Gastroenterology Flashcards
odynophagia (7)
pain on swallowing, oft worse when drinking a hot liquid, may be indicative of oesophageal ulceration or oesophagitis from GORD, or oesophageal candidiasis
cancer less likely as implies mucosal sensation is intact - dont dismiss this tho
may be urti, pharyngitis, epiglotitis
GORD (6 risk factors, 6 sx, 2x ix, 3 things main ix may show, risk of cancer from barrets, 6mx options)
may be due to hiatus hernia, gastroparesis, raised abdo pressure, and unhealthy diet; using NSAIDs regularly, and binge drinking
heartburn, esp on bending; fluid/food regurgitation on squeezing, waterbrash, nocturnal cough (gastric fluid reflux to larynx when flat), chest pain (from oesophageal spasm), dysphagia or odynophagia (though rare unless complicated)
endoscopy if ALARMS sx or persistent despite PPI w/o H pylori infection; 24hr-pH measurement if considering surgery
endoscopy may show oesophagitis (+/- ulcers and strictures - these cause dysphagia and need endoscopic dilatation)
barret’s oesophagus: metaplasia of distal oesphageal epithelium from squamous to columnar, usually no symptoms but 10% lifetime risk of getting adenocarcinoma from it
conservative (lifestyle, weight loss, antacids), medical (PPI or H2ra), endoscopic and surgical if eg large hiatus hernia
achalasia (what it is, 2 causes of similar presentation, 5 sx, rare complication, 3ix, 2mx and their 2 main risks)
degen of ganglia in distal oesopgaus/LOS causes peristalsis and sphincter relaxation to fail, and the oesophagus to gradually dilate; more common in middle aged people
similar condition when myenteric plexus destroyed in Chagas disease or oesophageal cancers
presents: insidious, intermittent dysphagia, worse if swallowing when slouched, better for liquids than solids; heartburn and chest pain may occur, and in late stages regurg and aspiration; SCC is rare complication
upper GI endsocopy to exclude malignancy, barium swallow will show narrowing v distal with proximal dilatation and reduced peristalsis; oesophageal manometry is diagnostic, shows the absent peristalsis and raised LOS pressure
medical options not usually helpful
endoscopic dilation or botulinum injection help but inc risk of GORD and have small risk of perforation
fundoplication - 4 parts of LOS, 3 indications, commonest procedure inc how done and post-op problem, 4 types of hiatus hernia, HH 6 risk factors, 4 surgical indications, when to suspect scariest problem, general mx)
The intrinsic musculature of the distal esophagus, which is usually in a state of tonic contraction.
The sling fibers of the gastric cardia, which contribute to the high-pressure zone of the lower esophageal sphincter.
The crura of the diaphragm, which surrounds the esophagus at the esophageal diaphragmatic hiatus.
The gastroesophageal junction, which should be located intra-abdominally so that the intra-abdominal pressure on the distal esophagus prevents reflux.
generally if repeated aspirations, failure to control on maximal medical therapy, or unable/prefer not to take medications
nissen fundoplication commonest procedure, upper part of stomach (fundus) wrapped tightly around oesophagus to create a better seal; some dysphagia common afterwards while oedema settles
hiatus hernia t1 >95% of all is sliding type where GOJ displaced upwards, t2 when stomach into mediastinum, t3 when t2 + t1 giving GOJ and stomach in mediastinum, t4 when extra organ like colon, SI, spleen also herniate into chest
HH risk inc’d by age (lost muscle strength and elasticity); also raised intra-ab pressure eg obesity, pregnancy, chronic constipation; also prev surgeries, trauma etc
generally manage resulting GORD medically first, then surgical indications as above or severe oesophageal inflam with strictures go for surgery, also if large or have volvulus; nissen fundoplication (among other types) usually done; suspect volvulus if have HH and unwell (chest pain and sweating but no ACS, hyper or hypotension, nausea etc, may dev coffee ground vomiting)
oesophageal carcinoma (ACC where, other type where, where is most common, 5 risk factors, 6 sx, 3ix, 4mx)
ACC in lower third, SCC anywhere, more common in middle and far east; smoking, alcohol, betel nut, tobacco chewing, achalasia are risk factors
presentation: painless, rapidly progressing dysphagia, weight loss; late focal invasion will give chest pain or hoarse voice, spread to cervical lymph nodes; may form fistula from oesophagus to bronchus giving coughing after eating, pneumonia or pleural effusion
upper GI endoscopy to find and biopsy, barium swallow will show length of tumour if endoscope couldnt pass by it; abdo, thorax CT for staging or endoscopic US
if operable, oesophagectomy; if not then stent it to relieve dysphagia, radiotherapy and analgesics
px of minor oesophageal conditions (pharyng pouch, eosin oesoph, oesoph rings/webs, MW tear)
pharyngeal pouch: dysphagia, night time cough, halitosis, lump in throat; diagnose with barium swallow
eosinophillic oesophagitis: vomiting in kids or dysphagia in adults
oesophageal rings/webs: intermittent dysphagia to solids over years, rings distal and webs proximal; usually spotted by radiology
mallory-weiss tear: mucoasal tear leading to haematemsis; typical history will say initial vomitus does not contain blood; will usually settle spontaneously, acid suppression or endoscopic therapy needed in rare cases
foreign body ingestion - 2 types, 9 suggestive sx of impaction, signs of a complication to look out for, urgent endo 3 crit, surgery 3 crit, 2 mx otherwise; for food bolus 2 mx
may be true foreign body or impacted food bolus
Emesis, retching, blood-stained saliva,
hypersialorrhoea, wheezing and/or respiratory distress in non-communicative patient are suggestive; may vomit and have retrosternal pain or foreign body sensation
look for signs of perforation (inc cervical)
Urgent endoscopy if foreign body in the upper third part of the oesophagus, complete obstruction, sharp foreign bodies or button batteries
Enteroscopy and surgery should be considered for long, sharp/pointed foreign bodies, batteries or magnets that have passed the duodenojejunal angle
Otherwise if in oesophagus then OGD in 24hrs, if reached stomach and doesn’t fit above crit then will likely pass
for food bolus: if can’t swallow saliva then urgent, otherwise remove in 12-24hrs, less if not soft food eg a bone; trial 1mg IV glucagon but many studies haven’t shown benefit
haematemesis inc how far down can source be, 7 causes in order of likeliness, 5 ix, 3mx choices (inc 3 reasons for urgent instead of day case)
prox to jejunum (ligament of Treitz);
peptic ulcer > gastric erosion/gastritis > mallory weiss tear > oesophageal varices (10%) > duodenitis > oesophagitis > tumour
check FBC, LFT, VBG, clotting status; crossmatch blood if type unknown
upper GI endoscopy as day procedure or emergency if varices likely/large Hb drop or unstable haemodynamically otherwise transfuse if needed and monitor
if bleeding after endoscopy, high chance of surgery being needed
dyspepsia (5 causes inc 5 medications, ALARMS sx and deciding whether to do endoscopy, 3 step management pathway, mx of Barrett’s inc risk of progressing)
Gastro-eosophageal reflux disorder (GORD)
Gastritis
Peptic ulcer disease
Cancer
Medications: calcium antagonists, nitrates, NSAIDs, steroids, bisphosphonates
Non ulcer dyspepsia- endoscopy negative
ALARMS symptoms
Anaemia
Loss of weight
Anorexia
Recent onset symptoms/progressive
Melaena/haematemesis
Swallowing difficulty
-> if yes, or >55yo, then endoscopy
if no then Stop drugs causing dyspepsia.
Lifestyle changes: eat less spicy food, caffeinated/fizzy drinks
Over the counter antacids
Review after 4 weeks
not improved? urea breath test
- if neg, PPI/H2Ra 2 weeks, if still no improvement consider ogd
-if pos, eradicate with trip therapy;
after 4 weeks urea breath test, if shows bacti eradicated then endoscopy
barrets: velvety epithelium; frequent endoscopic surveillance + random biopsies
If any dysplasia identified – resection/ablation
10% risk progressing to ACC
dyspepsia in children
Recognise the following as possible complications of GOR in infants, children and young people:
reflux oesophagitis
recurrent aspiration pneumonia
frequent otitis media (for example, more than 3 episodes in 6 months)
dental erosion in a child or young person with a neurodisability, in particular cerebral palsy.
Recognise the following as possible symptoms of GOR in children and young people:
heartburn
retrosternal pain
epigastric pain.
OGD for ALARMS type sx or if suspect sandifers syndrome, no improvement in regurgitation after 1 year old
persistent, faltering growth associated with overt regurgitation
unexplained distress in children and young people with communication difficulties
Consider performing an oesophageal pH study (or combined oesophageal pH and impedance monitoring if available) in infants, children and young people with:
suspected recurrent aspiration pneumonia
unexplained apnoeas
unexplained non‑epileptic seizure‑like events
unexplained upper airway inflammation
dental erosion associated with a neurodisability
frequent otitis media
a possible need for fundoplication
a suspected diagnosis of Sandifer’s syndrome
Investigate the possibility of a urinary tract infection in infants with regurgitation if there is:
faltering growth
late onset (after the infant is 8 weeks old)
frequent regurgitation and marked distress.
Consider a 4‑week trial of a PPI or H2RA for those who are unable to tell you about their symptoms (for example, infants and young children, and those with a neurodisability associated with expressive communication difficulties) who have overt regurgitation with 1 or more of the following:
unexplained feeding difficulties (for example, refusing feeds, gagging or choking)
distressed behaviour
faltering growth.
Consider a 4‑week trial of a PPI or H2RA for children and young people with persistent heartburn, retrosternal or epigastric pain.
Assess the response to the 4‑week trial of the PPI or H2RA, and consider referral to a specialist for possible endoscopy if the symptoms:
do not resolve or recur after stopping the treatment
Only consider enteral tube feeding to promote weight gain in infants and children with overt regurgitation and faltering growth if:
other explanations for poor weight gain have been explored and/or
recommended feeding and medical management of overt regurgitation is unsuccessful
reduce and stop enteral tube feeding as soon as possible.
Consider jejunal feeding for infants, children and young people:
who need enteral tube feeding but who cannot tolerate intragastric feeds because of regurgitation or if reflux‑related pulmonary aspiration is a concern
Consider fundoplication in infants, children and young people with severe, intractable GORD if:
appropriate medical treatment has been unsuccessful or feeding regimens to manage GORD prove impractical
oesophageal cancer (4ix and their roles, staging + mx, 3 complications, Barrett’s (inc what to stain for) and SCC histo)
ACC typically lower, SCC typically upper; Investigations
First-line: OGD -> CT -> pet-ct -> endo USS (+biopsy)
Endoscopic ultrasound – T staging and nodal disease; biopsy of these nodes possible too
CT scan – T staging and obvious metastases
PET -CT – subtle metastases
Local Disease – T1a = endoscopic removal alone (no chemo needed)
T1b-3 = radical oesophagectomy + chemo/radio, can include local nodal involvement
T4 = typically palliation (beyond adventitia to airways, diaphragm etc), same if M staging
problems: mechanical obstruction, poor food/fluid intake, infiltration into other organs
barrets histo: columnar lining, mucin, glandular tissue; dysplasia see nuclear enlargement and hyperchromasia, increased mitoses, loss of
nuclear polarity; stain for p53 can help identify areas of dysplasia; Her2 staining for if trastuzumab can be used
squamous: sharp transition to area with no glycogen light splodges, loss of tissue maturation towards surface, areas of necrosis
dysphagia (14 causes, 3 complications, indications for pouch surgery, commonest cause for dysphagia and 4 causes of strictures, OGD alternative, eosinophilia œsophagitis appearance, 2 associations, 2sx, ix, 3mx; achalasia cause, 4 sx, 3 ix, 3 types, 3mx; 4 general ix for dysphagia pathway; main mx for neuro/elderly cause
stroke, PD, MG, MS, MND; cancer, phar pouch; achalasia, chagas, CREST, foreign body, stricture, mediastinal mass
getting elderly by itself contributes to devloping dysphagia
dysphagia -> dehydration, malnut, rec pneumonia so multi admissions
pharyngeal pouch treated surgically if >2cm, herniation through killians dehiscence
GORD commonest cause -> erosive oesophagitis -> stricture from fibrosis as heals; 24hr pH monitoring helpful
candida, shatzki ring (maybe fe def)
barium swallow if unfit or unwilling for OGD
eosino oesph; white rough looking, rings and longitudinal ridges; oft men, oft atopy; dysphagia/food impaction, maybe heartburn
biopsy needed -> paired biopsy so can differentiate eosin and reflux disease (if eosins only in distal prob reflux, if both eos oesoph)
complex treatment but some combo of PPI, topical steroids, elemental diet
achalasia: Caused by degeneration of Auberbach’s plexus.
