Gastro Flashcards
Saliva - components and nervous system
• Saliva = hypotonic solution that has many components:
o Water- 97-99.5%
o electrolytes- Na, K, Ca, Mg, Po4, HCO3, Cl
o mucus- binds and lubricates food for swallowing
o Ptyalin- salivary amylase- enzyme that begins starch digestion in mouth
o lingual lipase- enzyme activated by stomach acid and digests fat after food is swallowed
o lysozyme- bactericidal
o IgA- inhibits bacteria growth
• Nervous system
o PNS (Ach) stimulates the gland to produce thin saliva rich in enzymes
Vasodilation
Interruption of PNS innervation = atrophy of glands
o SNS (NA) stimulates less salivation but more secretion of thick saliva with more mucous
Vasoconstriction - dry mouth with stress
Oesophagus - anat and embryo
- Key points
a. Has NO digestive glands/ enzymes, only briefly exposed to nutrients - Embryology
a. Oesophagus develops from the post-pharyngeal foregut and can be distinguished from the stomach by 4 weeks
b. Length of oesophagus is 8-10 cm at birth and doubles in the first 2-3 years of life to reach 25cm in adult
e. Swallowing seen as early as 16-20 weeks in utero – helping to circulate amniotic fluid
i. Polyhydramnios is the hallmark of lack of normal swallowing or oesophageal upper GI obstruction - Anatomy
a. 25-30cm long
b. Relation to adjacent structures
c. Epithelium
i. Luminal aspect of oesophagus covered by thick, protective, non-keratinized stratified squamous epithelium
ii. Changes to simple columnar at the stomach’s upper margin (gastroesophageal junction)
iii. Squamous epithelium is resistant to damage by gastric secretions
iv. Chronic irritation result in metaplasia of the cells lining the lower oesophagus from squamous to columnar
d. Layers
i. Epithelium lamina propria muscularis mucosae submucosa
iii. NO serosal layer
e. Sphincters
i. Upper esophageal sphincter (UES) at the cricopharyngeus muscle - striated muscle/voluntary
ii. Lower esophageal sphincter (LES) at the gastroesophageal sphincter – INTRA-ABDOMINAL - smooth muscle/involuntary
2. Tonically contracted
5. Relaxation by NO +/- VIP
- low pressure (~10mmHg)
f. Muscle type
i. Upper 1/3 striated
1. Innervated by spinal accessory nerves
2. Allows for voluntary initiation of swallowing
ii. Middle 1/3 mixed
1. Innervated by dorsal motor nerve of vagus
iii. Distal 1/3 smooth muscle
1. Innervated by dorsal motor nerve of vagus
Swallowing - phases
a. Buccal phase (voluntary)
i. Tongue collects food and presses it against the palate to form a bolus
ii. Tongue contracts and pushes bolus back into the oropharynx
iii. Bolus stimulates mechanoreceptors and activates the next phase - involuntary controlled by brainstem and swallowing centres
b. Pharyngeal phase (involuntary)
i. The root of the tongue blocks the oral cavity to prevent backflow
ii. The soft palate raises to block off the nasopharynx and
iii. The larynx moves upwards (via infrahyoid muscles) so that the epiglottis covers the airways
iv. The food bolus is driven downwards through the pharynx by relaxation then constriction of the upper, middle and lower pharyngeal constrictors
v. Fast peristaltic wave initiated by somatic innervation forces bolus into oesophagus
vi. Epiglottis and uvula move (glottis opens) and breathing resumes (6s delay)
c. Oesophageal phase (involuntary)
i. The inferior pharyngeal constrictor (upper oesophageal sphincter) relaxes to allow the bolus to travel down the oesophagus
ii. Stretch receptors in oesophagus trigger peristalsis via short myenteric reflex that causes circular muscle behind the bolus to constrict and that ahead of the bolus to dilate therefore pushing the bolus down
iii. Food is moved down the oesophagus to stomach at 2-6cm/s
iv. LES must relax for the bolus to enter the stomach, it then constricts to prevent reflux.
Oesophageal investigations
- Oesophageal manometry
a. Evaluates dysmotility from pharynx stomach
b. Pressure checked every 5 cm
c. Has been altered to make this high resolution shows transition zone between striated and smooth muscle
d. Catheter probe inflated at different regions to assess pressure
e. Can be difficult in young patients - pH monitoring
- Multichannel intraluminal impedance
a. pH independent detection of bolus movements
b. Can detect nonacid liquid reflux
c. Usually combined with pH monitoring
Dysphagia - general
- Key points
a. Sensation of food getting stuck
b. +/- pain
c. Indicates oesophageal problem
i. Oropharyngeal
ii. Oesophageal - Oropharyngeal dysphagia
a. Refers to inability to transfer food to the oesophagus
b. Food sticks immediately after swallowing
c. Aetiology
i. Neurological - Cortical – pseudobulbar palsy (UMN lesion) due to bilateral stroke
- Bulbar – ischaemia, tumour (LMN)
- Peripheral – polio, ALS
ii. Muscular - Muscular dystrophy
- Cricopharyngeal incoordination – failure of UES to relax with swallowing
- Zenker’s diverticulum (pharyngeal pouch)
- Oesophageal dysphagia
a. Mechanical = solid food only
- intermittent: lower oesophageal web/ring, EoE
- progressive: carcinoma (adults >50), peptic stricture
b. Non-mechanical = solid or liquid
- intermittent: DOS (?diffuse oesophageal spasm)
- progressive: reflux -> scleroderma, resp sx -> achalasia
Oesophageal obstruction - general
- Key points
a. Dysphagia to solids earlier than liquids – can manifest when solids start to incorporate into infants diet
i. Contrasts dysphagia from dysmotility – liquids is affected as early as, or earlier, than solids
b. Investigations
i. Fluoroscopy – may include videofluoroscopic evaluation of swallowing - Often first line test
ii. Endoscopy – if intrinsic lesion is suspected
iii. Manometry – if dysmotility suspected - Extrinsic
a. Oesophageal duplication cysts (rare)
i. Most commonly encountered in foregut duplication
ii. Lined by intestinal epithelium, well developed smooth muscle wall, and attached to normal GIT
iii. Affect the distal half of the oesophagus on the right side
iv. Most common presentation is respiratory distress caused by compression of adjacent airway
v. Dysphagia more common in older children
vi. Upper GI bleeding can occur due to acid-secreting gastric mucosa in duplication wall
b. Neuroenteric cysts (rare)
i. May contain glial elements and are associated with vertebral anomalies
ii. Diagnosis using barium swallow, chest CT and MRI
iii. Surgical excision
c. Mediastinal LN
i. Cause = infection (TB, histoplasmosis), neoplasm (lymphoma) – most common masses that compress the oesophagus and produce obstructive symptoms
d. Vascular anomalies
i. Often aberrant right subclavian artery or right-sided or double aortic arch - Intrinsic
a. Congenital or acquired
b. Eosinophilic oesophagitis = most common cause for oesophageal obstruction symptoms
c. Upper oesophagus
i. Congenital webs or rings
ii. Inflammatory stricture - following caustic ingestion or due to epidermolysis bullosa
iii. Cricopharyngeal achalasia can appear radiographically as a ‘bar’
d. Mid oesophagus
i. Congenital narrowing with oesophageal atresia-TOF complex
ii. Reflux oesophagitis can induce a ragged and extensive narrowing that appears more proximal than usual peptic stricture usually due to associated hiatal hernia
e. Distal oesophagus
i. Peptic strictures
ii. Thin membranous rings (Schatzki ring at the squamocolumnar junction)
Upper oesophageal motility disorders
Upper Oesophageal and Upper Oesophageal Sphincter Dysmotility = STRIATED MUSCLE
- Cricopharyngeal achalasia + incoordination
a. Cricopharyngeal achalasia = failure of complete relaxation of the upper esophageal sphincter
b. Cricopharyngeal incoordination = full relaxation of the UES but incoordination of the relaxation with the pharyngeal contraction
c. Both detected on videofluoroscopic evaluation of swallowing confirmed on manometry
d. Self-limited form of cricopharyngeal incoordination = occurs in first year of life and usually remits spontaneously
e. Non-self-limited cricopharyngeal achalasia
i. Need to exclude other deformities – eg. Arnold-Chiari malformation
ii. Can be severe enough to cause posterior pharyngeal diverticulum
iii. Treatment = botox, Transcervical myotomy - Systemic causes of swallowing dysfunction
a. MANY different causes
b. Include CP, Arnold Chiari malformation, bulbar palsy or cranial nerve defects, transient pharyngeal muscle dysfunction, SMA, muscular dystrophy, MS etc. etc.
Lower oesophageal motility disorders
Lower Esophageal and Lower Esophageal Sphincter Dysmotility = SMOOTH MUSCLE
Primary
- Achalasia: ONLY CONDITION SEEN IN CHILREN
- Diffuse oesophageal spasm diagnosed monometrically and Rx with nitrates or CCB
- Nutcracker oesophagus
- Hypertensive lower oesophageal sphincter
Secondary
- Hirschsprung disease
- Pseudo obstruction
- Inflammatory myopathies
- Scleroderma
- Diabetes
Achalasia - bg
- Key points
a. Mean age in children 8.8 years; uncommon before school age
b. Primary oesophageal motor disorder characterised by
i. Loss of LES relaxation (resting pressure > 30 mmHg)
ii. Loss of oesophageal peristalsis - Pathogenesis
a. Damage to smooth muscle innervation including LOS
b. Loss of myenteric ganglion cells - Aetiology
a. Idiopathic
i. Likely due to autoimmune process
ii. Possibly latent infection of HSV-1 in susceptible individuals
b. Chagas disease = Latin America
c. Secondary to cancer
d. Pseudochalasia - Associations
a. Triple A syndrome
i. Triad - Achalasia
- ACTH insensitivity (low BSL)
- Alacrima – from birth
ii. Associated with 12q13 deletion
iii. Can be delayed diagnosis
b. Rozycki syndrome = AR deafness, short stature, vitiligo, muscle wasting
c. Others = Chagas disease, sarcoid, Hirschsprung, Downs, pyloric stenosis
Achalasia - sx, ix
- Clinical manifestation
a. Regurgitation and dysphagia for solids and liquids
b. May be accompanied by undernutrition or chronic cough
c. Retained oesophageal food can produce oesophagitis - Investigations
a. CXR
i. Absent air in stomach
ii. Dilated fluid filled oesophagus
b. Barium fluoroscopy
i. Smooth tapering of lower oesophagus leading to the closed LES, resembling birds’ beak
ii. Retained food often present
c. Motility study/manometry = gold standard and required for diagnosis
i. Aperistalsis in distal oesophagus, incomplete or absent LES relaxation DIAGNOSTIC
ii. Classification - Class achalasia (type I) = negligible oesophageal contraction (big and baggy)
- Early stage (type II) = high amplitude contractions often repetitive, lacks orderly contraction/relaxation of LOS, associated with chest pain (vigorous achalasia)
a. Preservation of myenteric ganglia
b. Responds well to treatment - Earliest stage with spasm (type III) = characterised by rapidly propagated oesophageal pressurization attributable to spastic contractions
Achalasia - rx, cx
- Treatment
a. Goal = relieve symptoms, improve oesophageal emptying, prevent mega-oesophagus
b. Medical
i. CCB (nifedpine)
ii. PDE inhibitors
iii. Nitrates
c. Endoscopy
i. Endoscopic injection of botulinum toxin – partial preservation of post-ganglionic cholinergics pathway basis for botox effect
ii. Pneumatic dilatation – 50% successful, 5% perforation
d. Surgical (Heller) myotomy – common
i. Complication – reflux - Complications
a. Respiratory
i. Aspiration
ii. Bronchiectasis
iii. Lung abscesses
b. GIT
i. Malnutrition
ii. Increased risk of oesophageal cancer – chronic inflammation
Diffuse oesophageal spasm - general
- Key points
a. Normal peristalsis interspersed with abnormal high pressure waves
b. Unknown aetiology - Clinical presentation
a. Chest pain - Diagnosis
a. Barium oesophagogram – corkscrew pattern, pseudo-diverticula caused by spasm
b. Manometry - Treatment
a. No effective treatment
b. Medical
i. Nitrates
ii. CCB
iii. Anticholinergics
c. Surgery – long myotomy
Hiatal hernia - general
- Key points
a. Herniation of the stomach through the diaphragm
b. Diaphragm – flat horizontal muscle separating the torso from the abdomen
i. Usually has an aperture to allow oesophagus through
ii. If this is enlarged it allows stomach to rise up into the chest with respiration - Classification
a. Type 1 = sliding gastroesophageal junction slides into thorax
i. Often associated with GERD, especially in developmentally delayed children
b. Type 2 = paraesophageal fundus insinuated next to oesophagus
i. Can be isolated or congenital anomly, or associated with gastric volvulus
ii. May be encountered after fundoplication for GERD
iii. Fullness after eating and upper abd pain are usual symptoms
c. Type 3 = combination - Diagnosis
a. Upper GI series + upper GI endoscopy - Treatment
a. Manage GERD
b. Only if GERD is not well controlled correction of hernia with fundoplication
Oesophagitis - definition, causes
- Definition = histological diagnosis of inflammation
- Aetiology
a. GERD
b. Eosinophilic oesophagitis
c. Infectious oesophagitis
d. Pill oesophagitis
i. Tetracycline
ii. KCl
iii. Ferrous sulfate
iv. NSAIDs
v. Alendronate
e. Caustic ingestion
f. Radiation
g. Sclerotherapy
GORD - bg
- Key points
a. Most common oesophageal disorder in children of all ages
b. Does NOT cause SIDS but can be associated with BRUE
c. Reflux = passage of gastric contents into the oesophagus
i. Asymptomatic reflux in most people – ie. non-erosive gastroesophageal reflux (NERD)
ii. Physiological process that occurs several times a day in healthy persons
iii. Its clinical presentation of vomiting or regurgitation is very common in infants and in the majority of cases self-resolving and does NOT need treatment
b. Natural history
i. Peaks 4 months of age where 2/3 of healthy term infants have >1 daily episode of regurgitation
ii. Between 6-7 months of age the prevalence decreases to 1/5
iii. At 12 months only 5% have symptoms
c. Gastroesophageal reflux DISEASE
i. Reflux plus one of - Histopathological changes of oesophageal epithelial lining
- Symptoms of reflux (eg. FTT, oesophagitis, episodes of aspiration pneumonia)
ii. Rare but frequent in children with CP, Down syndrome, CF, upper GI malformation (tracheoesopahgeal fistula, hiatus hernia, pyloric stenosis) - Mechanisms
a. Hiatus hernia
b. Increased frequency of LOS relaxation (debated)
c. Decreased LOS pressure – anticholinergics, BDZ, caffeine, CCBs, ethanol, nicotine, nitrates, progesterone
d. Decreased oesophageal motility – achalasia, scleroderma, diabetes mellitus
e. Gastric emptying time – anticholinergics, cow’s milk allergy, diabetes mellitus gastroparesis
i. If the stomach is full when LES undergoes transient relaxation reflux - Natural history
a. Infant reflux becomes evident in the first few months of life, peaks at 4 months and resolves in 90% by 12 months
b. Symptoms in older children tend to be chronic, waxing and waning, but completely resolving in no more than half
GORD - p/phys
a. Normal antireflux mechanisms
i. Lower oesophageal sphincter
ii. Crura of the diaphragm at the gastroesophageal junction
iii. Valve like function of the oesophagogastric junction anatomy
iv. Acid is normally cleared by peristalsis and saliva
b. Transient LES relaxation (TLESR)
i. Primary mechanism allowing reflux to occur
ii. Occurs independent of swallowing
iii. Reduces LES pressure to 0-2 mm Hg lasting > 10 seconds
iv. Regulated by vasovagal reflex, stimulated by – gastric distension
v. Excessive numbers of transient LES relaxation may lead to reflux
vi. Whether GERD is caused by a higher frequency of TLESRs or by a greater incidence of reflux during TLESRs is debated
c. Chronic oesophagitis worsens the problem
i. Leads to oesophageal peristaltic dysfunction
ii. Decreased LES tone
iii. Inflammatory oesophageal shortening that induces hiatal herniation
GORD - sx
a. Infantile reflux
i. Regurgitation + vomiting
ii. Features suggestive of oesophagitis
1. Pronounced irritability with arching
2. Refusal to feed
3. Weight loss
4. Haematemesis
iii. Respiratory features
1. Chronic cough + wheeze
2. Obstructive apnoea, stridor
3. Note that reflux complicates primary airway disease eg. laryngomalacia, bronchopulmonary dysplasia
