Gastroenterology Flashcards
Symptoms of Vitamin A deficiency
Night blindness, dry eyes (xerophthalmia), poor growth, impaired immunity (esp at mucosal surfaces)
Symptoms of Vitamin D deficiency
Rickets, hypocalcaemia, hypophosphataemia
Symptoms of Vitamin E deficiency
Ataxia, progressive sensory and motor neuropathy, retinitis pigmentosa, loss of vision, haemolytic anaemia
Symptoms of Vitamin K deficiency
Bleeding, inc APTT and PT
Describe the mechanism of a1aT deficiency due to the common genotype PiZZ
- Most common form of alpha1-antitrypsin deficiency is homozygous PiZZ
- Serum levels 2.5 – 7 µmol/L (10-15% of normal)
- The genetic defect alters the configuration of the alpha1-antitrypsin molecule and prevents its release from hepatocytes therefore decreased serum levels
- Low alveolar concentrations causes excess protease activity leading to destruction of alveoli and emphysema
- Accumulation of excess a1aT in hepatocytes leads to destruction of these cells and liver disease
- Morbidity/mortality only in 5%
Describe the anatomy of the oesophagus
- Stratified squamous epithelium
- Outer longitudinal muscle, inner circular muscle
- Myenteric plexus located between
- Blood supply from aorta (thoracic) and gastric (abdominal)
Describe the anatomy/function of the stomach
- Columnar epithelium
- Chief cells - produce pepsin
- Parietal cells - produce gastric acid and intrinsic factor
- Produced 3L/day of secretions - stimulated by gastrin, vagal stimulation, histamine via H2 receptors
- Supplied by the coeliac axis
Describe the function and blood supply to the small intestine
- Ileum absorbs Vit B12 and bile salts
- Blood supply via SMA
Describe the blood supply to the colon
- Supplied by SMA until the distal transverse colon, then the IMA
Describe the function and blood supply to the pancreas
- Exocrine 98%, endocrine 2%
- Supplied by the coeliac axis
Oligosaccharides and disaccharides are hydrolysed to monosaccharides and then absorbed. Describe the pairings
- Maltose and isomaltose -> glucose
- Sucrose -> glucose and fructose
- Lactose -> glucose and galactose
Describe the exocrine function of the pancreas
- Produces trypsin, chymotrypsin and elastase
- These convert proteins into oligopeptides and amino acids in the duodenum
- These then enter the portal vein and are carried to the liver
Gene mutations associated with pancreatitis?
- SPINK1 - AR pancreatitis, heterozygotes usually asymptomatic
- CFTR mutations may cause pancreatitis with or without other manifestations of cystic fibrosis, inherited in an AR manner or in conjunction with a SPINK1 mutation
- PRSS1 mutations are present in 80% of patients with autosomal dominant hereditary pancreatitis
What is absorbed in the duodenum?
Iron
What is absorbed in the jejunum?
CHO, proteins, fat, vitamins
What is absorbed in the ileum?
Bile acids, vit B12
What is the breath hydrogen test for?
Diagnosing lactose malabsorption, sucrase deficiency or small intestinal bacterial overgrowth.
What is the gene associated with Hirschsprungs?
RET gene
Pseudoappendicitis is caused by?
Yersinia enterocolitica
Describe Progressive familial intrahepatic cholestasis (PFIC)
- 1/3rd of childhood cholestasis, usually presents weeks-months age
- PFIC1 and PFIC2 are characterised by a low-normal GGT (type 3 high GGT)
- Usually a maternal history of pregnancy-induced cholestasis
- Three subtypes (PFIC1, PFIC2, PFIC3), all of which are inherited in an autosomal recessive pattern
- PFIC2 is most common, most severe, onset in neonatal or early infantile period with jaundice and pruritus. Medical therapy with urso, but progress to liver failure and transplant
- Plumbing correct, but bile stuck in hepatocytes due to error in pumps
What is the incubation period of Hep A?
