Gastroenterology Flashcards
Absorption small bowel
Achalasia
incidence: 1.6/100,000
pathophysiology:
- lack of peristalsis of lower 1/3 oesophagus/relaxation LES
- LES only opens when pressure of accumulated food in oesophagus>LES tone
causes:
- autoimmune, malignancy, Chagas disease (parasites)
clinical:
- dysphagia, reflux, weight loss, nocturnal cough
diagnosis: barium swallow, manometry
management: medications (nitrates/CCB), botox, dilatation, myotomy
Acid/Base diarrhoea
volume: up to 6L loss per day
fluid: electrolyte poor except for HCO3
pathophysiology:
- renin released secondary to hypovolaemia
- increased renal Na absorption and H/K secretion (H>K)
- loss of Na poor fluid with increased Na reabsorption
investigations
- metabolic acidaemia
- hypernatraemia/hyperosmolality
Acid/Base vomiting
electrolytes: high HCl/K
pathophysiology:
- renin, increased NA reabsorption limited by hypokalaemia/alkalaemia
investigations:
- metabolic alkalosis, hypernatraemia, hypokalaemia
Albumin
synthesis: in liver at twice basal rate
half-life: 3 weeks
2/3 stored: extravascular/extracellular
Alkaline Phosphatase (ALP)
production: liver, bile duct, kidney, bone
increase: biliary obstruction, liver disease, bone disease, hyperPTH, adolescence
decrease: hypophosphatasia, anaemia, fulminant Wilson’s disease
Allergic proctocolitis
timing: day 1 to 3 months
symptoms: streaks blood/mucous in stool with occassional diarrhoea
investigations: increased WCC/eosinophils in stool, nodular lymphoid hyperplasia (25%)
cause: hypersensitivity to cow’s milk, less commonly soy sensitivity
treatment: protein hydrolysate formulas (neocate)
prognosis: usually resolves within 1 year
Alpha 1 Antitrypsin deficiency
Defective production alpha 1 antitrypsin
>100 alleles AAT
Deficient: Z allele most common type
SERPINA 1 gene
AAT is an antiprotease: protects against proteases from neutrophils
Excessive abnormal protein destroys cells in lung/liver/skin
Lung: elastase not inhibited, destruction elastin, emphysema
- lung symptoms >20years
Liver: AAT form accumulates in hepatocyte ER causing injury
- presents in childhood: neonatal cholestasus, hepatomegally with increased aminotransferases, liver disease, bleeding
Cirrhosis and liver failure in 15%
Leading cause of liver transplantation in neonates
Investigations: serum level<35% normal
Management:
- IV infusion, transplant
Alanine Transaminase
location: high concentration in liver, small in muscle
- more specific to muscle than AST but longer half life
Antacids
drugs/side effects:
- aluminium hydroxide: constipations, low Ph and seizures
- magnesium hydroxide: diarrhoea, hypotonia, coma
- calcium carbonate: chelate other drugs
Antidiarrheals
Bile acid sequestrants
- drugs: cholestyramine
- use: diarrhoea caused bile excess bile secretion
Bismuth subsalicylate
- drug: peptobismul
Opiod receptor agonists
- drug: loperamide
- mechanism: enteric nerves, epithelial cells, muscles causing decreased GI secretion/absorption
(low CNS penetration)
Antiemetics
drugs:
- serotonin antagonists: ondansetron
- dopamine antagonists: prochlorperazine
mechanism: centrally acting
side effects: constipation
Aspartate Aminotransferase (AST)
High conc in liver, heart, SM, kidney, pancreas, lung, WBC, RBC
Shorter half life
Autoimmune hepatitis
Type 1: classic
- ANA and/or ASMA; ASMA thought to be reflective of more specific anti-actin Ab
- women in all age groups
Type 2:
- Ab to liver/kidney microsomes (ALKM-1) and/or to liver cytosol antigen (ALC-1)
- disease of girls and young women
Symptoms
- asymptomatic to fulminant hepatic failure
- many present with cirrhosis: nausea, abdo pain, itching
- associated arthritis
- associated autoimmune disease
Diagnosis: elevated transaminases>bilirubin/ALP, elevated globulins + IgG (80%)
Histology: chronic necroinflammatory disorder
Management: corticosteroids, azathioprine, 6-MP, transplant
Prognosis: SMA/ANA more severe disease
Biotin
Deficiency: dermatitis, seborrhoea, anorexia
Biliary atresia
1: 10,000
cause: progressive postnatal obliteration of entire extrahepatic biliary tree at or above porta hepatis
symptoms: jaundice, pale stool
Ultrasound: lack of gallbladder, heterogenous large liver
Management: Kasai procedure (hepatoportoenterostomy) less than 8 weeks
- if flow not establishes 1st months: progessive obliteration/cirrhosis
Complications: portal hypertension
Campylobacteriosis
definition: gram negative rod bacteria flagella
source: contaminated food
timing:
- onset diarrhoea 2 to 5 days after infection
- symptoms lasting 8 days
clinical:
- inflammatory bloody diarrhoea, cramps, fever, pain
pathogenesis:
- infect jejunum, ileum, colon
- produce toxin inhibits immune system
- adherence and invasion
- taken up by cytoplasmia vacuole
- assoc guillaine barre syndrome
treatment:
- macrolide (azithromycin)
Campylobacter jejuni
Fimbriae attached and invade intestinal epithelium
Bacterial surface proteins (PEB1, CadF) help to colonize and invade cells
Causes acute mucosal inflammation with edema, cellular infiltration lamina propria, crypt abscess formation
Similiar to salmonella/shigella
Carbohydrate absorption
Carbohydrate digestion
All carbs require hydrolysis to monosaccharides before absorption
Glucose and galactose are transported by Na-dependent active transport
Fructose is transported by Na-independent facilitated diffusion
Caroli disease
1:1000,000
autosomal dominant assoc ARPKD
segmental dilation intrahepatic bile ducts
symptoms: fever, abdominal pain, hepatomegally
Pathophysiology: stagnation of bile, biliary sludge, intraductal lithiasis
Imaging: demonstrates bile duct ectasia
increased risk cholangiocarcinoma
Causes of pancreatic insufficiency
- CF
- Schwachman-Diamond
- Starvation
Celiac disease autoantibodies
Sensitivity/Specificity
Tissue transglutaminase 90-100/95-100
Anti-endomysial Ab 93-100/98-100
Antigliadin Ab Ig A 52-100/72-100
Antigliadin Ab Ig G 83-100/47-94
Cholestasis
Conjugated hyperbilirubinaemia always pathological
- prolonged elevated conj bili>14days and pale stools, dark urine
- term: neonatal hep/biliary atresia (70-80%)
- preterm: TPN/sepsis
Intrahepatic:
- hepatocyte injury: metabolic, viral
- bile duct injury: intrahepatic bile duct paucity
Extrahepatic:
- biliary atresia
- choledochal cyst
Chronic liver failure
symptoms: scleral icterus, palmar erythema, clubbing, wasting, portal HTN, cholestasis, hypotonia
management:
- liver transplant: 86% long term survival
- medications: immunosuppression, antibacterial, antifungal, antiviral, antiHTN, supplements, bile drainage
Chronic pancreatitis
30-40% risk DM
May not have raised enzymes
Causes: obstructive, genetic (cationic trypsinogen gene defect SPINK1)
Clostridium Difficile
Gram positive rod
Toxin A (enterotoxin): act on intestinal mucosa
Toxin B (cytotoxin): increases vasc permeability
- both cause cell death
Increased infection 2nd/3rd generation cephalosporin
Diagnosis C-difficile or toxin in stool
Culture doesn’t differentiate toxin producing from non toxin producing
Sigmoidoscopy: nodules/plaques
Treatment vancomycin or metronidazole
Coeliac disease
1:100 F:M, 2:1. Caucasians mainly.