b. Older children
i. Complaints of chest and abdominal pain
ii. Respiratory = asthma or laryngitis/sinusitis
c. Occasionally children present with food refusal and neck contortions (Sandifer syndrome)
d. Other respiratory complications = sinusitis, otitis media, lymphoid hyperplasia, hoarseness, vocal cord nodules, laryngeal oedema – all associated with GERD
GORD - ix
a. USUALLY NOT REQUIRED
b. Relief with antacids or PPI
c. 24 hour oesophageal pH monitoring = provides information about reflux
i. Normal values of distal oesophageal acid exposure (pH <4) are <5-8% of the total monitored time
ii. Most important indication fare for assessing efficacy of acid suppression, evaluating apneic episodes in conjugation with pneumogram and perhaps impedence, and evaluating atypical GERD presentations (chronic cough, stridor, asthma)
d. Endoscopy = allows diagnosis of erosive oesophagitis, identification of complications such as strictures, and Barrett’s oesophagus (biopsy)
e. Other
i. Manometry = not commonly done
ii. Milk study = determine reflux associated aspiration with radiolabeled milk
iii. Barium meal = performed in children with vomiting and dysphagia to evaluate for achalasia, oesophageal strictures and stenosis, hiatal hernia, and gastric outlet or intestinal obstruction
iv. Intraluminal impendence = sometimes done
v. Laryngotracheobronchoscopy = assess for airway signs associated with GERD such as posterior laryngeal inflammation, vocal cord nodules
GORD - rx
a. Do NOT encourage changing formulas or changing from BF to formula
b. Conservative measures/ lifestyle
i. Infant
1. Positioning measures
a. Prone after feeding (only when awake)
b. Sleeping upright
2. Normalization of any abnormal feed techniques, volumes and frequency – smaller more frequent
3. Thickening of feed
4. Hypoallergenic diet (CMP)
ii. Older children
1. Avoiding eating before bed, acidic foods + fatty foods
2. Avoid agents that decrease LOS tone – anticholinergics, nicotine, ETOH
iii. No evidence but can be tried – avoid exposure to tobacco, avoid overfeeding, avoid aerophagia, try small frequent feeds
c. Pharmacotherapy
i. PPIs = first line for reflux
1. Most effective medical therapy improvement in 70-90%
2. Does not stop reflux, but reduces acidity
3. Some are more efficacious than others with respect to acid suppression – can be useful to try different drug within same class
4. Note AE with long-term use, mostly demonstrated in adults:
a. Respiratory infections
b. C diff infections
c. Bone fractures
d. Hypomagnesmia + low B12
e. Tubulointerstitial nephritis
ii. H2 antagonists eg. ranitidine, nizatidine, famotidine
iii. Prokinetic agents – NOT used in children
1. Improve gastric emptying + oesophageal clearance
2. None affects the frequency of TLESRs
iv. Baclofen = considered in neurologically impaired children
v. Gaviscon/Mylanta can be used PRN
d. Surgery
i. Feeds = allow time for baby to outgrow reflux
1. Continuous NG feeds
2. Continuous NJ feeds
ii. Fundoplication
1. Effective for those with refractory GERD or complications
2. More common in children with comorbidities (eg. CP)
3. Indications
a. Neurological disease
b. Not responding to medical therapy
c. Complications of oesophagitis
i. Peptic strictures
ii. Barrett’s oesophagus
d. Gastrostomy feeds
e. Respiratory disease
4. Efficacy
a. Symptom improvement in 60-90% of children
b. Failure rate of 2-50%
5. Complications
a. Suture breakdown, adhesions
b. Difficulty vomiting causing “gas bloat syndrome”
c. Slip of wrap into thoracic cavity
d. Distal oesophageal obstruction (anatomical or functional, dysphagia, retching)
e. Feed volume intolerance (reduces accommodation of stomach due to wrap)
f. Dumping syndrome (inability to accommodate)
GORD - cx
- Oesophagitis and sequelae – stricture, Barret oesophagus, adenocarcinoma
a. Oesophagitis
i. Infants = manifest as irritability, arching, feed aversion
ii. Older children = chest or epigastric pain
iii. Haematemesis, anaemia, Sandifer syndrome in ANY age
b. Erosive oesophagitis = found in 12% of children
c. Strictures = prolonged esophagitis strictures dysphagia
d. Barret’s oesophagus
i. Caused by prolonged esophagitis metaplastic transformation of the normal oesophageal squamous epithelium into intestinal columnar epithelium (columnar metaplasia)
ii. Risk of adenocarcinoma
iii. VERY RARE IN CHIDLREN – usually not until 5th decade
iv. Requires surveillance - Nutritional
a. May result in FTT due to caloric deficits - Respiratory
a. GERD can produce respiratory symptoms by direct contact of the refluxed gastric contacts with the respiratory tract (aspiration, laryngeal penetration or microaspiration) OR by reflexive interactions (inducing laryngeal spasm or closure)
b. Often GERD and a primary respiratory asthma (eg asthma) interact
c. Apnoea and stridor
i. Apnoea and BRUE caused by reflux is generally obstructive, owing to laryngospasm - at the time of such apnoea, infants have often been provocatively positioned and have recently fed
ii. Stridor triggered by reflux generally occurs in infants anatomically predisposed (laryngomalacia, micrognathia)
iii. Reflux laryngitis can be attributed to GERD
Eosinophilic oesophagitis - bg, sx, ix
- Key points
a. Chronic oesophageal disorder characterised by infiltration of the oesophageal epithelium with eosinophils
b. Most patients male
c. Mean age at diagnosis 7 years - Epidemiology
a. First described in the late 90s – increasing in incidence
b. More common in those with atopic conditions – asthma, hayfever - Clinical manifestations
a. Infants and toddlers = vomiting, feeding problems and poor weight gain
b. Older children and adolescents = food dysphagia with occasional food impactions or strictures, and may complain of chest or epigastric pain, slow eating
c. Many patients have co-existing atopic disease or positive family history, with food allergies - Pathogenesis
a. T helper type 2 cytokine mediated pathways leading to production of a potent eosinophil chemoattractant, eotaxin-3 by oesophageal epithelium - Diagnostic criteria
a. Symptoms related to oesophageal dysfunction
b. ≥15 eosinophils/hpf on oesophageal biopsy
c. Persistence of eosinophilia after a proton pump inhibitor trial
d. Secondary causes of oesophageal eosinophilia excluded - Investigations
a. Peripheral bloods = may have peripheral eosinophilia and elevated IgE
b. Endoscopy = features seen macroscopically
• Longitudinal furrows
• Trachealisation
• White exudate
• Wall friability
• Narrowing
• Loss of vascular pattern
c. Biopsy = eosinophilia
d. Skin prick = assess for allergic trigger
EoE vs GORD
EoE • Food impaction in older children and adults • Male: female = 3:1 • Usually atopic comorbidities • Impedence studies and pH: Normal • Longitudinal furrows • Trachealisation • White exudate • Wall friability • Narrowing • Loss of vascular pattern • Proximal and distal inflammation • Epithelial hyperplasia • >15 eosinophils/hpf
GORD
• Food impaction rare
• Male to female ratio = 1:1
• Occasionally atopic commodities
• Impedence and pH studies: Evidence of acid reflux
• Distal oesophagitis
• Scanty eosinophils (sometimes widespread)
Eosinophilic oesophagitis - rx, cx, prog
- Management
a. Food bolus obstruction
i. Requires endoscopic removal ASAP
b. Dietary
i. Successful in 60-80% of children
ii. Target elimination diet = removal of foods from diet identified on allergy testing or patient history
iii. Six food elimination diet = elimination of food commonly associated with allergy - Milk and wheat – most frequently implicated
- Eggs, soy, nuts, seafood
iv. Elemental diet = all food intake changed to liquid; not practical
c. Medical
i. PPI = 40-50% of patients respond - Anti-inflammatory effect on oesophagus
- Improves integrity of the gap junctions between cells
ii. Topical steroids = fluticasone and budesonide - Usually administered by swallowing glucocorticoid solutions which would usually be inhaled -> symptomatic and histological remission in 90%
iii. Biological agents coming - Anti-IL5 antibodies = mepolizumab, relizumab
d. Endoscopic = dilatation - Monitoring
a. Require regular endoscopy to ensure remission (<15 Eo/hpf)
i. 3-5 gastroscopies over 2 year period to find a treatment which works
b. High rate of relapse off treatment - Complications
a. Stricture
b. Oesophageal perforation
c. No long term risk of cancer yet identified - Prognosis
a. Unclear
b. Chronic remitting/ relapsing disorder
Infectious oesophagitis - general
- Key points
a. Rare in immunocompetent hosts - Risk factors
a. Diabetes
b. ETOH
c. Glucocorticoids
d. Immunosuppressants
e. Broad spectrum antibiotics - Aetiology
a. Candida albicans – most common
b. Viral – HSV, CMV
c. Bacterial – uncommon
i. Trypanosoma cruzie
ii. Cryptosporidium - Clinical manifestations
a. +++ odynophagia
b. Dysphagia – solids and liquids
c. Fever (uncommon)
d. Bleeding (uncommon) - Diagnosis
a. Endoscopy
i. Candida = white plaques
ii. Herpes = vesicles
iii. Biopsy for definitive - Treatment
a. Candida = fluconazole 200 mg PO daily for 3-4 weeks
b. HSV = aciclovir 400 mg 5x per day for 2 weeks
c. CMV = ganciclovir, foscarnet
d. Antacids, topical anaesthetics, sucralfate
Oesophageal obstruction - sx, aetiology
- Four areas of anatomic narrowing at risk for FB
a. Cricopharyngeus (upper esophageal sphincter)
b. Aortic arch
c. Left main stem bronchus
d. Diaphragmatic hiatus - Clinical presentation
a. Complete
i. Unable to swallow
ii. Drooling
iii. Violent retching
iv. Pain from neck to epigastrium
b. Proximal
i. Stridor
ii. Sudden cyanosis - Compression of trachea by food in upper esophagus or oropharynx
- Aetiology
a. Foreign bodies – coins, food, batteries
b. Anatomic anomalies
i. Carcinoma
ii. Stricture – peptic/ chemical
c. Extrinsic compression
i. Thyroid enlargement
ii. Aortic arch
iii. Anomalous right subclavian artery
iv. Bronchogenic carcinoma
Oesophageal obstruction - ix, rx
- Investigations
a. Endoscopy = gold standard for diagnosis and treatment
b. Plain X-ray = AP/lateral
i. If FB suspected – not seeing does not rule out
c. Contrast studies
i. Gastrograffin vs barium
d. CT scan - Management
a. Oropharyngeal = retrieve with Kelly/ McGill forceps
b. Esophageal
i. Endoscopic removal – rigid or flexible
ii. Foley catheter
c. Lower esophagus
i. Often food impaction
ii. Glucagon 1 mg IV (maximum 2 mg) - Relax sphincter enough to allow passage of food in 50% of patients
- Affects only smooth muscles so not helpful for proximal obstructions or strictures
iii. Flexible endoscopy - Specific objects
a. Sharp objects
i. Urgent intervention
ii. Cause intestinal perforation in 15-35%
iii. If reaches duodenum – watch and wait
b. Batteries
i. “Button batteries” urgent removal
ii. Zn, Li, Hg – leakage causes toxicity – positive and negative sides in contact with esophagus creates a current causing a thermal injury rapid ulceration and perforation with resultant mediastinitis
Oesophageal perforation - bg, sx
- Key points = rare, potentially life threatening
- Aetiology
a. Cause
i. Iatrogenic – endoscopy
ii. Foreign body ingestion
iii. Trauma - Majority in children due to blunt trauma
b. Spontaneous = Boerhaave syndrome (cough, childbirth)
i. Less common in children
ii. Associated with sudden increase in intra-oesophageal pressure eg. vomiting, coughing, straining
iii. Children and adults with eosinophilic oesophagitis have been described with Boerhaave syndrome in the setting of forceful vomiting - Clinical manifestations
a. Upper oesophagus: Neck/ chest pain, Dysphagia, Respiratory distress, Fever
b. Lower oesophagus: Abdominal pain/ pain radiating to back, Pneumothorax, Pneumomediastinum, Subcutaneous emphysema
c. Other
i. Tachycardia
ii. Cold water polydipsia in attempt to soothe pain in throat
iii. Perforation in proximal thoracic oesophagus pneumothorax, effusions LEFT side of chest
iv. Signs of more distal tears manifest on the RIGHT
Oesophageal perforation - ix, rx
- Investigations
a. CXR/ upright AXR
i. Subcutaneous emphysema
ii. Pnuemo-mediastinum
iii. Mediastinal widening
iv. Pleural effusion
b. Contrast studies = gastrograffin/barium
c. CT
i. Mediastinal air
ii. Extra luminal contrast
iii. Fluid collections - Treatment
a. Aggressive treatment
i. Unstable – NBM, NG tube (careful)
ii. Contamination of mediastinum/pleura
iii. Treat with broad spectrum antibiotics
b. Conservative
i. Stable, afebrile
ii. Endoscopic injury
iii. Delayed presentation
Foreign body ingestion - general
- Key points
a. Majority (80%) of FB occur in children 6 month to 3 years
b. Older children and adolescents with developmental delays
c. Presence of FB lodged in oesophagus = emergency significant morbidity + mortality
d. Coins and small objects most common
e. Food impactions less common in children than in adults – associated with eosinophillic oesophagitis, repair of oesophageal atresia, and fundoplication
f. Most lodge at the level of the cricopharyngeus (UES), the aortic arch, or just superior to the gastroesophageal junction (LES) - Clinical presentation
a. 30% of children with oesophageal FB may be totally asymptomatic – any hx of foreign body should be taken seriously and investigated
b. Initial bout of choking, gagging and coughing may be followed by excessive salivation, dysphagia, food refusal, emesis, pain in neck, throat or sternal notch
c. Respiratory symptoms (stridor, wheezing, cyanosis, dyspnoea) may be encountered if FB impinges on larynx or membranous posterior tracheal wall
d. Cervical swelling, erythema or SC crepitations suggest perforation - Investigations
a. Plain AP of neck, chest and abdomen with lateral views of neck and chest
i. Disc batteries look like coins – high risk of burns and necrosis
ii. Materials such as plastic, wood, glass, aluminum radiolucent
b. CT = sometimes required to see FB - Treatment
a. MUST ASSESS RISK OF AIRWAY COMPROMISE
b. Endoscopy = required to remove object
c. Sharp objects, disc button batteries or those associated with respiratory symptoms urgent ETT and endoscopy
d. Asymptomatic blunt objects and coins can be observed for 24 hours to see if they passage into the stomach
e. Meat impactions can be observed for 12 hours
Caustic ingestion - general
- Key points
a. Most cases are accidental ingestion of liquid alkali substances that produce severe, deep liquefaction necrosis the more that is ingested
b. Acidic agents are bitter so less may be consumed produce coagulation necrosis and a thick protective eschar - Complications
a. Oesophagitis
b. Necrosis
c. Perforation
d. Stricture formation - Clinical presentation
a. Vomiting, drooling, refusal to drink, oral burns, dysphagia, dyspnoea, abdominal pain, haemtemesis, and stridor
b. 20% develop strictures - Treatment
a. Dilution by water or milk is recommended as acute treatment – neutralization, induced emesis and gastric lavage are contraindicated
b. Strictures may require dilatation
Oesophageal stricture - general
- Key points
a. Along with FB most common cause of oesophageal obstruction
b. Benign or malignant (rare in children)
c. Oesophagitis/inflammation scarring stricture - Causes of oesophagitis which can result in stricture
a. GORD
b. Eosinophilic oesophagitis
c. Infectious oesophagitis
d. Pill oesophagitis = particularly tetracyclines
e. Caustic ingestion
f. Radiation
g. Sclerotherapy - Treatment
a. Dilatation
i. Bougie dilators – done blindly, inserting increasing size calibers
ii. Balloon dilators – done under radiological guidance
Globus hystericus - general
• Lump in the throat, globus sensation
• Criteria:
o Persistent or intermittent non-painful sensation of lump or foreign body in throat.
o Occurrence of sensation between meals.
o Absence of dysphagia and odynophagia.
o Absence of evidence GOR causing symptoms.
o Absence of histopathology based oesophageal motility disorders.
o Criteria fulfilled for 3 months with symptoms onset at least 6 months before diagnosis.
