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
