome)
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.
What is the dominant protein implicated in CMPI?
Casein majority; also whey
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
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)
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
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.
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
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.
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
What are reducing sugars?
Glucose
Lactose
Maltose
Fructose
Galactose
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
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
- Conditions and syndromes assoc w coeliac disease
- 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
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
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 diet (ex - monogen formula if infant)
What condition features the following?
What is the underlying pathophys?
Whats the clinical progression
- 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)
Shwachman-Diamond Syndrome
Inheritance
Key features
Mx
Prognosis/main future risk
Inherited AR condition (mutation SBDS gene on chrom 7q11)
Features
- Pancreatic exocrine insufficiency -> fat malabsorption from birth
- Bone marrow failure -> (pancytopaenia) -> thrombocytopaenia, anaemia and cyclical neutropaenia. HIGH HbF
- 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
- Pancreatic exocrine insufficiency -> fat malabsorption from birth
- Bone marrow failure -> thrombocytopaenia, anaemia and cyclical neutropaenia. HIGH HbF
- Skeletal abnormalities -
= What condition?
Shwachman-Diamond Syndrome
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
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
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
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
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
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:
- PUD
- First degree relative with gastric Ca (as H pylori chronic infection carries incr risk of ulceration, gastric carcinoma and gastric MALT lymphoma)
- 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)
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
What is main causes of ulcers in children?
What ix to confirm?
Mx?
H pylori
Ix
- 13c urea breath test (as H pylori makes urease)
- gastroscopy with biopsy -> see gram negative spiral rods in surface layer of gastric antrum and erythematous lumpy/bumpy (Nodular) appearance of gastric mucosa
- FBE, iron studies; may have assoc iron def anaemia
Mx
- H pylori eradication triple therapy: omeprazole + combination of 2 of amox, clarith or metronidazole
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
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
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)
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)
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
Histopth of Crohns lesions
Most common cause of IBD
Can affect whole GIT, mouth to anus
- Non caseating granulomas
- Transmural inflammation
- Patchy involvement
Indicaitons for surgery in chrons disease
- Complications (more frequent than in UC) - Abscess, perforation, obstruction, bleeding
- Disease unresponsive to medical tx -> wide resection with R subtotal hemicolectomy
BUT HIGH recurrence risk so resection is NOT a cure.
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
- Ca, vit D supps
+/- TPN
+/- Surgery
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)
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
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:
- serum alkaline phosphatase (ALP) > 1.5x the upper limit of normal for longer than 6 months
- cholangiography demonstrating biliary strictures or irregularity consistent with PSC
- 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)
pANCA in UC vs CD
70% positive in UC
20% positive in CD
What is this a comlication of?
Toxic megacolon - complication of UC
- Radiololical diagnosis, colon width >2.5 vertebrae
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
Management of UC
- 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) - Long-term maintenance of remission
- 5-ASA agents
- Thiopurines.
Prevention of coeliac disease
Delayed introduction of gluten does not help, neither does early introduction (same incidence)
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)
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)
What rash is associated with coeliac disease?
Dermatitis herpetiformis
-> intensely itchy blisters filled with a watery fluid
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)
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
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
GOR mechanism
transient inappropriate relaxation of lower oesophageal sphincter
Adverse effects of PPIs
Incr risk of
- Acute gastroenteritis
- CAP
- Candida
- Interstitial nephritis
- Fundal Polyps
- Liver enzyme derangement
Duration of tx with PPI for GORD
4 week trial period to see if any benefit
takes 4 days to reach therapeutic levels
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.
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.
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)
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’)
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
how is h pylori transmitted?
faecal oral route
Which form of IBD is assoc w strictures, fistulas and perianal disease?
Crohns (complications less common in UC)
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
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)
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.
Kayser-Fleischer rings are a feature of what condition?
how do u diagnose this condition
what is the first 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
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
what is the commonest form of OA?
Type C (84%) which is blind ending proximal oesophagus with trachea-(distal) oesophageal fistula
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)
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
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.
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)
What condition?
EoE
Scope features
- rings
- furrows
- exudates
- oedema
- strictures
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
What is dermatitis herptiformis associated with
Coeliac disease
What do you suspect in a patient with these + diarrhoea + LOW and iron deficiency?
Erythema nodosum
Feature of Chron’s disease
What do you suspect in a patient with these + diarrhoea + LOW and iron deficiency?
pyoderma gangrenosum
= ulcerative colitis
What do you suspect in a patient with these + diarrhoea + LOW and iron deficiency?
Apthous ulcer
Feature of chron’s disease
Clinical signs of acute haemmhoragic pancreatitis
Grey turner sign - bruising to flanks
Cullen sign - bruising to periumbilical region (C around the belly button)
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
- Melanocytic freckles/pigmentation to lips, gums (often present before age 5, can fade w time)
- 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)
- Predisposition to malignant tumours
- GI (lifetime risk of 39 percent)
- Pancreatic
- Breast cancer
- Uterine, ovarian cancer
- Lung cancer
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
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
PEllagra
what is it?
presentation?
= Niacin deficiency (from animal products - fish, meat, milk, eggs)
Features - 3 Ds
- Dermatitis - erythema to sun exposed areas; red tongue, angular stomatitis
- Dementia - depression, encephalopathy, psychosis
- Diarrhoea (also constipation)
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
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