Usually presents 10-40yr
High risk groups: 10% 1st degree relative risk, T21 (16% affected), T1DM (2-5%), IgA deficiency (10%), Turner’s, William’s, Autoimmune thyroiditis (2-5%)
Genetics:: MHC short arm ch6 – gene cluster of HLA class II. HLA-DQ2 and/or DQ8 found in 99% of ppl w coeliac (40% in the general population)
Pathophysiology: gluten to gliadin, enters cell via injury, deaminated gliadin picked up HLA FQ2 + DQ8, T cell activation, B cell activation, inflammatory cascade, produce antigliadin/endomysium/tTG
Biopsy: villous atrophy
Tx: gluten free diet, resolution of symptoms weeks to months
Colonic duplication
tubular or spherical structures firmly attached to intestine with common blood supply
associations: anomalies of urinary/genital anomaly
presentation: volvulus, intussusception at lead point
symptoms: abdominal pain, mass, GI bleeding
Congenital chloride diarrhoea
genetic: AR mutation SLC26A3
cause: defective chloride/bicarb transport mechanism distal ileum/colon
clinical: severe watery diarrhoea at birth
investigations: hypokalaemia, hypochloremia, alkalosis, stool Cl>Na
management: IVF
Cow’s milk protein allergy
Immune mediated igE or non IgE response
Most common allergy in young child (2% <4yrs)
3rd most common cause of anaphylaxis
Onset days- weeks after introduction cow’s milk
IgE mediated: mild anaphylaxis minutes to 2 hrs
Mixed IgE/nonIgE: atopic eczema, allergic eosinophilic gastroenteritis
NonIgE: delayed >2hrs
GI allergy is NonIgE
Most develop tolerance
Diagnosis: Food challenge or Cow’s mild specific IgE RAST
Treatment: soy formula (10-20% soy allergy also), extensively hydrolysed, AA formula
Crigler-Najjar
Type 1: AR severe
- absent UGT
- jaundice d2-3
- phototherapy for life
Type 2: AD milder
- UGT levels low but detectable
- responds to phenobarbitone
- late onset childhood/adulthood
Crohn’s disease
7/100,000 peak 8-14yrs M:F 1:1
Relapsing remitting
Site: any part GIT
- favors terminal ileum
- 35% involves ileum alone
- 45% involves ileum and colon
- 20% involves colon alone (preference for right side)
- Colonic involvement right-sided*
- Rectosigmoid often spared*
- Upper GIT more commonly involved in kids >adults*
- skip lesions
Histology:
- transmural, non caseating granulomas, goblet cells present, islands normal tissue
Smoking:
- twice as common in smokers
Symptoms: malaise, fever, anorexia, nausea, vomiting, weight loss, bleeding rate exept with colitis
Examination: RIF mass, fever, clubbing, abdo tenderness, anorectal disease, perianal disease (25%), oro-facial granulmoatosis, apthous ulcers
Diagnosis:
- pANCA (20%) – if +ve, more likely to have UC like distribution
- ASCA (40-80%): ASCA assoc with more severe disease, fistulising disease
- Anti-OmpC : potential marker of IBD (50%)
- CBir1 – other antimicrobial antibody
Treatment: steroids, 5-ASA, thiopurines (azathiopurines, 6-MP), infliximab
Cryptosporidiosis
definition: parasitic protozoan cryptosporidium
source: transmitted as microbial cysts via faecal-oral route
timing: may be acute or chronic
- symptoms 5-10 days after infection and last up to 2 weeks
clinical:
- significant watery diarrhoea, fever, abdominal pain, jaundice, reactive arthritis
- can spread to biliary tract causing cholestasis
pathogenesis: (adherence/inflammation)
- parasite attaches duodenal brush border damaging it
- malabsorption and osmotic diarrhoea
- enveloped membrane and become intracellular
- excreted as oocytes
detection: microscopy, staining, Ab detection
Cryptosporidium
- Implicated as cause of persistent diarrhoea in developing world
- Transmission through infected animals; person-person; contaminated water
- Incubation 2-14 days
- Assocated with profuse, watery, nonbloody diarrhoea +/- vomiting, abdo pain, nausea, anorexia, myalgia, weakness, headache, fever
- Malabsorption, weight loss, malnutrition in severe cases
- Usually self limiting in immunocompetent patients, although diarrhoea may persist for several weeks (oocyst shedding may persist many weeks after symptoms resolve)
- Rx: nitazoxanide
Cyclic vomiting
- = at least 5 attacks, or a minimum of 3 attacks in 6 months
- Severe episodes, well between, each episode similar
- Early morning
- Positive FHx of cyclical vomiting OR migraine
- Chronic sinusitis – only infective correlation
- Metabolic
- Consider malrotation
- Rx: anti-migraine
Cystic Fibrosis (gastric issues)
clinical: early abdo/bowel distension, vomiting, rectal mucus plugging
complications: meconium ileus (15%), 50% associated volvulus, jejunoileal atresia, bowel perforation, meconium peritonitis
AXR: distended/thickened loops of intestine
- meconium with swallowed air: ground glass sign
Dermatitis herpetiformis
Most common skin condition associated coeliac disease
Extensor surfaces and trunk
Itchy
Diagnosis Coeliac disease
Biopsy to confirm anyone with positive serology or high risk CD
Dubin Johnson Syndrome
incidence: AR, rare except in sephardic jews
genetics: ABCC2 gene
pathophysiology: increased conjugate bilirubin due to impaired excretion of bilirubin glucuronidase
clinical: mild conjugated hyperbilirubinaemia
Duodenal atresia
epidemiology: 1/10,000, 50% prems, 50% chromosomal abnormalities (33% T21)
cause: failired re-canalisation of duodenal lumen due to persistence of replicating epithelial cells
pathophysiology: thin membrane occluding lumen, fibrous cord between, gap between 2 segments, web
associated: CHD (30%), malrotations (20%), annular pancreas (30%), renal (15%), TOF (10%)
clinical: bilious vomiting w/o distension 1st day life, hx polyhydramnios
AXR: double bubble
treatment: drip and tuck, surgical correction
prognosis: 90% survival
Enterohaemorrhagic ecoli
definition: gram negative rod
source: food (raw beef), milk
timing: onset 1-8 days lasting 5-10 days
clinical: severe bloody diarrhoea, pain, vomiting
- sometime renal failure causing HUS (10%) (<5yrs) in which RBCs destroyed causing anaemia/thrombocytopaenia and kidney failure
