liver and friends :) Flashcards
if your liver was removed what would you die of
hypoglycaemia
what does the liver do
food processor - sugars fats amino acids, carbohydrate metabolism
detox/excretion - ammonia, bilirubin, cholesterol, drugs, hormones, pollutants
protein synthesis - albumin, clotting factors
defences against infection - kupfer cells (macrophages) reticulo-endothelial system
stores - glycogen, b12, iron and vit a/d
producing and secreting bile
regulates blood volume - albumin
breaking down old or damaged red blood cells
blood clotting factors
what is the unit of the liver and what does it contain
the lobule
contains - hepatocytes, central vein which feeds into hepatic vein, bile ductules, portal veins and hepatic artery, sinusoid where artery and veins join
how does cirrhosis cause oesophageal varices + splenomegaly
cirrhosis causes the liver to lose its elasticity and therefore less availability for all the blood it normally holds
causes back log to portal vein which shunts onto the OGD area and ascites and encephalopathy
the liver ends up essentially being bipassed to these other areas which causes the liver function to worsen
causes of acute and chronic liver injury
acute viral - A,B,E, EBV, CMV drug - mushrooms alc autoimmune vascular - ischaemic onstruction congestion preg - fatty liver
chronic
viral -B,C
alc
autoimmune - hepititis, primary biliary cholangitis, sclerosing cholangitis
metabolic - fat, iron, copper, the conditions
vascular - budd-chiari
drug - uncommon
acute liver syndrome
may get viral prodrome
malaise, nausea, anorexia, jaundice
rarer- confusion, bleeding, liver pain (if pres consider obstruction/malignancy), hypoglycaemia,
chronic liver disease manifestations
may have none - picked up on abnormal liver enzymes
fatigue, anorexia, wasting
itching (ductular disease)
bruising
endocrine - amenorrhoea, infertility, impotence
poor QoL
signs - clubbing, liver flap, leukonychia, palmar erythema, spider naevi/scratch marks
specifics - haematemesis - variceal bleed
ascites, oedema - portal HTN
renal failure
encephalopathy - build up of ammonia and aggravated by shunting
infection susceptibility
hepatocellular carcinoma
monitoring patients with cirrhosis:
liver failure
hepatocellular carcinoma
varices
liver failure - LFTs, (fall in serum albumin)
hepatocellular carcinoma - 6monthly USS, MRI/CT to confirm
oesophago-gastric varices: 2-3 yrly gastroscopy (can be prevented with BB)
ALSO - decide on potential for transplant
Reliable clinical signs of liver disease
> 5 spider naevi
prognostic scores in chronic liver disease
model for end-stage liver diease (MELD) - bilirubin, INR, creatinine - used to decide on transplantation
UK MELD- bilirubin, INR, creat, sodium
child-pugh - bilirubin, albumin, prothrombin time, ascites, encephalopathy (estimates cirrhosis severity)
maddrey score - for alc hepatits only, to decide if they have poor prog and benefit from steroids - bilirubin, prothrombin time
useful in predicting 1-2 year survival
serum liver enzymes and what they tell you
ALT + AST (<40U/L)- dont tell you about function mainly just the liver isnt happy, RISE means active liver cell damage or death, can also be raised by muscle or heart
Alk phos (<140U/L) - rise = bile duct damage/obstruction
Gamma-GT (<45U/L) - ductular form - usually rises in parallel with alk phos
- hepatocyte form - induced by drugs, alc
IF THERE IS DUCTULAR DISEASE there will be a parallel rise in Gamma-GT and alk phosp
clinical patterns of hepatocellular vs ductular liver injury
hepatocellular - if acute = juandice, dark urine, wont itch, ALT/AST raised
ductular - if acute = jaundice and dark urine, will itch, raised alk phos and gamma-gt
anyone with liver disease - non-invasive liver screen to find cause
viral serology - hep B + c antigen
immunology - autoantibodies - anti-mitochondrial, anti-nuclear (autoimmune hepatitis), coeliac, ASMA
immunoglobulins
biochem -
iron studies- ferritin, % iron sats,
copper - caeruloplasmin, 24hr urine copper,
alpha1 antitrypsin deficiency -phenotype
lipids, glucose
imaging - USS, CT/MRI, endoscopic - cholangiopancatography, USS
what does a haeminitc screen include
iron
b12
folate
compare pre hepatic and cholestatic (hepatic and post-hepatic) jaundice
prehepatic - unconjugated bilirubinaemia - clinically will appear normal + normal LFTs. caused by haemolysis and gilberts.