Presentation –dysphagia: episodic in nature; solids + fluids, chest pain, regurgitation of food
Investigations – Endoscopy to rule out malignancy
Manometry – high LOS pressure; type 1 no contraction, type 2 panoesoph pressure, type 3 spastic premature contractions; can also show
absent peristalsis, oesophageal spasm etc
Barium swallow – ‘birds beak’ sign
Management
Intra-sphincteric injection of botulinum
Balloon dilatation
Heller cardiomyotomy
dyphagia do endo, biopsy if abnorm; no abnorm still biopsy for eosin oesoph (may look normal), if neg for that then high resolution
mannometry + ambulatory pH monitoring
and dont forget neuro + elderly association, where dietary advice mainly is intervention after SALT review; other options include risk feeding, NGT as a bridge to PEG feeding (usually latter more if younger eg MND, former is old or coming towards end of life)
h pylori management - endoscopy when, other 2 tests, triple therapy variants, when you repeat main ix
Consider endoscopy if ALARMS symptoms OR >55
Test for H pylori after 4 week trial of conservative measures – urea breath test; consider stool cultures as alternative, each test is about as good as the other
It is found in the antrum of the stomach
urea breath test works as follows: patient ingests a small amount of urea labeled with carbon 13 (13C) or carbon 14. If urease is present (produced by the organism), the urea is hydrolyzed and the patient exhales labeled carbon dioxide that is then collected and measured
H pylori positive –> triple therapy for 7 days: PPI e.g. omeprazole + amoxicillin + clarithromycin/metro; 2nd lineis same as first for 7 days but can switch clari and metro; 3rd line for 10 days is PPI + bismuth subsalicylate + 2 abx of clari, metro, tetracycline, levoflox - needs micro d/c
if pen allergic first line metro + clari, 2nd line metro + levo; 3rd line as above but use eg rifabutin after micro d/c
H pylori negative 🡪 PPI
if symptom free dont need to repeat urea breath test, if sx still then repeat to see if bacti eliminated
h pylori infection paeds
H. pylori infection rarely causes symptoms in children in the absence of peptic ulcer disease; Further evaluation should be reserved for when epigastric pain is closely associated with the intake of food or when there are associated ‘red flag’ features; Testing is not indicated for suspected functional abdominal pain or gastroesophageal reflux disease. Parents should be counselled that, in the absence of PUD, eradication may not relieve symptoms however is still probably required to reduce the carcinogen risk
red flags:
Localised epigastric pain
Right upper or right lower quadrant pain
Dysphagia
Odynophagia
Persistent vomiting
Overt gastrointestinal blood loss
Weight loss
Decelerating linear growth
Delayed puberty
Unexplained fever
Family history of inflammatory bowel disease, coeliac disease or PUD
first-line diagnosis based on stool antigen testing, followed by eradication if positive. Children should only be referred for gastroenterology opinion and endoscopy when they have failed to have a successful primary eradication of H. pylori confirmed by a positive repeat stool antigen test
Patients should be off acid suppression for at least two weeks and antibiotics for four weeks before testing. The use of Gaviscon preparations should not affect test results
For patients where the antibiotic sensitivity and resistance patterns are not known (the majority of non-biopsied patients) our recommendation is triple therapy for 14 days with:
Omeprazole, HIGH DOSE amoxicillin and metronidazole; Where peptic ulcer is strongly suspected, 3 months of acid suppression should also be used to promote healing
To maximise treatment effectiveness, second-line treatment should be discussed with your local gastroenterology team
Patients who have previously taken clarithromycin and/or metronidazole should be considered at high-risk for resistance.
Confirmation of eradication
The long-term risk and uncertainty regarding gastric carcinoma mean confirmation of eradication is MANDATORY.
Eradication of H. pylori infection should be confirmed 4-8 weeks after treatment using stool antigen testing.
Patients should be off acid suppression for at least two weeks and antibiotics for four weeks before testing
Patients with H. pylori should be referred for opinion and endoscopy when they have failed to have a successful eradication with confirmatory positive post-treatment stool antigen test.
Persistence of dyspeptic symptoms after a trial of appropriately dosed acid suppression or dependence on long-term acid suppressants with/without H. pylori are further indicators for consideration of endoscopy.
haematemesis clinical path (inc scoring sx, main ix and deciding when to do, initial mx 6 things, what if ogd cant stop, what is coffee ground vomiting more likely to represent, 2 things to give if suspect varicosities and when to give, target time to OGD for all admissions, 3x mx for varices, mx for erosive inflam, mx for tear)
blatchford score calculates who can safely be discharged w/o endoscopy; rockall score is less sensitive but can be used for predicting risk of mortality and so stratifying how urgent OGD needed and whether to involve CCOT etc
initial management 2x cannulae, resus with fluids or blood, IV pantoprazole, reverse anticoag (continue DAPT, if major bleed continue only asp; vit K for warf, withold DOAC and if major bleed monoclonal to reverse); later endoscope
major haemorrhage protocol and CCOT r/v if haem unstable, transfuse only aiming for Hb >70 (note takes time for Hb to fall as is a concentration, needs autotransfusion to dilute); in all UGIB keep plats >50 with transfusion if required
However note that there’s decent evidence that giving FFP to variceal bleeds INCREASES mortality and INCREASES the chance that bleeding won’t be controlled at initial OGD. We think this is because INR is a poor representative of the overall haemostatic balance in liver patients, and all the FFP is really achieving is increasing her circulating volume, thereby increasing portal pressures and bleeding tendency, but without the life-sustaining property of red blood cells
if endo can’t control bleeding -> CT angiography, maybe radiological intervention
coffee ground vomit likely milder more chronic bleed eg gastritis
Patients with suspected varices should receive terlipressin prior to endoscopy + proph antibiotics (ceftriaxone or ciproflox); octreotide is an alternative to terlipressin, and terlipressin needs to be stopped if chest pain, ECG changes or distal dyanosis
Ideally all patients admitted with upper gastrointestinal haemorrhage should undergo upper GI endoscopy within 24 hours of admission.
Varices should be banded or subjected to sclerotherapy. If this is not possible owing to active bleeding then a Sengaksten- Blakemore tube
Patients with erosive oesophagitis / gastritis should receive a proton pump inhibitor.
Mallory Weiss tears will typically resolve spontaneously
terlipressin - what it is, what it binds (inc effect on the kidneys), mechanism, main 3 complications and ix to counter this
synthetic peptide analogue of the hormone vasopressin
binds V1/V2r but with much lower affinity than vasopressin, also binds V1 6x more strongly than V2 so whilst antidiuretic effect is there it is minimal - and if you improve hypotension and thus kidney perfusion you might even improve urine output
by causing splanchnic vasoconstriction it reduces GI bleeding, and also reduces the splanchnic fluid redistribution that contributes to HRS
it also causes vasoconstriction elsewhere and so need to be careful - check for cardiac history, get an ECG before starting terlipressin and at least one after to minimise risk of precipitating ACS; you can also worsen diastolic HF and MR due to the increased afterload
sengstaken-blakemore and minnesota tubes
Sengstaken–Blakemore tube (3 lumen) vs Minnesota tube (4 lumen) as allows aspiration of both gastric and oesophageal contents, not just gastric contents; used to tamponade if not responsive to medical or endoscopic therapy, or in emergencies
patient is often endotracheally intubated first to prevent aspiration, then insert via mouth via laryngoscopy into the oesophagus
confirm position on CXR (gastric balloon in stomach)
inflate gastric balloon using 50mL increments up to 250 -300ml for SBT or 450-500ml for Minnesota tube
pull balloon back until against gastric fundus to tamponade blood flow
note that re-bleeding on balloon deflation occurs in ~50% of cases
can get pressure necrosis if in situ for more than 24-36 h, and should deflate then re-inflate after 12
how quickly does Hb drop after acute bleeding? 2 sources of haemodilution, how long until it reaches max depletion? and by how much?
immediate circulating volume can be maintained with blood in reservoirs - large veins, spleen, and liver (alone will 250ml of mobilizable blood), then after this exhausted haemodilution
haemodilution from autotransfusion and kidneys retaining fluid takes time -> may see some change within minutes, changes rapidly initially then change slows until lowest level reached up to 3 days after the blood loss and then rises again; if you give non-blood fluids the Hb drop will be even faster
all that said, within 30mins to 1.5hrs of bleed the Hb should match the clinical picture approx, and dilution is usually complete within 12-24hrs
it will fall by about 10g/L for every 500ml blood lost (can be 5-20g/L)
Transjugular Intrahepatic Portosystemic Shunt (TIPS) - what it is, 4 indications, 2x complications
tract created within the liver using x-ray guidance to connect portal vein to hepatic vein and then stented open
used to treat the complications of portal hypertension, including:
variceal bleeding, esp if endoscopy failed
portal gastropathy, an engorgement of the veins in the wall of the stomac
severe ascites
Budd-Chiari syndrome
up to 25% of patients who undergo TIPS will experience transient post-operative hepatic encephalopathy caused by increased porto-systemic passage of nitrogen from the gut
in rare cases, suddenly shunting portal blood flow away from the liver may result in acute liver failure secondary to hepatic ischemia and this may require emergency shunt closure
tracheo-oesophageal fistula repair 4 complications
anastomotic leaks, strictures at site of anastomosis (may need balloon dilatation), GORD, aspiration (rec cough, bronchitis, pneumonia)
note in most cases surgical strictures are due to scarring
TOF
Suspected TOF? eg lots of secretions and resp distress
Pass size 8/10 feeding tube - confirmed in stomach then feed as normal
If tube fails to enter stomach get ANNP/surgeon/senior to attempt
If still not enter stomach check CXR to see if coiled in upper pouch to confirm TOF
A combined CXR and AXR must be performed: if gas is present in the stomach
and bowel a TOF must exist whereas if the abdomen is gasless the diagnosis is likely to
be pure oesophageal atresia. A double bubble shadow suggests a co-existing duodenal
atresia. Assessment of vertebral bodies from thoracic to sacral spine should be
requested.
IV fluids as per protocol.
Broad-spectrum intravenous antibiotics as per local guidelines.
Nurse supine with the head elevated by approximately 45°.
All babies should have a long line placed as soon as is practical and PN initiated
until full enteral feeds established postoperatively
Open right sided thoracotomy, closure of the fistula and oesophageal anastomosis is
the standard method
VACTERL ix should be performed
Type A: OA with no fistula
Type B: OA with proximal fistula
Type C: OA with distal fistula (90% cases)
Type D: OA with proximal and distal fistula
Type E: TOF with no atresia
OA/TOF cannot be diagnosed with certainty in the antenatal period.
The combination of polyhydramnios and a small or undetectable stomach on a
prenatal ultrasound scan is suggestive for OA
Oesophageal atresia
Inability to feed.
Coughing / Choking.
Excessive frothing at mouth.
Inability to pass a nasogastric tube.
Cyanotic episodes.
Signs of aspiration.