pathogenesis:
- strains of ecoli with shigella like toxin
- A/B subunits allow attachment/uptake/apoptosis
diagnosis: Ecoli O157:H7 requires special media to grow
Energy content foods
protein: 4kcal/g (15% intake)
carbohydrate: 4kcal/g (50% intake)
fat: 10kcal/g (30-50% intake)
Enterotoxigenic E.coli
Colonises and adheres to enterocytes small bowel via surface pili
Hypersecretion of fluids/electrolytes
2 toxins: heat labile enterotoxin (LT) or heat stable enterotoxin (similiar structure to cholera toxin)
Enterotoxigenic ecoli
- leading cause of bacterial diarrhoea developed countries
source: water/food contaminated faeces
timing: incubation 1-3 days, duration 3-7 days
clinical: watery diarrhoea, cramps, vomiting, fever
pathogenesis:
- enterotoxins LT/ST presence produces more severe diarrhoea
- B subunit attaches/A enters causing secretion Cl/H2O
diagnosis: stool culture
Eosinophilic oesophagitis
Mixed IgE/nonIgE food protein allergy
Boys>girls, caucasian
Causes: genetic, environment, Tcell
Clinical, dysphagia, abdo pain, vomiting, food impaction, GORD, diarrhoea
Associated atopy
Diagnosis: biopsy (mucosal inflammation, eosinophilic infiltrates/microabscesses/furrowing)
Treatment: elimination diet (milk most common trigger), steroids, topical
Extensively hydrolysed (neocate, MCT peptide)
eg neocate, MCT peptide
- Amino acids, coconut/vegetable oils (combo of MCT>LCT), carb = glucose
- Very high osmolarity
- Indications: SBS, pancreatitis, severe multiple food protein allergy
Extrahepatic Biliary Atresia
1:10,000
inflammation of the bile ducts leading to progressive obliteration of extrahepatic biliary tract
Symptoms: jaundice, hepatosplenomegally, acholic stool
US: absence of gall bladder
Assessment: hepatobiliary scintigraphy
Treatment: Kansai procedure
Familial Adenomatous Polyposis
FAP
genetics: AD variant tumour suppressor gene APC (adenomatous polyposis coli)
incidence: 1/10,000
clinical: multiple colorectal adenomatous polyps (>100)
- GI bleeding, abdominal pain, diarrhoea
diagnosis: suspected if >10 colorectal adenomas and then genetic testing
Fat digestion
dietary fat: triglycerides (3 fatty acid molecules + glycerol backbone)
digestion:
- lipase in stomach emulsifies lipid droplets
- pancreatic lipase/colipase/esterase/phospholipase hydrolyse TG in duodenum to 2 FA + monoglycerides
- products of lipolysis are insoluble (require bile salts)
- bile salts (micelles) solubilise FA by incorporating them into their structure
absorption:
- in cell monoglycerides + FA re-esterified to TG (in phospholipid/cholesterol/protein to form chylomicrons) which go into the lymphatics
- MC TG are water soluble don’t need micelles; they are unchanged FFA in the portal venous system
Folate
(vitamin B9)
source: liver, kidney, yeast, green vegetables, nuts
amount: 50microg/day, lasts 3-4 months
absorption: duodenum/jejunum
decreased absorption: methotrexate, trimethoprim, OCP, phenytoin, phenobarbiton
cells: enters cell via specific receptor
- folic acid to dihydrofolate reductase to tetrahydrofolate FH4
causes of deficiency:
- congenital folate malabsorption (AR, onset 3 months)
- congenital DHF reductase deficiency (onset infancy)
clinical: anaemia, glossitis, jaundice, bleeding, infections, NO NEURO SX
diagnosis: macrocytic anaemia, normal B12, low folate/methylmalonic acid, increased homocysteine
Food Allergy Syndrome
Hereditary fructose intolerance
incidence: rare AR
definition: IEM with absence enzyme aldolase B
clinical: vomiting, hypoglycemia, jaundice, hemorrhage, hepatomegaly, hyperuricemia and potentially kidney failure after introduction of fruit into diet
diagnosis: DNA screening, fructose challenge
treatment: avoid fructose
Gamma-glutamyl Transpeptidase
Biliary tree and hepatocytes
Raised in obstruction (with ALP)
Inducible enzyme
Gastric acid secretion
INCREASE gastric acid secretion:
- Histamine (via H2 receptors)→↑cAMP
- Acetylcholine (via M3 muscarinic receptors)→ ↑ intracellular free Ca2+
- Gastrin (via enterochromaffin-like cells)→ ↑ histamine release
DECREASE acid secretion:
- PGE2 (decreased intracellular Ca+)
- ? sympathetic drive, intestinal peptides eg. CCK, secretin
Gastric rugal hypertrophy
aka Menetrier’s disease
definition: hyperplasia of gastric pits and superficial epithelium causing large mucosal folds of stomach
(Replacement normal gastric glands and parietal cells by hyperplastic mucus secreting cells)
pathophysiology:
- increased permeability results in hypochlorhydria/protein loss
clinical: epigastric pain, vomiting, upper GI bleeding
causes: childhood form associated CMV
Gastrin
Released by G cells in stomach, duodenum, pancreas
Stimulates secretion HCl by parietal cells of the stomach/aids in gastric motility
GERD
GERD is physiological
40% infants vomit once per day
Resolution 50% by 6m, 75% 1yr, 95% 18m
Gastric acidity increased in first 4 months
Cause: transient LES relaxations
Anatomical issues: hiatus hernia, defective crural/diaphragmatic musculature, intermittent intestinal obstruction
Functional: achalasia, increased intrabdominal pressure, theophylline
GI anatomy
- Foregut = from pharynx to upper ½ of duodenum (including liver, gallbladder and pancreas)
- Midgut = distal ½ of duodenum to proximal 2/3 of transverse colon
- Hindgut = distal 1/3 of transverse colon to rectum
GI blood supply
Giardia Lambia
Definition: protozoan parasite
Incidence: most common intestinal paracyte
Tranismission:
- faecal oral transmission via water/food disease
Pathophysiology:
- ingest cysts (10-100), each ingested cyst then makes 2 trophozoites
- trophozoites colonize the lumen of the duodenum, and proximal jejunum, where they attach to brush border and multiply in a binary fission
- cause villous atrophy
Incubation: 1-2 weeks
Clinical:
- diarrhoea, malaise, foul smelling/fatty stool, abdominal pain. bloating, vomiting, fever
- NO blood/mucous/WCC in stool