cholestatic - hepatic or post hepatic- conjugated bilirubinaemia
urine dark, male be pale stools, maybe itching, LFTs is always abnormal. hepatic causes = viral, drugs, immune, alc, ischaemia, neoplasm, congestion. post hepatic = gallstone in bile duct, mirizzi stricture - malignant, ischaemia, inflam
clinical approach to jaundice - 6 steps
- ?large duct obstruction or liver disease - scan!! USS! (if in doubt post then MRCP) cant tell from bloods, hx suggestive = rigors, biliary pain for duct ob, for hep + post-hep = dark urine, pale stools, itching?
- ?severe liver injury - ill patient? very high transaminases? coagulpathy/encephalopathy? - get help if so
- ?potential drug cause - started recently, stop/change any that might be causing it
- any other obvious cause?
- alc excess/IVDU
- viral hepatitis (contact/sexual hx, prodrome, travel)
- preg
- HF
- cancer, transplant..
- occupational - fast track the liver screen test (on another flash card) - as in phone the lab explain the worry and ask them to phone in the results as soon as they have them
- liver biopsy - specialist decision
pathogenesis of ascites in cirrhosis
three things happen in cirrhosis that link to this:
- increased intrahepatic resistance -> portal HTN -> ascites
- systemic vasodilation:
- > portal HTN etc
- > secretion of renin-angiotensin, noradrenaline, vasopressin -> fluid retention, hyponatraemia, renal failure - low serum albumin -> ascites
causes of ascites
transudate - chronic liver disease (+/- portal vein thrombosis, hepatoma), 75% cirrhosis cardiac causes nephotic - lost protein low albumin - loss of oncotic
exudate -
infection - TB, pancreatitis
neoplasia (ovary, uterus, pancreas)
ascites investigations
detectable clinically with 1500ml - shifting dullness, fluid thrill
FBC, UE, LFT, tumour markers
abdo USS - when >500ml
CT (whole abdo)
diagnostic paracentesis:
- albumin (serum-ascites albumin gradient SAAG) <11g/L transudate
>11g/L exudate
-microscopy - (for peritonitis) differential WCC, gram stain, culture
- cytology - malignant cells
ascites management + comps
fluid and salt restriction
diuretics - spiro 100-400mg/day (in cirrhosis but beware of hyperkal)
+/- furosemide 40-120mg
monitor weight (3 kg/week loss) + abdo girth
U+Es
large volume paracentesis + albumin cover
trans-jugular intrahepatic portosystemic shunt (TIPSS)
proph abx - oral cipro or norloxacin
comps
Infection (SBP) or hepatorenal syndrome
TIPSS what is it effective for what main prob not possible if
what is it
trans-jugular intrahepatic portosystemic shunt
effective for
comps of portal HTN: ascites, bleeding varcies
main prob
encephalopathy
not poss if
MELD score >18
HF
pulm HTN
Causes of coma in patients with liver disease
hepatic encephalopathy (ammonia) - infection - GI bleed - constipation - hypokalaemia drugs - sedatives, analgesics hyponatraemia hypoglycaemia intracranial event
why do patients with chronic liver disease ‘go off’ (become very unwell)
constipation
drugs - sedatives, analgesics, NSAIDs, diuretics, ACE blockers
GI bleed
infection - ascites, blood, skin, chest…
HYPO - nat, kal, glyc
alc withdrawal
other - cardiac, intracranial
what do you need to be careful with when prescribing to patients with liver disease
analgesia - sensitive to opiates, NSAIDs cause renal failure, paracetamol safest,
sedation- short-acting benzodiazepines
diuretics cause:
- excess weight loss
- hyponatraemia
- hyperkalaemia
- renal failure
antihypertensives:
- can often stop
- avoid ACE inhibs -renal failre
aminoglycosides - avoid
rules when managing liver patients
- THINK SEPSIS
blood culture, ascitic fluid taps, fluid resus, prompt abx
look for sites of infection - ascites, chest, urine, skin, brain, heart - U+E
very common to get hypos in kal, natr, magn, phosph, glyc, bicarb (met acid)
monitor and CHASE results - READ THEIR RECORDS -
HBV/HCV?
