Gastrointestinal system Flashcards
What is H. pylori
gram - microaerophilic bacterium usually found in stomach
Differences in H. Pylori infection in children and adults
- Gastric ulcer is absent
- duodenal ulcer reduced
- Treg response increased
- Th1, 17 responses decreased
ESPGHAN recommendations in testing for H. pylori
- diagnostic testing for h. pylori is usually not recommended in children with abdominal pain
- when there are first-degree relatives with gastric cancer, test for h. pylori
- in children with iron-deficiency anemia, we should also test
Extraintestinal manifestations with H. pylori infection
- otitis media
- upper resp tract infection
- periodontal disease
- food allergy
- SIDS
- idiopathic thrombocytopenic purpura
- short stature
Two hypotheses for allergic and autoimmune diseases
old friends hypothesis –> nowadays less diversity of human microbiota
hygiene hypothesis –> lack of exposure to a childhood infection, less “good” microbiota
Hygiene hypothesis in allergy and autoimmune diseases
allergy: Th1 > Th2
Autoimmune: Th2> Th1
Old friends hypothesis in allergy
Th1 > Th2, incr Treg
Definition of Constipation
Difficulty with defecation for at least 2 weeks, which causes significant distress to the patient
Diagnostic criteria for funcitonal constipatipn for a child under 4 years
must include 2 or more of the following occuring at least once a weel for over a month
- under two defecations a weeks
- fecal incontinence over one week
- history of retentive posturing or excessive volitional stool retention
- history of painful or hard bowel movements
- presence of a large fecal mass in the rectum
- history of a large diameter stool
Diagnosis of functional constipation
based on history and physical examination
Constipation risk factors
- Family history
- obesity
Fear to defecate (circle)
- passage of painful stool
- fear related to defecatin
- retention of stool
- increased water reabsorption
What muscles relax during defecation
- m. puborectalis
- m. ext. anal sphincter
Organic constipation causes
- celiac disease
- Hypothyroidism, hypercalcemia, hypokalemia
- DM
- Dietary protein allergy
- Drugs
- Botulism
- Cystic fibrosis
- Hirschsprung disease
- Anal achalasia
- Colonic inertia
- Anatomic malformations
- Pelvic mass
- Spinal cord anomalies, trauma, tethered cord syndrome
- Abnormal abdominal musculature
- Pseudoobstruciton
- Multiple endocrine neoplasia type 2B
Alarm signs and symptoms in constipation
- constipation starting early in life
- family history of hirschsprung disease
- fever
- failure to thrive
- bilious vomiting
- blood in stools in absence of fissures
- severe abdominal distention
- abnormal thyorid gland
- perianal fistula
- tuft of hair on spine
- sacral dimple
- anal scars
Clinical symtpoms of constipation
- difficulty to defecate
- encopresis
- abdominal pain
- enuresis daytime and nighttime
- UTI
Treatment of constipation
- Teaching (use toilet 15 min after meal, right position)
- Disimpaction
- PEG or Enema
- PEG 4000 dose 1-1.5 g/kg/day for 3-6 days
- PEG 4000 + electrolyt4es - Change diet, surgery if necessary, more medication
PEG
- PEG 4000 or 3500 or 4000 + electrolytes
- osmotic agent which attach water to stool
- indicated for children and adults, breastfeeding mothers, pregnancy
- no reabsorption and biotransformation in gut
Rectal laxatives/ enemas
- NaCl
- Bisacodyl
- Mineral oil
- Na phosphate
- Na docusate
Oral laxatives
- PEG
- Lactulose
- Bulking agents (bran, psyllium)
- Fecal softeners (mineral oil)
- Stimulant laxatives (bisacodyl)
- Senna
- Na picosulfate
PEG 4000 dosage
dispimpaction: 1-1.5 g/kg/day (3-6 days)
maintenance: 0.2-0.8 g/kg/day (over 2 mo)
- takes 24-48 hours to work
Prebiotics and probiotics in constipation treatment
not recommended
Food that increases constipation
- rice
- chocolate
- bananas
- black tea
- white flour products
- excessive milk intake
Food that decreases constipation
- plum
- kiwi
- apricot
- coffee
- decrease weight in obesity
What is celiac disease?
