Gut Flashcards
How do you classify imperforated anus?
Into High vs Low. Based on relation to puborectalis muscle.
What do you see in Alagille liver on biopsy?
fibrosis, absence of bile ductules, normal hepatic arterioles and central vein.
What neural aetiology has been proposed in pyloric stenosis?
Localised lack of NO synthase, reduction in neurofilaments, adhesion molecules.
What other conditions are associated with pyloric stenosis?
Aneuploidy - Turner's, trisomy 18 Cornelia de lange Oesophageal atresia Hirschprung's PKU Congenital rubella.
What percentage of Hischprung’s is long segment?
10%
What is the pathophysiology of Hirschprung’s disease?
- Failure of neural crest cells to migrate to correct location in bowel - absence of ganglion cells. Absence of inhibitory innervation - tonic contraction and colonic obstruction. (increase acetylcholinesterase staining)
- Abnormal nerve fibres (hypertrophic with thickened bundles
- Muscular neural cell adhesion molecule (abnormal expression prevents craniocaudal migration
- Lack of NO fibres
- Scarce interstitial cells of Cajal
What is genetics with Hirschprung’s?
Isolated in 70%
Associated chromosomal abnormality in 12% (90% Down’s)
Additional congenital anomaly in 18% (GI malfrmation, cleft palate, polydactyly, cardiac septal defects, craniofacial abnormality
Associated with neurocristopathies (NC) - gives rise to neuronal, endocrine, craniofacial, conotruncal heart and pigmentary tissues - MEN2, Waardenburg.
RET (proto oncogene) associated with LS
Endothelin B receptor associated with SS
What is the inheritance of Peutz-Jeghers? What are some complications?
AD
Intussusception, malignancy (GI and other)
- can get polyps in bronchi
What are some risk factors for achalasia?
Oesophageal atresia
CP patients
CF
What is the treatment for Achalasia?
- Medical - Nitrates, CCB, Botox
- Pneumatic dilatation (5% perforation risk)
- Heller’s myotomy - Reflux.
What is relaxation of lower oesophageal sphincter mediated by?
NO
What is abnormal oesophageal pH?
Lower than 4.
What is Sandifer’s syndrome?
GORD with spasmodic torticollis, dystonia.
What is a histological marker of aspiration pneumonia?
Lipid laden macrophages in BAL.
What is the failure rate of fundoplication?
5-20% (better with neurologically normal kids)
How do you diagnose H. Pylori?
Endoscopy - antral nodularity. Gram negative rods in surface mucosa 13C-urea breath test (children) Serology IgG (no use for 6 months post therapy) - does not confirm eradication.
How do you differentiate between osmotic and secretory diarrhoea?
- Stool sodium (70mEq/L in secretory)
- Stool osmolality (Increased in Osmotic - >(Na+K)x2.
- Stool pH (less than 5 in osmotic)
- Stool reducing substances (positive in osmotic)
- Volume (200mL/day in secretory)
- Changes when oral intake ceased (ceased with osmotic, persists with secretory)
What are the causes of secretory diarrhoea?
- Infection (cholera, E. Coli, Salmonella)
- Mucosa necrosis/atrophy
- Laxative use
- Bile acid malabsorption
- Congenital electrolyte transport defect
- Hormone secreting tumours (Phaeo)
- Mastocytosis.
What are the causes of osmotic diarrhoea?
- Osmotic laxatives
- CHO malabsorption (i.e. Glu-Gal transport defects, congenital lactase and sucrase deficiency)
- GI infections (enterovirus)
- Coeliac disease
- CMP/soy allergy
- Inflammatory diseases
- Auto-immune enteropathy
- Bacterial overgrowth.
What are some disorders associated with selective IgA deficiency?
- URTI
- Otitis media
- Sinusitis
- Bronchiectasis
- Allergic disorders
- IVIG allergy
- Giardiasis
- Strongyloidiasis
- Nodular lymphoid hyperplasia
Coeliac Achlorhydria HSP Inflammatory bowel disease GI lymphoma PBC Cholelithiasis Hep C.
What are risk factors for baterial overgrowth?
PPI, Blind loops, strictures, achlorhydria, dysmotility, inflammation, ileocaecal valve problems, PEM.
What are clinical features of bacterial overgrowth?
Steatorrhea (deconjugation of bile salts)
Megaloblastic anaemia (utilization of cobalamin)
Distention/flatulence (gas production)
Malabsorption (mucosal damage)
Hypoproteinemia
d-lactic acidosis. Normal histology but decreased disaccharidases.
Lactulose breath test +ve.
What is the incidence of coeliac disease in australia?
1%
What is the pathophysiology of coeliac disease?
Gliadin crosses gut epithelium, presented with HLA-DQ2 by APC to alpha/beta T cell receptor.
TTG deamidates, inducing stronger T cell response.
Cytokines induce damage (interferon gamma, IL-4, TNF-alpha)
What is seen on histopathology?
Lymphocyte proliferation
Elongated crypts
Partial to total villous atrophy.
What are some DDx of villous atrophy?
CMP/soy protein sensitivity Intractable diarrhoea syndromes Giardiasis Primary immunodeficiencies Topical sprue Bacterial overgrowth Intestinal lymphoma
What are associated conditions with coeliac disease?