Foregut/midgut/hindgut development
a. Primitive gut recognized by the 4th week of gestation
b. Composed of the foregut, midgut and hindgut
i. Foregut upper GI tract including oesophagus, stomach and duodenum to the level of bile duct insertion
ii. Midgut rest of small bowel and large bowel to the midtransverse colon
iii. Hindgut colon and upper anal canal
c. Enteric nervous system is derived from neural crest cells that migrate in a cranial to caudal fashion
d. Migration of the neural crest tissue is complete by the 24th week of gestation
Interstitial cells of Cajal
Specialised pacemaker cells located in the wall of the stomach, small intestine and large intestine – responsible for migrating motor complex which result in waves in peristalsis
Stages of gastric secretion
a. Cephalic phase (minutes) – stomach responds to sight, smell, taste or thought of food (olfactory and taste receptors – hypothalamus – PNS) – 20% secretion
b. Gastric phase (3-4hours) – swallowed food and protein activate mechanoreceptors which stimulate short and long reflex action to increase gastric secretion – 70% secretion
c. Intestinal phase (hours) – duodenum response to acidic chyme entering, activates hormonal and nervous reflexes - 10% gastric secretion
Stomach cell types
a. Oxyntic cells/ parietal cells = HCl, intrinsic acid
i. Found mostly in upper half of gland
ii. Body of stomach and pylorus
b. Chief cells = pepsinogen
i. Activated by acid in stomach, deactivated by high pH in duodenum
ii. Dominate in lower half of gastric glands
iii. Body (absent in fundus and pylorus)
c. Enterochromaffin-like cells = histamine
i. Concentrated in lower end of gland and secrete hormones and paracrine messengers that regulate digestion
d. Mucous cells = mucous
i. Thick and alkaline to protect from acid
ii. Prominent in cardia and pyloric regions
iii. Concentrated in the neck of the gland where it opens into pit
e. G cells = gastrin
i. Located in the antrum
2. Gastrin – stimulates secretion of acidic gastric juice by stomach glands AND motor functions of stomach
Parietal cell - physiology
- Key points
a. Gastric glands produce 2-3L gastric juice per day, made of water, pepsin and HCl
b. pH 1-4 (low as 0.8) - Parietal cell functions
a. Secrete HCL acid
b. Intrinsic factor for B12 absorption - Function of stomach acid
a. Activates pepsin and lingual lipase
b. Converts ferric iron 3+ to ferrous iron 2+ for absorption
c. Breakdown of CT in plant cell walls
d. Bactericidal - Physiology
a. Stomach parietal cell produces HCl due to presence of carbonic anhydrase which converts CO2 into carbonic acid and then H+
b. H+ then pumped into the stomach by H-K antiporter
c. K+ enters cell then exits again down concentration gradient
i. Gradient maintained by Na-K+ ATPase on basal membrane
d. Simultaneously bicarbonate is exchanged for chloride in the blood creating chloride shift and chloride is pumped into lumen to join H+
e. HCL accumulates in stomach, bicarbonate in blood (alkaline tide as pH blood leaving stomach has higher pH)
HCl secretion (+omeprazole)
a. Gastrin – secreted from G cells
i. Binds to G receptors
ii. Increased intracellular calcium
iii. Increase PKA activity
iv. Stimulated H-K pump
b. Ach – from PNS nerve endings
i. Binds to M3 receptors
ii. Increased intracellular calcium
iii. Increase PKA activity
iv. Stimulated H-K pump
c. Histamine – released from mast cells or ECL (enterochromaffin like cells)
i. Activates H2 histamine receptors
ii. Activated adenylyl cyclase leading to cAMP production
iii. cAMP activates PKA leading to activation of H-K pump
Omeprazole/PPI blocks H/K/ATPase (antiporter) -> blocks acid secretion in response to all stimuli (vs H2 receptor antagonist e.g. ranitidine)
- dose dependent irreversible inhibition, maximal effect at day 5
- > 20mg inhibits all intragastric acidity in most individuals
Gastritis - general
- Definition
a. Histological diagnosis of inflammation of gastric mucosa - Aetiology
a. H pylori
b. NSAIDs
c. Corrosive agents
i. Bile
ii. Ingested acids/ alkalis
d. Ethanol, potassium, iron
e. Malignancy, ulcer (eg. Crohn’s)
f. Other infectious organisms – viral, mycobacteria - Clinical presentation
a. Variable and non-specific
b. Asymptomatic
c. Abdominal pain
d. N+V
e. GI bleeding (rare)
f. Shock (rare) - Complications
a. Ulcer
b. Perforation
c. Gastric outlet obstruction - Diagnosis
a. Often clinical
b. Must rule out other causes of potential pain
c. Endoscopy +/- biopsy useful if symptoms severe or persistent
i. Ulcers – Crohn’s
ii. Haemorrhage – viral
iii. Nodular – H pylori - Treatment
a. Antacids
i. PPI
ii. H2 antagonists
b. Thermal/Argon Plasma (APC) – if bleeding
c. Consider H Pylori eradication
d. Immunosuppression for Crohn’s
Peptic ulcer disease - bg
- Key points
a. Erosion = superficial to muscularis mucosa, no scarring
b. Ulcer = penetrates muscularis mucosa, scarring
i. End result of inflammation
c. Multifactorial – final common pathway is the action of acid and pepsin-laden contents of the stomach on the gastric and duodenal mucosa, and the inability of normal mucosal defenses to allay its effect
d. Gastric ulcers = located on the lesser curvature (unclear if just applies to adults but greater curvature ulcers considered to be malignant, also just more common on lesser curvature)
e. Duodenum = 90% found in the duodenal bulb
f. Rates in childhood very low - Pathogenesis
a. Acid production
i. By age 3-4 years gastric acid secretion similar to adults
ii. Acid secreted by oxyntic acid has a pH of 0.8, whereas pH of the stomach is 1-2
iii. Excessive acid secretion associated with large parietal cell mass, hypersecretion by antral G cells, and increased vagal tone
iv. Gastric acid secretion promoted by = vagus nerve, histamine secreted by enterochromaffin cells, gastrin
v. Gastric acid secretion reduced by = prostaglandins
b. Mucosal defense
i. Mucous gel = mucous production and secretion stimulated by prostaglandin E2
ii. Epithelium secrete bicarbonate into the mucous coat regulated by PG
iii. If mucosal injury occurs, active proliferation of cells occurs to protect the area
Peptic ulcer disease - aetiology and location, sx
Aetiology Duodenal Gastric H pylori 90% 60% NSAIDs 7% 35% Stress-induced <3% <5% Zollinger-Ellison <1% <1%
- Clinical manifestations
a. Vary with age of patient
b. Abdominal pain (95%)
c. Gastric ulcer
i. Generally epigastric
ii. Usually worse 2-4 hours after meal
iii. Often pain 2-3AM (HCl secretion highest)
iv. Relieved with antacids
d. Duodenal ulcer
i. Pain worst before meal
ii. Relieved by meal
e. Other features
i. Haematemesis or malaena – half of patients with PUD
ii. School age children and adolescents – epigastric pain or fullness, nausea and dyspepsia
iii. Infants and young children – feeding difficulty, vomiting, crying episodes, haematemesis or malaena
iv. Pain often described as dull or aching
v. Nocturnal pain waking the child common in older children
Peptic ulcer disease - ix
a. Endoscopy
i. Clean, well demarcated, benign looking
ii. All should be biopsied as risk of cancer (adults > children)
b. Upper GI contrast
c. Bloods = FBE, UEC, LFT, lipase
d. Imaging = CXR/AXR if suspect perforation
e. Diagnosis of H pylori
i. Endoscopy – GOLD standard (gastric biopsy, urease testing, culture, histopathology); endoscopic findings range from normal to gastritis with prominent rugal folds, nodularity or ulcers; antrum often appears normal
ii. Enzyme immunoassay on stool – highly sensitive/specific
iii. Serology – NOT recommended; IgG may persist for years after resolution of the infection
iv. Urea breath test
Peptic ulcer disease - primary ulcers
a. H pylori
i. Almost all non-NSAID ulcers due to H pylori
ii. GN rod – produces catalase and oxidase
iii. Lives in upper GI tract between epithelial surface and mucous
iv. Faecal-oral or oral-oral transmission
v. Risk factors = socio-economic status, family members
vi. All children infected with H. pylori develop histological chronic active gastritis but are often asymptomatic
vii. Can result in abdominal pain or vomiting, less often iron deficiency or growth retardation
viii. Rarely associated with autoimmune thrombocytopaenia
ix. Increased risk of
1. Duodenal ulcer (DDx NSAIDs)
2. Gastric cancer (adenocarcinoma)
3. Mucosal associated lymphoid tissue lymphoma (MALT)
b. Idiopathic ulcers
i. H pylori duodenal ulcers in children with no Hx of NSAIDs represents 15-20% of paediatric duodenal ulcers
ii. Patients do not have nodularity in the gastric antrum or histologic evidence of gastritis
iii. In idiopathic ulcers, PPI suppression alone adequate
iv. High rate of recurrence
Peptic ulcer disease - secondary ulcers
a. Aspirin and NSAIDs
i. Can result in bleeding ulcers or gastric perforation
ii. More common in the stomach than the duodenum, more common in the antrum
iii. Pathogenesis
1. Direct effect
a. Diffuse into mucosal cells
b. Become trapped and directly damage cell
i. Inhibition of PG secretion
ii. Reduce mucous production
iii. Reduced cell turnover
2. Indirect effect
a. Systemic inhibition of COX decreased production of PG
b. ‘Stress’ ulceration
i. Occurs within 24 hours of a critical illness
ii. 25% of children in PICU have macroscopic evidence of gastric bleeding
iii. Intracranial = Cushing ulcer
iv. Severe burn = Curling ulcer
Peptic ulcer disease - cx
a. Upper GI bleed (15%)
i. Posterior surface – gastroduodenal artery
ii. Treatment – resuscitation, endoscopy, PPI, surgery
b. Perforation (7%)
i. Usually anterior duodenal ulcers
ii. Sudden generalised peritonitis
iii. Diagnosis = free air on CXR
iv. Treatment = surgery – oversew ulcer and patch, antrectomy and vagotomy
c. Gastric outlet obstruction (2%)
i. Nausea/vomiting
ii. Caused by edema and scarring
iii. Treatment = surgery, gastrectomy
d. Penetration
i. Posterior duodenal ulcers can erode into pancreas
ii. History of epigastric pain that worsens and radiates to back – becomes refractory to treatment
iii. Investigations = elevated amylase
Peptic ulcer disease - rx
a. Lifestyle modification
i. Stop NSAIDs
ii. Reduce caffeine, EtOH, spicy foods, smoking cessation
b. NSAID induced ulcer
i. Stop NSAID
ii. PPIs = more potent in ulcer healing
1. Block the gastric parietal cell H+/K+ ATPase in a dose dependent fashion
2. Reduce basal gastric acid secretion
iii. H2 receptor antagonists
1. Competitively inhibit binding of histamine to the H2 subtype receptor of the gastric parietal cell
c. Not taking NSAID
i. PPI
ii. Exclude Crohn’s, malignancy
iii. Treat for H pylori
1. The goal of therapy is to eradicate H pylori on the first attempt
2. Triple therapy with two antibiotics and a proton pump inhibitor is recommended
3. Longer duration of therapy (up to 14 days) has been associated with higher eradication rates
4. Current first-line therapy (10 - 14 days) = amoxicillin + clarithromycin + omeprazole
a. Multiple regimens and commercially packaged – Nexium HP7 (amoxicillin/ clarithromycin/ omeprazole) for 7 days
5. If more than one family member is affected, it is our practice to treat individuals concurrently, to minimise reinfection within the household
6. Increasing resistance
7. Difficult to eradicate
a. Longer durations sometimes needed
b. Back to back and triple vs quadruple therapy under investigation
c. Biopsy for culture and sensitivity
Zollinger-Ellison syndrome
Rare, characterised by severe, refractory PUD
Neuroendocrine tumour - gastrinoma -> excessive/autonomous gastrin->gastric acid secretion
Usually also diarrhoea
98% patients have elevated gastrin levels
A/W MEN1, NF, TS
H pylori - bg
a. H pylori infection varies between the developed and developing world (40% vs 90% in adults aged 40 years)
b. Commonest bacterial pathogen in humans – infecting >50% of world’s population
c. Prevalence is higher in developing countries and older age groups
d. Usually acquired during first 2 years of life, but disease consequences rarely arise in childhood
e. Children
i. 10% adolescents in developed world + 80% adolescents in developing countries
ii. Neonatal infection rare
f. Risk factors
i. Socioeconomic differences are the most important predictor of H pylori
ii. Household crowding
iii. Ethnicity
iv. Migration from high prevalence areas
v. Infected parent, particularly mother
vi. Contaminated water
g. Route of transmission = faecal-oral, oral-oral or gastric-oral
H pylori - sx
- Clinical manifestations
a. Asymptomatic in absence of ulceration
b. Commonest paediatric cause of chronic gastritis
c. Gastritis always present – but can be microscopic
d. Infection associated with gastritis, GU and DU
e. Role in recurrent abdominal pain uncertain - H-pylori associated disease
a. Gastric
i. Asymptomatic
ii. Chronic gastritis
iii. Peptic ulcer – gastric, duodenal
iv. Gastric adenocarcinoma
v. B cell MALT lymphoma
b. Extra-gastric
i. GERD
ii. Iron deficiency anaemia
iii. Short stature
H pylori - ix
a. Endoscopy
i. Involves antrum, occasionally body
ii. Antral nodularity (specific, not in adults)
iii. Gram negative rods in surface mucosal layer
b. Summary
i. Serology should NOT be used as does NOT test for active infection and 50% of positive is a false positive
ii. Tests for active infection
1. H pylori stool antigen (good sens/spec 94-95%)
2. Urea breath test (95-96% sens/spec)
3. Endoscopy (invasive)
iii. All patients with dyspepsia who do not have alarm symptoms, have not been using NSAIDs, should be tested for an active infection test before being prescribed PPIs
iv. Stool antigen is the most cost effective means of detecting active infection – can be used to diagnosis, monitoring and eradication confirmation for patients of all ages
H pylori - rx
a. Triple therapy
i. Ampicillin + clarithromycin + omeprazole
1. Metronidazole substituted for either antibiotic – but high resistance
ii. Indications for Tx
1. Children with ulcers + proven infection
2. Children with histologically proven infection w/ gastro symptoms
3. Children with gastric lymphoma + proven infection
4. Children with atrophic gastritis w/ intestinal metaplasia + proven infection
5. Children with refractory IDA + proven infection
Gastroparesis - bg
- Aetiology
a. Idiopathic
b. Post-infectious – viral
c. Anorexia – primary or secondary
d. Diabetic
e. Autoimmune
f. Neurological
g. Post-surgical – vagal damage - Pathophysiology
a. Loss of pacemaker cells - due to deinnervation
b. Gastric dysrhythmias -tachy/ bradygastrias or incoordinate
c. Not responsive to usual emptying signals (hot meals, hypogylcaemia, ghrelin, motilin) - Pathophysiological classification
a. Gastric dysrhythmia and gastroparesis
i. Severe gastric myoelectrical disorder
ii. Rx – N+V, prokinetic therapy, gastro/jejunostomy, TPN , gastric electrical stimulation, pacemaker
b. Normal gastric rhythm and gastroparesis
i. Due to pylorospasm/ obstruction at pylorus/ duodenum with electrocontractile dissociation
ii. Rx – botox/ balloon dilatation, surgical relief of obstruction, prokinetics and antinausea
c. Gastric dysrhythmia and normal emptying
i. Gastric myoelectric disorder
ii. Rx – N+V, prokinetic therapy
d. Normal gastric rhythm and normal emptying
i. Visceral hypersensitivity/ nongastric causes
ii. Rx – N+V, antidepressant therapy, drugs for fundic/ antral relaxation. Further Ix for other causes
Gastroparesis - sx, ix, rx
- Symptoms
a. Feed intolerance
b. Bad breath
c. Nausea
d. Early satiety
e. Reflux
f. Vomiting - Diagnosis
a. Clinical history
b. Barium meal
c. NM scintigraphy
d. Antro-duodenal manometry - Treatment
a. Re-feeding – slowly grading up
b. Nizatidine – prokinetic
c. PPIs
d. Domperidone – dopamine receptor antagonist
e. Erythromycin – acts on motilin receptors in stomach
f. Botox – open sphincter and improve gastric emptying
g. Jejunal feeding (PEJ)
PEG tubes - general
- Key points
a. Can be fastened with button or balloon systems
b. Once the PEG has been placed a tract forms between the stomach and the abdominal wall, this happens quite quickly
c. Note however that the external bumper should be 1-2cm from the abdominal wall
i. It is not the external bumper that prevents leakage - Complications
a. Early
i. Wound site infection and bleeding
ii. Pneumoperitoneum post procedure
iii. Ileus
iv. Oesophageal and gastric perforation = rare
b. Late
i. Deterioration of gastrostomy site
ii. Buried bumper syndrome
1. Long-term consequence of tight apposition of the external bolster of the gastrostomy tube against the abdominal wall
2. Internal bolster gradually erodes into the gastric wall – resulting in pain and inability to infuse feeding
