intestinal Flashcards
two features of ileum histology not seen in duodenum/jejunum
1) peyer’s patches - lymphoid tissue in lamina propria
2) lacteals - white core of villi that house lymphatic system
four hormones found in duodenum in intestinal phase of digestion, and their jobs
1) Secretin: inc NaHCO3 from pancreas + bile from liver
2) CCK: inc pancreas enzymes + bile from GB, slows gastric emptying
3) GIP: main role to inc insulin
4) motilin: moves things along
what are tinea coli and haustra?
a. Tinea coli – muscularis externa concentrated in three thickened strips
b. Tinea coli contract to form haustra (non-permanent infoldings of mucosa and submucosa)
examples of: mono, di and polysaccharides
1) mono: fructose, galactose, glucose
2) di:
- Sucrose = glucose + fructose
- Lactose = glucose + galactose
- Maltose = glucose + glucose
3) poly: glycogen
breakdown of carbohydrates: explain process
1) mouth: salivary amylase
2) CCK -> pancreatic alpha amylase
- amylases can only break from poly to di (1,4 links only)
3) intestinal brush border:
a - Glucoamylase + dextrinase = maltose
b - Sucrase-isomaltase
i) Sucrose glucose + fructose
ii) Maltose glucose + glucose
c- Lactase
when does lactase action drop usually?
5-7yo
how are monosaccharides absorbed in the SI?
- Glucose + galactose – Na+ dependent glucose transporter (SGLT1) [basis of ORS]
- Fructose – facilitated diffusion via GLUT5
- All monosaccharides are transported across basal border by GLUT 2 transport
breakdown of protein in digestion: explain the process
1) chief cells > pepsinogen > (gastric acid)//pepsin
2) AA in duo/jej > CCK > panc zymogens
3) enterokinase in epithelium activates trypsinogen -> trypsin, which autocatalyses and actives other zymogens
4) panc peptidases at brush border: oligopeptides into tri, di and single AAs
types of pancreatic peptidases
- Endopeptidases = trypsin, chymotrypsin, elastase
a. Act at interior peptide bonds - Exopeptidases = pancreatic carboxypeptidases
a. Act on terminal amino acids
how efficient is fat absorption, and how much exocrine function do we need for normal fat absorption?
- Fat absorption >95% efficient (85% in infants)
- 2-3% exocrine function allows normal fat absorption
breakdown of fats: explain the process
1) lingual lipase + gastric lipase»_space; (TG)»_space; glycerol+FA
3) CCK > panc enzymes (panc lipase, chol ester hydrolase + phospholipase A2) + bile salts
4) colipase binds to panc lipase to prevent bile salts from acting
left with: glycerol, FA, monoglycerides, cholesterol
5) micelle formation by bile acids
absoprtion of fats: explain the process
1) micelle transports lipids to apical membrane
2) then can dissolve, and TG+MGs enter
3) then:
SCFA (FA <12 C) direct to portal system (ie. MCT)
FA >12 C re-esterified to TG > chylomicrons > lacteals > lymphatic system
i.e. no active transport required
stool fat globules vs crystals - what does it mean?
Fat globules = maldigestion eg. pancreatic insufficiency, cholestatic liver disease
Fat crystals = malabsorption
length of bowel at birth vs adult
At birth length of the bowel = 200-250cm
Adulthood = 300-800cm
bowel resection in infant: how little does one need to be able to survive and wean off TPN?
15cm with IC valve, or 20cm without
in short gut - what is the worst part of the SI to lose? What happens when you lose that bit?
Ileum - jej can’t compensate for it:
- no distal ileum = no bile salts / b12
- net Na+H2O absorption ++ in ileum -> malabsorption
prox jej is responsbile for what absorption
first 100-200cm responsible for CHO, protein, iron and water soluble absorption
5 causes of short gut - most to least common
- NEC
- mec ileus
- abdo wall defect e.g. gastroschisis
- intestinal atresia
- volvulus
pattern of age distribution of IBD
bimodal - 10-20yo (20% all cases for both UC and CD <18yo), then 50-80yo
paeds: which more common - UC vs CD
CD higher incidence
4 factors involved in IBD pathogenesis
i. Genetic susceptibility
ii. Environmental triggers
iii. Changes in gut microbiota and dysbiosis (defining event); shift from symbiote microbes (friendly) to pathobiome microbes (harmful)
iv. Immune response
does UC or CD have more genetic infuence
- CD more genetic influence
first IBD gene identified
NOD2 (CARD15); but up to 70% CD don’t have it
inheritance of IBD:
- risk if both parents affected
- risk with affected sibling
- both parents: >35%
- single sibling: CD 30%, UC 10%
genetic disorders associated with IBD (3)
turners
GSD
Immunodeficiency
what must we always think about that can mimic ileitis
abdominal TB - esp Asian/African origin
ASCA vs pANCA association in IBD
ASCA - CD
pANCA - UC
most common EIM of IBD? most common skin EIM?
