Gastro Flashcards
acute intermittent prophyria pathophysiology and triggers
auto dom
porphobilinogen deaminase deficiency
PBGD on chromo 11
latent in most heterozygotes
block in haem synthesis at PBGD reaction stage
> increased ALA and PBG synthesis
> increased urinary excretion of porphyrin precursors and porphyrins
precipitating factors:
- ALAS1 induction
- P450 enzymes
- alcohol
- barbiturates, sulfonamides, enzyme inducers (carbamaz, phenytoin, OCP, rifampicin)
- fluctuations in female sex hormones
- infections
- starvation
manifestations of acute intermittent porphyria
- autonomic neuropathy
> abdo pain, constipation, vomiting, tachyc, HTN, postural hypot, peripheral neuropathies - dark/red urine
- bulbar paresis > resp failure
- cerebellar signs
- hypothalamic dysfunction > SIADH
- hyponatraemia (SIADH, GI and renal loss)
- confusion, agitation, disorientation, hallucinations
managing acute intermittent porphyria
IV fluids
IV haemin
alternatively 300g dextrose IV
prophylaxis:
non cyclic- haem arginate IV once or twice weekly (risk of iron overload)
cyclic attacks in women- preventative GnRH
liver transplant
complications of acute intermittent porphyria
HTN
CKD
hepatocellular ca
types of acute pancreatitis
mild- no complications or organ dysfunction
mod- local complications and/or organ dysfunction that resolves within 48h
severe- persistent organ dysfunction leading to local complications (necrosis, abscess, pseudocysts), potentially fatal
causes of pancreatitis
Gallstones
Ethanol
Trauma
Steroids
Mumps, coxsackie B
Autoimmune
Scorpion sting
Hyperlipidaemia, hypercalcaemia, hypertriglyceridaemia,
ERCP
Drugs (azathioprine, OCP, steroids, antiretrovirals, fibrates, thiazides)
pathophysiology of pancreatitis
intrapancreatic activation of enzymes due to outflow obstruction or acinar cell injury
> autodigestion of parenchyma
> inflammatory cells go to parenchyma and release cytokines
> inflammation
enzymes also cause vascular injury
> vasodilatation and increased permeability
> third space loss
> hypotension, tachyc, shock, multi organ dysfunction
acute vs chronic pancreatitis investigation findings
acute:
raised amylase 3x, lipase (lipase remains raised longer)
sentinel loops of adynamic bowel next to pancreas on AXR
CT may confirm inflammation if amylase/lipase levels are not raised
chronic:
speckled calcification on XR, CT
irregular dilatation and stricturing of pancreatic ducts on ERCP, MRCP
endoscopic USS
PABA testing (exocrine function)
faecal elastase (exocrine insufficiency)
OGTT
surgical management of gallstone pancreatitis
consider early ERCP for decompression
cholecystectomy during same admission or within 2/52 of discharge once acute symptoms have settled
poor prognostic factors of acute pancreatitis
age > 55
WCC > 15
urea > 16
pO2 < 8
calcium < 2
albumin < 32
glucose > 10
LDH 600
AST 200
pathophysiology of alcoholic fatty liver disease
alcoholic dehydrogenase concerts alcohol to acetaldehyde to acetic acid to CO2 + H20
> reduces NAD to NAD + H
increases NADH : NAD ratio
increases fatty acid synthesis decreased fatty acid oxidation
pathophysiology of alcoholic hepatitis
acetaldehyde binds to macromolecules in hepatocytes
> immune system detects complexes
> neutrophil infiltration
> hepatocyte necrosis and inflammation
dilutional anaemia blood test
reduced haematocrit
SAAG and portal hypertension
serum albumin minus ascitic albumin
> 1.1 g/L suggests portal HTN
increased SAAG:
cirrhosis, alcoholic hepatitis, schisto, budd chiari, portal v obstruction, cardiac disease, SBP
low or normal SAAG:
nephrotic syndrome, protein losing enteropathy, peritoneal carcinomatosis, TB peritonitis, pancreatic duct leak, biliary ascites
autoimmune hepatitis genetics and environmental triggers
HLADR3 and HLADR4 (type 1)
HLA DQB1 and HLA DRB (type 2)
viruses, nitrofurantoin, diclofenac, atorvastatin
type 1 and type 2 autoimmune hepatitis
1: most common
antiSMA and ANA
increased IgG
good response to immunosuppression
2: often in children
commonly > cirrhosis
less treatable
ALKM-1, ALC-1
ANA and aSMA neg
autoimmune hepatitis histopathology
piecemeal necrosis
mononuclear infiltration of portal and periportal areas
may see fibrosis
pharmacalogical management of autoimmune hepatitis
for mod/severe inflammation (serum AST 5x upper limit, serum globulins 2x upper limit normal, necrosis on biopsy)
4/52 prednisolone
alternatively budesonide
steroid + immunosuppressant e.g. azathioprine
budd chiari vs veno-occlusive disease
both cause hepatic venous outflow obstruction