iii. Colocutaneous fistula
iv. PEG tract
c. Any time
i. Tube dysfunction
1. Clogging = managed with irrigation of warm water (better than cola or juice)
2. Tube deterioration = can leak and break which makes tube feeding difficult or impossible
3. Early balloon deflation (internal bolster)
ii. Infection
iii. Bleeding = rare
iv. Peristomal leakage = most common within first few days but can also be seen with mature gastrostomy tract
1. More likely in malnourished patients and those with diabetes
v. Ulceration
vi. Gastric outlet obstruction
1. Gastrostomy tubes can migrate forward into the duodenum and cause gastric outlet obstruction
2. Occurs if the external bolster on the gastrostomy tube is allowed to migrate away from the abdominal wall, allowing the gastrostomy tube to slide forward through the gastrostomy tract and into the duodenum
vii. Inadvertent removal
1. If removed within 4 weeks of placement should NOT be replaced blindly at the bedside; tract may not have matured and gastric wall and abdominal wall may have separated
viii. Leakage of gastric contents or tube contents into peritoneal cavity
1. Results in peritonitis
2. If contents include tube feeding – chemical peritonitis
Upper GI bleeding - causes
Neonates
• Swallowed blood
• Haemorrhagic disease of newborn + other coagulopathies
• Structural problems – intestinal duplications, vascular anomalies
• Gastritis / ulcers(rare)
• Milk protein allergy (rare – usually lower GI)
Children • Mallory Weiss tear • Oesophagitis • Oesophageal varices • Peptic ulcer disease/GI • Pill oesophagitis • Foreign body/ingestions
Stress (critically ill)
Small intestine - anat/phys
- Anatomy
a. 270 cm long at birth, increases to 450-550 cm by 4 years of age
b. Major features
i. Ileocecal valve: prevents backflow from colon to the small intestine
ii. Ileocecal sphincter: remains mildly constricted, slows emptying of ileal contents into the cecum
c. Microscopic features
i. Mucosa composed of villi – finger like projections
ii. Brush border contains digestive enzymes and transport mechanisms
iii. Cells of villi originate in crypts, become more absorptive as they migrate up (crypts are secretory)
iv. Villi present by 8 weeks of gestation in duodenum, by 11 weeks of age in the ileum
v. Renewed every 4-5 days - Structure
a. Permanent plicae circulates – involve mucosa and submucosa
b. Mucosa lined with villi that increase SA for absorption
i. Goblet cells – mucous secretion
ii. Enterocytes – absorption
iii. Core of villi – capillary network, smooth muscle, lymphatics
iv. Form brush border – each villi consists of microvilli to increase SA for absorption, contains enzymes for contact digestion
v. Between bases of villi are intestinal crypts – upper half goblet cells and enterocytes, lower half stem cells for replacement
vi. Paneth cells – secrete lysozyme, phospholipase and defensins which protect against bacterial infection
vii. Brunner glands – in duodenum secrete bicarbonate rich mucous to neutralize stomach acid and allow pancreatic enzyme action
viii. Peyer patches – in ileum large lymphatic nodules with lymphocytes - Physiology
a. Food entering the small intestine triggers
i. Intestinal phase gastric secretion – vasovagal PNS
ii. Enterogastric reflex – duodenum inhibits stomach – SNS
iii. CCK release – gallbladder contraction and pancreatic secretion
iv. Secretin release – bicarbonate release into pancreatic/hepatic secretions
v. Enteroendocrine release of – secretin, cholecystokinin, gastric inhibitory peptide (suppress gastric activity, promote pancreatic/bile secretion)
Large intestine - anat/phys
- Overview
a. 75-100 cm tube, 3 strips of longitudinal muscle (taenia coli)
b. Gross function
i. Absorption of water and electrolytes (mostly proximal half)
ii. Storage of fecal matter until expulsion - Key features
a. Tinea coli – muscularis externa concentrated in three thickened strips
b. Tinea coli contract to form haustra (non-permanent infoldings of mucosa and submucosa)
c. Colonic crypts, no villi
d. Caecum, ascending, transverse, descending, sigmoid colon
e. Rectum and anal canal (simple columnar epithelium changes to non-keratinized stratified squamous)
i. Arterial supply – superior 2/3 IMA, inferior 1/3 systemic circulation
ii. Venous drainage – superior 2/3 portal, inferior 1/3 systemic
iii. Sphincters – internal (smooth muscle- involuntary), external (skeletal muscle- voluntary)
iv. Innervation – superior 2/3 ANS, inferior 1/3 somatic
v. Mucosa – superior 2/3 endodermal columnar, inferior 1/3 ectodermal squamous
f. Regulated by
i. Gastrocolic + duodenocolic reflexes (stretch movement of colon)
ii. Irritation - Defecation
a. Rectum is usually empty of faeces due to weak functional sphincter between sigmoid colon + rectum AND sharp angulation
b. Presences of faeces in the rectum induces reflex contraction of rectum and relaxation of anal sphincter
c. Prevention of faecal dribble prevented by
i. Internal anal sphincter (immediately inside anus)
ii. External anal sphincter – striated voluntary muscle that surrounds internal sphincter - Controlled by pudendal nerve
d. Defecation reflex – consists of two nervous system actions: local enteric and parasympathetic
i. Intrinsic reflex: local enteric nervous system rectal wall, initiates peristaltic waves moving feces towards anus - This initiates internal anal sphincter relaxation through myenteric plexus inhibitory signals
ii. Fortified by parasympathetic defecation reflex: PNS fibres via pelvic nerves intensify peristaltic waves and relax the internal anal sphincter
e. Last step is conscious relaxation of the external anal sphincter - Bacterial flora
a. Involved in digestion (bilirubin and bile acids)
b. Provide body with vitamins (B and K)
c. Trains immune system
d. Elimination of pathogenic bacteria
Absorption - overview
- Duodenum
a. Iron
b. Folic acid - Jejunum
a. CHO
b. Folic acid
c. Water soluble vitamins - Duodenum + jejunum
a. Calcium/Magnesium/Phosphate - Proximal 100-200cm of intestine
a. CHO
b. Protein
c. FFA + TG (more distal)
d. Water soluble vitamins - Throughout the small intestine
a. Monoglycerides and fatty acids as micellar complexes
b. MCT directly into portal circulation - Distal ileum
a. Vitamin B12
b. Bile salts
c. Fatty acids - Colon
a. Water
b. Electrolytes
Carbohydrate digestion/phys
- Intake
a. 200-300 gm/day (adult)
b. 50% starch, 50% sugars (30% sucrose, 10% lactose)
c. CHO provides 50% energy requirements - Dietary forms
a. Polysaccharides = starch (glucose polymer) digested in human gut
i. Glycogen = from animals in long chain (1:4 alpha), with branch (1:6 alpha)
ii. Amylopectin (major diet) = from plants only (1:4 alpha), rare branches
iii. Amylose = 1:4 alpha chain
b. Disaccharides
i. Sucrose = glucose + fructose
ii. Lactose = glucose + galactose
iii. Maltose = glucose + glucose
c. Monosaccharides = glucose, galactose, fructose - Digestion
a. Mouth
i. Salivary amylase - inactive at acid pH ie. in stomach
b. Intestinal lumen
i. In duodenum, salivary amylase is reactivated when pH is returned to neutral by bicarbonate in pancreatic juice and secreted from duodenal epithelium
ii. Pancreatic alpha-amylase secreted due to CCK release from duodenal mucosa
iii. Both salivary and pancreatic alpha-amylase are effective against 1:4 alpha linkages but ineffective at 1:6 alpha linkages, thus leaving a variety of oligosaccharides intact
iv. Glucose, disaccharides and oligosaccharides are brought up against brush border membranes of the mucosal enterocytes (especially tips of villi)
v. Amylases can only break down polysaccharides to disaccharides
c. Intestinal brush border
i. Several different enzymes in brush border break up oligosaccharides and disaccharides
ii. Glucoamylase + dextrinase = maltose
iii. Sucrase-isomaltase - Sucrose glucose + fructose
- Maltose glucose + glucose
- Effective against 1:6 alpha linkages
iv. Lactase - Lactose glucose + galactose
- Peak activity at birth
- 50% of world population has drop – decline 5-7 years of age
- Infectious gastroenteritis – monosaccharide malabsorption due to transient lactase deficiency; can also have transient sucrase deficiency
- Lactase is NOT inducible; sucrase-isomaltase and brush border oligopeptidases CAN be inducible
- Absorption
a. Glucose and fructose are rapidly absorbed in duodenum and jejunum
i. Glucose + galactose – Na+ dependent glucose transporter (SGLT1) [basis of ORS]
ii. Fructose – facilitated diffusion via GLU5
b. All monosaccharides are transported across basal border by GLUT 2 transport
Protein - requirements, digestion, absorption
- Requirements
a. 0.75 g/kg/day high quality protein
i. Maintenance of nitrogen balance
ii. Adequate supply of essential amino acids
iii. Higher intake for illness, growth pregnancy and lactation
b. 20 amino acids = 9 essential, not synthesized by mammals
i. Histidine, leucine, isoleucine, lysine, methionine, phenylalanine, threonine, tryptophan, valine
c. Dietary proteins vary in composition - plant protein less digestible
d. Protein absorption > 90% efficient
e. Process = Intraluminal hydrolysis brush border peptidases - Digestion
a. Stomach
i. Digestion begins in stomach with pepsin
ii. Pepsin = hydrolyses bonds between aromatic amino acids (phenylalanine, tyrosine) and a second amino acid polypeptides of diverse sizes (as it only acts at limited places in a protein) - Secreted from chief cells as pepsinogen (A/C) (pro-enzyme)
- Stimulus for secretion
a. cAMP (secretin, VIP, adrenaline, PG)
b. Intracellular Ca2+ (ACh, CCK, gastrin) - Activated/cleaved by gastric acid to pepsin (active form) (pH optimum 1.6-3.2)
iii. Inactivated at neutral pH (not effective once it gets out of the stomach and into the duodenum)
b. In duodenum and jejunum
i. CCK release triggered by amino acids causes secretion of pancreatic proteases in form of inactive proenzymes
ii. Pro-enzymes activated first by enterokinase in epithelial membrane - Trypsinogen to trypsin
- Trypsin is an endopeptidases resulting in a cascade to activate other proenzymes
- Producing chymotrypsin, elastase, carboxypeptidase A and B
- Results in formation of oligopeptides
iii. Pancreatic peptidases - Endopeptidases = trypsin, chymotrypsin, elastase
a. Act at interior peptide bonds - Exopeptidases = pancreatic carboxypeptidases
a. Act on terminal amino acids
iv. Peptidases at the brush border break oligopeptides down into dipeptides, tripeptides and amino acids - Produces 40% free amino acids, 60% oligopeptides
- Absorption
a. Protein can enter the cell by separate non-competitive carriers that can transport individual amino acids or dipeptides and tripeptides
b. Brush border
i. Amino acids - Multiple transport systems
ii. Peptides - Small peptide transport independent of amino acid uptake
- Peptide transport often faster than free amino acid
a. Absorption faster in jejunum (amino acid faster in ileum) - Active transport
c. Basolateral membrane (to portal blood)
i. Systems: Na independent (3), Na dependent (2)
Fat - bg
- Adult intake
a. Consumption 120-150g
b. Biliary lipid 40-50g
c. 3 physical forms
i. Fat or oil droplets
ii. Membranes
iii. Skin lipids (animal and vegetable) - Key events
a. Emulsification = starts in stomach (peristalsis)
b. Lipolysis = lingual, gastric + pancreatic
c. Micelle formation = bile salts + lipids
d. Absorption
e. Fat absorption >95% efficient (85% in infants)
f. 2-3% exocrine function allows normal fat absorption - NOTE:
a. Fat absorption is less efficient in the neonate compared with adults
b. Premature infants can lose up to 20% of their fat calories compared with 6% of an adult
c. Decreased synthesis of bile acids and pancreatic lipase and decreased efficiency of ileal absorption are contributing factors
d. Medium chain fatty acids (10C) portal venous system
e. 85% of CF patients have no pancreatic function when born – reasonable absorption up to 50% - due to lingual and gastric lipase
Fat - digestion, absorption
- Fat digestion
a. Lingual lipase = active in stomach, digests up to 10% TG
b. Gastric lipases = less important – although if pancreatic insufficiency activity increases
i. Greater role in infants
c. Pancreatic lipases
i. CCK release leads to secretion of pancreatic lipolytic enzymes (and bile)
ii. Trypsin activates colipase colipase activates lipase
iii. Act on emulsified fats
iv. Hydrolyses 1,3 bonds – products are FFA and 2MG
d. Bile salt activated lipase
i. Hydrolyses cholesterol esters
ii. Fat soluble vitamins, phospholipids - Micelle formation
a. Emulsified by bile acids micelles with phospholipids and other fat soluble substances
b. Micelles composed of 20-40 bile acids in circle with hydrophilic outwards and hydrophobic inward
c. Bile cholesterol and phospholipids form core
d. Function to absorb fat soluble vitamins, cholesterol, FFA and monoglycerides
e. Transport to SI wall where fat absorbed into enterocyte (terminal ileum) - Fat absorption
a. Lipids inside micelles brought to apical surface of epithelial cells, at tips of villi
b. When in contact with membrane fat soluble lipids can dissolve in membrane and enter cells (as lipid soluble)
c. Bile salts – poorly absorbed in proximal gut (absorbed in terminal ileum)
d. Lipid absorption
i. FA <12 C direct to portal system (ie. MCT)
ii. FA >12 C re-esterified to TG - Leave cell with cholesterol esters
- Coated with protein, cholesterol and phospholipid as chylomicrons via lymphatics
e. NO active transport required - Chylomicron formation + transport
a. In epithelial cells, fatty acids and monoglycerides reform triglycerides in smooth ER (membrane structure in which they can dissolve)
b. Golgi processes them into chylomicrons by combining with phospholipids and cholesterol
c. Secreted by exocytosis into extracellular space
d. Chylomicrons exocytose at basal membrane and enter lacteals
e. Lacteals enter the lymphatics and join blood supply as they go into the larger blood vessels where they can be transported to the liver
Fat globules vs crystals on faecal microscopy
Fat globules = maldigestion eg. pancreatic insufficient, cholestatic liver disease
Fat crystals = malabsorption (e.g. giardia)
Water soluble vitamin absorption
• Na cotransport o Ascorbic acid Actively transported, Na coupled Simple diffusion if concentration high o Also riboflavin, thiamine, niacin, pyridoxine, biotin, pantothenate
• Na independent
o Folate – hydrolysis before entry, jejunal absorption, saturable
Vitamin B12
- Intake
a. From animal sources
b. 10-20 ug ingested/day – only 1-2 ug needed - Digestion + Absorption
a. Food bound B12 is released by gastric acid and pepsin and binds preferentially with salivary R protein in the stomach
b. Proteolysis of R protein by trypsin release B12 for binding with IF
c. This then binds specific ileal receptors and this is then released at an intracellular site – transported across the BL membrane – and taken up transcobalamin II for transport to portal circulation for distribution
d. Absorption occurs in distal small intestine - NOTE:
a. PPI may lead to B12 deficiency due to proximal effects with respect to B12 release
Fat soluble vitamin absorption
- All ingested with dietary fats
- Absorbed in terminal ileum with micelles
- Protein bound in plasma
- Must be activated
- Absorption of fat-soluble vitamins commonly impaired more than absorption of dietary fats
Calcium absorption
- Functions and dietary sources
a. Adult body 1200g of Ca (99% bone/teeth)
b. 1% nerve conduction, muscle contraction, membrane permeability, protein kinases etc
c. Dairy 55% , also leafy green vegetables, Ca fortified - Pathways of intestinal Ca absorption
a. Small intestine and colon
b. At high dietary intakes, passive diffusion (paracellular)
c. At low intake, saturable energy dependent transcellular - depend on vitamin D 3- 1,25(OH)2D3 - Absorption
a. Efficiency 30-80%
b. Activity in upper small intestine most important
c. Diffuses through apical membrane then binds to calbindin cytoplasmic protein
d. Exits basal membrane via calcium ATPase
e. Vitamin D – increases calbindin and calcium-ATPase
f. Factors affecting absorption
i. 1,25 DHCC Ca+ binding protein, Ca++-H+ATPAse (calbindin-D – alters rate not final amount)
ii. Increased Ca2+ reduction in 1,25 DHCC
iii. Low Ca2+ increased 1,25 DHCC
g. Some passive diffusion
Iron absorption
- Role
a. Cellular oxidative energy metabolism (redox enzymes)
b. Oxygen transporting proteins (Hb, myoglobin) - Balance
a. Losses generally small – 0.6-1.2 mg/day