- symptoms last up to 2 weeks and may become chronic
- varying degrees of malabsorption occur – sugars, fats and fat soluble vitamins
- may become chronic in 50% of patients waxing/waning for months
Diagnosis:
- stool microscopy (90% diagnosed 3 stool specimens)
Gilbert’s Disease
2-5% (30% carriers)
autosomal recessive
decrease UDPGT activity (30-40%)
asymptomatic unconjugated SBR in illness/stress/fasting
normalises with phenobarbitone
increases with nicotinic acid
decreased clearance free FA
Crigler-Najjar
autosomal recessive
cause: deficiency bilirubin UGT (uridine diphosphate glucuronosyl transferase)
Investigations: normal LFTs/liver histology
Types:
type 1- AR, high risk kernicterus, lifelong phototherapy/liver transplant
type 2-AD, may require PT, phenobarbitone activates some enzymes
Gilbert’s syndrome
chromosome 2 repeat in TATA box
incidence: 7% M>F
cause: mild bilirubin UGT deficiency
symptoms: jaundice
tx: no treatment, normal lifespan
Glucose-galactose malabsorption
CGGM
incidence: 1/500,000
definition: AR mutation sodium/glucose co-transporter (SGLT-1)
clinical: early osmotic diarrhea, dehydration, acidosis
diagnosis:
- reducing substances in stools
- glycosuria despite hypoglycaemia
- breath H2 positive
treatment: fructose based diet
GORD
transient lower oesophageal sphincter relaxation
physiology: full stomach, LES relaxation, secondary peristalsis of oeso
neonates: 40-50x per day, resolves by 12months, uncomplicated in 60%
complications: reflux apnoea, reflex bronschospasm, pain, bleeding, Barret’s
associated: poor weight gain
management: conservatively, trial cow’s milk elimination (3 days), breast feed, thicken feeds, drugs not 1st line, fundoplasty
H2 Blockers
drugs: ranitidine, cimetidine
pharmacology: decrease parietal HCl secretion
use: GORD, PUD, gastritis
Hepatitis B
virus: hepadnavirus
prevalence: <1%
pathogenesis: lifelong non curable immune mediated cell injury
risk factors:
- age: younger higher risk chronic hep ?(neonate 95%, early child 25%, later child 10%)
- perinatal exposure to HBsAg +ve mother (highest HBeAg positive (80% infected) negative (10%))
- breast feeding DOES NOT increase risk
- IVDU
- sex
- blood transfusion: HBV 1:150,000
- needstick: HBV 33%
clinical:
- acute HBV: 6-7wks post exposure: ALT, lethargy, anorexia, malaise, 8-9wks jaundice for 4 weeks
- chronic HBV (10% of acute): HBsAg >6m, cirrhosis, HCC
treatment: only if abnormal LFTs
- IFNa2b: 25% eradication rate
Hepatitis B testing
Perform HBsAg, Anti-HBs, Anti-HBc
- HBsAg first to rise in infection but falls rapidly
- Anti-HBc IgM rises realy and remains mths-years
- Anti-HBs marks recovery and protection
- Vacinated Anti-HBs Ab positive
- Previous infection Anti-HBc and Anti-HBs positive
- HBeAg present in active or chronic infections
Hepatitis C
virus: hepacivirus
risk factors: blood, sex, usually perinatal in babies (high HCV titre/HIV positive)
perinatal transmission (6% if mother HepC RNA +ve)
- develop 90% chronic infection, 10% transient viremia
- breastfeeding NOT contraindicated
- HepC Ab at 12-18 months
pathologenesis: direct cytotoxicity to hepatocytes
clinical: acute illness mild
serology: HCV RNA diagnostic, anti-HCV Ab useful for chronic
- chronic HCV: persistent anti-HCV and HCV RNA
treatment: PEG IFN-a-2b + Ribavirin for 6/12
- 50% chance clearance
prognosis: slowly progressive
- 85% remain chronically infected with mild hepatitis
- children: 50-90% elevated LFTs, 40-60% positive RNA, cirrhosis 1-8%, HCC
Hepatitis D
virus: hepatitis D RNA virus
transmission: blood
replication: requires HBV co-infection or superinfection
Hepatitis E
virus: hepatitis E RNA virus
transmission: faecal oral
epidemiology: similar to HAV
clinical:
- peak >15yrs
- 3-8 weeks: lethargy, nausea and fatigue
- usually self limiting
- fatal in pregnant women and immunocompromised: fulminant liver failure
Hepatoblastoma
incidence: 80% liver cancer in kids
- usually <3yrs with abdominal mass
pathogenesis: immature liver precusor cells usually R lobe
investigations: elevated AFP, thrombocytosis, calcification
associated: FAP, prematurity, BWS, Meckel’s, Trisomy 18, cardiac anomalies, biliary atresia, Prader-Willi
metastasis: lung, CNS
treatment: resection, chemo, transplant
Hepatomegally
neonate: >3.5cm BCM, size 4.5-5cm
child: >2cm BCM, size 6-8cm
Hirschsprung’s
definition: aganglionic bowel from anal sphincter
incidence: 4:1 male to female
clinical:
- no meconium 24 hrs then abdominal distension, vomiting
- 80% present first 6 weeks
- causes 15-20% neonatal obstruction
- infrequently enterocolitis
AXR: no gas in rectum
diagnosis: full thickness rectal biopsy
Hirschsprung’s
sporadic
cause: failure migration of nerve cells causing absence ganglionic cells in submucosal and myenteric plexus
epidemiology: 1/5000, M:F 4:1, assoc family history, T21, microcephaly, abnormal facies or palate
location: extends proximally from anus, 80% short segment (only rectosigmoid), 15% long segment (proximal to rectosig)
clinical: delayed mec >48hrs, distension, bilious asp, constipation, enterocolitis, toxic megacolon (proximal dilation and bacterial colonisation)
diagnosis: rectal biopsy, AXR
treatment: surgical resection aganglionic segment
Hydrogen breath test
indication: bacterial overgrowth (eg short gut syndrome)
method: give patient CHO load and measure expired hydrogen
Idiopathic neonatal hepatitis
causes: sporadic or familial
prognosis: generally good if well at 12 months
poor prognosis:
- jaundice >6months of age
- acholic stools
- persistent hepatomegaly
- severe inflammation on biopsy
- familial occurrence
- low GGT (disorder of bile acid transport/synthesis)
Infliximab
drugs: monoclonal TNF antibody
use: Crohn’s, rheumatoid arthritis
side effects: infection, fever, hypotension
Intestinal lymphangiectasia
definition: obstruction of lymphatic draininage of the intestine
cause:
- congenital: Turners, Noonan’s, Klippel-Trenaunay syndrome