- autoimmune-mediated systemic disorder
- elicited by gluten and related prolamines (wheat, barley, rye)
- in genetically susceptible individuals
Celiac disease is characerized by
- presence of variable combination of gluten dependent clinical manifestations
- CD antibodies (EMA, tTG, DGP)
- HLA-DQ2 or DG8 halotypes
- Enteropathy
HOw celiac disease is affecting the whole body
- General: grwoth and pubertal delay, malignancies, anemia
- Gut: diarrhea, vomiting, malnutrition, weight loss, hepatitis, cholangitis
- Skin: dermatitis herpetiformis, aphthous stomatitis, hair loss
- Bone osteoporosis, fractures, arthritis, dental anomalies
- CNS: ataxia, seizures, depression
- Heart: carditis
- Reproductive: miscarriage, infertility
Risk groups of celiac disease
- type I diabetes
- thyroid disease
- Sjörgens syndrome
- Down syndrome
- IgA deficiency
Gluten consists of:
- Prolamins and Glutenins
Different types of prolamines
Wheat: gliadin Barley: hordein Rye: secalin Oats: acenin Corn: zein
Spectrum of gluten-related disorders
- celiac disease
- wheat allergy
- non-celiac gluten sensitivity (NCSC)
What is non-celiac gluten sensitivity
- adverse reactions to gluten or other wheat proteins
- overlaps with IBS and food hypersensitivities
- GI and extra-intestinal symtpoms
Three cohorts of cases in celiac disease
- Born before WWI: few chances to rech adult age
- Born after WWII: many classical cases, mostly pediatric age
- Born in the last three decades: full chance of surviving and reachign adult age, more and more atypical
genetics of celiac disease
- polygenic disease
- most important factor HLA locus chromoseome 6p21.3
- HLA is necesasry, but nut sufficient
Classification of celiac disease
- symptomatic CD
- Typical CD: GI symtpoms
- atypical CD: non-GI symptoms - Asymtpomatic CD
- silent disease
- latent disease
- potential disease
Clinical picture of CD
- diarrhea
- weight loss
- muscle wasting
- failure to thrive
- vomiting
- constipation
Silent celiac disease
mostly in risk groups
- fist degree relatievs
- patients with other autoimmune disease
- other associated conditions (down syndrome)
Celiac disease complications
Early complications:
- malabsorption
- anemia
- hypoproteinemia
- coagulopathies
- Rickets
- failure to thrive
Late complications:
- autoimmune diseases (thyroid, Sjörgens)
- Osteoporosis
- liver damage
- gynecological disorders
- neurological disorders (calcifications, cerebellar pathology)
- malignant diseases (EALT, CIT carcinoma)
Lactose intolerance in CD
- sometimes the leading symtpom
Diagnosis of CD (ESPPGHAN)
- tTG2 IgA > 10x UNL and normal total IgA
and - EMA IgA positive
- aTG2 IgA < 10x UNL and normal total IgA
and - Duodenum biopsy (marsh 2,3)
Golden standard of diagnosis of CD
Intestinal biopsy –> tissue diagnosis
Diagnostic criteria of CD
1 biopsy and serological markers AGA, EMA, t-TG
Histological changes in CD
mucosal atrophy, villous atrophy, crypt hyperplasia, IEL count
Marsh classification in CD
type 0: preinfiltrative phase type 1: infiltrative phase type 2: infiltrative-hyperplastic phase type 3: (a,b,c): destructive phase type 4: atrophic-hypoplastic phase
Celiac disease diagnosis - genetics
HLA DQB1 typing
- DQ SSP Low Resolution kit
- PCR
- HLA DQB1 alleles
Treatment of CD
- life-long glluten-free diet
- 20 ppm (mg(kg) of gluten
Cured by gluten free diet (GFD)
- celiac enteropathy
- dermatitis herpetiformis
- celiac hepatitis
Not cured by GFD
- IDDM