b. Intake 20 mg/day (haem and nonhaem iron)
i. Fe2+ best absorbed (haem)
ii. Dietary Fe3+ reduced in gastric acid to Fe2+ (vitamin C)
iii. Diet affects iron availability (phytates, phosphate, oxalate inhibit)
c. Stores regulated by intestinal absorption
i. Amount absorbed = amount lost (usually)
d. Deficiency = hypochromic microcytic anaemia
i. Celiac most common cause of proximal small intestinal disease – therefore common cause of iron deficiency
ii. Always think intake, absorption + losses
e. Overload = oxidant damage (haemochromatosis) - Absorption
a. Absorbed in duodenum
b. 10% of dietary intake is absorbed and this depends on iron status
c. Most is in the ferric form Fe3+ that is converted to the ferrous form Fe2+ at the apical membrane by ferroreductase which is induced by hypoxia and deficiency
d. 3 pathways are proposed for absorption – divalent metal transporter, Para cellular, and a separate pathway from haem iron
e. Within the cell one or more iron binding proteins take up the iron and transfer it to the BL membrane of transfer across this and binding to transferrin
Water and electrolyte absorption
• Water
o Water balance – 2L/day ingested, 7L/day secreted, 98% absorbed
o Water follows osmotic gradients set by Na+
o Active transport with Na-coupled transporters
o Daily stool water loss about 200ml
• Sodium absorption
o Na+ actively absorbed down concentration gradient established BL Na-K-ATPase associated with Cl
o Na coupled transport for glucose and amino acids enables solute transport
o Coupled NaCl transport (uses 2 exchangers, Na-H, and Cl-HCo3)
• Chloride transport
o Chloride absorbed in the distal ileum in exchange for bicarbonate – active transport
o Enters cells via basolateral Na-K-2 Cl cotransport
o Secretion via Cl channels
o Regulated by protein kinases
o Regulated by PK-A and cAMP (cholera)
• Potassium transport
o K secretion partly down electrical gradient
o Absorbed by concentration gradient
o Active secretion of K increased by aldosterone (Chronic diarrhoea > low K)
B vitamin deficiency - summary
- B1 (thiamine) Beriberi (infantile form affects heart>nerves)
- B2 (riboflavin) angular cheilitis, stomatitis, seborrheic dermatitis, eye problems
- B3 (niacin) pellagra (3 D’s – dermatitis, diarrhoea, dementia)
- B6 (pyridoxine) neuro, hypochromic anaemia
- B12 (cobalamin) neuro, megaloblastic anaemia
Passive diffusion in upper small intestine - except for B12 which requires intrinsic factor and distal ileum
Investigations - stool parameters
- pH: Alkaline < 6 suggests osmotic diarrhoea
- Reducing substances: <0.25 g/dL = negative, 0.25-0.5 g/dL = suspicious, >0.5 g/dL = abnormal
- Osmolality: Equal to serum ~300 mOsm/kg, < 220 suggests hypotonic dilution, >330 poorly stored specimen
- Osmolar gap 290 – 2x (Na+K): 50-100, > 100 suggests osmotic diarrhoea ( eg laxatives), < 50 suggests secretory diarrhoea
- Sodium: ~ 30, >70 suggests osmotic diarrhoea
- Potassium: 75
- Chloride: 20-30, > 60 in infants/ > 100 in adults suggests congenital/ secondary chloridorrhoea , < 20 in laxative use
Secretory versus osmotic diarrhoea
Osmotic
- Caused by non-absorbed nutrients in the intestinal lumen dragging water out into gut with glucose (gut hyperosmolar to blood)
- cease with fasting: Yes (as no more sugar)
- volume: <200 ml/day
- sodium: <70 meq/L
- osmotic gap: High >100, > (Na + K) x 2
- reducing substances: Present
- pH: <5
- explosive, excoriated: ++
- aetiology:
• Osmotic laxatives (eg. lactulose, sorbitol, mannitol)
• Mucosal injury – infective (eg. post-rotavirus), inflammation (IBD), immune mediated (celiac), vascular
• Disaccharidase deficiency
• Monosaccharide transport defect (eg. glucose-galactose deficiency)
• Transport overload (increased sugar, fruits)
Secretory
- Drags water out into gut with sodium (due to reduced absorption of electrolytes or abnormal ion transport into intestinal epithelial cells)
- fasting: No effect
- volume: >200 ml/day
- sodium: >70 meq/L
- osmotic gap: Low <50, = (Na + K) x 2
- reducing substances: Absent
- pH: >6
- explosive, excoriated: +/-
- aetiology:
• Congenital transport and mucosal defects eg. chloridorrhoea, microvillus inclusion, tufting enteropathy
• Secretagogue
o Toxigenic bacteria – cholera (turn on cAMP), E coli (toxigenic), Salmonella, C difficile, cryptosporidium, Yersinia
o Bile acid malabsorption (bile acids turn on cAMP)
• Tumours producing hormones (eg. VIP-5HIAA)
• Short gut
• Rapid transport
Stool osmotic gap
• Stool electrolytes and calculating an osmotic gap can help distinguish secretory and osmotic diarrhoea
• 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+})
o Osmotic gap of >100 mOsm/kg suggests an osmotic diarrhea ie there is a low concentration of Na and K in the stool
o Gap of <50 mOsm/kg suggests a secretory diarrhea ie there is a high concentration of Na and K in the stool driving the diarrhoea
Gastro investigations - imaging
Contrast
- Barium swallow
a. Fluoroscopic form of imaging
b. Assess motility and anatomy
c. Useful for – strictures, hiatal hernia, pyloric stenosis, external oesophageal compression - Modified barium swallow
a. For H-type tracheoesophageal fistula
b. Esophagus distended with barium via a nasogastric tube with patient lying prone
c. Various consistencies of barium used
Endoscopy
- Endoscopy
a. Direct visualisation of oesophageal mucosa
b. Therapies – removal of foreign bodies, treatment of varices, biopsies - Fiberoptic endoscopic evaluation of swallowing
a. Nasopharyngeal endoscopy used to visualize pharynx + larynx during swallowing
b. Useful for – laryngeal penetration, aspiration
Breath hydrogen excretion
a. Breath samples every half hour post ingestion of lactose
b. Hydrogen level will rise due to bacterial fermentation of lactose (as it is not absorbed )
c. BUT false negative may be obtained if relevant bacteria not present
d. Negative test must be compared to lactulose test not absorbed, looks for fermentation by bacteria
e. Can also be used as test of gastric emptying
Malabsorption - gen bg
- Key points
a. All disorders of malabsorption are associated with diminished intestinal absorption of one or more nutrients
b. Can result from a defect in nutrient digestion in the intestinal lumen or defective mucosal absorption
c. Categorized into general mucosal abnormalities usually resulting in malabsorption of multiple nutrients, or malabsorption of specific nutrients
d. Almost all malabsorption disorders are accompanied by chronic diarrhoea which worsens malabsorption
Types/Categories Mucosal disorders (coeliac, CMPA) Protein losing enteropathy (lymphangiectasia, Crohns) Congenital bowel mucosal defect Immunodeficiency disorders Autoimmune enteropathy (IPEX) Miscellaneous (short bowel syndrome)
Malabsorption - general hx/ex
a. Variation in clinical presentation based on age
i. Nutritional consequences of malabsorption more dramatic in toddlers due to limited energy reserves and higher proportion of calorie intake being used for weight gain and linear growth
ii. In older children, malnutrition more often results in growth retardation
b. Common presenting symptoms
i. Diarrhoea
ii. Abdominal distension
iii. Falling growth centiles
iv. Failure to gain weight – particularly toddlers
v. Anorexia
vi. Specific to underlying condition
1. Diarrhoea
a. Onset in infancy congenital defect
b. Secretory diarrhoea caused by disorders such as congenital chloride diarrhoea and microvillus inclusion disease stool watery and voluminous can be mistaken for urine
c. Explosive watery diarrhoea suggests CHO malabsorption
d. Loose, bulky stools are associated celiac disease
e. Pasty and yellowish offensive stools exocrine pancreatic insufficiency
f. ‘Peas and carrots’ with green stool Toddler’s diarrhoea
2. Anorexia
a. Many children have good appetite
b. Exocrine pancreatic insufficiency – faecal losses of up to 40% of ingested protein and energy does not lead to malnutrition provided increased caloric intake
c. In conditions associated with villous atrophy or inflammation (celiac disease, post-infectious enteropathy), fecal protein and energy losses are usually modest, but associated anorexia and reduced food malnutrition
3. Onset of symptoms after food intake eg. sucrose in sucrase-isomaltase deficiency
c. Examination findings
i. Abdominal distension
ii. Muscle wasting
iii. Disappearance of SC fat lose skin folds
iv. Specific to underlying condition
1. Edema – usually associated with protein losing enteropathy
2. Digital clubbing – CF, celiac disease
3. Perianal excoriation and gaseous abdominal distension – CHO malabsorption
4. Perianal and circumoral rash – acroderma enteropathica
5. Abnormal hair – Menkes syndrome
6. Facial features typical of Johanson-Blizzard syndrome
d. Nutritional assessment
i. Calcium and vitamin D malabsorption reduced BMD and metabolic bone disease, increasing risk of fractures
ii. Vitamin K malabsorption coagulopathy
iii. Severe protein losing enteropathy (often associated with malabsorption syndromes celiac disease, intestinal lymphangiectasia) hypoalbuminaemia and edema
iv. Iron malabsorption IDA and low reticulocyte count
Malabsorption - investigations overview
a. Stool tests
i. Microscopy/Culture RBC/WBC associated with inflammatory conditions
ii. Microscopy for ova/cysts/parasites Giardia
iii. Antibody tests for parasites
iv. pH and reducing substrates CHO malabsorption
v. Quantitative stool fat identify fat malabsorption
vi. Alpha-1 antitrypsin protein malabsorption
vii. Elastase exocrine pancreatic insufficiency
viii. Calprotectin IBD
b. Blood tests
i. FBE + film
1. Microcytic anaemia Fe deficiency
2. Lymphopenia Lymphangiectasia
3. Neutropenia Shwachman syndrome
4. Acanthocytosis Abetalipoproteinaemia
ii. Serum IgA and tTG antibodies celiac disease
Malabsorption - ix specifics
a. CHO malabsorption
i. Stool pH and reducing substrates – acidic stool with >2+ reducing substrates suggestive
ii. Hydrogen breath tests – can identify specific CHO being Malabsorbed
iii. Small bowel mucosal biopsies – can measure mucosal disaccharidase (lactase, sucrase, maltase, palatinase) concentrations
1. Primary enzyme deficiencies = low levels and normal morphology
2. Celiac disease or following rotavirus = partial or total villous atrophy with associated reduction in enzymes (return to normal after mucosal healing)
b. Fat malabsorption
i. Fat globules in stool – suggestive of fat malabsorption
ii. Quantitative 3 day stool collection – allows you to calculate coefficient of fat absorption
iii. Nutritional deficiencies (ADEK) – associated with fat malabsorption
c. Protein-losing enteropathy
i. Hypoalbuminaemia
1. Most common cause in children is renal disease – urine protein excretion must be determined
2. Other potential causes include liver disease + inadequate protein
ii. Stool alpha1-antitrypsin
1. MW similar to albumin, however resistant to digestion in the GI tract
2. Excessive alpha-1 antitrypsin excretion in the stool should prompt further Ix to identify the specific cause of gut or stomach (Mentrier disease) protein loss
d. Exocrine pancreatic function
i. Cystic fibrosis most common cause of exocrine pancreatic insufficiency – needs to be excluded
ii. Faecal elastase 1 – sensitive test to assess exocrine function
1. Cannot distinguish between primary exocrine pancreatic deficiency and exocrine dysfunction secondary to intestinal villous atrophy
2. Mucosal atrophy can lead to reduced CCK/pancreozymin secretion reduced hormonal stimulation for exocrine enzyme secretion
3. False positives can occur in diarrhoea
iii. Serum trypsinogen
1. Screening for exocrine pancreatic insufficiency
2. In CF – levels elevated in early life, then gradually fall
3. Shwachman syndrome – serum trypsinogen low
e. Intestinal mucosal disorders
i. Biopsy often required
Coeliac disease - bg
- Key points
a. Immune-mediated systemic disorder elicited by gluten and related prolamines
i. Wheat, rye and barley; oats appear to be safe (however reports of some reactivity)
b. Characterised by the presence of a variable combination of gluten-dependent clinical manifestations, celiac-specific antibodies, HLA-DQ2 an DQ8 haplotypes, and enteropathy - Epidemiology
a. Common – 1% prevalence
b. Rare in Central Africa and East Asia
c. Associated disorders - essentially autoimmunes (T1DM, thyroid, addison, Sjogren, cholangitis/hepatitis, PBC) - Genetics
a. Genetic predisposition suggested by family aggregation + concordance in monozygotic twins – approaches 100%
b. Risk in first degree relative 10%
c. Strongest association is with HLA DQ2 and DQ8
i. 90-95% express HLA DQ2, 5-10% carries HLA DQ8
ii. 40% of the general white population are DQ2 +ve, 40% DQ8 +ve - Pathogenesis
a. T cell mediated chronic inflammatory disorder with autoimmune component
c. Immunodominant epitopes from gliadin are highly resistant to intraluminal and mucosal digestion
d. Gliadin peptides stimulate the innate immunity (particularly IL-15) -> T cell activation
f. Pattern of cytokines dominated towards IFN-g (Th1 type skewed); IL-21 also increased
g. Downstream T cell activation, a complex remodeling of the mucosa
h. Severe impairment of intra-epithelial lymphocytes (IELs) homeostasis is present
Coeliac disease - sx
a. <2 years
i. Intestinal symptoms
ii. FTT
iii. Chronic diarrhoea
iv. Vomiting, abdo distension
v. Muscle wasting
vi. Anorexia and irritability
vii. Occasionally rectal prolapse, intussusception or constipation
b. >2 years
i. Extraintestinal manifestations become more common
ii. Most common – iron deficiency anaemia not responsive to iron
iii. Other - short stature, arthritis and arthralgia, epilepsy with bilateral occipital calcifications, peripheral neuropathies, cardiomyopathy, isolated hypertransameinasemia, dental enamel hypoplasia, aphthous stomatitis, and alopecia
c. Most common extra-intestinal manifestation is iron deficiency anaemia, not responsive to Fe supplements
d. Silent celiac disease increasingly recognized – mainly in asymptomatic 1st degree relatives identified with screening – small bowel biopsy can show severe mucosal damage
e. Presentation in T1DM
i. Unpredictable BGL
ii. Recurrent hypoglycaemia
iii. Poor glycaemic control
iv. Growth failure (GIT symptoms less likely)
Vit D/Ca malabsorption -> rickets
Thiamine/B12 deficiency -> neuropathy, epilepsy, ataxia
Coeliac disease - ix/dx
- Investigations
a. Diagnosis is a combination of symptoms, antibodies, HLA and biopsy (MCH gastro team no interest in HLA)
b. Can be confirmed by clinical response to gluten free diet and reducing antibody titre
c. Serology
i. Current serology - Tissue transglutaminase (IgA)
- Deamidated gliadin peptide (DGP) IgG
ii. In practice, both tests have >85% sensitivity and >90% specificity
iii. Note the DGP assay has replaced the whole-protein anti-gliadin antibody (AGA) assay because of improved specificity; however, many labs will report the DGP result as the ‘anti-gliadin antibody’
iv. The anti-endomysial antibody (EMA) test measures tTG antibodies, but is labour-intensive, user-dependent and less widely performed
v. The tTG assay has lower sensitivity in children under three years of age - Ensure DGP-IgG testing is performed alongside tTG-IgA to overcome this issue
d. Genetic studies
i. HLA DQ2, DQ8 - If negative, it can be used to exclude coeliac disease
- If positive, not useful as 30% of the population is DQ2 or DQ8 positive; 1% have coeliac disease
- NOT useful as a screening tool
e. Biopsy
i. Gold standard for diagnosis
ii. Duodenal biopsy
iii. NEEDS to be while individual consuming gluten
iv. Histological features - Increased intraepithelial lymphocytes
- Loss of villi – partial to total villous atrophy
- Elongated crypts
- Increased mitotic index in crypts
- Loss of brush border, abnormal flattened epithelial cell
- Diagnostic guidelines
a. New European guidelines, based on evidence that high-titre tTG is strongly predictive of coeliac disease in children, suggest small intestinal biopsies can be avoided if children meet the following criteria:
i. Characteristic symptoms of coeliac disease
ii. tTG-IgA levels >10× upper limit of normal
iii. A positive endomysial antibody (EMA) on a different blood sample
iv. Positive HLA susceptibility for coeliac disease
Coeliac disease - rx, cx
- Treatment
a. Lifelong strict adherence to gluten free die (wheat, barley and rye); usually exclude oats
b. Wheat, Rye, Barley ‘oats’ (in Australia due to contamination)
c. Note rice and maize are okay!