BC: any level from small hepatic veins to junction of IVC and RA
VOD: occlusion of terminal hepatic venules and sinusoids
BC associated w/ myeloprolfierative disorders, hypercoagulable disorders, behcet, SLE, sjogrens, mixed CTD, IBD, sarcoid, pregnancy and post portum
secondary BC: external compression or invasion by abscess, tumour or trauma
causes of venous occlusive disease
haematopoietic cell transplant
ctx e.g. oxaliplatin
pyrrolizidine alkaloids jamaican bush tea
high dose rtx to liver
post liver transplant
preventing veno-occlusive disorder
given ursodeoxycholic acid or heparin to patients undergoing haematopoietic cell transplant
complications of chronic pancreatitis
pancreatic duct obstruction
pseudocysts
neuropathic pain
pancreatic ascites, pleural effusion
diabetes
exocrine insufficiency
pancreatic cancer
pancreatic pseudocysts
necrotic/haemorrhagic material and enzymes within or near pancreas
no epithelial lining
found on CT
confirmed w/ EUS and FNA
larger cysts > obstruction, vomiting
occur following acute/chronic pancreatitis or trauma
pancreatic divisum
congenital
dorsal and ventral ducts do not connect
> dorsal duct drainage is disrupted
asymptomatic or recurrent pancreatitis
dx w/ MRCP or ERCP
cirrhosis pathophysiology
activation of stellate cells
> accumulation of collage I and III in parenchyma and Disse space
> stellate cells become contractile
> increased portal resistance
> blood shunted away from liver
portal HTN > spleen congestion
> hypersplenism and platelet retention
coeliac histopathology
loss of brush border
villous atrophy
crypt hyerplasia
coeliac blood tests and biopsy results
IgA-tTG
endomysial antibody EMA if IgA-tTG unavailable or weakly positive
biopsy: intra-epithelial lymphocytes, villous atrophy, crypt hyperplasia
supplementation for coeliac
calcium and vit D for all
iron only if deficient
HNPCC vs sporadic colorectal ca
younger age of dx
more likely to develop in proximal colon
rapid transformation from benign to malignant
HNPCC non colon associated cancers
endometrial
ovarian
gastric
biliary, urinary, brain, small bowel, pancreas
lymphatic spread in colorectal ca
regional nodes > para aortic nodes > thoracic duct
supraclavicular nodes in advanced cases
upward spread more likely for rectal carcinoma than lateral or downward spread
transcoelomic spread of colorectal ca
deposits of malignant nodules throughout peritoneal cavity
occurs in 10% after resection
spreads to ovaries (Krukenberg tumours)
distribution of colorectal tumours
75% in rectum and sigmoid
FAP/HNPCC- more right sided
3% w/ primary carcinoma will have another tumour at the time
75% will have an associated benign adenoma
3% of successfully treated cases will get another colorectal tumour within 10 y
TNM staging
T0- no evidence of primary tumour
Tis- in situ
T1- submucosa
T2- muscularis mucosa
T3- subserosa or non peritonealised pericolic/perirectal tissues
T4- directly invades other organs or perforates visceral peritoneum
N0- no lymph node mets
N1- mets in 1-3 regional nodes
N2- mets in 4 regional nodes
M1- distant mets
dukes staging
A- bowel wall
B- through wall but no nodes
C- nodes involved
D- distant mets
right vs left colon ca
Right:
proliferative, soft, friable
change in bowel habit, PR blood
abdo pain and perforation
more likely to be asymptomatic
Left:
annular and constricting
change in bowel habit, constipation
obstruction, colic, perforation
more overt bleeding and mucus PR
25-30% present as obstruction or perforation
rectal:
bleeding usually presenting complaint
tenesmus, palpable prolapsing mass
symptoms worse in morning
altered bowel habit
colorectal ca adjuvant ctx
indicated in TNM III, maybe TNM II
6/12 5-FU + folinic acid (FUFA)
or
1/52 5-FU by continuous infusion
not indicated for TNM stage I
colorectal ca pre op
staging CT
colonoscopy or barium enema
MRI or endorectal US for local involvement
2 day of liquid only diet + picosulfate to reduce bowel lumen bacteria
metro and cephalosporin prophylaxis
curative intent surgery for unobstructed colorectal ca
right sided, non obstructed:
right hemicolectomy and primary anastamosis, sparing middle colic arteries
transverse or splenic, non obstructed:
extended right hemi, take middle colic arteries
sigmoid or middle/upper rectum:
anterior resection, take inferior mesenteric artery and sigmoid and superior rectal branches
low rectal and anorectal:
abdominoperineal excision and end colostomy, taking inferior mesenteric artery
some may be done as transanal excision