3 weeks, spread via faecal-oral route
What are the expected insensible water losses for a extreme preterm and a larger preterm on day 1 of life?
- Very immature preterm infants (<1kg): 2-3 mL/kg/hr (immature skin, lack of subcutaneous tissue, and a large exposed surface area)
- Larger premature infants (2-2.5kg) nursed in an incubator: 0.6-0.7 mL/kg/hr
What is the role of glucokinase?
- Facilitates phosphorylation of glucose to glucose-6-phosphate. It occurs in cells in the liver, pancreas, gut, and brain
Describe the passage of chylomicrons
Enter the lymphatic system, travel to the thoracic duct, then enter the bloodstream
What is the role of gastrin?
- Stimulated by vagal, and stomach distension
- Stimulates peptin, gastric acid and intrinsic factor
- Causes gastric emptying and pancreatic secretion
What is the role of secretin?
- Stimulated by intraluminal acid
- Stimulates pancreatic bicarb secretion
- Inhibits gastric acid and peptin secretion
- Delays gastric emptying
What is the role of cholecystokinin-pancreozymin?
- Stimulated by intraluminal food
- Stimulates pancreatic bicarb/enzyme secretion
- Causes gallbladder contraction, inhibits gastric emptying, and gut motility
Describe the process of bile flow and bile acid formation
- Bile is made in the liver and stored in the gallbladder, then secreted into the duodenum
- Bile acids are formed from cholesterol
- Primary acids are conjugated with amino acids which form secondary bile acids. These are then deconjugated in the intestine and reabsorbed from the terminal ileum. They are then transported back to the liver bound to albumin
What are the components of breast milk?
10% protein is secretory IgA. Also contains lymphocytes, macrophages, complement
What are the benefits of breast milk?
- Reduces risk of GI and resp infections, NEC, atopic eczema (only if born to atopic mother), diabetes
- Improved response to HiB vaccine
Discuss iron studies and iron deficiency
- Deficiency leads to microcytic hypochromic anaemia
- Decr Fe, inc transferrin = deficiency. Decr Fe, decr transferrin = chronic disease
- 5-10% of dietary iron is absorbed
- RF: excess cow’s milk, tea, chronic blood loss, malnutrition, dietary deficiency
Discuss folate studies and folate deficiency
- Deficiency leads to megaloblastic anaemia, poor weight gain, thrombocytopenia, chronic diarrhoea
- Serum folate reflects recent changes, red-cell folate reflects total body stores
- Not an acute phase reactant
- RF: dietary deficiency, malabsorption (eg coeliac), incr requirement (pregnancy, infant), methotrexate, OCP, trimethoprim
Discuss B12 deficiency
- Deficiency leads to megaloblastic anaemia, inc methylmalonic acid + homocysteine in urine
- Anaemia, glossitis, peripheral neuropathy, optic atrophy, subacute combined degeneration of the cord
- RFs: pernicious anaemia (inc +ve gastric/parietal cell antibodies), vegan, malabsorption (short gut, loss of terminal ileum)
- Tx: IM B12 3-monthly
Discuss zinc deficiency
- Causes anaemia, growth retardation, peri-orofacial dermatitis, diarrhoea, immune deficiency
- Acute phase - decr zinc, decr metallothionein (zinc-binding protein)
- Not an acute phase reactant
- Can cause acrodermatitis enteropathica
Describe acrodermatitis enteropathica
- AR, impaired zinc absorption
- Perioral and anal skin rash, diarrhoea, recurrent infections, thrush, ocular changes, paronychia, alopecia and red-tinged hair
- Tx: PO zinc
What are the fat soluble vitamins?
A, D, E, K
Describe abetalipoproteinemia
- AR, failure of chylomicron formation, lack of fat malabsorption
- FTT, abdominal distension, foul-smelling bulky stools in early infancy, Vit E deficiency (ataxia, neuropathy)
- Decr cholesterol and triglycerides, absence of betalipoprotein
- Tx: medium chain triglycerides (absorbed cia portal vein, not via thoracic duct), Vit ADEK replacement
What is the difference between marasmus and kwashiorkor?