d. Clinical improvement ~ 3 weeks
e. Improvement in histology and serology may take 6-18 months - Complications
a. Osteoporosis
i. 70% of untreated adults have osteopenia, increases with age at diagnosis
ii. Gluten free diet allows improvement within 1 year
iii. Low bone density in 27-40% of CD
b. Autoimmune diseases
c. Increased risk of cancer
i. 20X RR for small bowel lymphoma (EATL)
ii. 30x RR for small bowel adenocarcinoma (uncommon generally, one of few conditions which causes)
iii. 2-4X RR for esophageal cancer
Non-coeliac gluten sensitivity - general
- IgE mediated wheat allergy
a. May have overlapping symptoms with celiac disease
b. More often presents without an enteropathy but with symptoms of atopy (urticaria, angioedema, eczema, asthma, rhinitis)
c. Diagnosed by the presence of IgE antibodies to wheat (serum specific or skin prick test)
d. Symptoms occur classically soon after ingestion - Gluten sensitivity
a. Area of uncertainty in paediatrics
Congenital defects in intestinal mucosa
a. Microvillous inclusion disease (congenital microvillus atrophy)
i. Key points
1. Autosomal recessive disorder
2. Manifests at birth with profuse watery secretory diarrhoea
3. Most severe cause of congenital diarrhoea
4. Polyhydramnios may be present antenatally
5. Many cases run in the same family in highly consanguineous union; suggests autosomal recessive
ii. Pathogenesis
1. Light microscope shows thinning of the mucosa, with hypoplastic villous atrophy and no inflammatory infiltrate
2. Electron microscopy shows enterocytes with absent or sparse microvilli; hallmark is presence of microvilli within involutions of the apical membrane
iii. Clinical manifestations
1. Very early onset of severe watery diarrhoea (up to 200-330 ml/kg/day) dehydration + FTT
2. Disease fatal without long term TPN
3. Most children die in infancy or early childhood
4. Intestinal transplantation only definitive treatment
b. Tufting enteropathy
i. Manifests in the first few weeks of life with persistent watery diarrhoea; accounts for a small fraction of infants with intractable diarrhoea of infancy; persists despite bowel rest and TPN
ii. Distinctive feature on small intestinal mucosal biopsy is focal epithelial ‘tufts’ involving 80-90% of the epithelial surface
vi. No treatment effective; requires TPN +/- intestinal transplantation
c. Enteric anendocrinosis
i. Mutations in NEUROG3 gene
ii. Generalised mucosal malabsorption, vomiting, diarrhoea, FTT, dehydration and hyperchloraemic acidosis
iii. Oral alimentation with anything other than water produces diarrhoea
iv. Staining for neuroendocrine cells demonstrate a complete absence of this cell lineage with preserved goblet and Panathe cells
v. Treatment = TPN +/- transplantation
Proprotein convertase 1/3 deficiency
a. Autosomal recessive condition ; mutation in PCSK1 gene
b. Chronic watery neonatal onset diarrhoea
c. Hyperinsulinism, hypoglycaemia, hypogonadism and hypoadrenalism
d. Small bowel biopsy shows non-specific enteropathy
e. Siblings have marked obesity and Hyperphagia
f. Elevated levels or proinsulin highly supportive
Autoimmune enteropathy
a. Usually occur AFTER the first 6 months life – present with chronic diarrhoea, protein-losing enteropathy, malabsorption and FTT
b. Histology – partial or complete villous atrophy, crypt hyperplasia, and an increase in chronic inflammatory cells in lamina propria; cf. celiac disease NO increased number in intra-epithelial lymphocytes
c. Immunologic shows presence of anti-enterocyte antibodies and anti-autoimmune enteropathy
d. Extra-intestinal autoimmune disorders = arthritis, membranous GN, IDDM, thrombocytopenia, hepatitis, hypothyroidism, immune deficiency
e. Must exclude primary immune deficiency – can be linked to IPEX syndrome
f. Treatment options limited – based on immunosuppression
Bile acid malabsorption
a. Mutation in the ileal sodium-bile acid cotransporter gene (SCL10A2) -> congenital diarrhoea, steatorrhoea, interruption of enterohepatic circulation of bile acids, and reduced plasma cholesterol levels
b. Usually only 10% of bile acids escape reabsorption
Abetalipoproteinameia
a. AR disorder of lipoprotein metabolism -> severe fat malabsorption from birth
b. Defect in chylomicron assembly
c. Clinical features
i. Steatorrhoea
ii. Vitamin ADEK deficiency -> peripheral neuropathy (vit E deficiency)
iii. ID
iv. Ataxia with loss of position + vibration sense due to vit E deficiency
v. Atypical retinitis
d. Diagnosis
i. Acanthocytes and fat inclusions on peripheral blood smear
ii. Low plasma levels of cholesterol, triglycerides and LDL
e. Treatment = supplementation
- HOMOZYGOUS HYPOBETALIPOPROTEINAEMIA
a. AD disorder similar to abetalipoproteinemia
b. Differentiated on small bowel biopsies
Bacterial overgrowth - general
a. Definition
i. Small bowel bacterial overgrowth – meaning colonic bacteria found proximally in small bowel
1. Small bowel usually populated by aerobes- enterococci, gram positive, lactobacilli
2. Colon usually anaerobes – bacteroides, lactobacillus, clostridium
b. Predisposing conditions
i. Dysmotility – short bowel syndrome (due to adaptive changes in SI), pseudo-obstruction, malnutrition
ii. Biliary obstruction – cirrhosis
iii. Pancreatic insufficiency – chronic pancreatitis
iv. Absent ileocaecal valve / communication – intestinal fistula, bowel strictures, short bowl
v. Other – diabetes, prematurity
c. Pathogenesis
i. Bacteria usually only present in a small number in the stomach and small bowel – excessive numbers can be harmful
ii. The role of enteric bacteria
1. CHO – salvage unabsorbed dietary sugars by fermentation to FA – absorption in colon
2. Produce vitamins folate and vitamin K
3. Prime immune response – preventing reaction to protein antigens in diet
4. Inhibit pathogenic bacterial population causing disease
iii. Mechanisms protecting against excessive SI colonization
1. Motility – peristalsis, migrating motor complex
2. Gastric and bile acid destruction
3. Digestion by proteolytic enzymes from pancreas
4. Ileocaecal valve – inhibits colonic bacterial reflux
5. Immune system and secretory IgA
6. Mucosal defenses such as mucin and Ig
d. Clinical manifestations
i. Excessive fermentation (CHO malabsorption – abdominal distension, diarrhoea, flatulence)
ii. Protein malabsorption (protein losing enteropathy)
iii. Fat malabsorption
iv. B12 deficiency (anaemia and neurological effects)
v. Inflammation by unwelcome bacteria (immune dysregulation = arthritis)
e. Diagnosis
i. Culturing small bowel aspirate
ii. Lactulose hydrogen breath test = not digested by mucosal brush border enzymes + fermented by bacteria high baseline hydrogen and a quick rise suggests bacterial overgrowth (false pos common)
f. Treatment
i. Correction of underlying disorders eg. partial obstruction
ii. Antibiotics = 2-4 weeks of metronidazole, cycling of bactrim, azithromycin, ciprofloxacin, metronidazole
1. Other options – aminoglycosides, nitazonxaide, rifaximin
Infections a/w malabsorption
- POST-INFECTIOUS DIARRHOEA
a. In infants and very young toddlers chronic diarrhoea can appear following infectious enteritis
b. Pathogenesis - unclear
i. Secondary lactase deficiency
ii. Food protein allergy
iii. Antibiotic associated colitis
c. Treatment = supportive; may include lactose free diet - BACTERIAL OVERGROWTH (SIBO)
- separate flashcard - TROPICAL SPRUE
a. Natives and expats of certain tropical regions can present with a diffuse lesion of the small intestinal mucosa – topical sprue – long after migration
b. Etiology unclear; infectious etiology suspected
c. Leading cause of malabsorption in India
d. Diagnosis = small bowel biopsy, shows villous flattening, crypt hyperplasia and chronic inflammatory cell infiltrate
e. Treatment = nutritional supplementation, including folate and vitamin B12
i. To prevent recurrence oral folic acid + 6/12 of tetracycline or sulfonamide
ii. Relapse in 10-20% of patients who live in endemic tropical region - WHIPPLE DISEASE
a. Chronic systemic infectious disorder
b. Rare disease, especially in childhood
c. Caused by infectious agent Tropheryma whipplei
d. Treatment = bactrim for 1-2 years
Immune related malabsorption
- IMMUNODEFICIENCY DISORDERS
a. Malabsorption can occur with congenital immunodeficiency disorder, and chronic diarrhoea with FTT is often the mode of presentation
b. Defects of humoral or cellular immunity, eg:
i. IgA deficiency = usually asymptomatic, malabsorption may be caused by giardiasis or non-specific enteropathy in which bacterial overgrowth can occur
ii. CVID = malabsorption in 60% of patients, usually non-infectious
iii. Agammaglobulinaemia
iv. SCID
v. Wiskott-Aldrich syndrome
vi. CGD = phagocytic function impaired and granulomas develop along the GI tract mimicking Crohn’s disease - IMMUNOSUPROLIFERATIVE SMALL INTESTINAL DISORDERS
a. Malignant lymphomas of the small intestine (Burkitt most common and involves terminal ileum, NHL, Mediterranean lymphoma) - EOSINOPHILIC GASTROENTERITIS
a. Eosinophilic digestive diseases are a group of rare and heterogenous conditions characterized by patchy or diffuse eosinophilic infiltration of GI tissue
b. Eosinophilic gastroenteritis based on GI symptoms, GI eosinophilic infiltrates, and the absence of other infections
c. Peripheral eosinophilia and elevated IgE variably present but not diagnostic
d. Most patients have history of allergic disorders
e. 10% of patients have immediately family member affected
g. Diagnosis requires biopsies
h. Symptoms = abdominal pain, vomiting, nausea, abdo distension; diarrhoea and weight loss occur due to malabsorption if small bowel involvement with villous blunting is extensive
i. Nutritional exclusion (or elemental) diets + corticosteroids are mainstay of treatment - Autoimmune enteropathy/ immune enteropathy
a. Protracted diarrhoea with severe enteropathy and villous atrophy
b. Starts in first few weeks of diet
c. Frequent episodes of dehydration, electrolyte imbalances and malnutrition
d. PN dependent
e. No response to exclusion diets
f. Presence of circulating anti-enterocyte antibodies, anti-goblet cell antibodies, or evidence of other autoimmune disease
g. Genotyping of suspected mutations based on clinical presentation
h. Examples
i. IPEX = chronic diarrhoea, dermatitis, autoimmune endocrinopathy (diabetes, thyroiditis)
ii. APS1
CHO enzyme deficiencies
- CHO MALABSORPTION
a. Symptoms = loose watery diarrhoea, flatulence, abdominal distension pain
i. Some children symptoms depend on CHO load
b. Pathogenesis = unabsorbed CHO enter large bowel and are fermented by intestinal bacteria -> organic acid and gases -> discomfort and osmotic diarrhoea
c. Aetiology = disaccharidases are present on the brush border membrane -> genetic deficiency or secondarily by damage to epithelium (inflammatory, infectious)
d. Diagnosis = hydrogen breath test - LACTASE DEFICIENCY
a. Congenital lactase deficiency -> rare (50 cases worldwide)
b. Primary adult-type hypolactasia
i. Caused by a physiological decline in lactase activity that occurs following weaning in most mammals
ii. Varies between ethnic groups (less common Caucasian)
c. Secondary lactose intolerance
i. Follows small bowel mucosal damage (celiac disease, rotavirus)
ii. Diagnosed with hydrogen breath testing
iii. Treatment avoidance of cow’s milk; live-culture yoghurt contains bacteria that produces lactase enzymes so usually well tolerated - FRUCTOSE MALABSORPTION
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 resolves sx without need for ix
c. Fructose H2 breath testing can help diagnosis
d. Caused by reduced abundance of GLUT-5 transporter on the surface of the intestinal brush border membrane, which occurs in 5% of the population - SUCRASE-ISOMALTASE DEFICIENCY
a. Rare autosomal recessive with a complete absence of sucrase and reduced maltase digestive enzyme
b. 2% of Europeans and Americans are heterozygous
c. Clinical manifestations
i. Symptoms begin when the infant is exposed to sucrose or glucose polymer diet
ii. Diarrhoea, abdominal pain and poor growth are observed
d. Diagnosis
i. Stools are acidic and contain sugar – reducing substances NEGATIVE (sucrose + maltose are non-reducing sugars)
ii. Hydrogen breath test
e. Treatment
i. Dietary restriction of sucrose-containing foods
ii. Enzyme replacement - GLUCOSE-GALACTOSE MALABSORPTION
a. >30 mutations in sodium/glucose co-transporter (SGLT1) identified
b. Cause a rare autosomal recessive disorder of intestinal glucose and galactose/Na+ cotransport that leads to osmotic diarrhoea – present with severe acidosis and dehydration
c. Most dietary sugars are polysaccharides or disaccharides with glucose or galactose, diarrhoea follows the ingestion of glucose, breast milk, or conventional lactose-containing formulas
d. Diagnosis
i. Stools are acidic and contain sugar – reducing substances +ve
ii. Hydrogen breath test
e. Treatment = rigorous restriction of glucose and galactose; fructose is the only sugar which can be given safely
Protein enzyme deficiencies
- ENTEROKINASE (ENTEROPEPTIDASE) DEFICIENCY
a. Deficiency of enterokinase – a key enzyme produced in the proximal small bowel and is responsible for the activation of trypsinogen to trypsin, manifests clinically as exocrine pancreatic insufficiency
b. Rare autosomal recessive disorder
c. Treatment = pancreatic enzymes + protein hydroylsed formula + MCT oil in infancy - TRYPSINOGEN DEFICIENCY
a. Rare syndrome similar to enterokinase deficiency
b. Results in severe diarrhoea, malabsorption, FTT and hypoproteinaemic edema
c. Treatment as above
Exocrine pancreatic insufficiency
a. Cystic fibrosis – most common congenital disorder associated with exocrine pancreatic deficiency
b. Shwachman-Diamond syndrome – second most common congenital disorder
d. Autoimmune polyendocrinopathy syndrome type 1 – rare autosomal recessive disorder caused by a mutation in AIRE
i. Chronic mucocutaneous candidiasis is associated with failure of the parathyroid gland, adrenal cortex, pancreatic beta cells, gonads, gastric parietal cells and thyroid gland
ii. Pancreatic insufficiency and steatorrhoea are common
Hydrogen breath test
Background
- normally, lactose -> glucose/galactose -> absorbed
- abnormally, lactose -> large intestine -> digested by microbiota -> short chain FA, hydrogen, methane
- hydrogen + methane -> dx lactose intolerance
- some individuals won’t produce hydrogen -> test for methane instead
Interpretation
- late peak = malabsorption
- early peak + late peak = SIBO (bacterial overgrowth)
Lactose intolerance - general
Presentation
- abdo pain, flatulence, bloating, vomiting
- diarrhoea: bulky, watery, frothy
- PERIANAL EXCORIATION due to acidic stool
- note lactase NOT inducible -> at high enough intake everybody has lactose intolerance/malabsorption and positive stool reducing subtances
Classification
- ethnic: asian/african level decrease by 2-5 years, Caucasian typically persists
- congenital: rare, decreased expression of lactase-phlorizin hydrolase, diarrhoea from birth + hypercalcaemia and nephrocalcinosis
- congenital: sucrase-isomaltase deficiency, glucose-galactose malabsorption
- developmental: premature infants have reduced lactase
- secondary: bacterial overgrowth, bowel stasis, short gut syndrome, post infectious, coeliac, CMPA, microvillous inclusion disease, tufting enteropathy
Diagnosis
- symptoms + positive lactose tolerance (blood following lactose ingestion)/hydrogen breath test
- stool reducing subtances - suggestive if >0.25% and pH <7.5 (CHO malabsorption)
Rare inborn defects causing malabsorption
- Overview
a. Some congenital (primary) malabsorption disorders originate from a defect of integral membrane proteins
b. Histological examination of the small and large bowel is typically normal
c. Most inherited in autosomal recessive pattern
d. Most are rare, and patients present with broad phenotypic heterogeneity - Classification
a. Disorders of CHO absorption
- eg Fanconi-Bickel syndrome (GLUT2 mutation)
b. Disorders of amino acid and peptide absorption
- Hartnup disease
- cystinuria
- iminoglycincuria