6 causes of recurrent aphthous ulcers (and details on behcets - 7sx, gene association, reaction to blood test, course)
most idiopathic but linked to crohns, UC, coeliac, behcets, neutropenia
behcets has oral/genital ulcers, eye pain/iritis, neuro involvement (aseptic meningoenceph, pseudotumour cerebri); may get lesions like erythema nodosum, migratory thrombophleb, medium/large joint arthritis; HLA-B5 associated; bullous pustular reaction to subcut puncture (in eg blood test); is relapsing-remitting
parotitis (acute and chronic - commonest cause, 2 bugs and which pts for acute supp, acute siad due to what and which gland, what to check for if recurrent parotitis, 4 things for rec paro of childhood, 2 causes for chronic paro, 4 ix in all cases)
commonest cause is mumps so check MMR status; submandib glands can also be affected
acute supp parotitis commonly by staph aureus and strep pyogenes; occurs in debilitated patients who are dehydrated
acute sialadenitits (usually submandib) due to duct calculus
rec parotitis may be HIV infection
also rec parotitis of childhood (no stones or strictures, may be unilat or bilat, w erythema around stensens duct + maybe pus discharge)
chronic parotitis due to sialectasis, sjogrens (slightly tender, dry eyes/mouth)
ix in all cases inc x-rays, MC&S of expressed pus, sialograms, possibly HIV test
gut tube embryology - membrane at either end and how connects to yolk sac, how two curvatures develop and how they move, 4 regions and transcription factor for each, how endoderm and mesoderm interact, midgut growth and how it rotates (inc how many degrees total), how omphalocele forms, meckels diverticulum prevalence, cause, 2 problems it causes, something it can contain and what problem that can cause, two variants within it, problems abnormal rotation can cause, 2 things omphalocele associated with, difference from gastroschisis
craniocaudal and lateral folding generate gut tube, which is initially blind ending foregut and hindgut connected by midgut which connects to yolk sac via vitelline duct; hindgut ends at cloacal membrane and foregut buccopharyngeal
thoracic part of foregut with dorsal wall growing faster than ventral such that greater/lesser curvatures develop; 90 degree rotation about craniocaudal axis then brings greater curvature to left and orients vagus trunks ant/post; further caudal tilting then orients greater curvature inferiorly
regional specification begins once lateral folding brings 2 sides together; TFs in different regions with SOX2 for stomach/oesophagus, PDX1 for duodenum, CDXC for SI and CDXA for LI; initial patterning stabilised by reciprocal interactions between endoderm and visceral mesoderm initiated by SHH expression in gut tube upregulateing mesoderm factors that in turn determine gut tube structures eg caudal midgut/hindgut express SHH making mesoderm express Hox genes which direct formation of caecum/colon etc
extensive midgut growth, particularly region that will form ileum, means it grows more rapidly than abdo so primary intestinal loop forced out through umbilical cord, carrying its arterial supply; herniated loop undergoes 90 degree rotation counterclockwise; jejunal/ileal lengthening continues giving rise to series of folds and gut tube retracted with further 90 degree rotation; caecum moves inferiorly and final 90 degrees rotation gives total of 270
if umbilical ring doesn’t close, loop of intestine may remain outside cavity as an omphalocele in 2.5 in 10,000 births
meckel’s diverticulum in 2-4% of people, 3-5 times more prevalent in males and becomes inflamed in ~1/3 of people, causes by failure of regression of vitelline duct and connected to umbilicus typically by fibrous cord or fistula around which rest of gut may rotate and become obstructed; contains ectopic gastric mucosa in 50% of people which may ulcerate/perforate; vitelline cyst may occur or full fistula
abnormal rotation can cause range of problems such as freely suspended coils of intestine prone to torsion or volvulus resulting in obstruction or even obstructed blood supply
omphalocele associated with trisomies, beckwith-weidemann; defect in body wall eg incomplete ventral folding gives gastroschisis, similar to omphalocele but loops not in sac
cleft lip and palate (7 influences, how different types of feeding affected, general mx approach)
some genetic influence but also if during preg mum takes steroids, BZDs, sod val, phenytoin; also maternal smoking or alcohol
may have difficulty bottle feeding but breast feeding is usually okay
surgery and mdt management to achieve best aesthetics; foetal surgery offers prospect of scarless healing
oesophageal perf - 2 main causes, 5 rarer causes (and thing that links them), 5 other causes; 5 sx (+diff from MW tear), 3sx if in neck, 2 complications that can dev, 3ix, 6 mx
usually iatrogenic (endoscopy inc dilation for strictures or achalasia)
Also boerhaave syndrome from severe vomiting or retching
very rarely from other raised abdo pressure inc Heimlich manouevre, defaecation, status eplilepticus, parturition, weight lifting
very rarely from blunt or air blast trauma; also from any penetrating injuries to this region; also ingestion of caustic fluids, either accidentally or with suicidal intentions; also cancer
acute sudden chest pain radiating to back or left shoulder often; vomiting and sob pos, subcut emphysema also poss; may see pneumomediastinum; haematemesis typically not seen, helps differentiate from eg mallory weiss tear and epigastric/chest pains
may have speech problems and cervical pain if perf was in neck, also cervical crepitus
pt often distressed with fever and tachy; SIRS can dev and poss bacterial mediastinitis
CXR: suspect if pneumoperit, subcut emphy, PTX; water soluble contrast swallow will show and consider CT with oral contrast; endoscopy if suspect strongly but CXR neg
NBM, fluids, analgesia, broad spectrum antibiotics iv; iatrogenic, small, contained perfs can have conservative management; also if perf from inoperable malig; operative treatment otherwise
GI hormones (3 main families, 3 other egs, function of gastrin, CCK, secretin, VIP, ghrelin, motilin, somatostatin)
GIT is largest endocrine organ
3 main families: gastrin-CCK, secretins (secretin, glucagon, VIP), somatostatins
others: motilin, sub P, ghrelin, and many more
gastrin made by G cells in stomach, stimulates the secretion of gastric acid, pepsinogen, intrinsic factor, and secretin; promotes gut motility
CCK made by enteric nerves in SI, Stimulates gallbladder contraction and intestinal motility; stimulates secretion of pancreatic enzymes, induces satiety
secretin stimulates pancreas enzyme release, reduces motility, decreases gastrin release
VIP relaxes sphincters, suppresses gastric acid but promotes bile/pancreas, increases motility and intestinal bloodflow
ghrelin - promotes appetite and stomach emptying
motilin - increases motility
somatostatin - from delta cells in antrum, duodenum, pancreas; decreases intestinal bloodlow, slows gastric emptying, inhibits pancreatic enzyme release inc glucagon and insulin, suppresses other GI hormones
octreotide (somatostain receptor mechanism x2, 8 things that it reduces, 6 indications, 6 complications)
Somatostatin receptors are Gi-protein coupled receptors. Activation of such a receptor inhibits intracellular cAMP production; it also activates potassium channels, hyperpolarising the membranes of excitable tissues; practically speaking, somatostatin (and thus octreotide) prevent secretion from glands
depresses secretion of: GH, calcitonin, ACTH, insulin, glucagon, ifn-g, gastrin (+gastric acid); it also reduces splanchnic blood flow
can reduce GI bleeding and HRS through splanchnic vasoconstriction, control diarrhoea through less GI secretion, decrease chyle flow in chylothorax, reduce hormone release from neuroendocrine tumours, and slow output through stoma or down pancreas or bowel fistula (by inhibiting CCK, VIP, and secretin that promote motility and GI secretion); induce selective splanchnic vasoconstriction by inhibiting the release of vasodilator glucagon and through blunting of postprandial splanchnic hyperemia - minimal systemic s/e compared to terlipressin but lasts less long
biliary stasis may inc risk of gallstones, can get hyperglyc, hypoadrenalism, poor wound healing (GH def), constipation, delayed gastric emptying
peptic ulcers path and drugs - gastrin release and effect of binding (+ what receptor), remaining steps in upreg of proton secretion, somatostatin 2x counter-reg; 2 med choices and why one is preferred, effect of PS nerve stim, 3 ways NSAIDs involved, what is arthrotec
used to reduce gastric acid secretion: g cells release gastrin, bind to CCK2r on ECL cells, raising Ca and causing histamine release which acts on H2 on parietal cells: PKA phosphos proteins involved in trafficking of K/H pumps, enhancing their activity to enhance H efflux; somatostatin is negative regulator of this directly via Gi coupled SSTr on parietal cells, indirectly by same r’s on G/ECL cells to reduce gastrin/histamine release
CCK2r antag proglumide reduces histamine secretion but surpassed by H2r antags like cimetidine (though can inhibit p450 so ranitidine surpassed it); now PPIs like omeprazole used preferentially to H2r antags as irreversible block of last step so more effective; antacids used to counteract stomach pH; cholinergic blockade and vagotomy were used but now obsolete, ACh on M3r on parietal cells enhances acid release which atropine would stop
NSAIDs inhibit PGE2 (which acts on ECL EP2/3R to inhibit acid secretion, and EP4R which enhances mucin secretion, and EP1/2R to increase bicarbonate secretion); so stop taking NSAIDs
combo pills like arthrotec (mix of NSAID diclofenac and misoprostol (PG analogue binding PGEP2/3/4r), used in treatment of rheumatoid arthritis with the misoprostol prophylactic against peptic ulcer
peptic ulcers inc which commoner with diff age, 4sx and g vs d, investigation and malignancy risk for each type, 4 risk factors, perforation 3 things, gastric outlet obstruction when and 4 sx + 4mx
penetrate the mucosa, may be from distal oesophagus through to duodenum
gastric more common in elderly and duodenal more in <40yos
present with: epigastric pain (g - after eating and relieved by antacids, d - nocturnal and relieved by food), vomiting (rare for duodenal, common for gastric), gastric common to lose appetite/weight but duodenal may even gain weight, may present with haematemesis
endoscopy to diagnose, can biopsy for H pylori or in gastric case to check for malignancy at edge of ulcer, should do second endoscopic scan to check healing of gastric ulcers due to risk of malignancy; duodenal wont go malignant but have higher risk of perforation
besides H pylori, risk inc’d by smoking, NSAIDs, stress (esp due to chronic disease eg cirrhosis etc)
perforation: severe upper abdo pain rapidly generalising, air under diaphragm, rigid and silent abdo
gastric outlet obstruction if near pylorus: distension, vomit old food, dehydration, hypokalaemic alkalosis, NG aspiration of stomach contents then endoscope to investigate; drip n suck (iv nutrition, NG aspiration); treat with balloon dilation
gastric carcinoma (where it’s esp common, 4 risk factors, 5sx/signs, 5ix)
v common cancer death worldwide, esp china and japan; incidence falling in UK
often from chronic ulcers, diets with lots of pickled or smoked foods; smoking and alcohol
epigastric pain unrelated to meals, relieved by acid suppressants; weight/appetite loss; haematemesis rare except in late disease; supraclavicular lymph node and migratory thrombophlebitis are rare but classic signs
endoscopy will show irregular ulcer looking thing, biopsy the edges; FBCs and LFTs, CXR, abdo CT can help with staging
gastric cancer 4 types and 2 subtypes for first type, association for second type, for third type appearance histo and common mutation + treatment
aaa 10 complications/aorto-enteric fistula (2 sx, 2 ix)
90% ACC, also lymphoma (MALT), GIST, neuroendocrine; ACC subtypes: intestinal type (glands), diffuse type (signet rings - krukenberg, intraperit spread)
Gastric MALT lymphoma is frequently associated (72–98%) with chronic inflammation as a result of the presence of Helicobacter pylori
GIST looks like dome in stomach wall; often spindle cells on histo; immunohistochem to identify for sure; often have RTK mutations so
imatinib
endoleak, expanding aneurysm sac, stent fractures and occlusions, graft infection, graft migration, aortoenteric fistula, aortic rupture, and ischaemic complications (limb, visceral and renal inc heart attack and stroke)
aorto-enteric fistula rare cause of haemat, after abdo AAA surg - herald bleed then rapid exsanguination, CT +/- OGD
gist cancer (arise where, what genes involved, what type of cancer and how this differs from most GI tumours, where they are, 10sx, how size effects, 2x mx; MALT lymphoma oft associated with that, what happens if address that)
arise in interstitial cells of cajal or other mesenchymal neoplasms, driven by mutation in KIT (CD117 pos), PDGFRA, or BRAF kinase; they are sarcomas and nonepithelial unlike most GI tumours; 70% stomach, 20% SI, 10% oesophagus
present with some of: trouble swallowing, GI bleeding, symptoms from mets (oft liver), anemia, blood in stool or vomit; abdominal discomfort; painless abdo lump; vomiting; fatigue; fever, night sweats, weight loss
small tumours generally benign, large malign and disseminate to liver, omentum
surgical resection potentially curative; most chemo and radio dont help much but imatinib and a couple other targeted drugs do
malt lymphoma v often associated with h pylori infection, and if low grade often resolves by itself if you treat the infection
gastric stasis and hiccups
Hiccups are very common in all age groups but especially children and are usually a mild and self-limiting condition requiring no formal treatment. However, if they are persistent (lasting over 48 hours) or intractable (lasting over one month), they can have a profound adverse impact on quality of life
Peripheral causes are usually triggered by irritation of the phrenic or vagus nerves. They can be subdivided into gastrointestinal causes such as reflux, gastroparesis, gastric irritation and non-gastrointestinal causes such as pneumonia and other chest infections, asthma, etc.
Central causes can be subdivided into neurological causes such as brain tumour, brain infections or brain trauma, non-neurological causes such as infection, metabolic such as electrolyte imbalance,
iatrogenic (from use of opiates, dexamethasone, chemotherapy agents for example), or from hypocapnia triggered by over breathing due to stress, fear, or anxiety.
Other potential causes should be considered and addressed before pharmacological intervention is considered – correction of metabolic causes where possible, strategies to reduce stress and anxiety, stopping or reducing medication known to potentially exacerbate hiccup such as opioids,
dexamethasone, chemotherapy agents and simple strategies to reduce gastric distension such as adjustment of feeds, regular winding, posture to reduce reflux
The most common cause of hiccups is gastric reflux and distension – due to ingestion of fizzy drinks, swallowing air, eating too much or too fast, gastrointestinal reflux, or especially in palliative care where gastric stasis or delayed gastric emptying may be present. Other triggers can include emotional stress, sudden temperature changes, spicy foods, alcohol etc
Medication should be avoided unless nonpharmacological measures have been tried unsuccessfully. These include breath holding, Valsalva manoeuvre, and other measures to stimulate nasopharyngeal irritation such as sipping iced water, eating granulated sugar off a teaspoon, and
rubbing the soft palate with the tip of a swab
For PERIPHERAL causes, simple over the counter remedies such as peppermint water or an antifoaming agent such as simethicone may offer simple effective relief, especially with upper gastrointestinal causes. If more formal prescribed medication is required, first line treatment should be a PPI as the most common cause is gastric irritation and reflux. Metoclopramide is an alternative or additional therapy, but only in a palliative care setting as neurological side effects limit its use
For CENTRAL causes, Baclofen, for its GABA receptor agonist activity, is usually recommended as the first line agent of choice in adults, although there is little evidence for this in children. It is used widely for other indications in children. Second line drug of choice is Gabapentin, and third line
suggestions include Haloperidol and Calcium channel blockers such as Nifedipine, which may block the hiccup reflex arc.