have a label of cirrhosis but no biopsy
diuretic intolerance - management of ceiling decisions - critical care, transplant, DNAR?
hepatocellular carcinoma
arterial flush, venous washout
what individual tests are a part of an LFT
total protein albumin globulin bilirubin ALT ALP
what cells are ALT + AST found in
hepatocytes
what other cells in the body contain AST
muscle, heart, kidney
what liver cells are ALP + GGT found in
ALP - cells lining the bile duct
GGT - endoplasmic reticulum of all cells except muscle. Mainly membrane bound.
what other cells in the body contain ALP - how do you know its from liver?
bone
intestine
placenta
if elevated with GGT then it will be liver if it was from bone then GGT would stay low
raised in bone when things like osteomalacia
what is unconjugated bilirubin
produced from breakdown of red blood cells bilirubin is water insoluble travels in blood bound to albumin pre-hepatic - haemolysis hepatic - gilberts
what is conjugated bilirubin
is what soluable by conjugation with glucuronic acid in the liver
excreted from the liver via the biliary tract to the small intestine
drugs that damage the liver
paracetamol/analgesics
methotrexate
amiodarone
abx - isoniazid, co-amox, fluclox, erythro
statins
dietry drugs - herbs
CNS drugs - chlorpromazine, carbamazepine, valporate, paroxetine
MULTIPLE COMBO?
LFTs are bad marker for liver function (lol ironic!!) - so what is?
INR
Prothrombin time
pathophys + causes of cholestasis and what you would see in LFTs
pathophys
Bile is secreted by hepatocytes and stored/concentrated in GB. In cholestasis bile cannot flow from the GB to the duodenum. This leads to retention of conjugated bilirubin and regurg to serum, increased serum concentration of unconjugated bilirubin, increased bile salts
CAUSES intrahepatic - hepatitis - primary biliary cholangitis - drugs - preg
extrahepatic
- stones + strictures
- ca head of panc
- portal hepatic LN mets
- sclerosing cholangitis
LFTS
elevation in ALP GGT +/- bilirubin
causes of cirrhosis and what you would see in LFTs
chronic alc excess
persistent Hep B or C
autoimmune
inherited metabolic - haemochromatosis, A1AT def, wilsons
LFTs
hypoalbuminaemia
prolonged PT
which LFT is specific for the liver
ALT - not found much else where
L for liver!!
GGT where is it found in body
things that make it go up
kidneys
pancreas
heart
brain
things that make it go up alc - just drinking fatty liver/ insulin resistance/ obesity enzyme inducing drugs - anticonvulsant - CBZ, phenytoin, phenobarb - warfarin - OCP
what levels of bilirubin causes clinical jaundice
50 umol/L
what causes decompensation of liver disease?
dejwdw
what raises globulin
autoimmune
anything that raises immunoglobulins
so would want to test ANA antibodies, antimitochondrial, anti smooth muscle
when are anti-mitochondrial antibodies seen
95% of primary biliary cholangitis cases
also in RA
explain the liver circulation
hepatic artery from the aorta supplies oxygenated blood. 25% of blood supply
it also receives blood from intestines, spleen and stomach that is deoxygenated on their way back to the heart in the portal vein, that is full of nutrients - 75% of blood supply
all this blood leaves the liver in the hepatic vein -> IVC
anatomy of the liver - ?lobes
4 lobes - 2 major ones
what is included in the portal triads
portal vein
bile duct
hepatic artery - IN
central vein in middle of lobule - OUT
what shape is a lobule
draw a full lobule
hexagon
google it love
what do these AST-ALT ratios indicate?