- secondary: constrictive pericarditis, HF, abdominal TB, retroperitoneal malignancies
pathophysiology:
- lymph rich protein leaks into bowel lumen
clinical:
- diarrhea/steatorrhea, nausea and vomiting
- peripheral oedema
- chylothorax or chylous ascites
diagnosis:
- hypoproteinemia, low albumin, IgA, IgG, IgM, transferrin, ceruloplasmin, clotting factors
- loss of lymphocytes into gut (lymphopenia)
- fat soluble deficiencies
investigations:
- small bowel contrast – thick, nodular folds
- endoscopy – scattered white spots
- histopath – dilated lymphatics at tip of villi
treatment:
- Low fat, high protein, medium chain triglyceride supplemented diet
- octreotide
- localised resection
Intussusception
age: 6months -3yrs
- uncommon < 3 months
clinical: sudden onset severe paroxysmal colicky pain
- associated straining effort with legs
diagnosis: ultrasound
treatment: air enema
Juvenille polyp
age: 2-10yrs
risks: 10-15% malignancy (multiple juvenille GIT polyps)
symptoms: bright red painless rectal blessing during or after defaecation
Lactase deficiency
congenital lactase deficiency: rare (<50 cases), genetic, symptoms with lactose ingestion
primary adult-type hypolactasia (15% white adults)
- decline lactase activity by 3 yrs
secondary lactase deficiency
- post small bowel injury/infection/bacterial overgrowth
- cows milk protein enteropathy
diagnosis: H2-breath test or small bowel Bx and measuring lactase activity
Liver and Prothrombin Time
Liver clotting factors: 2,5,7,9,10
- PT normal abnormal until 80% synthetic capacity lost
- Factor VII has short half life (6hrs) and senses rapid change in liver function
Lynch syndrome
Familial non-polyposis colorectal cancer
incidence: 2-7% CRC patients
genetic: AD loss of expression of MSH2 causing DNA mismatch repair
clinical: increased risk colorectal cancer, endometrial cancer, digestive adenoma
diagnosis:
- 3 or more relatives with CRC
- 2 successive generations
- 1 or more colon cancers <50 yrs
- FAP excluded
Malrotation
definition: incomplete rotation of the intestine in fetal development
clinical: volvulus in 1st week
- bilious vomiting then abdominal distension
- can progress to ischaemic bowel
diagnosis:
- XR double bubble sign
- US: malposition superior mesenteric vessels
- upper GI contract study
MALT lymphoma
definition: form of lymphoma involving the mucosa-associated lymphoid tissue
pathophysiology: 70-100% associated with chronic inflammation secondary to H.Pylori
diagosis: GI biopsy
treatment:
- early stage disease curable with eradication H.Pylori
- radiotherapy, chemotherapy
Meckel’s Diverticulum
incidence: common congenital abnormality GIT
associations: major malformations of umbilicus, GIT, CNS, CVS
rule of 2’s:
- 2% population
- M:F 2:1
- 2 feet from ileocaecal valve
- 2 inches long
- complications in 2% of patients
clinical
- usually clinically silent
- 50% present <10yrs painless lower GI bleeding
- ulceration small bowel from acid secretion of ectopic gastric mucosa in the Meckel’s (25%)
- chronic or acute
- meckel’s can be lead point for intussusception/volvulus
diagnosis: nuclear med 99m technetium detects gastric mucosa (sensitivity 85-90%)
- mesenteric arteriography: anomalous superior mesenteric artery branch feeding diverticulum
- HRCT
management: resect if symptomatic/palpable abnormality
Meckel’s formation
Mild unconjugated hyperbilirubinaemia
in neonates
pathogenesis:
- increased RBC breakdown: x2-3 production bilirubin
- decreased UGT activity until 14 weeks
- increased reabsorption due to sterile gut
Multiple food allergy of infancy
incidence: rare, onset 1 week
allergens: breast milk, cow milk, soy, extensively hydrolysed formula
clinical irritability, feed refusal, vomiting, diarrhoea
treatment: AA formula
Neonatal conjugated hyperbilirubinaemia
S: structural: biliary atresia, choledochal dyst, Caroli disease
M: metabolic: galactossaemia, CF, alpha-1-antitrypsin, bile acid transport defect
I: infection (TORCH/sepsis), idiopathic
T: TPN
E: endocrine (hypothyroidism/hypopituitarism)
Neonatal formulas
hydrolized protein: peptides with added AAs and fat (primarily MCTs)
- indications: cow milk/soy protein allergy, galactosemia
free AA acid formulas: non-allergic free AAs
- indications: multiple food allergies, severe protein allergy, malabsorption, SBS, eosinophilic GI disorders
- eg. neocate, elecare
low long chain fatty acid
- indications: FA met disorder, fat malabsorption, chylothorax, lymphangiectasia
- eg. enfaport, portagen, monogen
Bilirubin metabolism
source: 80% bilirubin from breakdown Hb
metabolism:
- bound to bilirubin
- dissociates for uptake into hepatocytes
- UGT catalyses conjugation with glucuronic acid for excretion in bile
- excreted into bile and broken down bacterial enzyme urobilin
- beta-glucuronidase deconjugates allowing reabsorption into entereohepatic circulation
Neonates to hep B mother
mother: HepBsAg positive
treatment of infant:
- immunise at birth then 2,4,6 and 12 months
- hep B IVIg within 24 hrs of birth
testing: 9-15 months
Niacin
(Vitamin B3)
deficiency: pellagra (dementia, dermatitis, diarrhoea)
- aggression, dermatitis, insomnia, confusion, diarrhoea
use: essential for electron transport
Non-alcohol Fatty Liver Disease
prevalence: 20% of obese children
- most common liver disease in children
risk factors: obesity, insulin resistance
pathogenesis (spectrum)
- fat accumulation in hepatocytes w/o inflammation
- fibrosis (simple hepatic steatosis)
- hepatic steatosis with necroinflammation (steatohepatitis) termed NASH
symptoms: may have RUQ pain, hepatomegally
diagnosis:
- US: increased echogeneity
- serum: elevated LFTs
- biopsy
management: weight control
prognosis: 1/2 NASH progress to cirrhosis
Oesophageal anatomy
Diameters
Cricopharyngeal sphincter: narrowest part 15cm from incisors
Constrictions at aortic arch (22cm), left main bronchus (27cm) and lower oesophageal sphincter
Opthalmia Neonatorum