- Autoimmune thyroiditis
- Sjörgen
- Biliary Cirrhosis
- Autoimmune hepatitis
GFD may help
- Gluten ataxia
- epilepsy with endocranial calcificaitons
- Chronic Autoimmune Urticaria
- Hypoparathyroidism
- Macroamylasemia
- Myocarditis/ ICD
- crohns disease
- Ulcerative colitis
- Indeterminate colitis
all part of inflammatory bowel disease
- Crohn’s: can affect any part of the intestine, associated with discontinuous transmural lesions of the gut wall
- Ulcerative colitis: lesions are continuous and superficial and inflammation si confined to colon and rectum
- Indeterminate colitis: colitis with overlapping fetures of ulcerative colitis and Crohn’s
Histology of Crohn’s disease
- Deep fissure ulcers
- patchy involvement of mucosa with normal mucosa in between
- chronic inflammatory infiltrate throughout wall of bowel
Histology of ulcerative colitis
- Mucosa diffusely inflamed, no islands of normal mucosa
- undermining horizintal ulcer
- generally ulcers no deeper than submucosa
Pathogenesis of IBD
- not clear yet
- heterogenous diseases characterized by exaggerated T cell response to the commensal enteric flora developed in genetically susceptible hosts
- -> luminal microbes
- -> genetic susceptibility
- -> immune response
- -> environmental triggers
Inflammatory markers in Crohns disease and ulcerative colitis
Chrons:
IL1, IL 12, TNFa, IFNg, Th17/23
Ulcerative colitis
IL5, IL10
TNF importance in Crohn’s disease
- T cells are activated and release TNFa
- IL6 and IL1 are released
- Inflammatory cell adhesion
- Leukotrienes, superoxides, NO and prostaglandins…
- inflammation and tissue damage of intestinal submucosa
Genetics of IBD
- chromosome 16
- NOD2 or CARD15
- cytoplasmic molecule involved in the sensing of microbial cell-wall components
- 3 single nucleotide polymorphisms independent risk factor for CD in caucasians
Early-onset disease (NOD2 mutation) in IBD
- more agressive
- greater family history
- greater need for surgery
- smaller bowel disease
NOD2/ CARD15 variants in IBD
- younger age of onset
- presence of ileal involvement
- tendency to develop strictures and fistulizing disease
Pediatric IBD Genotype / Phenotype
- Pediatric onset: M>F
- Childhood early onset < 10 years: colonic -predominant
- Children age < 5 yers: colonic- only disease, higher proportion of UC and indeterminate colitis
Ulcerative colitis clinical features
50-60% mild disease:
- rectal bleeding
- diarrhea (insidious onset and with hematochezia)
- abdominal pain
- usually confined to distal colon and responds well to therapy
30% moderate disease:
- bloody diarrhea
- cramps
- urgency to defecate
- abdominal tenderness
- anorexia, weight loss, low-grade fever and mild anemia
10% severe:
- over 6 bloody stools a day, abdominal tenderness, fever, anemia, leukocytosis, hypoalbuminemia
5% extraintestinal manifestations are dominating:
- growth failure
- arthropathy
- skin manifestations
- liver disease
Crohn’s disease clinical features
Symptoms with small bowel involvement:
- malabsorption includign diarrhea
- abdominal pain
- growth deceleration, weight loss
- anorexia
Symtpoms involving colon:
- bloody mucopurulent diarrhea
- crampy abdominal pain
- urgency to defecate
- perianal disease: painful defecation, brigth red rectal bleeding, perirectal pain
Types of Crohn’s disease
- Inflammatory
- Structuring
- Penetrating (fistulae)
Causes for growth failure in Crohn’s disease
- malabsorption (Fe, Zn, folate, Vit. B12…)