1
>25
<1
1 - ischaemia
>25 - alcoholic hepatitis
<1 - hepatocellular damage eg paracetamol OD
3 metabolic causes of liver disease
- hereditary haemochromatosis - deficiency of iron reg hormone hepcidin
- wilsons disease - hepatolenticular degeneration - accumulation of copper at tissues
- alpha-1 antitrypsin deficiency - affects liver and lungs (emphysema)
what is hepcidin + function
Hepcidin is produced by hepatocytes in response to high iron levels. It blocks iron absorption by blocking ferroportin at enterocytes and reduces iron exit from liver and macrophages (storage sites) in same way
what does transferrin do
Binds iron reversibly in blood
what is ferritin + function
Stores iron intracellularly, an acute phase protein
hereditary haemochromatosis inheritance patho genes epi pres ix mgmt comps
inheritance
AR
patho
Increased intestinal absorption of iron leading to accumulation in tissues: liver (fibrosis, cirrhosis, HCC), heart, skin, joints (arthropathy), pancreas (diabetes)
genes
HFE gene chromosome 6: most common C282Y (or H63D)
epi
40-50 yr old
pres
Early: fatigue, weakness, arthralgia, erectile dysfunction/amenorrhoea
Late: skin bronzing, diabetes, cirrhosis (liver signs), impotence, cardiac arrhythmia, arthropathy 2nd and 3rd metacarpophalangeal joints
ix
Iron studies
- Serum ferritin (high) - lots of iron in cells - low specificity as acute phase protein (so goes up with any inflam)
- Transferrin saturation (>45%) - lots of iron in blood specific
HFE genetic testing
LFTs
MRI - iron overloaded liver
Liver biopsy with Perl’s stain (blue)
*Liver fibroscan/transient elastography
ECG/ECHO for cardiomyopathy
Tests for other causes of hyperferritinaemia e.g. inflammation (CRP), alcohol, metabolic syndrome (BP, BMI, glucose, triglycerides)
mgmt Venesection/phlebotomy 4-500ml weekly desferrioxamine may be used second-line Liver transplant at decompensation of liver Monitor ferritin - <1mg/L = risk of serious liver damage <1% Low iron diet avoid alc genetic counselling
comps type 1 diabetes - iron build up in panc liver cirrhosis iron build up in pituitary + gonads = hypogonadism, impotence, amenorrhoea, infert cardiomyopathy hepatocellular carcinoma hypothyroidism chrondocalcinosis/pseudogout
what is an ERCP (+comps) and MRCP? what is the difference?
ERCP - endoscopic retrograde cholangiopancreatography - uses scope and dye, can intervention at the time, cant see past obstruction, comps = pancreatitis, bleeding, failure
MRCP - magnetic resonance cholangiopancreatography
gallstones RF classification pres mgmt
rf - female, fat, fertile , fair + forty
+ fh, oral contraception, hyperlipidaemia
classification CHOLESTEROL (ileum absorbs bile salts): - 80% of stones in UK - large, solitary, radiolucent - admirands triangle (1. Decreased dietary lecithin, 2. Decreased bile salts (impaired flow), 3. Increased cholesterol saturation of bile/loss of bile salts (ileal resection/Crohn’s)
PIGMENT stones 10%
- black calcium bilirubinate + mucin
- glycoproteins
- small friable, radiolucent
- result of haemo conds
- brown calcium bilirubinate + fatty acids
- result of stasis and biliary infection e.coli/klebsiella
MIXED stones 10%
- faceted - calcium salts + pigment + cholesterol
pres
as biliary colic or acute cholecystitis
mgmt
gallbladder - lapro cholescystectomy or bile acid dissolution therapy <1/3 success
bile duct stones - ERCP with sphincterotomy and: remove, crushing or stent placement. or surgery (large stones)
compare the presentation of gallstones in the gallbladder and bile duct
gallbladder:
biliary pain
cholecystitis
obstructive jaundice - maybe mirizzi
bile duct: biliary pain obstructive jaundice cholangitis pancreatitis
what is mirizzis syndrome?