definition: neonatal conjunctivitis in the 1st month
pathogens/treatment:
neisseria gonorrhoea:
- day 0-5
- purulent discharge/inflammation
- treat: bacitracin, 7 days IV ceftriazone
chlamydia trachomatis:
- 5 days -2 weeks
- more watery
- treatment: AB drops, PO erythromycin to prevent resp disease
less common pathogens:
- HSV-2, staph aureus,
complications: untreated may develop corneal ulceration
Oral Rehydration Solution
definition: isotonic with equimolar concentrations of sodium and glucose
properties:
- osmolality 200- 310 mmol/L
- glucose <20 g/L (111 mmol/L)
- sodium 60- 90 meq/L
- potassium 15- 25 meq/L
- chloride 50- 80 meq/L
mechanism water absorption: passive diffusion across osmotic gradient determined by
1. Na/H exchanger
2. electrochemical gradient
3. Na coupled transport
role of starch: increased non-absorbed CHO in colon is fermented into SCFA which are readily absorbed and increase Na reabsorption
Osmotic diarrhoea
causes: presence of non-absorbable solutes in the gut
(e.g. lactose or fructose in intolerance)
pathophysiology:
- intestinal damage (viral gastro)
- reduced functional absorptive surface (coeliac)
- defects in enzymes/nutrient carriers (lactase def)
- decreased transit time (functional)
clinical:
- STOPS when cease enteral feeds
- volume SMALLER <200mls
investigations:
- reducing substances PRESENT
- stool pH <6
- stool Na <60 (water drawn in dilutes)
- stool osmotic gap >100
Pancreatic function
function: secretes alkaline juice after eating
- exocrine function under hormonal (secretin and CCK)/neuronal control
Stimulated:
- secretin: released duodenal S cells in response to acid (stimulates pancreatic ductal cells)
- CCK: released duodenal I cells response to fats + proteins (stimulates acinar cells/GB contraction)
inhibited:
- somatostatin: duodenum/delta cells of pancreas
pancreatic enzymes:
- trypsinogen/chymotrypsinogen
- carboxypeptidase (protein)
- elastases (break down the protein elastin)
- lipase (triglycerides and fatty acids)
- amylase (starch, glycogen, other carbs)
- sterol esterase, phospholipase, nuclease
insufficiency causes maldigestion:
- fat globules when >90% exocrine function lost
tests:
- measuring pH/enzyme content of duodenal fluid after stimulation pancreas (e.g.meal/secretin/CCK)
- serum trypsinogen
- faecal fat ( >90% enzyme function lost)
- faecal chymotrypsin/faecal elastase-1
Pancreatitis
cause: 30% idiopathic, trauma, cholelithiasis
pathogenesis: premature activation of trypsinogen and pancreatic proenzymes causing autodigestion
diagnosis: serum lipase rises 4-8hrs, peaks 24-48 hrs, elevated 8-14 days
- US: evidence of inflammation
complications: death, pseudocyst, abscess
treatment: NBM 24hrs, octreotide DOESN’T WORK
Partially hydrolysed formula
e.g. pepti-junior, alfare
formula: di/tri peptides, AA, vegetable oil/MCT, carb maltdextrin (lactose free), low osmolarity
indications: fat malabsorption, intolerance whole protein, severe chronic diarrhoea
Pathological jaundice
increased production (haemolysis)
- autoimmune (ABO/Rh)
- RBC membrane defects (spherocytosis/elliptocytosis)
- RBC enzyme defects (G6PD, pyruvate kinase def)
- sepsis
decreased clearance (defects UGT)
- Crigler Najar/Gilbert
- maternal DM
- congenital hypothyroidism
- galactossemia
- structural (biliary atresia, alagille, caroli)
increased enterohepatic circulation
- breast milk
Pepsin
metabolism:
- precursor pepsinogen secreted chief cells
- converted by HCl acid to pepsin
function: breaks down proteins
Peptic ulcer disease
incidence: uncommon
causes:
- <10yrs: medications, more common gastric
- >10yrs: H-pylori, duodenal
- 20% idiopathic
- secondary H.pylori, medications, Zollinger-Ellison, SBS
symptoms: pain (alleviated by food), NV, perforation, iron def, ITP, SIDS
investigations: H.pylori stool antigen assay, urea breath test, H.pylori IgG serology (low sens/spec), endoscopy
management: triple therapy (PPI+clarithomycin+amoxi/metro)
Portal hypertension
definition: portal vein pressure >5mmHg or portal vein:hepatic vein gradient >10mm
symptoms: splenomegally (with thrombocytopaenia, anaemia, leukopaenia), varices (oeso, gastric, rectal), ascites, encephalopathy
causes: cirrhosis, pre-sinusoidal (portal vein thrombosis), post-sinusoidal (budd-chiari, venoocclusive disease)
management: variceal banding, transjugular intrahepatic portosystemic shunt (TIPSS)
Primary alactasia (lactose intolerance)
incidence: very very rare 1:60,000
definiton: complete inability to digest lactose from infancy
pathophysiology: complete absence of lactase
Primary sclerosing cholangitis
incidence: 70% associated with UC
- complicates 1-3% UC
symptoms: jaundice, hepatomegally, cholestasis, fat malabsorption, bone disease
associated: cholangiocarcinoma (10-15%)
investigations: elevated LFTs (ALP highest), increased IgM, pANCA positive
ERCP/MRCP: short strictures in bile ducts with dilatation in between normal zones (beadin)
treatment: ursodeoxycholic acid, liver transplant
Prokinetics
Metoclopramide
- mechanism: D2 antagonist CNS and gut
- side effects: restlessness, dystonic reactions
Erythromycin
- mechanism: motilin receptor agonist
- side effect: prolonged QT, c.difficile, pancreatitis
Protein losing enteropathy
3 main causes:
1) Mucosal disease with protein loss across mucosa
eg. IBD, ulcer, lymphoma
2) Lymphatic obstruction causing protein rich chyle
eg. primary intestinal lymphangectasia, secondary obstruction due to cardiac disease, infection, neoplasm
3) Idiopathic alteration in mucosa permeability
eg. gastroenteritis, coeliac, Zollinger Ellison, SLE
Stool alpha 1 antitrypsin is a marker (resistant to proteolysis and degradation in the bowel)
Proton Pump Inhibitor
drugs: omeprazole, pantroprazole
pharmacology: irreversibly/noncompetibly block parietal cell H/K ATPase and decrease HCC secretion
use: GORD, PUD, gastritis
Reducing sugars
definition: sugars capable of reducing oxidizing agents in alkaline solution