GO SLIM
Growth, genetic predisposition - Down’s, Turner’s
Osteoporosis
Skin (dermatitis herpetiform)
Liver dysfunction
IgA nephropathy, autoimmune problems, iron deficiency anemia
Malignancy - Intestinal T-cell lymphoma, oropharyngeal and oesophageal carcinoma.
What’s the daily requirement for zinc?
12-15mg/day
Watery diarrhoea in neonatal period with consanguinity
Microvillous inclusion disease.
what kind of neonatal diarrhoea is associated with choanal atresia and keratitis?
Epithelial dysplasia (Tufting enteropathy)
What kind of diarrhoea occur 1-3 months with dysmorphic features, abnormal hair and SGA?
Phenotypic diarrhoea.
What kind of diarrhoea occur in infancy with autoimmune diseases i.e. DM, GN.
Autoimmune enteropathy.
What histological features do you see in congenital microvillous atrophy?
Villous atrophy WITHOUT crypt hypertrophy.
Surface microvilli missing but present within involutions of apical membrane.
Large lysosomal bodies with microvillous fragments.
Treat with TPN
What is the advantage of faecal alpha1 antitrypsin as marker of PLE?
Protein not in diet. Similar to albumin in molecular weight. Protease inhibitor, resists proteolysis and excreted without degradation.
What is the most common pathogen for gastroenteritis in children?
Rotavirus.
What are the pathogenetic mechanisms for E.coli diarrhoea disease?
ETEC (enterotoxigenic)
- produce heat labile toxin with increases adenylate cycloase. Also produces heat stable toxin with increase guanylate cyclase
EPEC (enteropathogenic)
Adhere to and change microvillus membrane. Does not invade mucosal cell.
EIEC (enteroinvasive)
Invade the mucosal cell and produce shigella-like toxin)
What pathological features do Rotavirus cause?
Duodenal villus injury
What is the seasonal peak in rotavirus?
Winter.
What’s the difference between rotateq and rotarix?
Rotateq - live PENTAVALENT. give 3 doses (no catch up dose if miss out 2 months dose)
Rotarix is LIVE ATTENUATED - 2 doses.
What is the risk for familiy members for IBD?
7-30%.
What is the malignancy risk in Crohn’s disease?
8% after 2 decades.
What are some risk factors for malignancy in IBD?
Time with disease
Lenght of colon involved
Presence of sclerosing cholangitis.
When do you start screening for malignancy in IBD?
8 years post diagnosis (2 years if PSC)
What is the malignancy risk for UC?
2% at 10 years, 8% at 20 years, 18% at 30 years.
What is the pathophysiology of Crohn’s disease?
Imbalance between microflora and immune system.
What are the genetic mutations associated with Crohn’s disease?
- NOD2 (CARD 15) - get more ileal disease and strictures. Decreased NF response in monocytes - impairs innate immune barrier.
- Autophagy pathway
- Interleukin 23
- Activates T cells
What is the monozygotic twin concordance in IBD?
50%
What is the increased risk in first degree relatives?
15-35x
What are extraintestinal manifestations of IBD?
- Musculoskeletal (arthritis, related to disease activity), spondylarthropathy, osteoporosis.
- Mucocutaneous - aphthous ulcer,s erythema nodosum
- Other - conjunctivitis, PSC, Nephrolithiasis.
Growth failure
What is the pathogenesis of osteopenia in Crohn’s?
- Suppression of bone production (poor dietary protein intake, malabsoption, Vit D deficiency, excessive cytokine production, steroid effects.
- Accelerated bone loss - steroid induced hypercalciuria, secondary hyperparathyroidism.
What are the treatment regimes for IBD?
- ASA, polymeric feeds, corticosteroids, ABx
- AZA/6MP, MTX, immune modulators (cyclosporin/tacrolimus
- Immune modulators - Infliximab
What is the most common side effect with sulfasalazine?
Dose related - HEADACHE, nausea, vomiting, anorexia, diarrhoea, macrocytosis, proteinuria.
2. non-dose related: RASH, agranulocytosis, infertility, pancreatitis, lung, vasculitis
What are side effects of AZP?
Agranulocytosis, pancreatitis, allergic reaction.
What are side effects of metronidazole?
peripheral neuropathy (30%), metallic taste, furry tongue, loss of appetitie.
What happens when you have abnormality in APC gene?
Familial adenomatous polyposis - 100% colonic cancer risk. Also increased risk of pancreatitis, duodenal, thyroid, braina dn hepatoblastoma.
What condition gives you lipomatous changes in pancreas?
Schwachman-Diamond syndrome (also associated with hematologic changes, pancreatic insufficiency, NORMAL sweat chloride)
What are some pulmonary function tests?
- Secretin, chlocystokinin direct measurements
- Lundhtest emal
- Faecal fat
- Faecal chymotrypsin
- Faecal elastase
- NBG-PABA
- Fluoresceine, ilaurate
What CFTR mutations are associated with pancreatic dysfunction?
W1282X
Delta F 508
G551D
What are the CF related gut issues?
- CF - pancreatic insufficiency (NUTRITION VERY IMPORTANT)
- Meconium ileus
- CF related liver disease
- CF related DM
- DIOS (abdo pain, palpable mass in caecum or bowel obsturction)
- CF liver disease. (urso, nutritional support)
- CF acute pancreatitis.
What are gene mutations associated with acute, relapsing and chronic pancreatitis?
Cationic Trypsinogen Gene mutations (CTG - enhanced activity of trypsinogen)
- Chymotrypsinogen gene
- Calcium sensing receptor gene.