For troublesome hiccup in the terminal stages of life, Midazolam is often used
gastroparesis - definition, 7sx, 12 causes, main ix and alt, 10 mx
delayed gastric emptying in the absence of mechanical obstruction
early satiety, postprandial fullness, nausea, vomiting, weight loss, bloating, and upper abdominal pain
idiopathic, diabetes, post-surgical (vagus nerve injury), parkinsons, MS, brainstem CVA/tumour, autonomic neuropathy, SCI, amyloidosis, scleroderma, autoimmune, drugs inc opioids, octreotide, TCAs (anticholinergic) etc
can diagnose with SGE (scintigraphic gastric emptying) assessment; gastric emptying breath testing is an alt
optimise DM/PD etc control, smaller more freq meals, reduce carbonated beverages, reduce smoking/alcohol (can delay gastric emptying), consider jejunostomy if not meeting nutritional requirements
metoclopramide, can try other antiemetics; domperidone better tolerated than metoclop in kids; another option is erythromycin but shows tachyphylaxis, can have some weeks on then some off to counter this; PPIs often also given as overlap in presentation with dyspepsia
gastric electric stimulation if refractory to medical mx
peg feeding indications (5+1 jejunal extension) and 5 complications + mx
indications for PEG feeding: lack of volition, nutritional support (eg CF), unsafe swallow, head/neck/oesoph cancer, oesoph dysmot
delayed gastric emptying eg gastroparesis in DM (use jejunal extension)
PEG blocked:
massage visible blockage and try to aspirate with 20mL syringe, then push and pull syringe with warm water, then again with 8.4% bicarb (let it sit for a couple hours then flush if blockage removed), then try again with creon dissolved in bicarb
Redness around PEG:
exclude infection, leak, granulation tissue; then if psoriais or contact dermatitis give eumovate ointment for 2 weeks, wash the site twice daily, and apply greasy emollient oil; if allergic reaction refer derm
Granulation tissue:
wound irrigation solution clean daily for 2 weeks, then salt rx 2 weeks, then hydrocort 2 weeks, then seek advice
Leaking:
Test pH, if <5 is leaking from stomach; if <72 stop using, make child NBM, call surgeons; otherwise check if fitted right, stoma right etc
Infection:
If cellulitis (warm, spreading, pus) or candida (satellite lesions) swab and rx with oral abx/fluconazole + clean site, clotri + HC cream, and foam dressing
rigs and pegs (NBM instructions, how procedure done, how often tube changed, 5 contras, what to consider when thinking if pt would tolerate)
NBM for 6 hrs prior, no fluids for 2hrs before
RIG (radiologically inserted gastrostomy) insertion under sedation, NGT to put air into stomach, then US to locate stomach; local anaesthetic then stitches to secure stomach to abdo wall, and pass tube in; tube changed every 3-6 months
PEG (percutaneous endoscopic gastrostomy) is similar, under sedation, but endoscope passed down with light on end that is visible externally then cut made to insert tube
contraindications would include INR >1.5 or other bleeding risk, gastric varices, peritoneal dialysis, organomegaly
you also need to consider if pt could tolerate the procedure eg lie flat for >30mins
cyclic vomiting syndrome (how it presents including length of episode, precursor to what in kids + 5 associations; 4 features of prodrome, 2 sx, what is the between episodes like, 16ddx and input from who needed, 6ix, how to identify triggers, 3 things that can work as prophylaxis, 3 mx during episode inc best 3 meds (and routes for first), 3 options for prophylaxis
recurrent episodes of intense nausea and vomiting that can last from hours to days without any functional or infectious illness
exact cause of CVS is unknown. In the pediatric patient, CVS is considered by many to be a precursor to migraines later in life; Allergies to foods, stressful triggers, and lack of sleep are also associated with CVS. There is an increased frequency during patient menstrual cycles, suggesting a possible hormonal trigger for CVS. Longterm cannabis use has been associated with CVS as well
patient will often describe a sudden onset of vomiting. Abdominal pain is a common complaint as well. Many describe prodrome of nausea, anorexia, sweating and fatigue prior to the onset of vomiting. These episodes may last hours to days. In between episodes, patients describe pain-free and symptom-free intervals that last weeks to months. The hallmark of this disease is the recurrence of vomiting cycles
dd: Gastroenteritis, gallbladder disease, peptic ulcer disease, appendicitis, pancreatitis, infectious or toxic causes, mechanical obstruction, irritable bowel syndrome, psychiatric causes, neurological causes, metabolic causes, and pregnancy; also consider cannabinoid hyperemesis syndrome, functional dyspepsia (will not have phases), rumination syndrome, and bulimia; gastroenterology input is needed
Full blood count, urea and electrolytes, liver function testing, amylase, urinalysis (including a pregnancy test in patients of child-bearing age), and plain film radiography can be undertaken to exclude any obvious organic cause of nausea and vomiting, and can help to eliminate potential complications of CVS
exam findings and bloods normally non-specific, may find pt dehydrated
triggers can be identified with sx diary and can include stressful events (both positive and negative), travel/motion sickness, sleep deprivation, food, weather changes, menstrual cycle; sleep hygiene and meditation can be helpful as well as trigger avoidance
during episodes: IVF/rehydration, anti-emetics, and rest in dark quiet room
ondansetron is best anti-emetic choice (SL or PR), can combine with a benzo; intranasal sumatriptan can stop attacks, especially if migrainous features; TCAs are first line prophylaxis, others inc topiramate or aprepitant
10 causes of an abnormal jejunal biopsy
taken for malabsorption, histo shows villous atrophy
coeliac disease - definitive diagnosis is initial biopsy + normal one after 6 weeks gluten free diet; repeat biopsy more important in child <2yo as transient gluten intolerance more common
transient gluten intolerance (usually sec to gastroenteritis)
post-gastroenteritis
cow’s milk/soya milk protein intolerance
giardiasis
SCID
post-chemo
hypogammaglobulinaemia (this may be due to giardiasis)
kwashikor
tropical spruce malabsorption syndrome
stomach problems in children - pyloric stenosis (sx, usual age, one sign, ix, mx), GORD (5 sx in infants, 1sx in kids, assessment needed, what onset tells you (eg of dd), 10 red flags and what they suggest, prev, when to reassess x2, 5mx)
pyloric stenosis - projectile vomiting w/o bile in, usually after feeding, usually present when 2-12weeks old; mass may be palpable in abdo; uss can confirm, and surgery will treat
gord - effortless regurg of feeds common in infants <1yo, so suspect if accompanied by crying, has chronic cough, an episode of pneumonia, feeding difficulties, faltering growth; if >1yo may have heartburn
take feeding history, ensure person with appropriate training does feeding assessment; ask about onset - usually ~8weeks and if after 6mo may be something else eg uti; red flags: if forceful may be stenosis, if bilious may be obstruction, if distension may be obstruction, haematemesis suggests upper gi bleed, bulging fontanelle or lethargy suggests meningitis, headache and vomiting worse in morning w/w-o head circ inc >1cm per week suggests raised icp (tumour, hydrocephalus). blood in stool suggests cows milk allergy or gastroent, chronic diarrhoea or atopy suggests cows milk allergy; dysuria (esp if lethargy, jaundice, irritability, haemat) suggests uti; onset after 6mo or persisting after 1yr suggests cause besides gord
reassure (affects 40% babies), becomes less freq over time and resolves; reassess if red flags emerge, new concerns, persists past 1yo
if symptoms persist after breastfeeding assessment trial alginate eg childrens gaviscon
if formula fed reduce feeds if excessive for childs weight (>150ml/kg/24hrs; trial smaller more freq feeds; trial feed thickener, if unsuccessful trial gaviscon infant added to formula
gaviscon fails breast or bottle fed trial PPI or H2RA for 4 weeks, and consider endoscopy
upper GI cancers (ref crit for oesoph (6), panc (6 + tumour marker, 3 early signs), stomach (4, what may delay), GB (3), liver (1))
2ww for oesoph if dysphagia or 55yo+ w weight loss and one of reflux, dyspepsia, upper abdo pain; non urgent endoscopy for oesophageal cancer if haematemesis, treatment resistant dyspepsia, upper abdo pain + low Hgb levels; upper abdo pain/weight loss + n&v, or any of those with raised platelets
2ww pancreatic cancer if >40yo have jaundice, or over 60yo with weight loss and any of diarrhoea, back or abdo pain, n&v, constipation, new onset diabetes; early signs are epigastric discomfort or dull backache, usually worse when supine, steatorrhoea; ca19.9 is most useful tumour marker as baseline to guide treatment/follow-up
2ww if upper abdo mass consistent with stomach cancer; or dysphagia, or >55yo w weight loss and 1+ of upper abdo pain, reflux, dyspepsia or any of the other oesophageal criteria; as symptoms vague high threshold for referral of at risk pts with recent onset dyspepsia; PPIs delay diagnosis
2ww for GB cancer if ruq mass consistent with GB cancer; cholangiocarcinoma may cause obstructive jaundice w hepatomeg, maybe courvoisiers sign
2ww if <40 and heptomegaly for liver cancer
acute panc (7 sx, 5 severe sx, 10 causes, 2 pancreatic markers (which is better, when one might be normal), 5 further ix for diagnosis (and what theyre ruling out/looking for), 5 things early suggesting severe, then scoring system and 8 components for deciding on severe - why electrolyte used, 9mx if mild, 4 diffs if severe, 4 crit for ERCP and what comes after, process for deciding whether to debride)
acute onset of severe abdo pain (+/- rif pain) oft radiating to back, retching and vomiting; pt lies still or leans forward to relieve pain; recent alcohol binge or problems with biliary colic poss, pyrexia, tachycardia, upper abdo tenderness; if severe may have shock, gen perit (but often milder as deep structure), grey turner and cullens signs, signs of hypocalc
it is almost always gallstones or alcohol but remember GETSMASHED:
G: gallstones, genetic - cystic fibrosis
E: ethanol (alcohol)
T: trauma
S: steroids
M: mumps (and other infections)/malignancy
A: autoimmune
S: scorpion stings/spider bites
H: hyperlipidaemia, hypercalcaemia, hyperparathyroidism
E: ERCP
D: drugs (tetracyclines, furosemide, azathioprine, thiazides and many others)
first confirm, then quantify severity
serum amylase >3x normal upper limit (but can be back to normal if pt presents >24hr after onset of pain, also can be up to 4x normal in most acute abdo problems); serum lipase better
ecg to exclude ACS; erect CXR to rule out perf and check for complications (ARDS or pleural effusion); supine AXR to rule out obstruction;
USS for gallstones, if severe or deteriorating then oral contrast enhanced panc protocol CT to look for pan nec/abscess
then quantify disease: def severe if in shock or has organ failure; otherwise obesity, pleural effusion or CRP >150mg/L; or glasgow scoring scale: paO2, age >55, WCC >15x10^9, BM >10, urea >16, hypocalc, albumin <32, LDH >600; hypocalc may be due to fat necrosis around the pancreases releasing FFAs which bind Ca, thus lower Ca means more severe damage
mild: admit, enteral feeding (via NG/NJ tube if required), thromboproph, catheter and iv fluids, O2 and insulin if needed, morphine and antiemetics prn; daily bloods for risk surveillance
severe: same as above + itu, NG definitely, central line for CVP monitoring; bloods and ABGs twice daily instead of once; note even many severe cases will be managed medically
Urgent therapeutic ERCP should be performed in patients with acute pancreatitis of suspected or proven gall stone aetiology who satisfy the criteria for predicted or actual severe pancreatitis, or when there is cholangitis, jaundice, or a dilated common bile duct; cholecystectomy should also be done later
All patients with persistent symptoms and greater than 30% pancreatic necrosis, and those with smaller areas of necrosis and clinical suspicion of sepsis, should undergo image guided FNA to obtain material for culture 7–14 days after the onset of the pancreatitis
Patients with infected necrosis will require intervention to completely debride all cavities containing necrotic material
acute pancreatitis paeds
Presenting symptoms of pancreatitis include epigastric or diffuse abdominal pain (80-95% of cases), nausea and vomiting (40-80% of cases), abdominal distension, fever, breathlessness, irritability, and impaired consciousness. This can be accompanied by more systemic signs such as pyrexia, low oxygen saturation, tachypnoea, tachycardia, hypotension, abdominal guarding, ileus and/or oliguria. However, it should be noted that often symptoms are vague
(especially in younger children) and that pain radiating to the back (which is classically described in older patients) may not always be present
causes align with those in adults ie GETSMASHED
Serum amylase and/or lipase (NV usually <110 IU/L), triglyceride levels, full blood
count, CRP, renal and liver function tests (e.g. ALT/AST, GGT, bilirubin, ALP), glucose,
calcium and capillary blood gas should be obtained at presentation
consider taking blood cultures if pyrexial and a full coagulation screen (e.g. PT, APTT, Fibrinogen) if there are concerns about DIC/SIRS
Immunoglobulins, IgG subclasses (1-4) and autoantibodies (i.e. liver screen [e.g. anti-SMA, anti-LKM1, ANA, anti-mitochondrial] and diabetes screen [e.g. anti-GAD, antiIA2, anti-ZnT8]), especially if suggestive pancreatic imaging and/or past medical or family history of autoimmune disorders
Transabdominal ultrasound (fasted) should be performed in all CYP with a clinical
diagnosis of pancreatitis looking for evidence of pancreatic abnormalities
(parenchymal and ductal) and local complications.
* Chest x-ray if clinical concerns to identify any pleural effusion.
* If the diagnosis remains uncertain or there is persistence/worsening of clinical and/or
biochemical picture, then MRI/MRCP or CT are indicated
There is no clear indication for axial imaging (CT/MRI) within the first week of
presentation in uncomplicated cases. However, in patients with evidence of chronicity on initial US examination an MRCP would be beneficial within the first 6-8 weeks following presentation as an outpatient.
* In contrast, if the child is pyrexial and jaundiced with bile duct dilatation on US,
suggestive of cholangitis, early MRCP or endoscopic ultrasound (EUS), with a view or
proceeding straight to ERCP, sphincterotomy and stone extraction should be considered. In these cases, early discussion with either a specialist paediatric centre (or local adult colleagues depending on the age/weight of the child) is strongly
recommended
Based on assessment of hydration status/hemodynamic status, if evidence of
hemodynamic compromise, a bolus of 10 to 20 mL/kg is recommended.
* Children with diagnosis of acute pancreatitis should be provided 1.5 to 2 times maintenance IV fluids with hourly monitoring of urine output over the initial 24-48 hours. Adjust fluid intake based on overall fluid balance.
* Reduction of intravenous fluids and initiation of enteral feeds depending on tolerance and clinical status
analgesia, starting with IV para + NSAID and escalate as needed +/- urgent pain team review if PCA needed
following discussion with a specialist centre, especially in those with refractory pain, octreotide may be considered.
* There is some evidence that octreotide may be useful in the treatment of pancreatic pseudocysts, a common complication of pancreatitis, although again specialist advice should be sought
Discuss with a specialist centre about the indication for Endoscopic Ultrasound (EUS)
if: the diagnosis is not clear and there is indication for tissue diagnosis (Fine Needle
Biopsy) or there is pseudocyst formation that requires draining (cyst gastrostomy)
Encouragement with oral intake within the first 24 hours is strongly advised once the patient has been safely fluid resuscitated. If oral intake is not tolerated in this time an alternative safe route of enteral feeding, (e.g. NG tube) should be considered within the first 48-72 hours of presentation unless direct contraindications to enteral feeding (including but not limited to ileus, pancreatic laceration/transection/fracture or duct disruption)
In cases of worsening epigastric pain, high gastric aspirates, a significant spike in
pancreatic amylase or lipase directly associated with feeding or vomiting with oral or nasogastric (NG) feeding, feeding via the jejunal route (NJ) feeding may be indicated.