3 stage approach for obstructed colorectal ca
1- primary decompression w/ proximal loop colostomy
2- resection of tumour at later date, leaving the colostomy to protect anastomosis
3- closure of colostomy
hartmann’s procedure
primary resection with end colostomy
relieves obstruction and resects tumour
avoids complications of anastamosis under suboptimal conditions
reversal has high complication rate
options for obstructed colorectal ca
primary resection and anastomosis
hartmanns
3 stage approach
anastamotic leak
typically 7-10 days post op
higher risk in low anastamoses
most common site of perforation
caecum
Rome IV criteria
constipation
less than three times per week
drug causes of constipation
iron and calcium
NSAIDs
antimuscarinics (procyclidine, oxybutynin)
TCAs
clozapine, quetiapine
carbamazepine, gabapentin, phenytoin
antihistamines (hydroxyzine)
antispasmodics (hyoscine)
CCB
diuretics
metabolic causes of constipation
hypercalcaemia
uraemia
hypermagnesaemia
hyperkalaemia
extra intestinal manifestations of crohns
pauci articular arthritis
erythema nodosum
aphthous mouth ulcers
episcleritis
osteopenia, osteoporosis, osteomalacia
sacroiliitis, spondylitis
polyarticular arthritis
pyoderma gangrenosum, psoriasis
uveitis
crohns vs UC
crohns:
ulcers
neutrophil infiltrates
fistulae
B12 and iron def
UC:
crypt abscesses
inflammatory cell infiltrates
iron def
managing crohns
- pred to induce remission
- thiopurines or MTX as adjunct for acute exacerbations and for maintaining remission after complete macroscopic resection
- biologics next line to induce/maintain remission
- aminosalicylates if steroids not tolerated
congenital vs acquired diverticulosis
congenital involve all layers of colon wall
acquired involve areas of mucosa that herniate through muscular wall
most common location of diverticular disease
sigmoid and descending colon
right sided more common in Asian patients
benign vs malignant stricture
smooth walled
no mucosal disruption
no apple core appearances
tend to be longer
drugs causing DILI
paracetamol
halothane
NSAIDs
isoniazid
penicillins, cephalosporins
sulfonamides
ketoconazole
thiazoladinedione
ezetimibe
kava root
antidepressants for IBS abdo pain
TCA e.g. amitripyline
2nd line fluoxetine or citalopram
gallstones risk factors
progesterone, oestrogen (female, OCP, HRT, parity)
clofibrate
crohn’s, short bowel syndrome
age
haemolysis
diet
diabetes
NAFLD
obesity
gallstones composition
70-90% are cholesterol and bile pigment
10% pure cholesterol
pure pigment stones are rare (except in chronic haemolysis)
pigment- bilirubin and calcium salts
what causes pale stools and dark urine in obstructed jaundice?
pale stools- lack of stercobilinogen
dark urine- increased conjugated bilirubin
LFTs in gallbladder disease
ALP raised- ALP lines biliary tree
GGT raised- reflects acute liver damage as bile backs up into liver
ALT and AST will rise with ongoing obstruction due to damage to hepatocytes
amylase/lipase raised in pancreatitis
investigating gall stones
abdo USS
MRCP next line
EUS if non invasive investigations fail to demonstrate cause
ERCP not used for diagnosis of obstructive jaundice
indications for cholecystectomy
acute cholecystitis (within 1/52)
symptomatic GB stones
symptomatic or asymptomatic CBD stones (also requires clearance of bile duct)
gallstone pancreatitis once acute symptoms settle
cholecystitis vs cholangitis
fever and RUQ pain
cholangitis- also jaundice
gastric ca risk factors
japanese
h pylori
hypochlorydia (pernicious anaemia, chronic atrophic gastritis, partial gastrectomy)
FHx inc FAP
male, age
salt, nitrates, processed diet
polyps
50% of gastric cancers are in cardia
usually adenocarcinoma from glandular epithelium
2WW referral criteria for suspected gastric ca
- abdo mass consistent w/ stomach ca
- dysphagia or > 55y with weight loss and epigastric pain/reflux
gastric ca treatment
HER2 testing for metastatic adenocarcinoma > trastuzumab
triple therapy for h pylori
PPIs for ulcers
adjuvant chemo for adv disease
Lauren classification of gastric ca
diffuse- poorly differentiated, faster rate of mets
intestinal- well differentiated, slow growing, M>F
GIST tumours
GI stromal
submucosal, malignant potential
stain with CD117
abx for entamoeba histolytica
metronidazole then diloxanide
abz for campylobacter
erythromycin
abx for shigella and salmonella
not usually indicated
give cipro if immunocompromised or bloody diarrhoea
trimethroprim can also be used for salmonella
what protease inhibitor is particularly likely to cause diarrhoea?