- most common: arthritis (30%)
- skin: erythema nodosum
EIM of IBD: mnemonic
A PIE SAC:
Arthritis, Ankylosing spondylitis, anaemia
Pyoderma gangrenosum/vegetans ,Perianal skin tags, Psoriasis, Pleuritis, Pericarditis, Pancreatitis
I for eye signs: Iritis, uveitis, episcleritis, conjunctivitis
Erythema nodosum
Sclerosing cholangitis, Sacroilitis
Aphthous ulcers
Clubbing of fingers, Cholelithiasis, renal Calculi
EIM that correlate with disease activity, and those that don’t
Correlate with disease activity:
- peripheral arthritis
- erythema nodosum
- anaemia
Don’t correlate:
- PSC
- pyoderma gangrenosum
- hepatitis
- ank spond
more common EIM with CD vs UC
CD: aphthous ulcers, fevers, erythema nodosum, gall/renal stones, OROFACIAL CD, peripheral arthritis
UC (4): pyoderma gang, sclerosing cholangitis, ank spond, hepatitis
compare UC vs CD features
UC:
• rectum always, limited to colon. continuous
• No granulomas, skip lesions
• Mucosal inflammation
• Cx: TMG (abscess/structure rare)
• no recurrence post-colectomy
CD:
• Any part of GIT, Discontinuous
• Non-caseating granulomas, skip lesions, cobblestoning
• Transmural inflammation
• Cx: strictures, fistulae, perf, abscess
• Perianal disease more common
• cramping, watery diarrhoea / steatorrhoea
• can recur post-colectomy
pathogenesis of growth failure in IBD (esp CD)
- malabsorption
- inc losses
- steroids
- inflammation
what increases risk of malignancy in IBD
time of disease
length of colon
presence of sclerosing cholangitis
FHx of CRC
what is stool calprotectin?
leukocyte derived protein
calpro:
- sensitivity and specificity
- when not to use it
- sensitivity = 96%
- specificity = 87%
- don’t use: <4yo, likely infection, nsaids/ppi
classic presentation diarrhoea / abdo pain / wt loss - more common UC or CD?
UC. only 20% present with this in UC
most common part of GIT for CD involvement
ileocolonic 50%
most common presenting complaint of CD
growth failure - can precede other symptoms by 1-2 years, and much more common in CD
conditions a/w coeliac
• first-degree relatives with CD
• autoimmune conditions: T1DM, thyroid disease, liver disease
• Down syndrome
• Turner syndrome
• Williams-Beuren syndrome
• IgA deficiency
Rx for crohn’s disease
Induction
1st line - complete EEN
2nd line - steroids
Maintenance
- mild: 5-aminosalicylates (mesalazine)
- mod/severe:
Immunomodulators
1) thiopurines (aza / 6-MP) - effect 3-4 months
2) MTX (+folic acid) - effect 6-8 weeks
Biologics:
- infliximab / adalimumab
- vedo / usteikinumab
describe role of allopurinol in thiopurines
- AZA -> 6MP
1) —(TMPT)-> 6MMP - hepatotoxic
2) — (hPMT) -> TGN
3) —(xanthine oxidase) -> byproduct
-ppl with higher TMPT activity make lots of 6-MMP
- so allopurinol will shunt active 6-MP towards making more TGN
side effects of thiopurines
dose dependent
- bone marrow suppression
- hepatotoxicity
dose independent
- nausea
- pancreatitis
- infection: HSV, HPV
- malignancy: HSTCL, lymphoma, melanoma, EBV associated lymphoma
risks of biologics
- HSTCL (esp with AZA)
- TB - screen with CXR + QFN
- cytopaenia
- lupus
when is screening indicated for CRC in Crohn’s / UC?
Crohn’s: after 10 years of colonic disease, needing regularly colonoscopies
UC: after 8-10yrs of disease duration
xray findings of UC
may show loss of haustral markings in an air filled colon or marked dilatation in toxic megacolon (in an adult diameter > 6cm)
Rx for UC
Induction:
1. 5-aminosalicylates (mesalazine / sulfasalazine)
2. steroids
Maintenance:
mild - 5-aminosalicylates (oral, rectal combo better than just oral)
mod - thiopurines, biologics
Salvage:
biologics, cyclosporin, tacro
*probiotics - adjuvant to 5-asa
*curcumin!
long term prognosis for UC better if …
… if achieve clinical remission (PUCAI <10) within first 3 months
what concommitant condition with IBD increases risk of CRCdramatically?