* Parenteral nutrition should be only considered in cases where enteral nutrition is not possible for a prolonged period (longer than 5–7 days) such as in ileus, complex fistulae, abdominal compartment syndrome
whipples (4 things removed, what are joined, 4 complications and mx)
usually a whipple’s pancreaticoduodenectomy (pancreas head, duodenum, cbd, gallbladder removed and anastomoses between jejunum and duct in tail of panc, cut hep duct and the first anastomosis, and between stomach and jej
complications: suspect anastomotic leak in all patients who become unwell after a whipple: pain, tachy, fever, olig, resp rate inc (oft first sign); wound may discharge - send fluid for amylase measurement; abdo CT, drain, further laparot if needed
delayed gastric emptying common after whipple, presents similar to gastric outflow obstruction (high volume vomiting every 1-2 days): NG drain, abdo CT to rule out obstruction, TPN or nasojejunal feeding, prokinetic agent like metoclop, takes several weeks to settle
upper gi bleed from anasotomosis sites, or leak of bile into RUQ giving pain
panc tumours (hard to tel from what, may produce what 7 things, associated with what?, insulinoma 10 sx, oft when sx bad (2x), what relieves and what might you see bc of this, what might be misdiagnosed as), gastroma 4 sx, 2 other places these can be found, how often linked to MEN?
often may be difficult to distinguish chronic panc from some of these, even after surgery
rare tumours are neuroendocrine, producing some mix of glucagon, insulin, somatostatin, serotonin, gastrin, VIP, ACTH (cushings); can be associated with MEN
insulinoma gives hypoglyc (weak, sweat, tremble, confusion, hemiplegia, seizures, coma) + hunger, abdo pain, diarrhoea; often present when pt hungry esp first thing in morning, and relieved by eating; gross weight gain common w/excessive appetite, and commonly misdiagnosed as psyche problem; exercise can also induce symptoms
gastrin producing ones trigger zollinger-ellison syndrome: excess production of gastric acid leading to diarrhoea, oesophagitis, very commonly peptic ulcer (present with bleeding or perf and multiple duodenal ulcers), malabsorption; gastromas can also be in duodenum or rarely in stomach; part of MEN 25% time, can be malig
panc carcinoma (how likely to be in each place, 4 structures it can compress/invade and the consequences, spreads where first? 9 sx, 4 ix, 2 mx options)
60% in head, 25% body, 15% tail
middle aged and elderly (50% cases in >75s)
may get obstructive jaundice
spread into duod giving obstruction or occult/gross upper GI bleed
portal vein giving thromb or ascites and portal hypertension
SMA giving thrombosis or h+
ivc giving bilat leg oedema
Can spread via lymph, or via blood to liver and lungs; peritoneal seeding and ascites generally can occur
painless progressive jaundice if tumour near CBD/ampulla; >50% pts have dull ache in epigastrium which may radiate to back; recent onset DM in elderly is suspicious; migrating thrombophlebitis; anorexia and weight loss; GB may be palpable via Courvoisier’s law, hepatomeg oft, epigastric mass maybe
CT to visualise tumour, endoscopic USS to give info about its relationship to SMA and portal vein plus local lymph nodes to define operability, needle aspiration; serum amylase rarely elevated; elevated levels of Ca 19.9 (but not specific)
only 15% cases operable, with whipple; follow-up chemo; chemo and palliative operations for the rest
chronic pancreatitis: 6 causes, 6 symptoms, 8 investigations
chronic: 80% due to alcohol abuse but also duct obstruction from strictures, metabolic disease eg hypercalcaemia or hypertriglyceridaemia, mutations in CFTR or spink1, autoimmune
pain: epigastric, radiating to back often (10-15% patients have no pain)
malabsorption: rec inflam gives gland destruction until exocrine insufficiency; carbs/proteins/fats not absorbed properly, weight loss and steatorrhoea
diabetes: linked to above but endocrine insufficiency, may see polyuria, polydipsia, malaise
blood tests after convalescent phase (so acute attack doesnt alter blood results) look for high TGs and Ca as well as LFTs for biliary obstruction; fasting glucose can be tested, and faecal elastase to test exocrine function
US (exclude a biliary disease cause), CT to assess calcification; MRCP to investigate parenchyma and ducts; ERCP if cholelithiasis not ruled out
pancreatic carcinoma (usually what type, mean age, 3 scans, biopsy 2 ways, prognosis inc why poor and what palliation has)
usually adenocarcinoma, 2x more common in men, mean age 55
CT or MRCP preferred scan, ERCP if obstructive jaundice; fine needle aspiration under CT or endoscopic US guidance
<6% survival, presents late and extensive lymphatic drainage so hard to completely resect; chemo and radiotherapy palliation
pseudocyst (associated with what, 6sx, 5 complications, 2 rarer causes, initial ix, 3 reasons to intervene, 3 options to drain)
associated with pancreatitis, more oft chronic than acute but can be either
may be asymp, but as get larger cause pain, dyspepsia, nausea and vomiting, bloating, weight loss
may become infected, block part of the SI, or rupture; rarely can cause jaundice or sepsis
abdo trauma or neoplasm may also sometimes cause these
CT for initial assessment and follow up
endoscopic USS guided drainage or transpap drainage if in panc head, for any symptomatic or non-symp but pressure on great vessels, risk of infection or rupture
if EUS unsuitable or fails then laparoscopic or open drainage can be performed
liver blood supply, liver lobule structure; liver zonation; perisinusoidal space; kupffer cells
one fifth to one third is supplied by the hepatic artery; two thirds of the hepatic blood supply is portal venous blood; liver receives 25% of CO in total
hepatic arterial resistance is proportional to portal venous blood flow, such that a reduction in portal venous flow causes a decrease in hepatic arterial resistance and increases hepatic arterial flow
This is probably mediated by adenosine; symp innervation of hep artery and PVT, with alpha action on PVT helping to mobilise blood; VIP, glucagon, secretin help to inc blood flow; sinusoids are low pressure, low flow to maximise time for metabolism and prevent backflow into PVT
high pressure, well-oxygenated arterial blood mixes completely with the low-pressure, less well-oxygenated, but nutrient-rich, portal venous blood within the hepatic sinusoids (capillaries); the sinusoids then lead to the liver lobules
liver lobules are roughly hexagonal, and consist of plates of hepatocytes, and sinusoids radiating from a central vein towards an imaginary perimeter of interlobular portal triads consisting of branches of hep art, portal vein, and common bile duct; bile canaliculi run between hepatocytes back to merge into bile ducts at the perimeter; Hepatocytes possess a toolbox of genes which encode enzymes that can modify a huge range of different types of compounds (for example, the cytochrome p450 family of enzymes), and they perform metabolic functions while blood passes between them; because the characteristics of the blood and the liver environment (ie, amount of bile or oxygenation) change as it passes from the portal to the central vein, the liver cells at different places on the journey perform different metabolic tasks. This is a property called zonation. For example, because oxygen is more freely available near the portal veins (because there is also a branch of the hepatic artery here), metabolic tasks requiring oxygen are carried out here (such as oxidizing fats)
perisinusoidal space (or space of Disse) is a location in the liver between a hepatocyte and the sinusoid endothelium; Microvilli of hepatocytes extend into this space, allowing proteins and other plasma components from the sinusoids to be absorbed by the hepatocytes. Fenestration and discontinuity of the endothelium facilitates this transport; perisinusoidal space also contains hepatic stellate cells (also known as Ito cells), which store fat or fat soluble vitamins including vitamin A). A variety of insults that cause inflammation can result in the cells transforming into myofibroblasts, resulting in collagen production, fibrosis, and cirrhosis
Kupffer cells are liver-specific macrophages that reside in the sinusoidal lumen where they are exposed to the systemic circulation via the hepatic artery and to the splanchnic circulation via the portal vein. straddle inside the sinusoidal space like a spider in ambush for particulate substances passing through the hepatic circulation. Kupffer cells account for approximately 15% of the liver cell population; clear circulating endotoxin from the blood and secrete cytokines, prostanoids etc into the blood
bile cycle (duct system, how much bile ends up in GB initially and what happens to it there, what happens when food enters SI, what happens to bile salts in SI, how many times do bile salts cycle, what 3 things happen to bile salts that make it to LI)
Bile flows out of the liver through the left and right hepatic ducts, which come together to form the common hepatic duct. This duct then joins with a duct connected to the gallbladder, called the cystic duct, to form the common bile duct. The common bile duct enters the small intestine at the sphincter of Oddi (a ring-shaped muscle), located a few inches below the stomach.
About half the bile secreted between meals flows directly through the common bile duct into the small intestine. The rest of the bile is diverted through the cystic duct into the gallbladder to be stored.
In the gallbladder, up to 90% of the water in bile is absorbed into the bloodstream, making the remaining bile very concentrated.
When food enters the small intestine, a series of hormonal and nerve signals triggers the gallbladder to contract and the sphincter of Oddi to relax and open. Bile then flows from the gallbladder into the small intestine to mix with food contents and perform its digestive functions.
After bile enters and passes down the small intestine, about 90% of bile salts are reabsorbed into the bloodstream through the wall of the lower small intestine. The liver extracts these bile salts from the blood and resecretes them back into the bile.
Bile salts go through this cycle about 10 to 12 times a day. Each time, small amounts of bile salts escape absorption and reach the large intestine, where they are broken down by bacteria. Some bile salts are reabsorbed in the large intestine. The rest are excreted in the stool.
thus you can also see that the gallbladder, though useful, is not necessary
bile acid malabsorption (symptoms, 1 prim and 4 sec causes, ix and how it works, mx)
a cause of chronic diarrhoea. This may be primary, due to excessive production of bile acid, or secondary to an underlying gastrointestinal disorder causing reduced bile acid absorption. It can lead to steatorrhoea and vitamin A, D, E, K malabsorption.
Secondary causes are often seen in patients with ileal disease, such as with Crohn’s. Other secondary causes include:
cholecystectomy
coeliac disease
small intestinal bacterial overgrowth
Investigation
the test of choice is SeHCAT
nuclear medicine test using a gamma-emitting selenium molecule in selenium homocholic acid taurine or tauroselcholic acid (SeHCAT)
2 scans are done 7 days apart to assess the retention/loss of radiolabelled 75SeHCAT; >15% retention normal, less suggests excessive loss
Management
bile acid sequestrants e.g. cholestyramine
LFTs (bill what is normal when do you get jaundice, what AST/ALT indicate, when to worry about ALP and what it might indicate, what raises GGT, 2 things hypoalbuminemia may suggest but what is preferred indicator of hepatic function and why, AFP use; how to interpret AST:ALT ratio)
bilirubin - normal adult makes 450 micromol/day; serum conc up when biliary track blocked; usually <21micromol/L and when >~35 get jaundice
aminotransferase activity is sensitive but non-specific indicator of acute hepatocyte damage (infection, toxicity/overdose, cardiac failure/shock) - AST/ALT
alkaline phosphatase activity up indicates cholestasis (>2x the normal upper limit of activity range), as well as indicating infiltrating lesions eg tumours, and in cirrhosis - note though that if cause such as above not indicated by other stuff too, alkaline phosphatase activity is found in other structures like the bone so cant just use this
gamma-GT activity raised with cholestasis, alcohol, phenytoin, and also parallel the changes in aminotransferases; note GGT is not always raised in congen cholestasis due to bili metab defect
hypoalbuminaemia suggests advanced chronic liver disease or notably severe acute liver disease
AFP conc increased in 80-90% hepatocellular carcinoma cases,
prothrombin has v short half life, so prothrombin time increase may be earliest indicator of reduced hepatic synthesis and is preferred to albumin usually
AST:ALT scores >2 are, therefore, strongly suggestive of alcoholic liver disease and scores <1 more suggestive of NAFLD/NASH
ALP isoforms (what types, how much does bone normally contribute, 5 reasons bone portion might be raised, 6 other reasons might be raised, 8 reasons it might be low, how and what IEM can you get)
4 isoenzymes: intestinal, placental, germ cell, and tissue non-specific (liver/bone/kidney)
bone normally contributes half normal level, and esp when bone being laid down eg children (esp growth spurt), pagets, hyperparathyroid, fracture, bone mets; other reasons to be raised inc CKD, IBD, coeliac, rickets, liver disease, pregnancy (can be 3x normal upper limit)
low if postmenopause on oestrogen, hypophos or hypomag, hypothyroid, achondroplasia, after severe enteritis in children, if taking OCP, if malnourished
deficiency of TNSALP gives IEM hypophosphatasia (rickets or osteomalacia, seizures)
you can test for specific ALP subtypes
deranged LFTs interpretation (inc R value, causes 12:7)
R value is a proposed score aimed to aid physicians in determining the pattern of liver injury based on the upper limit of normal (ULN) of certain enzymes. R value = (ALT ÷ ULN ALT)/(ALP ÷ ULN ALP). R value > 5 is suggestive of hepatocellular pattern, > 2 to < 5 is suggestive of a mixed pattern, and < 2 suggestive of cholestatic pattern
with HC pattern causes: ALT-predominant: Acute or chronic viral hepatitis, steatohepatitis, acute Budd-Chiari syndrome, ischemic hepatitis (aka shocked liver), hemochromatosis, medications/toxins, autoimmune, alpha1-antitrypsin deficiency, Wilson disease, Celiac disease
AST-predominant: Alcohol-related, steatohepatitis, cirrhosis
with cholestatic pattern: Bile duct obstruction, primary biliary cirrhosis, primary sclerosing cholangitis, medication-induced, infiltrating diseases of the liver, cystic fibrosis, hepatic metastasis; also consider bone and renal causes, infection/inflam, lymphoma
why does alcohol affect AST more than ALT?