Mirizzi’s syndrome is a rare complication in which a gallstone becomes impacted in the cystic duct or neck of the gallbladder causing compression of the common hepatic duct, resulting in obstruction and jaundice. The obstructive jaundice can be caused by direct extrinsic compression by the stone or from fibrosis caused by chronic cholecystitis (inflammation). A cholecystocholedochal fistula can occur
types drug induced liver injury
hepatocellular
cholestatic
mixed
steatosis
progression from normal to liver decompensation
why are liver patients vulnerable to infection and common sites
reasons: impaired reticulo-endothelial function reduced opsonic activity leucocyte function permeable gut wall
sites: spont bacterial peritonitis septicaemia pneumonia skin urinary tract
spontaneous bacterial peritonitis what is it pres ix mgmt prog
what is it
intra-abdo sepsis
pres - vague symps fever mild abdo pain vom triad of peritonism: gaurding, rebound tenderness, pain on palpation
ix diagnostic paracentesis - culture + amylase - neuts in ascitic fluid >250 cells/ul - gram stain ascitic fluid often gram neg (e.coli, enterococcus)- use blood culture bottles FBC - leukocytosis LFTs U+E imaging?
mx
abx proph - IV 3rd gen cephalosporins eg cefotaxime
liver transplant
prog
50% chance of death in 1 year - liver transplant asap
causes of renal failure in liver disease
drugs - diuretics, NSAIDs, ACEi, aminoglycosides
infection
GI bleeds
myoglobinuria
renal tract obstruction
beside tests for encephalopathy
subtract 7 from 100 and continue
WORLD backwards
how many animals can you count in a minute
draw 5 point start
number connection test (dot to dot basically)
consequences of liver dysfunction + mgmt of these
malnutrition - NG tube
coagulopathy - impaired coagulation factor synthesis, vit k deficiency (cholestasis), thrombocytopenia
variceal bleeding - endoscopic banding, propanolol, terlipressin
endocrine - gynaecomastia, impotence, amenorrhoea
hyperglycaemia (+/-)
encephalopathy - lactulose
ascites/oedema - salt/fluid restriction, diuretics, paracentesis
infections - proph abx
key points in a liver history
pmh - alc probs, biliary surgery, autoimmune disease, blood products
social - alc, sex, contacts, travel, IVDU
DH - all review
ddx for hepatitis (hepatocellular damage picture on LFTs)
viral - A,B,C, CMV, EBV
drug-induced
autoimmune
alcoholic
draw a table and fill this out for autoimmune hepatitis, primary biliary cholangitis and primary sclerosis cholangitis: which raised gobulin autoantibody present other autoimmune disease? female:male familial risk genetics response to IS therapy
AIH IgG antinuclear, anti sm, liver-kidney microsome 41% have other AI - various 4:1 familial - 5x risk HLA DRB1 0301/0401 response to IS - good
PBC IgM antimitochondrial 33% various 10:1 10x HLA D8 limited
PSC variable antineutrophil cytoplasmic (ANCA) 70% - mainly colitis 0.6:1 9-39 x HLA class I (b) response to IS therapy - little
if unsure on diagnosis + scan what can you do
liver biopsy
prognostic score for PBC
mayo clinic
uses bilirubin, albumin, PT time
treatment of cholestatic itch + fatigue in PBC
Ursodeoxycholic Acid - antihistamines (little help)
cholestyramine - 50% helps
rifampicin is effective - occasionally damages liver :/
opioid antagonists
UV light, plasmapheresis, liver transplant
FATIGUE - check for any other causes and correct
modafinil
alpha 1 antitrypsin deficiency inhertiance mech genes onset features ix mgmt comps
inheritance
AR
mech
A1AT is a glycoprotein produced in the liver. It is a serine protease inhibitor and controls inflammatory cascades and balances the action of neutrophil elastase in the lung (cigs/inflammation). NE will break down elastin leading to alveolar destruction. In A1ATd an abnormal protein is produced which cannot leave, congests in liver cells and causes destruction.
genes
SERPINA1 gene chromosome 14. M alleles are normal variant. MS or MZ are carriers.