- Marasmus - muscle wasting, low body fat stores
- Kwashiorkor - oedema, flaky/peeling skin, rash
- Usually a combination of both is seen
What are the causes of intestinal failure?
- Short bowel syndrome: NEC, atresia, volvulus, trauma, Chron’s, resections
- Motility disorders: chronic idiopathic pseudo-obstruction
- Mucosal disorders (present early with intractable diarrhoea) e.g. microvillus inclusion disease, tufting enteropathy, SCID, autoimmune enteropathy (usually TPN-dependent, may need SB transplant)
Stool fat globules vs fatty acid crystals vs reducing substances
- Fat globules = maldigestion, failure of enzyme process or bile to suspend fats
- Fatty acid crystals = malabsorption, mucosal/brush border issue (fatty acid not absorbed)
- Reducing substances suggests carbohydrate malabsorption.
Features of bacterial overgrowth
- Anaemia, fat malabsorption, steatorrhoea, decr fat-soluble vitamins
- Arthritis, nephritis, hepatitis, vesiculopustular rash
- Short stature, weight loss, abdo pain, night blindness, ataxia
- Risks: recurrent antibiotics, loss of ileocaecal valve, motility disorders, GI surgery, short gut
- Ix: faecal fat, breath test (indicates sugar malabsorption)
- Tx: treat underlying cause, metronidazole, probiotics
What faecal test can confirm that hypoalbuminaemia is related to gastrointestinal losses?
- Stool level of alpha-1 antitrypsin is an excellent screening test for protein losing enteropathy, as alpha-1 antitrypsin is a nondietary, serum protein synthesized in the liver. Its molecular weight is similar in size to albumin, and it is resistant to intestinal and proteolytic digestion distal to the stomach.
Describe Peutz-Jagher syndrome
- AD
- Hyperpigmented macules (especially lips and intraoral), and multiple GI hamartomas (small intestine, colon, stomach)
- Increased risk of intussusception and cancer (GI, breast, reproductive)
- Most due to a mutation in LKB1/STK11
In the presence of insulin, the liver converts glucose to which forms for storage?
Glycogen and triglycerides
Food poisoning caused by improperly stored rice or meats is caused by?
- Bacillus cereus
- Toxin-mediated cause of gastroenteritis, rapid onset of vomiting and/or watery diarrhoea
- It does not cause fevers or invasive disease in immunocompetent patients. Management is supportive.
Melanosis coli is associated with?
- Laxative abuse with anthraquinone-containing laxatives (e.g. senna)
- It appears as a dark brown discoloration of the colon with lymph follicles shining through as pale patches
Describe the different vitamin Bs and their deficiencies
Cobalamin - B12: macrocytic anaemia, elevated homocysteine, peripheral neuropathy
Folate - B9: macrocytic anaemia, elevated homocysteine
Niacin - B3: pellagra (diarrhoea, dementia, dermatitis), weakness, insomnia
Riboflavin - B2: ariboflavinosis (sensitivity to sunlight, angular cheilitis, glossitis, dermatitis or pseudo-syphilis, pharyngitis)
Thiamin - B1: beriberi (weight loss, emotional disturbances, Wernicke’s encephalopathy, weakness and pain in the limbs, arrhythmias, and oedema)
Describe hereditary fructose intolerance
- Rare, AR
- Deficiency of fructose-1,6-bisphosphate aldolase in the liver, kidney, and intestine
- Appears with the ingestion of fructose-containing food
- Early clinical manifestations resemble galactosemia and include jaundice, hepatomegaly, vomiting, lethargy, irritability, and convulsions
Describe short bowel syndrome
- Caused by: NEC, atresia, volvulus, gastroschisis, trauma, surgical resection, radiation enteritis
- If <40cm bowel left in infancy often need long-term TPN support
- Ileum adapts better than jejunum
- Loss of ileocaecal valve = faster transit, bacterial overgrowth (backflow as no valve)
- Aim early introduction of enteral feeds
What are poor prognostic factors in short bowel syndrome?