Alcohol is thought to cause injury to the mitochondria which contains AST but not ALT (both present in cytoplasm). In addition, in chronic alcoholics, pyridoxine (vitamin B6) deficiency may reduce the synthesis of ALT more than AST because the former is more B6-dependent
however also note that the raised AST:ALT ratio is generally only once disease is advanced, and in early stages you might not see this even if pt is drinking very large amount of alcohol
bilirubin metabolism
post-mature erythrocytes -> removed by reticuloendothelial system w globin broken down to aa and iron reutilised to make haem -> biliverdin (water soluble) -> biliverdin reductase converts it to unconj bilirubin (water insoluble) -> bound to albumin and taken to liver
binding affinity for albumin to bilirubin is extremely high, and under ideal conditions, no free (non-albumin bound) unconjugated bilirubin is seen in the plasma
taken up by hepatocytes and in smooth ER UDP glucuronyl transferase conjugates with 2x glucuronic acid to make it water soluble conj bili
then active transport into bile canaliculi thence to intestine where in terminal ileum /colon hydrolysed by bacti to release free bilirubin which is reduced to urobilinogen which has 3 fates
most oxidised to stercobilin (faecal pigment), some absorbed by terminal ileum then back to liver by enterohepatic circulation, and some reabsorbed into blood and excreted by kidney
unconj hyperbili (what’s in urine, 4:7:3 causes)
as water insoluble no bilirubin in urine, but inc’d urobilinogen in urine
can be inc’d production: haemolysis, sepsis, haematoma, polycythaemia
decreased bili uptake or metab: gilbert syndrome, crigler-najjar, lucey-driscoll, hypothyroidism, sepsis/acidosis/hypoxia, heart failure, physiological jaundice
altered enterohep circulation - breast milk jaundice, intestinal obstruction, abx
conjugated hyperbili - picture for intrahep vs extrahep causes, 3 signs, 7 neonatal hep causes, 2 syndromes causing abnormal bili secretion, 10 non-neonatal hep, causes of intrahep cholestasis, 5 causes of extrahep cholestasis)
intrahep causes mainly mixed picture, extrahep mainly conj picture
conj bilirubin is water soluble and so found in urine, so dark urine and pale stools + pruritus
neonatal hepatitis (rubella, CMV, toxoplasmosis, A1AT def, CF, metabolic disorders inc wilsons, gaucher etc), idiopathic giant cell hepatitis
abnormal bilirubin excretion by hepatocyte: dubin-johnson, rotor syndrome; note GGT is not always raised in these cholestatic conditions (and ALP may also be normal)
non-neonatal hep (A B C, ECHO, CMV, EBV, leptospirosis; chemical and drug induced, autoimmune)
intrahep cholestasis (various congen syndromes) and extrahep (biliary atresia, choledochal cyst, mass/neoplasia, stone, high intestine obstruction)
jaundice (prehep 2 main causes, hep cause egs, posthep signs and 9 causes inc 3 things that can cause hep and posthep, viral vs stone in young person, what is needed after bloods ix-wise)
prehep: inc production of bilirubin due to eg RBC haemolysis exceeds livers ability to conjugate, unconj up in blood; other cause may be reabsorption of large haematoma
hep: from hepatocyte damage, unconj and conj build up in blood; hepatitis, EBV, cholestasis from drugs (flucloxacillin, chlorpromazine), toxicity eg paracetamol, tumours, sepsis, cirrhosis
posthep/obstructive: stools pale, conj in blood excreted in urine turning it dark (may see in hep type too); hep and posthep can coexist if eg stone in CBD, as both outflow obstruct and biliary cirrhosis; tumour deposits in liver or cirrhosis may also both cause both as damage liver tissue and compress intrahep duct
posthep causes: cholelithiasis, CBD atresia or traumatic stricture, sclerosing cholangitis, tumour of CBD, tumour of head of pancreas, tumour of ampulla of Vater, pancreatitis, liver hilar lymphadenopathy
painless jaundice of sudden onset with tenderness in younger person usually viral; severe colic + intermit jaundice suggests stone
important: in all cases after bloods etc USS needed to see if ducts dilated before moving on to other scans and management
investigating jaundice (prehep/hep/posthep urine + LFTs, BM for all 3, PT for all 3, USS, other imaging for hep/post-hep, ix if prehep)
urine: prehep/hep urobilinogen, post hep bilirubin
serum bilirubin: prehep unconj, posthep conj, hep mixed
ALT/AST: prehep normal, hep raised, posthep normal/raised a bit
ALP: prehep normal, hep normal/raised a bit, posthep raised (but ALP may also be raised if concurrent bone disease inc eg bone mets)
blood glucose: prehep normal, hep normal or low if liver failure, posthep normal or high if panc tumour
prothrombin time: prehep normal, hep prolonged due to poor synthetic functino, posthep prolonged due to poor vit K absorption
USS: prehep normal, hep may have abnormal liver texture, posthep dilated bile ducts inc accurate at spotting stones
haemat investigation for haemolysis: coomb’s test, raised reticulocyte count
CT/MRI can then spot hep lesions for biopsy, or panc lesions; in posthep MRCP/ERCP can be handy
acute cholangitis (what it is, triad and pentad, 5 investigations, 2x mx)
bacterial infection of an obstruction within biliary tract (partial obstruction higher risk than complete)
charcot’s triad: fever, jaundice, RUQ pain (may be absent in elderly); severe cases may also have confusion and hypotension (reynolds pentad)
FBC, LFTs; ALT and AST may be elevated in early stage before bile duct dilated on US, so may be mistaken for viral hep
transabdo US has v high specificity but poor sensitivity for gallstones
MRCP and endoscopic ultrasonography are more sensitive
ERCP is gold standard and can procede to therapeutic stone removal etc, but is invasive
80-90% patients respond well to broad spectrum antibiotics
cholecystitis (what it is - 2 types; 4 sx, 3 complications, main mx and 3x parts of alternative mx)
chemical or bacti inflam of gallbladder following gallstones (calculous cholecystitis) but 5% dont (acalculous)
unremitting RUQ pain, anorexia, nausea/vomiting, fever
in severe acute cases get necrosis of the gallbladder
complications: perforation, pericholecystic abscess, fistulae
cholecystectomy to treat; antibiotics, low fat diet, and observation can be used in patients where surgery would be risky (eg a comorbidity)
primary sclerosing cholangitis (usually who, linked to what, what it is, 7sx (inc one due to effect of less bile acids in gut), 3 bloods, sign you might see, only mx that extends life is what?)
usually young men (40yo), linked to IBD; chronic progressive with inflam and stricture formation of intra/extrahepatic bile ducts
jaundice, steatorrhoea, pruritus, weight loss, reduced Ca and fat soluble vitamin absorption; though many patients no symptoms or just vague ruq discomfort
conjugated bilirubin and GGT up, ALP often 3x normal, xanthomas may be present
liver transplant only treatment to extend life
primary biliary cirrhosis (what it is, who gets it, 5 sx, what else might they have, definitive mx option)
autoimmune attack on epithelial cells lining intrahepatic bile duct; 10x more women than men, from late teens on but usually ages 30-65
fatigue, pruritus, hyperpigmentation, xanthelasmas, splenomegaly; may have other autoimmune diseases
liver transplant again only life extending treatment
UDCA hepatoprotectivity
UDCA is commonly used to treat patients with primary biliary cholangitis and may have a role in PSC
has also found use in the treatment of cystic fibrosis, graft vs. host disease involving the liver, liver allograft rejection, bile duct-paucity syndromes such as biliary atresia, and non-alcoholic steatohepatitis
bile acids damage cells by causing mitochondrial dysfunction. UDCA offers cytoprotection in hepatic epithelia by preserving cell structures, including plasma membranes and mitochondria while stimulating anti-apoptotic pathways. Additionally, UDCA can prevent Kupffer cells, the resident macrophages in the liver, from generating reactive oxygen species
UDCA competitively displaces the endogenous bile acids at the level of ileal absorption or the hepatocyte level, thus decreasing the concentration of toxic hydrophobic bile acids
UDCA induces vesicular exocytosis in cholestatic hepatocytes by indirectly increasing intracellular calcium levels leading to increased secretion of bile acids
DCA has been shown to reduce the expression of class I MHC antigens in several cholestatic liver disorders
cholangiocarcinoma (5main sx, 3 things advanced may have, first line ix, then 2 alt imaging pathways, 3 mx options)
abdo pain, palpable mass, hepatomegaly, weight loss; progressive obstructive jaundice; advanced disease may have cholangitis or acute cholecystitis, or anaemia from blood loss
ultrasonography first line investigation; abdo CT if mass like tumor, MRCP or ERCP if stricture causing tumour
complete surgical resection only chance of cure but stent, chemo etc for palliation
acute liver failure - 4 common causes, 3 types based on time, 23 causes, 21 ix (2 more in kids for any deranged LFTs)
either toxins, ischaemia, sepsis, or viruses - and of toxins, v oft paracetamol
hyperacute: 0-7 days, severe encephalopathy coagulopathy, and raised intracranial pressure; LFTs oft very deranged; best recovery chance
acute: 7-28 days
subacute: 28 days +, gradual, worst outcome
right heart failure, budd chiari, hepatic ischaemia (global or embolic), viral hep, EBV, CMV, HSV, VZV, HCC/mets/lymphoma, paracetamol, alcohol, TB meds, amanita mushroom, drugs of abuse, reye’s syndrome, reaction to NSAIDs or anticonvulsants, wilson’s, haemophagocytic syndrome, vasculitis, crush injury, hyperthermic injury, acute fatty liver of pregnancy, HELLP
ix: LFTs, FBC (eosins for drug reaction or autoimmune), paracetamol level, LDH, CK, anti HAV and HAV IgM, HBV core IgM (and other ix), coags, caeruloplasmin, urinary copper; EBV, CMV, HSV, VZV serology if immunocomp, dengue and yellow fever serology, anti SM ab/ANA/anti-mi ab + serum Ig (and in kids also anti liver-kidney-microsomal ab and coeliac screen)
echo, liver uss, CT abdo with contrats
acute liver failure consequences (how hyperdynamic circulation happens, ARDS difficulty in liver pt and 3 other reasons for hypoxia, hepatic enceph 9 sx + 3 indications for monitoring; hypercatab state + glucose levels; lactate levels and implications; renal and adrenal sequelae; interpreting the raised INR; bone marrow and immune system
damage allows shunt of ‘dirty’ portal blood into systemic circulation, exposing bowel bacti endotoxin to iNOS + cytokines and vasoactive GIT hormones wash through all leading to hyperdynamic circulation (+ failing liver not removing as much); SIRS or sepsis often also develops
ARDS will dev as part of SIRS, however due to ammonia causing raised ICP you can’t do permissive hypercapnoea; ascites may impair ventilation, and get portopulmonary shunt and hepatopulmonary syndrome
hepatic enceph: short attention span, tremor, then incoordination, lethargy, disorientation, then somnolence, asterixis, ataxia, coma; ICP monitoring if young, confused or worse on above scale, serum ammonia >150
hypercatabolic state will inc daily caloric requirements; hypoglyc common as less glycogen storage or release and elss gluconeogenesis
lactate will be raised as broken down in liver normally; higher levels suggest worst failure, may take a while to come down even after shock resolved
relative adrenal deficiency, may need hydrocort; HRS may dev but not all AKI will be this -> CRRT may be needed
raised INR in acute liver failure may overestimate bleeding risk as protein C/S also not made
bone marrow suppressed in 10% of ppl by cytokines, can range from mild too full aplastic anaemia; have dec’d complement so impaired opsonisation and phagocytosis, also have worse chemotaxis and neut function
note that liver cells store large amounts of B12, so damage to them (cirrhosis, carincoma/mets, PVT. liver abscess etc) causes high serum b12 level -> so if level high and not on replacement this is a sign of badness
hepatic encephalopathy - what happens with astrocytes, influence of ammonia on NTs, influence of ammonia on metabolism; why alcoholics might be protected from raised ICP; 10 other dd for collapsed/comatose drunk; dietary aspect of HE mx; ammonia normal why, EEG findings and role
urea cycle broken -> ammonia up
astrocytes combine it with glutamate to make glutamine but end up making massive amounts and swelling, giving cerebral oedema; also inc’s distance between neurons and caps giving nutrient diffusion defect
excess glutamine also made in BBB which inc’s transport of aas that exchange with glutamine to cross and impairs transfer of others, meaning less 5HT and DA made, and the excess wrong aa are made into unusual NTs like insect norad equiv, and these derange synaptic transmission
ammonia inhibs a-ketoglut dehydrogenase so stops TCA, and inhibs PDH; thus brain produces more lactate
alcoholics often don’t dev raised ICP as brain atrophied and due to chronic adaptation; however in certain conditions ICP is monitored
stroke, sepsis/CNS infection, CNS neoplasm, drugs (eg benzos for withdrawal regime), trauma eg SDH, hypoglyc, hyponat, UGIB, seizures/NCSE, alcohol toxicity
high calory diet, high protein intake (to stop catabolism of body protein), give branched chain aa as can enter TCA at later stage than alpha ketoglu dehydro
ammonia may be normal, as other neurotoxins also involved in HE eg manganese, short chain fatty acids
EEG can show high-amplitude low-frequency waves and triphasic waves but not specific, is still useful to exclude other things like NCSE
acute liver failure mx - first step, 6 steps for brain, 8 other steps, 2 scoring systems + 6 contras for transplant,
identify and remove causes eg NAC for paracet, l-carnitine for valproate etc
if HE: intubate and ventilate, keeping paCO2 low/normal, norad, propofol to sedate; consider ICP monitoring and get hypernat 145-155, consider therapeutic hypothermia, continuous haemodiafiltration to remove ammonia
dextrose infusion + crystalloid (careful not to fluid overload), PPIs to avoid bleed, drain ascites, vit K 10mg, daily blood cultures to watch for sepsis, give phosphate (new liver cells will hoover up and needed for ATP synthesis); NAC has been shown in newer trials to likely benefit even non-paracetamol acute liver failure, but can get advice on this
MELD score to decide if to do transplant (+ king’s college score); absolute contras are sepsis, malignancy, severe cardioresp disease, ongoing alcohol or IVDU, AIDS, likely poor compliance; liaise with transplant centre early
abx induced transaminitis (what it is, how long to dev, 9 associated abx, basic work up and mx, 2 reasons for biopsy, should you rechallenge and why?)