- e.g. glucose, fructose, maltose, lactose
- non reducing sugars: sucrose
Refeeding syndrome
symptoms:
- hypophosphataemia, hypokalaemia, hypomagnesia, hyperglycaemia
- vitamin depletion
- volume overload/oedema: Na/fluid reabsorption in kidneys
mechanism: surge of insulin pushes/PO4/K/Mg into cells
complications: CVS , resp failure (hypophosp), muscular weakness, raised liver transaminases (increased fat deposition), diarrhoea, neurological
prevention: slow feeding, careful monitoring, electrolyte replacement
Rotavirus
definition: dsRNA virus family reoviridae
clinical: foul smelling non bloody diarrhoea for 3-8 days
- associated nausea, vomiting, fever
- secondary lactose intolerance for weeks
pathophysiology:
Day 1: infects enterocytes of villous epithelium jejunum/ileum causing cell damage and loss of fluid/salt
Day 2-5: adjacent villi fuse reducing SA
Day 6-10: normal architecture
- loss of brush border enzymes with loss ability to digest complex sugars/CHO causing lactose intolerance
- secretory diarrhoea via non-structural glycoprotein NSP4 enterotoxin: calcium ion dep chloride secretion and disrupts water reabsorption
- enteric nervous systemic activation wiuth secretion
diagnosis: antigen stool immunoassay
- 1-4 days 94% detected
- 4-8 days 76% detected
- >2 weeks occassional
Salmonella typhimurium
definition: gram negative rod of enterobacteriacae family
source: contaminated food, hands, water
clinical:
- fever diarrhoea, anorexia, headache, stomach pain, vomiting
- mucousy/bloody stool
- 5% develop bacteraemia/meningitis/osteomyelitis (greater<3m)
pathophysiology:
- incubation 12-36 hours, duration 4-7 days
- enterocolitis with diffuse mucosal inflammation/edema with microerosion/abscesses
- attaches epithelial cells via fimbriae and invades cells by bacterial mediated endocytosis and remain in phagosome
- induce inflammatory response with IL8 secretion, neutrophil recruitment and pro-inflammatory mediators
diagnosis: faecal PCR
treatment: fluoroquinolones
Schwachman Diamond Syndrome
Autosomal recessive chromosome 7
Skeletal (>2yrs), Haematological
Normal sweat chloride
30% develop myelodysplastic syndrome
Neonatal sepsis secondary to neutropaenia
Lipomatous changes in pancrease: 50% pancreatic insufficiency age 4-5yrs
Secretory diarrhoea
Causes:
- electrolyte and water secretion into intestinal lumen
- stimulates Cl secretion or inhibition of NaCl absorption
bacterial toxins: bacillus cereus, clostridium perfringens, Enterotoxigenic Ecoli, cholera, giardia lamblia, crytosporidium, rotavirus
Feeds: CONTINUES when cease enteral feeds ***
Volume: LARGE >200mls/day
Features:
- NO reducing substances
- pH >6
- Stool Na >90
- Osmotic gap <50
Shigellosis
definition: shigella bacteria gram negative rod
source: food, faecal oral route
clinical: pain, fever diarrhoea with mucous/pus/blood, mucosal ulcerations
- assoc seizures
timing: onset 12-96hr lasting 5 to 7 days
pathogenesis:
- attach to and penetrate intestinal mucosa causing inflammation/desquamation
- spread to adjacent cells via fimbriae
- induce inflammatory reaction
treatment: bactrim if necessary
Short Bowel Syndrome
Loss >50% bowel
Generalised malabsorption disorder of specific nutritional def
Proximal jejunum main site CHO, protein, Fe, water soluble vitamin absorption
Fat over large length small bowel
Symptoms: watery diarrhoea, cholestatic liver disease, gastric hypersectrion, ulcers, bacterial overgrowth, nutrient/vitamin def, enteric hyperoxaluria (calcium binds fat in steatorrhoea) causing kidnet stones
Treatment: TPN, trophic feeds
Short bowel syndrome
0.02-0.1% live births
80% develop in neonatal period
Most common cause of intestinal failure (unable to achieve complete nutrition without supplementation)
Malabsorption marcro/micronutrients caused by massive resection small intestine
Causes: NEC (35%), mec ileus (20%), abdominal wall defects (12.5%), intestinal atresia (10%), volvulus (10%)
Mortality 20-40%
Management: PN, enteral nutrition (high fat, complex CHO), H2 blockers, vitamins, serial transverse enteroplasty
Staph food poisoning
onset: 30-8hrs post food
mechanism: staph aureus toxin
clinical: severe vomiting +/- diarrhoea
- resolves 24-48 hours
Stool osmotic gap
equation: 290-2(Na+K) = 50-100mosm/kg
*290 value of plasma osm
Interpretation
- if >100mosm/kg: osmotic diarrhoea
- if <50mosm/kg: secretory diarrhoea
NB. Sodium>70mmol/l suggestive of secretory diarrhoea
Sucrase-Isomaltase Deficiency
definition: rare AR absence of sucrase in small intestine
clinical:
- diarrhoea, abdominal pain, poor growth with exposure to sucrose or glucose (non lactose formula/pureed food)
diagnosis:
- H2 breath test
- NO reducing substances are present (sucrose isn’t a reducing sugar)
- direct enzyme assay on small bowel Bx
treatment: dietary restriction
Sulfasalazine
drug: sulfapyridine and mesalamine
pharmacokinetics:
- prodrug: 1/3 absorbed small intestine, 2/3 colon (splits into 5-ASA and SP)
use: Crohn’s, ulcerative colitis
toxicity: anorexia, nausea, vomiting, sulfur toxicity
Technetium pertechnetate scan
mucus secreting cells of ectopic gastric mucosa take up pertechnetate
sensitivity 85%, specificity 95%
Toddler’s diarrhoea
Many BAs per day but otherwise well + thriving
Daily, painless >3 large unformed stools, >4 week duration
Rx: trial lactose and low fructose (low fruit juice) diet
TPN related neonatal cholestasis
18% to 67% of infants who receive prolonged courses of PN develop liver injury and cholestasis
RF: low birthweight, long PN therapy, sepsis, bacterial overgrowth of the small intestine, and intestinal failure
Cause: The soybean-based lipid emulsion component of PN.
Treat: enteral feedings as early as possible to stimulate bile flow, gallbladder contraction, and intestinal motility. Ursodeoxycholic acid is theoretically of benefit by stimulating bile flow; however, there is no evidence of its efficacy in PNAC.