lopinavir
CMV colitis microscopy
owl eye sign from inclusion bodies in colonic mucosa
managing oral and oesophageal candidiasis in HIV
fluconazole 100-200mg 14/7
CMV colitis treatment
ganciclovir
microsporidium treatment
albendazole
cyclospora/isospora treatment
cotrimoxazole
salmonella/shigella dysentry treatment in HIV
azithromycin
TB length of treatment
RIPE for 2 months
continue isoniazid and rifampicin for another 4 months
9 month regime if pyrazinamide has to be stopped
what drugs can cause GORD?
TCAs
nitrates
CCBs
anticholinergics
indications for endoscopy for GORD
- > 55y w/ ALARM symptoms
Anaemia
Loss of weight
Anorexia
Recent onset progressive symptoms
Melaena or haematemesis - dysphagia
- treatment refractory symptoms
Gilbert syndrome genetics
UGT 1A1 auto recessive
Gilbert syndrome triggers of jaundice
fasting/dieting
surgery
heavy exertion
dehydration
alcohol
infection
lack of sleep
gilbert syndrome pathophysiology
reduction in UDP glucoronyl transferase
> reduction in conjugation of bilirubin
> increased unconjugated bilirubin
causes of raised conjugated bilurbin
gallstones
steatohepatitis
EBV, CMV
paracetamol, alcoholic hepatitis, erythromycin, oestrogens, corticosteroids
Wilsons, haematochromatosis
PBC, PSC, autoimmune hepatitis
cholangiocarcinoma, renal ca, mets
TB, lymphoma, amyloid, sarcoid infiltration
risks with gilbert syndrome
increased risk of drug toxicity from gemfibrozil and/or statin
may have higher risk of paracetamol OD toxicity
location of anal vascular cushions
3, 7, 11 o’clock
consists of rectal mucosa, arterioles, venules and their anastamoses
haemorrhoids degrees
1st- confined to anal canal. do not prolapse
2nd- prolapse on straining or defecating. spontaneously reduce
3rd- may prolapse spontaneously or on defecation. must be digitally reduced
4th- irreducible
HELLP syndrome treatment
IV Mg sulfate
IV dexa
control bp
replace blood products
deliver baby
LDH and AST in HELLP
both raised
LDH to AST ratio < 22
hepatic encephalopathy poor prognostic factors
worsening acidosis
rising PTT
falling GCS
precipitants of hepatic encephalopathy
alcohol, drugs
GI haemorrhage
infections
constipation
HCC risk factors
hep B and C
alcohol
haemochromatosis
cirrhosis
long term OCP
alfatoxin from Asperfillus flavus
smoking
cholangiocarcinoma risk factors
PSC
choledochal cyst
liver flukes
caroli disease (dilatation of intrahepatic bile ducts)
smoking
risk factors for carcinoma of gallbladder
UC
PSC
gall stones
gallbladder polyps
smoking
signs of cholangiocarcinoma
obstructive jaundice, pale stools
RUQ pain
swinging pyrexia
haemochromatosis genetics
auto rec
HFE mutation- C282Y, H63D
jaundice referral criteria
2WW if over 40y
obstructive LFTs > upper GI
hepatic LFTs > gastro
suspected ALD > gastro
visceral leischmaniasis
bangladesh, india, NE africa, brazil
parasite transmitted by sandflies
incubation 10 days to several years
fever, weight loss, hepatosplenomegaly
ix- biopsy lesions
tx: liposomal amphoteracin B
liver transplant contraindications
poor cardiac reserve
comorbidities incl HIV, severe respiratory disease
failure to abstain from alcohol
liver transplant immunosuppression
tacrolimus or ciclosporin (calcineurin inhibitors)
6 weeks steroids
azathioprine
managing flushing from NETs
somatostatin analogues
antihistamines
ondansetron 5HT3 antag
NAFLD liver function tests
3/12 or more persistently raised LFTs
ALT up to 3x upper limit normal
ALT > AST
management of oesophageal tumours depending on stage/grade
T1 adenocarcinoma: endoscopic mucosal resection
T1b adenocarcinoma: radical resection
T1bN0 squamous: definitive chemoradio or surgical resection
pancreatic cancer inherited cancer syndrome
hereditary pancreatitis
peutz jeghers
familial atypical multiple mole melanoma
familial breast ca
HNPCC
chemo for pancreatic ca
folfirinox
gemcitabine +/- capectitabine
parasite causing anaemia
hookworm
katamaya fever
acute schisto
4-8 weeks post infection
fever, urticaria, diarrhoea, hepatosplenomegaly, wheeze and cough
how does h pylori cause ulceration?