antibiotic-induced hepatotoxicity can often be detected early from elevations in ALT to >2x upper limit of normal
adverse effects may develop almost immediately, late in the course of prolonged antibiotic treatment or several months after the cessation of therapy
co-amox: cholestatic or mixed
ceftriaxone: biliary sludge as precipitates with Ca, normally asymp but occasionaly can course cholelithiasis type sx w/o LFT derangement, v rarely can dev cholestatic jaundice
co-trimox, macrolides are intermediate risk
TB drugs also high risk, and nitrofurantoin, fluclox, interferons and nevirapine
need to work-up inc abdo US, and basic liver blood screen; if suspect then stop the drug and rpt LFTs, they should improve; if they dont then consider biopsy if bloods might also support an autoimmune hep diagnosis, or if fails to regress or even worsens after abx stopped
Liver injury caused by unintentional rechallenge in clinical practice can confer a higher risk of mortality/liver transplantation and so shouldnt be done deliberately
ascites (inc causes (3:2 and how to use SAAG), 4 mx, minimising fluid shifts, abx when/what)
transudates: hydrostatic (portal hypertension), oncotic (hypoalbuminaemia), fluid retention (portal hypertension leads to renal hypoperfusion, renin release, secondary hyperaldosteronism, salt and water retention)
exudates: inflam or malignancy of peritoneal surface (inc panc, bowel obstruction)
calculate serum albumin conc - ascites albumin conc; if >11g/L then portal hypertension is the cause
treat underlying condition
low Na diet (or fluid restriction)
spironolactone
if tense ascites: paracentesis with 10g albumin given for each litre of fluid removed to minimise fluid shifts and subsequent haemodynamic consequences
ciprofloxacin if cirrhosis + ascites and ascitic protein 15g/L or less
ascites proph + SAAG interpretation, autoimmune hep 2x antibodies, iron overload tests, hepatic encephalopathy management 2 meds, NAFLD investigations x2
SAAG > 11g/L (indicates portal hypertension)
prophylactic oral ciprofloxacin if cirrhosis and ascites, total protein<15
autoimmune hep has ANA and anti smooth muscle antibodies, may present acutely but usually chronic
ferritin + transferrin sat up suggest iron overload (HH or multiple transfusions)
hepatic encephalopathy: lactulose first-line, with the addition of rifaximin (promote excretion/gut bacti metabolism of ammonia)
in NAFLD: enhanced liver fibrosis (ELF) blood test to check for advanced fibrosis, then refer for biopsy
ascitic drains - leave draining for how long, how much and what conc of HAS for how much fluid drained, 2 reasons to remove, how to remove each type, what to do after removing including if draining a lot, what it persistent leak
leave on free drainage for 4-6 hours
patients should be administered 100ml of human albumin solution 20% (HAS) for every 2-3 litres of ascitic fluid drained
generally remove when stops draining or after 4-6 hours (to reduce risk of SBP)
some patients with malignant ascites get radiologically-guided drains that can stay in so that they can drain some fluid off each day
removal: if straight/normal then pull out, if pigtail cut the string then pull out
after removal apply dressing and keep it dry for 48hrs; if draining a lot may need to place stoma bag over hole for over days to weeks
For persistent leak following drain removal, consider placing a suture (ask gastro)
hepatorenal syndrome -how it occurs, 6 crit to diagnose, 2 types, due to 3 things, 4mx
besides portal hypertension from compression by scarred tissue or general venous congestion, liver function may be down (hypoalbuminaemia); also cirrhosis causes splanchnic vasodilation as vasodilators (nitric oxide) accumulate in the splanchnic circulation when liver fails; systemic hypotension and renal hypoperfusion thus renin-ang activation, aldosterone release giving salt and water retention; sometimes this exacerbates as renal vasocons cant compensate so renin-ang system stays activated, inc’g renal vasocontriction until AKI; hepatorenal syndrome is result as renal hypoperfusion continues, this has high mortality via AKI
diagnosed if liver disease, AKI, not responding to fluids, not shocked, no nephrotoxics or abnormal renal USS - essentially diagnosis of exclusion; this also means must fail to respond to standard care and volume expansion for 48h in order to diagnose; how to differentiate it from ATN: use fractional excretion of sodium and urinary microscopy
usually HRS is due to acute decompensation of cirrhosis due to infection eg spont bacti peritonitis, GI bleed, alcohol intake - type 1, cr doubles in 2 weeks
a slower form with diuretic resistant ascites (as kidney function unable to excrete enough sodium to clear the fluid, this slower kind of HRS may be the end stage of ascites
can also occur due to acute liver failure
mx: HAS + terlipressin, can consider octreotide; definitive mx is transplant; can do TIPS but oft has poor outcome
portal vein thrombosis and budd chiari - PVT 7 sx, 1 ix, 12 causes, 5 mx; budd chiari 4 sx, 6 causes, 1ix, 1 mx
For PVT “nothing” or “vague unwellness” may actually be the only clinical findings, but more generally people will present either with features of portal venous hypertension (such as ascites) or with abdominal pain. May see variceal bleeding, haemorrhoids, worsening features of portal hypertension; may get venous infarct of liver or spleen
contrast CT abdo will show PVT
inflam near vessel: pancreatitis, cholecystitis, inflamed bowel inc diverticula, TB lymphadenitis, duodenal ulcer, neonatal omphalitis
injury to portal system from any abdo surgery
any abdo malig
cirrhosis or retroperitoneal fibrosis/mass giving venous stasis
congen or acquired prothromb states
90% will recanalise with time, and bear in mind bleeding risks in these pt; however if no varices and pro-thromb state then can do rx dose LMWH or warfarin; BB, spiro, TIPS are options
budd chiari: abdominal pain, ascites, and liver enlargement; may dev liver failure
hypercoag esp polycythemia, pregnancy, post partum, OCP, congen, then others; secondary due to compression by eg tumour
CT abdo with contrast, give hep/warf
cirrhosis causes (11 + 2 drugs)
Chronic EtOH
NAFLD/NASH
Chronic HCV (and HBV)
Rare:
Genetic: Wilson’s, α1ATD, HH, CF
Auto Immune: AH, PBC, PSC
Drugs: Methotrexate, amiodarone
etoh/nafld -> fatty liver disease; first Steatosis: Fat deposition in hepatocytes, Nuclei displaced
then Steatohepatitis: Neutrophil infiltrates Hepatocyte swelling/necrosis Mallory-Denk bodies; finally cirrhosis
cirrhosis 9 consequences and 7 investigations, what conj and uncon hyperbili mean in terms of what is happening to bilirubin, why ALT/AST higher in acute than chronic liver disease
cirrhosis consequences:
Breakdown
Bilirubin → Jaundice
Ammonia → Encephalopathy
Synthesis
Carbohydrate metabolism → Hypoglycaemia
Protein synthesis → Hypoalbuminaemia → oedema
Clotting factors → coagulopathy: PT affected more
Acute phase and other immune proteins -> immunodef
Storage
Iron → anaemia (small bleeds, hypersplenism from port hyp)
PVP up, and HCC risk; former: varicosities, organomegaly, ascites, hepatorenal syndrome
also hyperdynamic circuation (spider naevi, tachy, palmar erythema), na/fluid retention through hyperaldos
investigate with LFTs, Hepatitis serology and viral screen
Ferritin and iron studies
Alpha 1 antitrypsin
Autoantibodies (PBC, PSC, autoimmune hep)
AFP
Serum copper and caeruloplasmin
conjugated hyperbili: BR made it to liver but not into bile due to cholestasis, hepatocellular damage, disorders of secretion
unconj hyperbili: BR isnt reaching liver or is but not then conj eg haemolysis or impaired conj eg gilberts syndrome
ALT and AST are aminotransferases in many hepatocytes, some released all the time but more upon cell injury/death; thus highest levels in severe acute, then mild acute; in chronic conditions inc eg mild chronic HCV or cirrhosis there is little ongoing injury and so the levels are lower
liver/cirrhosis screen - done if jaundice of hepatic origin - 7 things
to be done if jaundice of hepatic origin; hepatitis screen, autoantibody profile (high levels IgM suggest PBC, high levels of IgG poss autoimmune hep), ferritin and transferrin saturation (haemochromatosis), alpha1 antitrypsin (def results in emphysema and/or chronic liver disease inc cirrhosis and failure), afp (raised in HCC often), caeruloplasmin, TFTs
liver scoring systems (first one uses what 5 things, pros/cons, three results; second type uses what 3 things, used for deciding what 2 things?)
childs-pugh uses bili, albumin, INR, ascites, encephalopathy; somewhat subjective, but predicts mortality well; should be done on admission; class A is well compensated, class B is compromised and class C is worst
MELD developed as more objective (weighted function of cr, INR, bili), used for transplant listing and eg TIPS procedures; it and child’s pugh have different strengths
NAFLD/NASH - who is at risk, diagnosing in children (what ix, when, monitoring if neg), what generally suggests possible NASH, first step when NASH suggested, monitoring for cirrhosis (test and interval, follow up if that test pos), 2 lifestyle mx, 2 other mx for adults (3 contras to this), another med you can use, 2 things for kids
at risk: T2DM/metabolic syndrome
in children do USS if above and no alcohol use, if normal keep repeating every 3 years; generally is suggested by deranged LFTs with suggestive US or negative liver screen
for adults, calculate NAFLD/FIB4 score and based on result can either be managed in primary care (Q risk and lifestyle factors), get ELF test, or straight referral to hepatology - or can go straight to ELF test
ELF every 3 years (2 if kids) for fibrosis; patients with NAFLD and suspicion for advanced fibrosis should have a liver biopsy to confirm findings
lose weight, exercise; adults can try pioglitazone or vit E (not if heart failure, previous or active bladder cancer, haematuria), kids could also try vit E -refer to paeds hepatology, liraglutide may also be used
wilsons (clinical features 1:2:1:3:1 (but 3 ways that 1 presents) 5x ix, 4x mx, and cu normal absorption and what happens in wilsons) and haemochromatosis (sx 1:3:1(where x3):1:1 and other sx to watch for, ix, mx 2 stages)
wilsons: Clinical features – CLANK
Cornea – Kayser-Fleischer rings
Liver – acute failure or eventual cirrhosis
Arthritis
Neurology – Ataxia, parkinsonism, psychosis
Kidney – Fanconi’s syndrome (prox tubule affected, giving type 2 RTA, ricketts/osteomalacia (due to loss of phosphate not vit d/ca problems), glycosuria (so polyur/dip/dehydration)
Ix: Serum/urine copper (serum low as caeruloplasmin would carry most, urine high over 24 hr collection) and caeruloplasmin (low, unless active inflam as is acute phase protein)
Once suspected, liver biopsy +/- genetic testing to confirm
Mx: Penicillamine lifelong (30% pts need to stop due to reaction inc skin, renal, lupus like), other binders and zn salts available + low copper diet advised for all; family screening will be performed; will need referral to paediatric hepatology
Copper enters the body through the digestive tract. A transporter protein on the cells of the small bowel, carries copper inside the cells and in response to rising concentrations of copper, an enzyme called ATP7A (Menkes’ protein) releases copper into the portal vein to the liver. Here, ATP7B links copper to ceruloplasmin and releases it into the bloodstream, as well as removing excess copper by secreting it into bile - does neither of these functions in wilsons disease
Copper accumulates in the liver tissue; ceruloplasmin is still secreted, but in a form that lacks copper that is rapidly degraded; When the amount of copper in the liver overwhelms the proteins that normally bind it, it causes oxidative damage to the liver giving hepatitis and cirrhosisliver also releases copper into the bloodstream that is not bound to ceruloplasmin. This free copper precipitates throughout the body, but particularly in the kidneys, eyes, and brain. In the brain, most copper is deposited in the basal ganglia, particularly in the putamen and globus pallidus and damage here gives neuropsych sx
haemochromatosis: MEALS
Myocardial: dilated cardiomyopathy
Endocrine: hypopituitarism (hypogonadism - ED, amenorrhoea), hypoparathyroid, hypopancreas (T2DM due to poor insulin secretion and insulin resistance related to liver disease)
Arthritis: MCP joints, knees, shoulder
Liver: Cirrhosis
Skin: Bronze/ Slate Grey colour
ED
Ix: Ferritin and iron studies
Mx: Venesection: 2 weekly initially (depletion) → 6 weekly (maintenance)
4 causes of low caeruloplasmin
wilsons, nephrotic syndrome, malabsorp/nutrit, protein losing enteropathy
A1AT - presentation in adults and infants, why levels may be falsely normal and what to do about it, inheritance pattern, mx
adults get early emphysema, infants neonatal cholestasis + cirrhosis
A1AT is acute phase protein and so levels may be normal if inflam going on for whatever reason, so also do protease inhibitor typing
types are ZZ, MZ, MM with co-dominant inheritance so ZZ have, MZ may or may not, MM don’t
treatment is liver transplant which converts recipient to protease inhibitor type of the donor
steatosis appearance on US, CT, MRI (inc comp to spleen), cirrgosis appearance on USS and MRI, what ix is preferred for early fibrosis