Smaller length of colon, IFALD, not achieved full enteral feeds after 5 years of TPN
What are indications for bowel transplant in short bowel syndrome?
Irreversible intestinal failure, lack of venous access, liver disease with coagulopathy, ascites, encephalopathy, life-threatening catheter sepsis
Describe lactose deficiency
- Usually acquired, commonly post rotavirus infection
- Lactase deficiency means cannot hydrolyse lactose to glucose and galactose
- Loose, explosive stools. REducing substances positive in stool
- Tx: lactose-free formula, low lactose intake in child
Describe galactosemia (= galactose-1-Phosphate Uridyl Transferase Deficiency)
- Rare, AR
- Rapid onset watery diarrhoea from 1st week of life. Resolves with withholding feeds
- Lactose in breast milk and formula = glucose and galactose. Unable to metabolize galactose-1-phosphate, the accumulation of which results in injury to kidney, liver, and brain.
- Injury may begin prenatally
- Jaundice, hepatomegaly, vomiting, hypoglycemia, seizures, lethargy, irritability, FTT, aminoaciduria, splenomegaly
- Reducing substances positive in stool + urine. Normal biopsy. Galactosuria.
- Tx: non-lactose containing milk
Infants with galactosemia are at increased risk of which infection?
E.Coli sepsis
Describe glucose-galactose malabsorption
- Rare, AR
- Rapid onset watery diarrhoea from birth, settles with withholding feeds
- Reducing substances positive in stool. Normal biopsy.
- Error in sodium/glucose cotransporter protein called SGLT1
- Tx: use fructose as main carbohydrate source
Describe sucrase-isomaltase deficiency
- Defect in carbohydrate digestion, lack of enzyme for hydrolysis
- Watery diarrhoea, FTT after introduction of sucrose or complex carbohydrates into diet (fruit, juice, grains). Can be mild
- Negative reducing substances in stool (non-reducing sugar)
- Tx: remove sucrose and complex carbs from diet
- Positive hydrogen breath test indicates carbohydrate malabsorption
Describe achalasia causes, symptoms, investigation, and treatment
- Failure of relaxation of the lower oesophageal sphincter
- Dysphagia, cough, regurgitation, chest discomfort
- Risk of oesophageal carcinoma if left untreated
- Dx: via barium swallow: fluid level and narrowing of distal oesophagus
- Tx: balloon dilation or Heller myotomy, botulinum toxin
Describe Zollinger-Ellison syndrome
- Gastrinoma (gastrin-producing tumour of the endocrine pancreas) leading to gastric acid hypersecretion and intractable peptic ulcer disease
- May be part of MEN1 syndrome (AD)
- Tx: ranitidine, omeprazole +/- surgery
Causes and red flags for chronic diarrhoea
- Persistent >2-3/52
- Post infectious, coeliac, food intolerance, short gut, pancreatic insufficiency, IBD, antibiotics, laxatives, immunodeficiency, abetalipoproteinemia
- If thriving: constipation with overflow, toddler’s diarrhoea, carbohydrate intolerance, IBS
- Red flags: FTT, weight loss, blood, night stools, fever/rash/arthritis
Describe the gold standard investigation for reflux?
- pH study - gold standard if uncertainty, poor treatment response, uncontrolled respiratory disease, considering surgery, pot-surgery
- If pH< 4 7-10% of time = mild, 10-20% = mod, 20-30% = severe
- Cannot detect anatomical abnormality, aspiration, alkaline reflux.
- Severity doesn’t correlate with symptoms or degree or oesophagitis
Barium swallow for reflux assessment
- Can overdiagnose physiological reflux, and miss reflux events
- Good for malrotation, anatomical abnormalities, duodenal webs
What is the use of esophageal impedance probes?