- inadequate nutrient intake
- increased losses
- increased metabolic demands
IBD skin and oral manifestations
- erythema nodosum
- pyoderma gangrenosum in CD
- Aphthous lesions in mouth
IBD ophthalmologic manifestations
- Episcleritis
- Anterior uveitis
- increased intraocular pressure and cataracts in children receiving corticosteroid therapy
IBD joint manifestation
- arthritis (in children may occur years before GI symtpoms develop)
- ankylosing spondylitis
IBD Hepatobiliary disease manifestation
- intrahepatic manifestations: chronic active hepatitis, granulomatous hepatitis, amyloidosis, fatty liver, peri cholangitis
- extrahepatic manifestations: primary sclerosing cholangiitis
children may present with liver disease first
increased serumaminotransferases are common
IBD urologic manifestations
- nephrolithiasis
- hydronephrosis
- enterovesical fistulae
IBD Thromboembolic manifestations
- DVT
- Pulmonary embolism
- Neurovascular disease
- Vasculitus affecting both the systemic and cerebral circulation
Other IBD extraintestinal manifestations
- pancreatitis
- fibrosing alveolitis
- interstitial penumonitis
- pericarditis
- peripheral neuropathy
Crohn’s disease classification
A1a: 0-10 years
A1b: 10-17 years
L1: distal 1/3 ileum
L2: colonic
L3: Ileocolonic
L4a: upper disease proximal to ligament of treitz
L4b: upper disease to ligament of treitz and proximal to distal 1/3 of ileum
B1: nonstricturing and nonpenetrating
B2: stricturing
B3: penetrating
B2B3: stricturing and penetrating
G0: no evidence of groth delay
G1: grwoth delay
Ulcerative Colitis Classification
E1: Ulcertive proctitis
E2: Left sided UC (distal splenic flexure)
E3: Extensive (hepatic splenic flexure)
E4: Pancolitis (proximal to hepatic flexure)
S0: never severe
S1: ever severe
Pediatric Crohn’s Disease Activity index (PUCAI)
mild: 10-27.5
moderate: 30-37.5
Severe: 40-100
Pediatric Ulcertive Colitis Activity Index
under 10: no activity
mild: 10.34
moderte: 35-64
severe: over or equal to 65
Ulcerative colitis complications
- toxic megacolon
- perforation
- inflammatory poyps (pseudopolyps)
- Colonic carcinoma
- hemorrhage
Diagnosis of IBD
- history
- fullness or mass in right lower quadrant –> CD
- ractal examination (fissures, fistulas)
- growth
- feces examination to rule out other causes
- colonoscopy with colonic and terminal ileal biopsies
Laboratory:
- CBC: hypochromic, microcytic anemia, thrombocytosis, elevated ESR, elevated CRP
- serum proteins
- fecal calprotectin –> nonspecific marker for colonic inflammation
Radiological:
- MRI
- US
- CT
Endoscopic findings in ulcerative colitis
mild: Erythema, decreased vascular pattern, mild friability
Moderate: marked erythema, absent vascular pattern, friability, erosions
Severe; spontaneous bleeding, ulcerations
Treatment of UC
- 5- ASA orally
- 5- ASA enemas
if no improvement after 7-10 days:
- i.v steroids
- then tiopurine for maintenance
if no improvement:
- anti-TNF and cyclosporines
- then anti TNF and thiopuring for maintenance
infliximab??
Treatment of CD
- exclusive enteral nutrition or steroids (budenoside) (prefer exclusive enteral nutrition!!!)
- Corticosteroids only for induction or remission, not for maintenance
- Asatriopin or methotrexate for the maintenance of remission
- TNFa antagonists (infliximab)
- psychosocial support
Crohn’s disease maintenance
- partial enteric nutrition may be an option together with other medications to maintain remission