- dicarboxylic aminoaciduria
c. Disorders of fat transport
- Tangier disease
- Sitosterolemia
d. Disorders of vitamin absorption
- B12/folate
e. Disorders of electrolyte and mineral absorption
- congenital chloride disorder
- congenital sodium diarrhoea
- Menke disease
Protein-losing enteropathy - bg
- Key points
a. Characterized by excessive loss of serum proteins into GIT
b. Hypoproteinaemia results in decreased intravascular oncotic pressure and leakage of fluid into third spaces
c. Results in:
i. Hypoproteinaemia/Hypoalbuminaemia
ii. Oedema
iii. Pleural or pericardial effusions
d. Considered in patients in whom other causes of hypoproteinaemia have been excluded - Pathogenesis
a. Inflammatory exudation
i. Mucosal injury results in exudation of protein rich fluids across the eroded epithelium
i. IBD, Coeliac, GI malignancies, Infections – shigella and salmonella (HUS), C Diff colitis, Eosinophilic gastroenteritis
b. Increased mucosal permeability
i. Altered integrity of the mucosa results in protein leakage into the lumen
c. Intestinal loss of lymphatic fluid
i. Lymphatic obstruction due to granulomatous or neoplastic involvement of the lymphatic system, congenital abnormalities, or disorders of venous stasis – increase lymphatic pressure
ii. Results in: - Decreased absorption of chylomicrons and fat soluble vitamins (ADEK)
- Reduced recirculation of intestinal lymphocytes into the peripheral circulation
- Leakage of lymph into intestinal lumen
EG:
i. Primary intestinal lymphangiectasia
ii. Secondary - Cardiac disease– CCF / restrictive pericarditis / Post-Fontan
a. Post-Fontan in 4-15%, 5 year survival 50% - Retroperitoneal LN enlargement due to chemotherapy, infection or toxic substances
Protein-losing enteropathy - sx, ddx
- Clinical manifestations
a. Manifestations of hypoalbuminaemia
i. Oedema
ii. Ascites
iii. Pleural effusion
iv. Pericardial effusion
b. Manifestations of underlying disease
i. Gastrointestinal symptoms = diarrhoea, steatorrhoea, abdominal pain, bloating, flatulence - DDx = Other causes of hypoproteinaemia
a. Decreased production – protein malnutrition, liver synthetic failure
b. Increase loss – protein losing enteropathy, nephrotic syndrome, burns
c. Redistribution - inflammation of vasculature, haemodilution
Protein-losing enteropathy - ix, rx
- Investigations
a. Hypoalbuminaemia
b. Reduced plasma concentration of gamma globulins, cholesterol, alpha-1 antitrypsin, fibrinogen, ceruloplasmin
c. Lymphopaenia – if due to loss of LYMPH (other causes of protein-losing enteropathy will NOT result in low lymphocytes)
d. Malabsorption of fat soluble vitamins
e. Stool alpha 1 anti-trypsin increased = paired serum and 24hour collection stool
i. Non-dietary, resistant to intestinal digestion, excreted intact in stool, stable levels
f. Nuclear medicine scan 99m technetium can help determine site of protein loss - Treatment
a. Diet
i. Low-fat, MCT supplemented diet – MCT bypass enteric lymphatics straight into portal system, and prevents rupture of lymphatics by exclusion of LCT
ii. High-protein – for replacement of losses
iii. +/- supplementation with calcium and water soluble forms of vitamins ADEK
b. Medical according to underlying cause
c. Surgical in refractory cases
Primary intestinal lymphangiectasia - general
- Key points
a. Diffuse or localised ectasia of enteric lymphatics
b. Often associated with lymphatic abnormalities elsewhere in the body (mucosa, submucosa or subserosa)
c. Affects children and young adults (mean age of onset 11yo)
d. Most cases sporadic - Associations
a. Turner’s
b. Noonan’s
c. Klippel-Trenaunay (hemiangiectatic hypertrophy - port-wine stain, lymphatic and venous malformations and soft-tissue hypertrophy of affected limb) - Clinical manifestations
a. Intermittent diarrhoea
b. Nausea, vomiting
c. +/- steatorrhoea
d. Peripheral oedema
e. Chylothorax and chylous ascites
f. Pleural effusions and ascites (from hypoproteinaemia) - Diagnosis
a. Hypoalbuminaemia
b. Decreased plasma proteins – gamma globulins, ceruloplasmin
c. Stool alpha 1 anti-trypsin increased
d. Lymphopenia (differentiates from other causes PLE)
e. Clotting factors frequently deficient (no clinical consequence)
f. Contrast study may show thickened, nodular mucosal folds (‘stacked coins’)
g. Endoscopy – macroscopic white spots on mucosa
i. Small bowel biopsy: Markedly dilated lymphatics most apparent at the tip of the villi in mucosa/submucosa - Treatment
a. Low-fat, high-protein, MCT supplemented diet +/- supplementation with calcium and water soluble forms of vitamins ADEK
b. May require intestinal resection or anastamosis of abnormal lymphatics to venous channels in refractory cases
Intestinal failure and short bowel syndrome - bg
a. Intestinal failure = significant amount of malabsorption of macro and micronutrients, not necessarily due to loss of bowel or length of bowel, usually due to SI malfunction due to; resection, congenital defect, or disease associated malabsorption
i. One pubmed definition: “the reduction of gut function below the minimum necessary for the absorption of macronutrients and/or water and electrolytes, such that intravenous supplementation is required to maintain health and/or growth”
b. Short bowel = loss of >50% of the small intestine, with or without a portion of the large intestine generalised malabsorption OR specific nutrient deficiencies, depending on region of bowel affected
i. IF = reduced gut function as above due to any cause, but most frequently due to SBS
ii. SBS = specific definition related to loss of length/amount of bowel
c. Length of bowel
i. At birth length of the bowel = 200-250cm
ii. Adulthood = 300-800cm
iii. Bowel resection in an infant has a better prognosis than in an adult due to the potential for intestinal growth
iv. An infant with as little as 15cm of bowel with an ileocaecal valve, or 20cm without, has the potential to survive and eventually be weaned from TPN
d. Site of bowel
i. The proximal 100-200cm of jejunum is the main site for CHO, protein, iron and water soluble absorption; whereas fat absorption occurs over the length of the intestine
ii. Depending on the region of bowel resected, specific nutrient malabsorption can result
iii. Vitamin B12 and bile salts are ONLY absorbed in distal ileum
iv. Net sodium and water absorption is relatively much higher in the ileum ileal resection has a profound effect on fluid and electrolyte absorption due to malabsorption of sodium and water by the remaining ileum
1. Ileal malabsorption of bile salts stimulates increased colonic secretion of fluid and electrolytes
e. Adaptation
i. Occurs in response to short gut
ii. Involves hypertrophy of villi to increase surface area for absorption
iii. Ileum can compensate for lack of jejunum (site of protein, CHO and fat), however jejunum cannot compensate for loss of ileum
Short bowel syndrome - aetiology
a. Congenital
i. Congenital short bowel syndrome
ii. Multiple atresias
iii. Gastroschisis
b. Acquired
i. Necrotising enterocolitis
ii. Volvulus +/- malrotation
iii. Long segment Hirschsprung disease
iv. Meconium periostitis
v. Crohn’s disease
vi. Trauma
Most-least common: NEC, meconium ileus, abdo wall defect, atresia, volvulus
Short bowel syndrome - treatment
a. Maintain fluid, electrolyte and nutritional state
i. Nutritional support via TPN
b. Bowel rehabilitation
i. Gradual reintroduction of enteral feeds – also reduces the complications of line
ii. Small volume trophic enteral feeds initiated with hydrolysed protein and MCT-enriched formula to stimulate gut hormones and promote mucosal growth
iii. Need to avoid oral aversion – offer breastmilk in neonatal period, introduce solids at appropriate age (avoid fruit)
iv. 50% of patients with short bowel syndrome achieve enteral autonomy within 5 years of bowel resection
c. Management of specific micronutrient and vitamin deficiencies
i. Monitor vitamins – C/M/P, Zinc, selenium, ADEK, Fe, Vit D – especially when weaning PN – B12 if they have no terminal ileum
d. Management of large stool output
i. Addition of soluble fibre and Antidiarrhoeal agents and anticholinergics can be used
ii. Cholestyramine beneficial for patients with distal ileal resection, but can deplete bile acid pool and cause increased steatorrhoea
iii. Bacterial overgrowth is common in infants with short bowel – empirical treatment with antibiotics often useful
iv. Diets high in fat and lower in CHO may be helpful
- Surgery
a. STEP procedure (serial transverse enteroplasty) to lengthen the bowel
b. Small bowel transplantation – for those who have repeated hospitalisations, or recurrent line sepsis
c. Liver and small intestine transplant – for those with PNALD
Short bowel syndrome - cx
a. TPN associated complications
i. CVL infection
ii. CVL thrombosis
iii. Hepatic cholestasis and cirrhosis – causes multifactorial:
1. Toxic defects of TPN on hepatocytes
2. Disruption of bile flow and bile acid metabolism
3. Frequent occurrence of bacterial translocation and sepsis with endotoxin release in portal circulation
iv. Gallstones
b. Other complications
i. Ileal resection -> B12 deficiency
ii. Other vitamin deficiency
iii. Renal stones – result of hyperoxaluria secondary to steatorrhoea (calcium binds to the excess fat and not to oxalate, so more oxalate is absorbed and excreted in the urine)
iv. Venous thrombosis and vitamin deficiency associated with hypohomocystinaemia in short bowel syndrome
c. Other points
i. Sepsis is a leading cause of death
ii. Lack of central line access is potential life-threatening
Intestinal transplant - general
- Key points
a. Intestinal failure describes a patient who has lost the ability to maintain nutritional support and adequate fluid requirements needed so sustain growth - dependent on TPN - Causes of intestinal failure in children requiring transplantation
a. Short bowel
b. Intestinal dysmotility = intestinal pseudoobstruction, intestinal aganglionosis (Hirschsprung disease)
c. Enterocyte dysfunction = microvillus inclusion disease, tufting enteropathy, autoimmune disorders, Crohn’s
d. Tumours = familial polyposis, inflammatory pseudotumour - Indications for transplantation
a. Paucity of venous access = 6 readily accessible sites (bilateral IJ, bilateral subclavian, iliac)
i. Usually occurs in the setting of recurrent catheter sepsis and thrombosis
b. Life-threatening infections = usually catheter related
c. Liver disease = cholestatic liver disease most serious complication of intestinal failure - Transplant operation
a. Donor selection
i. Usually procured from haemodynamically stable ABO identical brain dead donors who have minimal clinical or laboratory evidence suggesting ischaemia
ii. HLA antigen has been random, an cross matching not been a determinant of graft acceptance
b. Types of intestinal grafts
i. Isolated graft or composite graft (liver-intestine)
c. Recipient operation
i. Can be challenging due to multiple previous abdominal surgeries - Post-operative management
a. Immunosuppression
b. Allograft assessment
i. Gold standard for diagnosis is serial endoscopic surveillance
ii. Signs and symptoms of rejection or infection overlap and mimic each other
iii. Any change in clinical status should warrant evaluation for rejection
c. Rejection vs GVHD
i. Acute rejection rates for intestinal allograft are significantly higher than with any other organ – range of 80 to 90%
ii. Severe rejection may require treatment of anti-lymphocyte antibody rejection; as high as 30%
iii. Vascular rejection uncommon, chronic rejection 15%
iv. GVHD is infrequent but life threatening (80% mortality)
d. Infections
i. Infectious complications most significant cause of morbidity after intestinal transplant
e. Outcomes
i. Poor outcomes compared with other transplants
Inflammatory bowel disease - gen bg
c. Age of onset
i. 25-30% of all cases of CD and 20% of all causes of UC occur in individuals <18 years
ii. Onset most often in adolescent and young adulthood
iii. Bimodal pattern of distribution – onset 10-20 years and second smaller peak at 50-80 years
- Classification based on age
a. Paediatric onset = <17 years
b. Early onset = <10 years
c. Very early onset = <6 years
d. Infant/toddler = 0-2 years
b. 4 factors involved
i. Genetic susceptibility
ii. Environmental triggers
iii. Luminal microbial antigens and adjuvants
1. Changes in gut microbiota influenced by other environmental factors
2. Dysbiosis = definitive change of gut microbiota probably defining event in development in IBD; shift from symbiote microbes (friendly) to pathobiome microbes (harmful)
iv. Immune response
c. In susceptible individuals - dysregulated or inappropriate immune response to environmental factors in genetically susceptible host
d. Abnormality in intestinal mucosal immunoregulation
a. Believed to be a polygenic disease – NOT Mendelian
c. The younger age of onset the more likely a family history of IBD
d. Genetic influence lower in UC than CD
f. Inheritance = highly heritable
i. Sibling of affected individual – relative risk of CD 30 and UC 10
ii. Affected relatives likely 15-20% (usually first or second degree) in both UC/CD
iii. Child whose parents both have IBD >35% risk
iv. Concordance rates in twins is higher in CD (35-50%) than in UC (16%)
g. Genetic disorders associated with IBD = Turner syndrome, glycogen storage disease, immunodeficiency
Inflammatory bowel disease - gen ix
a. 1st line investigations
i. FBE – looking for anaemia and thrombocytosis
1. Usually due to iron deficiency
ii. ESR, CRP, albumin – red flags
1. HypoAlb from malabsorption or blood loss
2. ESR/CRP elevated in inflammation
iii. LFT – raised ALT, GGT
iv. Celiac serology
v. Stool MCS – to exclude infection, look for WBC, RBC, C diff
vi. Stool calprotectin
vii. Serology
1. Antibodies present in serum of patients with IBD
2. Examples = pANCA, ASCA, antiOmpC
a. CD – tends to be ASCA positive
b. UC – tends to be pANCA positive
3. Low sensitivity (40-65%) – poor screening tool
b. 2nd line investigations = endoscopy – gastroscopy + colonoscopy
- Infections that can mimic IBD
a. Mimic colitis
i. Salmonella, Shigella, Yersinia, Campylobacter
ii. C Diff
iii. E coli
iv. Entamoeba Histolytica
b. Mimic ileitis
i. Tuberculosis – major issue in Asia and Africa must ALWAYS CONSIDER
ii. Yersinia
Very early onset IBD - general
• May be cause by variety of genetic defects
• Collectively known as ‘monogenic IBD’
• Likelihood of these disorders is greatest in children <6 years of age, and higher in those in infancy
• Disorders include = IL-10 mutation, atypical SCID, CVID, CGD, neutrophil defects, Wiskott-Aldrich syndrome, agammaglobulinaemia, hypergammaglobulinemia M syndrome, familial HLH, IPEX
• Features which raise suspicion of VEO IBD
o Young age of onset (eg, younger than six years)
o Family history of IBD and/or immunodeficiency in multiple family members, particularly with male predominance, or consanguinity
o Recurrent infections or unexplained fever
o Associated features of autoimmunity (eg, arthritis, primary sclerosing cholangitis, anemia, or endocrine dysfunction)
o Very severe IBD and/or resistance to conventional therapies for IBD
o Symptoms or signs suggesting hemophagocytic lymphiohistiocytosis (hepatomegaly, fever, cytopenias, high ferritin)
o Lesions of the skin, nails, or hair
o Tumors
IBD - extraintestinal manifestations
- Extraintestinal manifestations slightly more common with Crohn’s disease than UC
- 10% of patients at diagnosis; 30% of patients within a few years of diagnosis
- Most common skin manifestation = erythema nodosum
Correlate with disease activity • Peripheral arthritis • Erythema nodosum • Anaemia No correlation • Pyoderma gangrenosum • Sclerosing cholangitis • Ankylosing spondylitis • Sacroilitis
More common in CD • Oral aphthous ulcers • Fevers • Erythema nodosum • Digital clubbing • Arthritis More common in UC • Pyoderma gangrenosum • Sclerosing cholangitis • Chronic active hepatitis • Ankylosing spondylitis
• Rare in children
o Glomerulonephritis
o Uveitis
o Hypercoagulable state
• Arthritis
o Arthritis occurs in 3 patterns and tends to be non-destructive