- Measures the resistance between electrodes on a catheter. Increased resistance indicates retrograde bolus/reflux
- Good for assessing temporal relationship with symptoms
What is manometry used for?
- Measures pressure
- Useful for achalasia and motor disorders
- Not good for reflux assessment
Management of gastroesophageal reflux?
- Reassurance, adjusting volume of feed and position
- Trial dairy free/ hydrolysed formula
- Antacids (gaviscon), thickeners
- H2 receptor blockers - ranitidine
- PPI - omeprazole (increases pH, good for erosive oesophagitis)
- Pro-kinetic drugs - metoclopramide, domperidone, erythromycin
- Nissen’s fundoplication +/- pyloroplasty (if delayed gastric emptying) +/- PEG: if no response to medical treatment, aspiration, chest pain, strictures
Differential diagnosis for gastroesophageal reflux?
Eosinophilic oesophagitis, candida oesophagitis, cow’s milk allergy oesophagitis, achalasia, Crohn’s disease
Describe eosinophilic oesophagitis
- Chronic allergic inflammation of the oesophagus
- Fails to respond to regular reflux treatment
- Dysphagia, food impaction, FTT, vomiting, heartburn
- More common with personal and FHx atopy
- Ix: endoscopy/histology - eosinophils >20/hpf, furrowed and ringed oesophagus.
What is the treatment for eosinophilic oesophagitis?
- Dietary elimination (wheat, cow/soy, fish, egg), topical fluticasone/budesonide, high dose PPI
- Likely relapsing course
What are the causes of congenital diarrhoea?
- Congenital microvillus/inclusion disease
- Tufting enteropathy
- Congenital chloride diarrhoea
- Autoimmune enteropathy
- Usually from birth, >4 diarrhoea per day, FTT
Describe congenital microvillus/inclusion disease
- Poor tolerance of even minimal enteral intake, TPN-dependant
- Poor survival rate, may be cured with transplant
Describe tufting enteropathy
- Epithelial dysplasia with tufts of epithelial cells on biopsy
- May be able to tolerate enteral feeds with age
- Associated with choanal atresia, imperforate anus, short stature, delayed bone age
Describe congenital chloride diarrhoea
- Usually polyhydramnios
- Severe watery secretory diarrhoea from birth, failure or chloride reabsorption
- Does not resolve with cessation of enteral feeds
- Hyponatremic, hypochloremic, metabolic alkalosis
- Raised stool pH and chloride
- Tx: Na and KCl supplements
What are the causes and treatment of exocrine pancreatic insufficiency?
- Chronic diarrhoea due to fat malabsorption
- Steatorrhoea, faecal elastase <150ug/g (can have false +ve in watery stools)
- Causes: CF, hereditary pancreatitis, Shwachman-Diamond syndrome, acute pancreatitis, coeliac disease, Crohn’s disease, SLE
- Tx: pancreatic enzyme replacement (Creon)
Describe intestinal lymphangiectasia
- Dilatation of the intestinal lymphatics, loss of lymph fluid into the gut, leads to protein-losing enteropathy and fat malabsorption
- Primary (congenital) or acquired (pancreatitis, pericarditis, malignancy, post-Fontan)
- Hypoalbumina, lymphopenia, hypogammaglobn
- Dilated lymphatics on biopsy. Elevated faecal a1aT level (measure of protein-leakage)
- Tx: medium chain triglycerides (absorbed directly into portal vein)
Describe features of protein-losing enteropathy
- Hypoalbuminaemia, oedema, low IgG, low lymphocytes
- Increased risk of infections
- Nutritional supplements required
What human leukocyte antigen complex is associated with coeliac disease?
HLA-DQ2 and HLA-DQ8 (100% of those with coeliac are positive for these, but so are most of the population. However, if your patient is negative for these then they don’t have coeliac)
What are the non-GI manifestations of coeliac disease?