increases release of acid production in duodenum
decreases release of acid in stomach to cause atrophic gastritis and gastric ulcers and increased risk of gastric ca
duodenal ulcers are more common than gastric
endoscopy testing for h pylori
antral biopsy w/ haematoxylin/eosin or Giema stain
urease CLO testing
peutz jeghers genetics
auto dom
STK11 tumour suppression gene on chromo 19
porphyria cutanea tarda clinical features
hypopigmentation, scarring
blistering and crusted skin lesions on backs of hands and other sun exposed areas
hypertrichosis
dark or red urine on standing
PCT triggers
iron overload
end stage CKD
myelofibrosis
testing for porphyria cutanea tarda
blood, urine faeces collected in dark container > elevated porphyrins
mildly elevated ALT, AST
iron overload
PCT management
avoid sunlight, ETOHXS, smoking, oestrogens
fortnightly phleb
consider low dose hydroxychloroquine if ferritin < 600
liver imagine and AFP levels due to increased risk of HCC
causes of portal hypertension
cirrhosis
portal v thrombosis (congenital, pancreatitis, tumour)
budd chiari (tumour, haematological, COCP)
intrahepatic tumours
constrictive pericarditis
RHF
splenic vein thrombosis
cause of varices
portal HTN
> collateral vessels enlarge
complications of pregnancy related liver disease
cholestasis:
intrauterine foetal demise, preterm delivery
meconium amniotic fluid
neonatal resp distress
fatty liver:
maternal liver failure
severe coagulopthy
foetal demise
pregnancy related liver disease risk factors
cholestasis:
age < 35y
previous or family history
multiple gestation
hep c
fatty liver:
previous or family history
multiple gestations
foetus male sex
pre eclampsia or HELLP
BMI < 20
fatty liver of pregnancy vs cholestasis
LFTs 3x normal (cholestasis less than 2x)
elevated bili and ammonia
low glucose
elevated creat, urea
proteinuria
elevated PTT, INR, APTT
low platelets and fibrinogen
stages of PBC
- destruction of interlobular ducts
- small duct proliferation
- fibrosis
- cirrhosis
PBC and PSC treatment
cholestyramine for pruritus
obeticholic acid +/- ursodeoxycholic acid
liver transplant (end stage liver disease, intractable pruritus)
recurrence is rare in PBC but 30% likely in PSC after transplant
features of SIBO
steatorrhoea (bile acids are deconjugated by bacteria)
megaloblastic anaemia (b12 is used by bacteria)
raised folate (synthesised by bacteria)
def of fat soluble vitamins
UC treatment
aminosalicylate
corticosteroids for acute phase
calcineurin inhib for acute phase
thiopurines or MTX to maintain remission second line to aminosalicylates
biologics third line
hepatitis virus types
hep A- RNA
hep B- DNA
hep C- RNA
hep D- incomplete
hep E- RNA
also EBV, CMV, HSV, yellow fever, rubella
hep B immunisation
anti HBs without anti HBc
whipples disease treatment
14/7 ceft or benpen
then a year of trimethoprim or sulfamethoxazole
high vs low SAAG
high:
cirrhosis, alc hep, schisto, fulminant liver failure, budd chiari, portal v obstruction, cardiac disease and SBP secondary to cirrhosis
low or normal:
nephrotic syndrome, protein losing enteropathy, peritoneal carcinomatosis, TB peritonitis, pancreatic duct leak, biliary