Tracheo-oesophageal fistula and oesophageal atresia
- TOF is a common congenital anomaly of respiratory tract
- 1 in 3500
- Typically occurs with oesophageal atresia
- OA and TOF are classified by anatomy
- Type C – account for 84%
- Defect in lateral septation of the foregut into oesophagus and trachea
- Associated with VACTERL (vertebral anomalies, anal atresia, cardiac anomalies, TE = tracheoesophageal fistula, renal anomalies, limb anomalies)
Clinical features
- Depends on presence or absence of OA
- In cases with OA (95%) – polyhydramnios occurs in 2/3rds of pregnancies
- However many are not detected antenatally
- Infants with OA because symptomatic immediately after birth
- Infants with H type –
- May present early if defect is large with coughing and choking associated with feeding as milk is aspirated
- However smaller defects may not be symptomatic in newborn period
- Can be diagnosed from 26 days to 4 years
- Prolonged history of mild resp distress associated with feeding and recurrent pneuomina
Diagnosis
- Pass catheter into stomach: not passed further than 10-15cm
- CXR: catheter curled up in upper oesophageal pouch
- Distal TOF can be seen on lateral chest CXR – both views will show gas filled GIT
- For isolated TOF – upper GIT series with barium & endoscopy & bronchoscopy
Management
- Surgical ligation of fistula
- With OA need to anastomose oesophagus
Outcome
- For isolated TOF – generally good
- With AO and TOF it is more guarded and depends on associated abnormalities
- Higher mortality if cardiac disease present
- Complications – anastomotic leak, oesophageal stricture, recurrent fistula
- GORD and aspiration
Liver cysts
usually asymptomatic
types: simple/solitary, polycystic, parasitic (hydatid cyst), neoplastic (cystadenoma, cystoadenocarcinoma, mets), duct related (Caroli, bile duct dupication), false cyst
Transient Hyperphosphatasemia
definition: elevated ALP in absense liver/bone disease
diagnosis: 5x normal and decreases <3 months
pathogenesis: unknown
investigations: Ca, Ph, ALT, AST, GGT, bilirubin, vit D, PTH, urea, Cr
Treatment neonatal jaundice
Phototherapy
- isomerisation to lumirubin (more soluble/less toxic)
- fluorescent blue light
Side effects: dehydration, rashes, loose stool, hyperthermia, bronze baby
Exchange transfusion
- replace 85% circulating RBCs to decrease bilirubin by 50%
- also infuse 1g/kg albumin
- above threshold OR signs of kernicterus
Side effects: infection, DIC, GVHD, thombosis, EUC abnormalities
Triple therapy
PPI, clarithromycin and amoxycillin
Ulcerative colitis
incidence: 11/100,000, M>F 1.8:1
pathology: contiguous large bowel mucosal, NEVER PERIANAL LESIONS
risk factors: twice as common in non-smokers
clinical:
- diarrhoea with bleeding/mucous
- abdominal pain
- urgency, tenesmus
- lethargy, anorexia, fever
- pyoderma gangrenosum (50%), erythema nodosum (4%)
Fulminant colitis: >5 bloody stools per day
complications: increased malignancy 8-10yrs post diagnosis, toxic megacolon
diagnosis: pANCA (70%), ASCA
treatment: 5-ASA, steroids, immunomodulators, colectomy (25% within 5 yrs dx)
Unconjugated jaundice
Causes:
- breast milk: benign, onset d3-5, persists >1wk, high levels beta glucoronidase causes deconj of bilirubin
- breast feeding
- haemolysis
- Crigler-Najjar
- Gilberts
Vibrio Cholerae
Toxin: 5 binding (B) subunits and 1 active (A) subunit
- B subunits bind GM1 ganglioside receptors on the small interstinal mucose
- A subunit enters cells and activate adenylate cyclase, increasing cAMP, blocking absorption of NaCl by microvilli
- increased secretion Cl/water by crypt cells
Vitamin A deficiency
causes: poor intake in developing countries, fat malabsorption
clinical:
- ocular: night blindness, retinopathy, xeropthalmia
- skin: hyperkeratosis, destruction hair follicles
- other: poor bone growth, infections, abnormal tooth enamel development
Vitamin B1 (thiamine)
deficiency: beriberi
- weight loss, emotional distubance, Wernicke’s, weakness, arrythmia, weakness
VItamin B12 (cobalamin)
source: meat/dairy
stores: 50% liver, 3 yrs until deficiency develops
absorption
- B12 unbound to protein and binds R factors in stomach
- B12 unbound R factors by pancreatic proteaases and bind to IF
- absorbed terminal ileum as B12-IF complex
plasma: bound to transcobolamins (TC I, II, III)
- TC II: most important, carries B12 to liver/BM, reflects tissue stores
cells:
- receptor mediated endocytosis into cells
- converts proprionyl CoA to succinyl CoA
- transfers methyl group from methylTHF to homocysteine to form methionine
Vitamin B12 deficiency
congenital causes:
transcobalamin deficiency: AR
- failure to absorb/transport B12 with normal serum B12 because T I/III unaffected
- manifests first weeks of life
- treatment: large parenteral doses B12
clinical:
- anaemia, glossitis, stomatitis, jaundice, bleeding, infections
- neurological: peripheral neuropathy, optic atrophy, MR, subacute cord degeneration
diagnosis:
- macrocytic anaemia >100, large/ovoid RBCs, anisocytosis, poikilocytosis, low reticulocytes
- low B12, normal folate, increased urine methylmalonic acid/homocysteine
Vitamin B2 (riboflavin)
deficiency: ariboflavinosis
clinical: glossitis, angular chelitis, light sensitivity, dermatitis
Vitamin B6 (pyridoxine)
Deficiency: irritability, seizures, anaemia
Vitamin C deficiency
causes: anorexia, neurodevelopmental delay
clinical: (scurvy)
- skin: hyperkeratosis, perifollicular haemorrhage, petechiae, ecchymoses, gingivitis
other: fatigue, arthalgias, anorexia, neuropathy, dyspnoea, hypotension, anaemia, impaired wound healing
Vitamin D
Deficiency: Rickets (up ALP), hypocalcaemia, osteomalacia, infantile tetany
- risk factors: poor sunlight/intake, exclusive breastfeeding, maternal def, prematurity, obesity, CRF, malabsorption, liver failure, drugs (anticonvulsants, antiretrovirals, steroids, ketoconazole)
Excess: hypercalcaemia, azotemia, poor growth, NVD, calcinosis
Vitamin E deficiency
causes: fat malabsorption
clinical:
- spinocerebellar syndrome: ataxia, hyporeflexia, loss of proprioreceptive/vibratory input
- haem: haemolytic anaemia
treatment: reversible<4yrs
Vitamin K
Deficiency: haemorrhage (factors II, VII, IX, X)
Wilson’s disease
incidence: 1/30,000
genetics: AR, chromosome 13 ATP7B
mechanism: defect in copper excretion with accumulation in liver/brain
symptoms:
- ocular: kaiser-fleisher rings (50%), sunflower shaped cataracts
- GI: abdo pain, jaundice, hepatomegaly, portal HTN
- neurological sx in 20’s: gait, tremor, dysarthria, basal ganglia copper deposition
- other: haemolytic anaemia, renal failure
investigations: low serum copper, low plasma ceruloplasmin, elevated transaminases AST>ALT, low ALP, raised urinary/liver copper, thrombocytopaenia, coagulopathy
prognosis: HCC, liver failure
Zinc deficiency
causes: crohn’s CF, sickle cell, liver disease, acrodermatitis enteropathica (congenital defect in absorption)
clinical:
- erythemtous/vesiculobullous rash to genitals and cheeks
- diarrhoea
- poor growth
- alopecia
- decreased ALP
Crohn’s disease
incidence: 5/100,000 (25% <18 years)
pathology: GI tract, patchy, transmural, perianal disease, oral lesions (10%)
clinical:
- abdominal pain, diarrhoea, rectal bleeding
- fevers, weight loss
- pyoderma gangrenosum
complications: strictures, fistulas, abscess
treatment: enteral tx, 5-asa, steroids, azathioprine, MTX, antibiotics, TNF mono Ab
Metabolism azathioprine
metabolism:
- 0.3% have low TPMT activity
- 11% intermediate TPMT activity
high levels TGN: increased therapeutic index/BM suppression
high 6-MMP: increased hepatotoxicity