Dermatitis herpetiformis (itchy papules and vesicles), iron-deficiency anaemia, osteoporosis, Rickets, fatigue/lethargy, short stature, delayed puberty, stomatitis, infertility
What is the risk of a 1st degree relative having coeliac disease?
10%
Who should be screened for coeliac disease?
T1DM, autoimmune thyroiditis, IBS, 1st degree relatives, HLA-matched siblings, monozygotic twins, T21, IgA deficiency, Turner’s syndrome
What are the gold standard investigations for coeliac disease?
- tTG-IgA (high sensitivity and specificity) and IgA - may have false -ve if IgA deficiency
- If above positive, then lab runs EMA
- If low IgA - lab runs DGP IgG (deamidated gliadin peptide) assay
- Small bowel biopsy (subtotal villous atrophy, crypt hypertrophy, plasma cell infiltrate, intraepithelial lymphocytosis)
What syndromes are associated with Hirschsprungs?
T21, MEN2A+B, central hypoventilation syndrome, Bardet-Biedl, Smith-Lemli-Opitz
Describe choledochal cysts?
- Congenital dilatations of the CBD. Can cause biliary obstruction and cirrhosis.
- In infants: cholestatic jaundice, ascites and coagulopathy
- In older child: abdo pain, jaundice, and mass occurs (33%)
- Acute cholangitis (fever, RUQ pain, jaundice, leukocytosis) may be present
- Dx: cysts seen on USS
- Tx: primary excision of the cyst and a Roux-en-Y choledochojejunostomy. Can get recurrent cholangitis or stricture at the anastomotic site
What are the red flags in abdominal pain?
Age < 5 years, fever, weight loss, skin rashes/joint symptoms, vomiting, waking from sleep, referred to back/shoulders, urinary symptoms, FHx IBD/peptic ulcer, perianal disease, blood in stools
List some function GI disorders
Cyclical vomiting, functional dyspepsia, IBS, abdominal migraine, childhood functional abdominal pain +/- syndrome (inc. loss of functioning, headache, limb pain, poor sleep).
What factors and symptoms are associated with functional GI disorders?
Anxiety, over-achievers, stress, school refusal, parental discord, recent viral illness, food intolerance, constipation, illness in family members
What are the treatments for functional GI disorders?
- Avoidance of over-investigating
- Reassurance, acknowledgement that the pain is real, lifestyle modifications (diet, exercise, regular school attendance)
- Ranitidine (dyspepsia), pizotifen (migraine), simple analgesia, antiemetics, anti-spasmodics
Crohn’s disease vs. ulcerative colitis
- CD: panenteric, skip lesions, granulomas/strictures/fissures, transmural inflammation, raised inflamm markers >UC, perianal disease, arthritis more common than in UC, M>F
- UC: distal bowel/colon, diffuse disease, can be pancolitis up to 60%, extra-intestinal manifestations, toxic megacolon, mucosal + submucosal inflammation (can be transmural in severe), can get backwash ileitis into terminal ileum
Describe the endoscopy/biopsy results in chron’s disease
- Focal lesions with transmural inflammation
- Granulomas in 40-60%
- Strictures, fissures
- Small bowel + perianal disease (can image with MRI)
Describe the endoscopy/biopsy results in ulcerative colitis
- Mucosal and submucosal inflammation
- Goblet-cell depletion
- Cryptitis and crypt abscesses
- NO granulomas
What are the extra-intestinal manifestations of ulcerative colitis?
- Arthropathy (ankylosing spondylitis)
- Erythema nodosum
- Iritis/uveitis
- Liver disease (autoimmune hepatitis, sclerosing cholangitis)
What is the most appropriate test to investigate hereditary fructose intolerance?
Serum aldose B enzyme measurement
pANCA and ASCA markers in IBD
ASCA +ve in 50-60% of CD
pANCA +ve in 70% of UC