Migratory peripheral arthritis involving primarily large joints
Ankylosing spondylitis = begins in 3rd decade and occurs most commonly in patients with UC have HLA-B27
• Symptoms include low back pain and morning stiffness
• Back, hips, shoulders and sacroiliac joints are typically affected
Sacroilitis
• Miscellaneous
o Patients with erythema nodosum or pyoderma gangrenosum have a high likelihood of having arthritis as well
IBD - Crohns versus UC
Presenting features
- more consistent with UC: rectal bleeding (90%) and diarrhoea
- more consistent with CD: abdo pain, weight loss, growth failure, perianal disease, EOI (erythema nodosum, anaemia, arthritis, mouth ulcers, fever)
UC • Colon only • Continuous • No rectal sparing • No granulomas • Mucosal inflammation • Abscesses very rare • Strictures rare • Cx: Toxic megacolon
CD • Any part of GIT • Discontinuous • Rectal sparing • Non-caseating granulomas • Transmural inflammation • Fistulae and abscesses • Strictures common • Ileum commonly involved • Perianal disease
IBD - gen long term cx
Iron Deficiency Anaemia
• Most common systemic complication (up to 75%)
• Causes: blood loss, reduced iron absorption
• Ferritin will be high due to chronic inflammation
Growth Failure
- Key points
a. Height velocity is most sensitive parameter to recognize impaired linear growth
b. More common in CD than UC - Pathogenesis
a. Multifactorial (malnutrition, inflammation, steroids) - Timing
a. Decreased height velocity has been reported in ~50% patients BEFORE onset of GI symptoms
d. Growth failure may be the ONLY feature of CD
h. Interventions should be initiated before completion of puberty - Consequences
a. Short stature can have significant impact on QOL/psychological function
Bone Disease
- Key points
a. Bone mineral density is often reduced in childhood with IBD - Therapy
a. Control underlying disease
b. Optimise nutrition
i. Calories/ protein
ii. Calcium/vitamin D
c. Promote physical activity
d. Should be managed in conjunction with a specialist in bone health
Psychosocial Issues + QOL
• 25-30% of children with IBD have symptoms of depression and/or anxiety
• Similar to rates in children with other chronic illness
Malignancy
• 2% at 10 years 8% at 20 years, 18% after 30 years
• Risk related to time of disease + length of colon + presence of sclerosing cholangitis
• FHX of colorectal CA
• Screening – begins at 8 years of widespread colitis
Stool calprotectin - general
- Leukocyte derived protein, accounts for 60% of neutrophil cytosolic protein
- Stable in stool for >7 days, resistant to degradation
Increased in: infection, inflammation, malignancy - False positives: NSAIDs, chest infection, bleeding into bowel
- Sensitivity 96%, specificity 87%, elevated in >95% of patients with IBD
- Cut off levels vary with age (?from MCH rotation needs to be >100 to be convincing)
- Indications: lower GI symptoms, chronic GI symptoms, to monitor IBD (correlates with activity)
- Do NOT use: young <4 years, where infection is likely/established, GI red flags / rectal bleeding
Crohn’s disease - bg
- Key points
a. Affects GIT from mouth to anus
b. Paediatric Crohn’s disease more likely to have extensive anatomic involvement
c. Bimodal age distribution – first peak beginning in teenage years
d. Diagnosis often delayed until 1-2 years after symptom onset
e. Only 20% present with diarrhoea, weight loss and abdominal pain
i. Most do NOT have diarrhoea; only 25% have GI bleeding - Classifying CD
a. Gastroduodenal (30%)
b. Jejunoileal (20%)
c. Ileal (30%)
d. Ileocolonic (50%)
e. Colonic (20%)
f. Perianal (20%) - Phenotypes
a. Types
i. Inflammatory
ii. Stenotic
iii. Fistulizing
b. Change over time
i. Most patients start with inflammatory disease
ii. Over time inflammation decreases but complications of stricturing/penetrating(=fistulizing)
iii. The longer time without treatment the higher chance of complication
Crohn’s - sx
a. Systemic signs and symptoms = fever, malaise and easy fatigability
b. Growth
i. Growth failure with delayed bone maturation and delayed sexual development
1. Can precede other symptoms by 1-2 years and is twice as likely in Crohn’s than UC
2. Decreased height velocity occurs in 90% of children with Crohn’s disease – often precedes GI symptoms
3. Can present with growth failure as only symptom
c. Sexual development = primary or secondary amenorrhoea and pubertal delay are common
d. Extra-intestinal
i. More common in Crohn’s disease than UC
ii. Particularly associated with Crohn’s disease
1. Oral aphthous ulcers, arthritis, erythema nodosum, clubbing, episcleritis, renal stones, gall stones
e. Intestinal
i. Spectrum of disease
1. At initial presentation >50% have disease that involves the ileum and colon (ileocolitis), 20% have exclusively colonic disease, and upper GI involvement (esophagus, stomach, duodenum) 30%
2. Isolated small bowel disease much less common in paediatric population
3. Isolated colonic involvement more common in children <8 y, difficult to distinguish from UC
4. Anatomic location of disease spreads over time
5. Perianal disease common (contrasting UC) (tag, fistula, deep fissure, abscess)
6. NOTE: orofacial and perianal inflammation can occur in the ABSENCE of bowel disease
- Examination
a. Often appear chronically ill
b. Growth failure – decreased height velocity (earliest sign)
c. Pale, decreased energy level
d. Abdominal tenderness – diffuse or localised to RLQ
e. Tender mass or fullness may be present
f. Perianal disease may be characteristic
g. Extra-intestinal manifestations
i. Oral aphthous ulcers
ii. Peripheral arthritis = non-deforming
iii. Erythema nodosum
iv. Digital clubbing
Crohn’s - cx
- Stricture = can result in partial bowel obstruction
- Penetrating disease = demonstrated by fistula formation
a. Enterohepatic or enterocutaneous fistulas = often asymptomatic but can contribute to malabsorption if they have high output or result in bacterial overgrowth
b. Enterovesical fistula (bowel and bladder) = originate from ileum or sigmoid colon and appear as UTI, pneumaturia, or faecaluria
c. Enterovaginal fistula (rectum and vagina) = cause faeculant vaginal discharge; difficult to manage
d. Enterocutaneous fistulas (bowel and skin) = often caused by prior surgical anastomoses with leakage
e. Perianal fistula = usually produce fewer symptoms than anticipated - Abscesses
a. Intra-abdominal abscesses = may be associated with fever and pain but might have few symptoms
b. Hepatic or splenic abscesses = can occur with or without a local fistula
c. Anorectal abscesses = often originate immediately above the anus at the crypts of Morgagni
d. Perianal abscess = usually extremely painful - Short bowel = extensive involvement, especially with surgical resection can lead to small bowel syndrome
- Terminal ileum dysfunction
a. Bile acid malabsorption with secondary diarrhoea and vitamin B12 malabsorption
b. Chronic steatorrhoea can lead to oxaluria with secondary renal stones
c. Increasing calcium intake can decrease the risk of renal stones secondary to ileal inflammation
d. Choledocholithiasis increased secondary to bile acid depletion
Crohn’s - ix
a. Peripheral blood tests
i. Anaemia, often iron deficiency
ii. Thrombocytosis
iii. CRP and ESR often elevated – but can be normal
iv. Alb – low, indicating small bowel inflammation and protein losing enteropathy, also acute phase reaction
b. Stool = faecal calprotectin
c. Investigations to map disease and distribution
i. Small bowel follow-through + CT scan – extremely high radiation load so avoided
1. Specific indications eg. abscess formation requiring drainage
ii. MRI = most commonly used imaging modality
1. Usually >7 years due to requirement for GA
iii. USS – in well-trained hands
iv. Capsule endoscopy – not standard
v. Double balloon endoscopy – not standard
d. Endoscopy
i. Macroscopic = patchy, unspecific inflammatory changes, aphthous ulcers, linear ulcers, nodularity, strictures
ii. Microscopic = non-caseating granulomas, transmural inflammation (surgical specimen)
Crohn’s - rx summary
i. Mild-moderate
1. Aminosalicylates – topical and oral (?more commonly UC)
2. Antibiotics
3. Enteral feeds
4. Corticosteroids – budesonide, prednisolone (oral or rectal)
ii. Moderate to severe
1. Induction
a. Enteral feeds = FIRST line
b. Corticosteroids - NOT for maintenance as does not alter disease course
i. Budesonide vs prednisolone
2. Maintenance = immunomodulators
a. 6MP
b. Azathioprine
c. Methotrexate
3. Biologics (induction + maintenance)
a. Infliximab (UC + CD)
b. Adalimumab (UC + CD)
c. Certolizumab - not available for children in AUS
Crohn’s - EEN
i. Exclusive enteral nutrition (EEN) – all patient’s calories delivered by formula
1. Elemental vs polymeric no difference - tend to use polymeric as more palatable
2. Usually administered via NG/PEG
3. Considered first line for inducing remission in children
ii. Effectiveness
1. Effectiveness in children 50-80%
2. Effective primary as well as adjunctive treatment
3. Rapid onset and as effective as other treatments including steroids as inducing remission
iii. Benefits
1. Avoids AE of steroids
2. Allows window to give vaccinations prior to biologics
3. Addresses nutritional concerns
4. No side effects
iv. Paediatric studies suggest similar efficacy to prednisolone for improvement in clinical symptoms, but EEN is superior to steroids for actual healing of mucosa
v. Controversy regarding influence of anatomic location (colon vs small intestine) – recent studies suggest no difference
Crohn’s - AZA/6MP
a. Dose
i. 6MP = 1.0-1.5 mg/kg/day
ii. AZA = 2-2.5 mg/kg/day
b. Beneficial effect can be delayed by 3-4 months; not helpful acutely
i. Earlier use of these agents can decrease cumulative use of prednisolone
c. Variants in thiopurine methyltransferase must be tested first
d. TPMT genotype (thiopurine methyltransferase) – genetically controlled enzyme activity; may identify patients at risk of drug-induced neutropenia
e. Common toxicities
i. Gastrointestinal symptoms
ii. Hepatitis – monitor
iii. Decreased cell counts – monitor
iv. Pancreatitis
f. Less common
i. Risk of malignancy = HL, NHL, NMSC
1. Slight increased risk of EBV associated lymphoma
2. Minimal if any risk of NHL
3. Benefit in maintaining remission lymphoma risk
4. No increased risk of colorectal malignancy
ii. Risk of skin infections = HSV, HPV
- HSTCL = hepatosplenic T cell lymphoma (>30 reported cases in paediatrics, usually if used with AZA)
- TB and increased risk of infections (histoplasma) – highlights importance of differentiating intestinal TB from CD at RCH screen with CXR and QFG
Crohn’s - biologics
- Anti-TNF-alpha
a. Infliximab = chimeric (must have other immunusuppression on board to avoid making antibodies!) monoclonal antibody to TNF-a
i. IV administration
ii. Rapid onset
iii. Usually given as 3 infusions over a 6 week (0, 2 and 6 weeks) period followed by maintenance therapy every 8 weeks
b. Adalimumab = full humanized antibody to TNF-alpha
i. S/C administration
ii. Usually administered once every 2 weeks
iii. High dose induction followed by maintenance
iv. 80% respond to infliximab – 50% remission after 1 year
v. Monitoring = infliximab trough levels and antibodies - Trough levels > 3 associated with higher likelihood of remission
- Newer agents
a. Vedoluzimab = anti-integrin A4B7 molecule
i. Gut selective anti-inflammatory
ii. Blocks trafficking of T lymphocytes out of vascular endothelium involving MAdCAM-1 use in UC
b. Usteikinumab = human MAb to IL-12/23
i. Involved in activation of T cells
Crohn’s - surgery
i. 90% develop complication over 20 year period – in one study 70% of patients required surgical intervention within 15 years of diagnosis
ii. Recurrence after bowel resection is very high (>50% by 5 years)
iii. Complications of surgery = development of fistula or stricture, anastomotic leak, post-operative partial small bowel obstruction secondary to adhesions, short bowel syndrome
iv. Must remove as limited length of bowel as possible – no evidence that removing bowel to margins that are free of histological disease improves outcome
v. Indication for surgery
1. Failure of medical therapy
2. Recurrent obstruction
3. Perforation
4. Fistula or abscesses
a. Often surgeon places seton through the fistula to keep the tract open and actively draining while medical therapy is administered
b. Only severe symptomatic perianal fistula fistulotomy
5. Haemorrhage
6. Growth retardation (if disease limited to terminal ileum)
7. Carcinoma
Crohn’s - long term cx/prognosis
- Long term complications
a. Osteopenia – particularly common in chronic poor nutrition and high dose corticosteroids
b. Permanent decrease in linear growth
c. Extra-intestinal manifestations can be a great cause of morbidity = sclerosing cholangitis, chronic active hepatitis, pyoderma gangrenosum, ankylosing spondylitis
d. Colon cancer = risk of colon cancer in patients with long-standing Crohn colitis approaches that associated with UC and screening for colonoscopy after 10 years of colonic disease is indicated - Prognosis
a. High morbidity but low mortality
b. Region of bowel involved and complications of inflammatory process increases with time
c. Majority of patients eventually require surgery – unlikely to be curative and should be avoided if possible
Ulcerative colitis - sx
- Clinical manifestations
a. Intestinal
i. Disease usually begins in the rectum and extends proximally for a variable distance
ii. When confined to the rectum = ulcerative proctocolitis; when involving entire colon = pancolitis
iii. 50-80% of paediatric patents have extensive colitis (adults more likely to have distal colitis)
iv. 30% of children who present with ulcerative proctitis experience proximal disease spread
v. Rarely noted to be present in infancy
vi. Symptoms - Blood, mucous and pus in the stool with diarrhoea
- Tenesmus, urgency, cramping, abdominal pain (especially with bowel movement), nocturnal bowel movements
- Constipation possible in those with proctitis
b. Extra-intestinal manifestations
i. More common in UC - Pyoderma gangrenosum
- Sclerosing cholangitis
- Chronic active hepatitis
- Ankylosing spondylitis
c. Other
i. Secondary amenorrhoea - Clinical course
a. Marked by remission and relapse, often without explanation
b. After treatment of initial symptoms, approximately 5% of children with UC have prolonged remission (>3 years)
c. 25% of children presenting with severe colitis require colectomy within 5 years of diagnosis, compared with only 5% of those with only mild disease
d. NSAIDs + intercurrent infection known to provoke disease - Fulminant colitis
a. Fever, severe anaemia, hypoAlb, leukocytosis and >5 stools per day
b. Colonoscopy should NOT be performed due to the risk of provoking toxic megacolon or causing perforation
Ulcerative colitis - ix, ddx
- Differential diagnosis
a. Infectious colitis
i. Bacterial, Parasites
iii. AIDS associated = cryptosporidium
b. Allergic colitis
c. Crohn colitis - Investigations (to diagnose and exclude other DDx)
a. Bloods
i. Anaemia - from chronic blood loss, decreased intake +/- anaemia of chronic disease
ii. Iron deficiency
iii. Hypoalbuminaemia
iv. CRP and ESR – often elevated, can be normal even with fulminant colitis
v. Elevated WBC – only seen with severe colitis
vi. Folate deficiency unusual
vii. Microangiopathic haemolysis + thrombocytopenia + renal impairment – indicates HUS
b. Stool
i. MCS, ova parasites, C diff – to exclude infectious etiology
c. Endoscopy
i. Macroscopic = rectum with erythema, edema, loss of vascular pattern, granularity ,and friability - With severe disease pseudopolyps are seen
ii. Microscopic = acute and chronic mucosal inflammation; typical findings are of cryptitis, crypt abscesses, separation of crypts by inflammatory cells, foci of acute inflammatory cells, edema, mucous depletion, branching of crypts - Granulomas, or full thickness involvement suggests Crohn’s
d. X-ray
i. X-ray = may show loss of haustral markings in an air filled colon or marked dilatation in toxic megacolon (in an adult diameter > 6cm)