PSC: so annual or bi-annual surveillance colonoscopy should be initiated from the time of PSC diagnosis
what cancer does PSC inc risk of?
cholangiocarcinoma - Serial CA19.9 and liver ultrasound/MRCP testing may thus be considered every 1 to 2 years
what is pyoderma gangrenosum?
neutrophilic dermatosis - not infectious/gangrenous!
diagnostic criteria of TMC
1) radiological evidence of colonic distension
- right colon > 6cm, absence of haustral markings
2) + at least 3 of: fever, HR >120, neutrophilic leukocytosis, anaemia
3) + at least one of: dehydration, altered GCS, electrolyte disturbances, hypotension
tpmt genotypes
90% homozygous for wild type TPMT = rapid metabolism of thiopurines, higher doses for clinical effect
10% heterozygous for wild type TMPT = metabolise slowly and respond to much lower doses
0.3% can’t metabolise
compare osmotic vs secretory diarrhoea:
- pathogenesis
- response to fasting
- volume
- Na
- osmotic gap
- reducing substances
- pH
osmotic:
- non-absorbed nutrients pulling water out
- Response to fasting (as no more sugar)
- <200 ml/ay
- Na <70 meq/L
- High >100; > (Na + K) x 2
- reducing substances present and pH <5
secretory:
- secreted ions pulling water out
- no response to fasting
- >200 ml/day
- Na >70 meq/L
- Low <50 osmotic gap; = (Na + K) x 2
- Absent reducing substances, pH >6
causes of osmotic vs secretory diarrhoea
Osmotic:
- laxatives
- mucosal injury - infective (eg. post-rotavirus), inflammation (IBD), immune mediated (celiac), vascular
- sugar transport defects
Secretory:
- congenital ion transport defects e.g. chloridorrhoea
- secretagogues
- bile acid malabsorption - turn on cAMP
- tumours e.g. producing VIP
- fast transit
describe how intestinal secretion of Na and water is mediated by chloride
- Cl enters crypt cell with Na/K/Cl transporter
- Cl»_space;> activation of cAMP
- cAMP activates CFTR > Cl secreted into lumen
- Cl accumulates in lumen > negative electric potential > Na pulled into lumen>water
how does vibrio cholerae cause diarrhoea
- have flagella, swim to attach to enterocyte, produce cholera toxins
- toxin B unit binds > enter the cell via endocytosis
- toxin A unit activates G protein > activates AC > inc cAMP
- high cAMP > CFTR > Cl secretion
how does ORS work?
Has salts, glucose and starch
Na/glucose co-transporter remains even in terrible infections -> brings water in more effectively
Starch that fermentable is added -> SCFA -> Na+fluid absorption
how quick should Na fall during hyperNa corrections
no quicker than 0.5mmol/hr
EIM of enteric infections, and which bugs cause them
1) Focal infections from systemic spread (all)
2) Reactive arthritis
- Salmonella, Shigella, Yersinia, Campylobacter, Cryptosporidium, C difficile
- 1-3 weeks after infection
3) Guillain-Barre
- campylobacter; few weeks after
4) Glomerulonephritis
- Shigella, Campylobacter, Yersinia
5) IgA nephropathy
- campylobacter
6) Erythema nodosum
- Yersinia, Campylobacter, Salmonella
7) HUS
- Shigella dysenteriae 1,EHEC O157:h7
8) Haemolytic anaemia
-camp,yersinia
DDx infant/toddler PRbleeding
Anal fissure
Food protein induced colitis
Intussusception
Meckel’s diverticulum
Lymph nodular hyperplasia
GI duplication cyst
Infantile and VEO IBD
DDx older children PR bleeding
Infectious colitis
HUS
IgA vasculitis (HSP)
Juvenile polyps
Anal fissure
Infectious colitis /IBD
Meckel’s Diverticulum
DDx PR bleeding by aetiology
Vascular - AVM, HSP, HUS, coagulopathy
Inflam/infectious - infection, allergic colitis, IBD, NEC
Neoplastic - rare
D - not really
Iatrogenic - c.diff
Congenital - hirschprung,
Anatomic - meckel’s, fissures, malrotation, intuss,haemorrhoids,polyps, duplication cyst
Trauma
Endocrine - not really