hepatic steatosis: echogenicity up on USS so walls of hept and portal veins cant be seen, looks more echogenic comp to kidneys/spleen; liver attenuation down in CT so look darker than spleen on unenhanced CT; MRI diagnostic with in phase and out of phase imaging, parenchymal signal reduction on out phase as water and fat signal cancel
cirrhosis: ascites, nodular margin, heterogeneous texture visible on USS, and fat suppressed in T2 weighted image; but generally imaging insensitive for fibrosis in early stages; possible solution: MR elastography- but biopsy ultimately used
viral hep (4 signs/sx and how deranged can LFTs be, HBV ratio for asymp to acute, how many get chronic in adults + kids, diagnosis, 2mx; HCV how many clear and how many get chronic, mx inc what aiming for; outcome of chronic disease for both; acute, chronic, prev infection, immunity due to vaccine results for HBV serology)
Flu-like prodrome
RUQ pain
Fever
Jaundice (mixed)
Deranged LFTs: >20x normal in acute disease, AST<ALT
HBV: 70% asymptomatic, 30% get acute. 5-10% adults then get chronic. Children are more likely to have chronic infection. (90% get)
diagnose w serology, treat w Pegylated IFN alpha, antivirals e.g. tenofivir
HCV: 15% clear virus, 85% get chronic liver disease; serology, confirmatory HCV RNA
Antivirals: aim for sustained virological response: absent HCV RNA at 6 months
for both: chronic diseases gives fibrosis, steatosis, cirrhosis, HCC
Acute: HBsAg, HbeAg, IgM anti-HBc
Chronic: HBsAg, ±HbeAg, IgG anti-HBc
Previous infection: anti-HBs and IgG anti-HBc
Immunity due to vaccine: anti-HBs
acute decomp of chronic liver disease (what is chronic liver disease, 6 decomp features, 13 reasons for decomp; 15 initial ix - and what you don’t need to measure, what else to record, 8 aspects of mx (inc king’s criteria)
chronic liver disease = any dysfunction lasting >6mo; acute decomp may present with any of jaundice, ascites, encephalopathy, AKI, GI bleed, sepsis/hypovol
sepsis, sbp, HBV/HCV reactivation, alcohol, drug toxicity, GI bleed, portal thrombosis, ischaemic insult (eg shock), surgery, autoimmune, dehydration, constipation, HCC
FBC, CRP, U&Es, LFTs, glucose, coags, bone profile, Mg, AFP, blood cultures, urine dip + MC&S, CXR, USS abdo
ascitic tap if any ascites present for culture, WCC, albumin - needs to be done before abx, within a few hours of starting abx culture may not grow anything and you’ve lost the chance to diagnose it; neut count raised but not massive, if very high consider perf
record recent daily alcohol
can get ammonia but not useful as not always raised in hepatic enceph - may be good if pt sedated/no other way to tell has encephalopathy
if >8 units a day alcohol (M) or 6 (F) or unclear then 2 vials pabrinex TDS, CIWA scoring, consider reducing chlordiazepoxide
if suspect sepsis start abx, if ascitic PMNs >250/mm^3 then abx and IV 20% HAS
if AKI then hold nephrotoxics, 250ml boluses saline or HAS 5% up to 1-2L, fluid balance chart + daily weights, aim for UO >0.5ml/kg.hr and if not reached by 6 hrs escalate to ITU
GI bleeding mx as for varices, and if PT prolonged give IV vit K 10mg stat; if INR >2 or PT >20 give 2-4 units FFP
if encephalopathy then lactulose, can request CTH to exclude SDH
LMWH prophylaxis unless plats <50 or actively bleeding, and needs GI/liver r/v, even if INR raised as still pro-thrombotic state until INR gets up to somewhere between 2.1-2.5 (only way to tell when the balance has been crossed is to do TEG, and when more likely to bleed is when LMWH should be stopped)
liaise with transplant team and consider early transfer based on king’s criteria: INR >6.5 or 3 out of: <11yo or >40yo, serum bili >300, time between jaundice onset and coma >7d, INR >3.5, drug toxicity; in paracetamol overdose it’s pH <7.3 + enceph, cr >300, INR >6.5
- > 90% of cirrhotic patients are sarcopenic, which is an independent predictor of mortality
- need 1.5g/kg of protein per day and 30kcal/kg per day
- NG feed if not meeting within 48h
VTE prophylaxis in liver disease (plat count and coag generally, when to withold proph and why not other times, what to use, what to do day before procedure (and what counts), when to restart); antiplats/anticoags prior to gastro procedures generally (3 to continue DAPT, 5 to just continue asp and when to stop second agent, main reason to consider not stopping and 2 situations when can stop anyway; warfarin and DOAC stop when and for how long, restart when, bridging how/when x2)
Platelet counts are often low in cirrhosis due to portal hypertension and “pooling” in the spleen, and PT/INR tends to be raised
patients with liver disease are at a high risk of thromboembolism even with a prolonged prothrombin time - only withhold VTE proph if actively bleeding or plats <50 (or if INR >2.5, discuss with seniors/haem)
generally can use LMWH
omit dose day before procedures: ERCP, TIPSS, biopsy etc
As long as there is no sign of post-procedure bleeding, VTE prophylaxis can commence 24 hours after the procedure if the patient remains in hospital
pre-procedure you can generally continue aspirin, and can continue DAPT for simple procedures (OGD, EUS, biliary stents) - for more complex (FNA, oesoph stent, ERCP, PEG, varices therapy), stop the second antiplat if IHD with no stent, PVD, CVA 5 days before procedure, liaise with cardio if IHD with stents but generally only stop the second agent if >1mo since metal stent or >12mo since drug eluting stent inserted
low risk procedures continue warfarin, omit DOAC morning of; for high risk omit DOACs for 48hrs before, stop warf 5 days before and ensure INR <1.5 (restart evening of procedure day)(if prosthetic mitral valve or any prosthetic valve and AF then bridge with LMWH until 24hrs pre-procedure)
refeeding syndrome - 9 at risk groups, 8 criteria for risk, pathophys; 4 steps to prevent,
at risk: anorexia nervosa, chronic alcoholism, malignancy, HHS, HIV/AIDS, chronic panc, bariatric surgery, elderly/frail, hyperemesis gravidarum - in short, anyone who is chronically malnourished for any reason (inc homeless etc)
criteria: one of BMI <16, unintentional weight loss >15% in past 3-6mo, minimal nutrient intake in past 10 days, refeeding picture in bloods; or two of BMI <18.5, unintent weight loss >10% in past 3-6mo, minimal nut intake for past >5days, history of drug or alcohol abuse
With the restoration of glucose as a substrate, insulin levels rise and cause cellular uptake of these ions. Depletion of adenosine triphosphate (ATP) and 2,3-diphosphoglyceric acid (2,3-DPG) results in tissue hypoxia and failure of cellular energy metabolism. This may manifest as cardiac and respiratory failure, with paraesthesiae and seizures; thiamine deficiency also contributes
phosphate stores are depleted during starvation while serum levels initially maintained, so vulnerable to fall with inc’d insulin that other pt groups aren’t
to prevent: slow refeed (10kcal/kg/d then build up 10% each day), pabrinex and vitamin B co-strong + multivit, daily refeeding bloods and replace electrolytes as required, dietician r/v
vitamin B co-strong (4 things it contains, 3 things ppl at risk of refeeding should be prescribed, 3 other indications and 2 caveats, what about alcohol use disorders - 4 cases?)
contain thiamine, riboflavin, pyridoxine, and nicotinamide
people at high risk of developing refeeding syndrome should be prescribed the following vitamins for the first 10 days of feeding. They should be prescribed oral thiamine 200mg to 300 mg daily, vitamin B compound strong 1 or 2 tablets, three times daily or a full dose daily intravenous vitamin B preparation, if necessary, and a balanced multivitamin and trace element supplement once daily. not much thiamine stored in body, can be depleted in 2-3 weeks, so anyone at risk of refeeding should be on prophylaxis of 100mg a day; also note if any hints of WE (inc alcohol detox delirium as you can’t fully tell the difference) will need pabrinex; pabrinex can be given IM if pt non-cooperative
Vitamin B compound strong may be prescribed if there is a medically diagnosed deficiency, chronic malabsorption, or following surgery that results in malabsorption.
This should be prescribed only under the advice of a specialist clinician or dietitian.
Please note that neither vitamin B compound nor vitamin B compound strong contain vitamin B12 so they should not be prescribed for vitamin B12 deficiency
doesn’t have enough thiamine for prophylaxis of WE, so offer prophylactic oral thiamine at a dose of 200mg to 300mg per day in divided doses, to harmful or dependent drinkers:
* if they are malnourished or at risk of malnutrition
* if they have decompensated liver disease
* if they are in acute withdrawal
* before and during a planned medically assisted alcohol withdrawal
(note, reason why such high doses of thiamine needed is firstly as no specific transporter across BBB so need to establish high gradient, and needs to be IV as oral bioavailability reduced in alcoholics)
pathology of thiamine deficiency - what thiamine turned into and used in what 2 pathways so if deficient what 2 things build up, third pathway affected and what you thus don’t make, 2 reasons giving glucose leads to cell damage, can you treat a hypo in a pt at risk of refeeding?
Thiamine is crucial for the formation of thiamine pyrophosphate - required for glycolysis and TCA cycle (inc needed for PDH and a-KGase to function) - so if deficient keto-acids and lactic acid formed
pentose phosphate pathway also needs thiamine to generate NADPH, so failure to synthesise this
giving glucose allows for much more lactic acid production as depletes whatever thiamine reserves there are quickly, combined with failure to generate NADPH to protect from ROS; this leads to cellular damage and ultimately apoptosis or necrosis
thus before giving glucose, TPN, or dextrose long-term you must make sure a refeeding risk pt is given thiamine -> HOWEVER, a single bolus of glucose alone won’t precipitate WE, if a pt has a hypo then treat it without waiting for thiamine
human albumin solution - why order from lab, 7 indications, 3 things that arent indications,
You order with a paper form as it is made from donor blood
Nephrotic Syndrome – in combination with diuretics.
During drainage of ascitic fluid to prevent renal dysfunction due to increased renin activity and hyponatraemia (thereby preventing post-paracentesis circulatory dysfunction). The dose is as per the ascitic fluid drainage protocol – 100 ml of 20% HAS for every 2 litres of ascites drained.
Severe burns after the first 24 hours (usage before this time has been demonstrated to cause paradoxical pulmonary oedema).
Acute Respiratory Distress Syndrome where use of diuretics has caused fall in effective plasma volume.
Acute liver injury to support plasma oncotic pressure and bind excessive bilirubin, activated plasmin, toxins etc. (you might try and evaluate resus with eg hartmanns first)
Renal dialysis if the patient becomes hypotensive.
Hepatorenal Syndrome (HRS)
The dose is as per HRS guideline – 1g/kg (Max 100g /day) per day for two or more days until improvement in renal function. Either 4.5% or 20% concentrations may be used depending on the fluid status of the patient; note also that patients with SBP may be at high risk of getting HRS and so should be given HAS
Inappropriate indication
Intravascular volume expansion after trauma or major surgery.
As part of total parenteral nutrition.
In long term supplementation of albumin in nephrotic syndrome
drugs metabolised in the liver - 34
ciclosporin, tacrolimus, sirolimus
most common chemo drugs
ketoconazole/itraconazole
clari/erythromycin
TCAs, SSRIs, venla, mirtaz
many antipsychotics
many opioids
diaz/clonaz/midaz
Z drugs
donepezil
statins (except prava/rovu)
CCBs
amiodarone
sex hormones
chlorphen/terfen
-vir and nevirapine antivirals
hydrocort/dexameth
warfarin
omeprazole
domperidone/ondansetron
eplerenone
propran, salmet, losartan, montelukast
some anti-epileptics
congestive hepatopathy - 2 main forms of cardiac hepatopathy, what it is and leads to, 6sx, 4 US findings, mx
two main forms of cardiac hepatopathy are acute cardiogenic liver injury (ACLI) (also referred as hypoxic hepatitis) and congestive hepatopathy (CH)
passive venous congestion in the setting of chronic right-sided HF; leads to sinusoidal hypertension, centrilobular fibrosis, and ultimately, cirrhosis and maybe HCC
oft asymp, but may have dull right upper quadrant pain and nausea. Other symptoms include anorexia, early satiety, and malaise. Of note, all of them may occur in the absence of overt ascites or lower extremity oedema
hepatomegaly, an irregular and nodular liver, dilation of inferior vena cava and hepatic veins with absence or attenuation of the normal variation of their diameter with respiratory movements
mx the underlying cardiac disease
enlarged liver (2x congen, 5 acquired (for last of these consider 5 things), if splenomegaly consider 4 things, if lymph nodes enlarged consider 2 things)
congenital (riedel’s lobe, polycystic liver disease (devs in adult life, cystic liver often associated with PCKD))
acquired: steatosis (fatty liver disease or poorly controlled DM), neoplasm (prim or mets), early cirrhosis, venous outflow limitation (heart failure, budd-chiari), infiltration (lymphoma, amyloidosis, glycogen storage/gaucher disease, histiocytosis, sarcoidosis)
if can feel liver see if can feel enlarged spleen, lymph nodes, any abdo masses; if spleen big too consider cirrhosis, haemat malig, amyloid, unusual infections; if lymph nodes also big consider lymphoma but could be EBV