onset
lung disease in 30/40s
pres
jaundice baby
young person with COPD - dyspnoea, wheeze, cough, emphysema typically in lower lobes
hepatits, cirrhosis (HCC), fibrosis
ix
serum A1AT low -> phenotyping
CXR + spirometry - obstructive
LFT + biopsy liver - shows cirrhosis + acid-Schiff-positive staining globules in hepatocytes
mgmt asymp - smoking and alc advise lung symps - as COPD liver - reg LFTs, rx cirrhosis, screen for HCC transplants
comps
hepatocellular carcinoma
hepatic vein occlusion
causes
pres
mgmt
causes thrombosis (budd-chiari) membrane obstruction veno-occlusive disease (irradiation, antineoplastic drugs) congestion causes acute + chronic
pres
abnormal liver tests, ascites, acute liver failure
mgmt
anticoag
transjugular intrahepatic portosystemic shunt
liver transplant
timeline of acute -> chronic liver
acute <12w
chronic >12w
classification of acute liver disease + common causes of each
O-Gradey
jaundice to enceph time
hyperacute - <7 days (best prog) - paracetamol, drugs, ?viral
acute 8-28 days - viral, ischaemic
sub acute: 29 days - 12 weeks (worst prog) - seroneg hepatitis (aka unknown), autoimmune
most common cause for ALF in UK and developing
UK - paracetamol
develop - viral hep (most common worldwide E)
highest risk factors for hepatocellular damage with paracetamol overdose
staggered alc malnutrition HIV, cancer chronic liver disease takes liver enzyme inducers (antiepileptic, rifampicin, spironolactone)
paracetamol overdose mgmt
IV NAC - check above treatment line in curve graph in BNF
IV crystalloids 100-250mls/hr
IV broad spec abx/antifungals (INR>2.5) - as at high risk of infections
call liver transplant centre - each day post overdose there is criteria for referral you can check
when testing for HBV, when sending for request what do you have to be careful of
the surface antigen takes 3 months to get back !!
send for HBV C IgM in acute setting or HBV DNA test
bile
what is it
define bile acids + secondary bile acids
function
bile = bile acids + phospholipids + cholesterol bile acids = cholic acid + chenodeoxycholic acid form by cholesterol liver metabolism secondary bile acids = bacterial metabolites of bile acid formed in colon function = fat digestion. absorption of fat, cholesterol and fat soluable vitamins - A,E,D,K. bole forms micelles - binds to fat/cholesterol and aids absorption through micellar transport system
what does lithiasis mean
stone
eg cholelithiasis = gall stones
choledocal-lithiasis = bile duct stone
signs of cholestasis
jaundice itch - resistant to antihistamines RUQ pain - intermittent colic or painless acute or chronic dark urine pale/white stool that floats as not absorbing fats weight loss lethargy anorexia
management of gallstones
laproscopic cholecystectomy
if not suitable for surg -
- ursodeoxycholic acid - dissolve over 2 years <50%
acute cholecystitis what is it pres ix mgmt comps
inflammation of gallbladder due to retained bile
gallstones obstruction
trauma
pres
biliary pain thats progressive -> right shoulder
sepsis signs - fever, vom, local peritonism
GB mass
history of prev attacks
MURPHYS sign = acute cholecystitis (2 fingers, breathe in, halts inspiration, negative on other side), NO? = biliary colic
ix raised WCC + CRP bil and alk phos could be high USS - thick walled tender GB (>3mm) with stones \+ fluid or air in gall bladder CBD dilatation - ?MRI (>6mm) ?ERCP/MRCP
mx
lap cholecystectomy
conservative = abx
comps
gangrene - perf, abscess
empyema
chronic cholecystitis - repeat attacks of cholecystitis, more likely to be fat intolerant
cholangitis
hydrops
porcelain gall bladder - increased risk of ca
biliary colic/acute cholecystitis differentials
pancreatitis appendicitis peptic ulcer disease liver abscess pneumonia MI perf bowel - DU
choledocolithiasis + cholangitis
what is it
ddx
mx
ddx
cancer ?painless/low grade - panc, bile duct, gall bladder, metastatic
liver disease
mx
ERCP - remove stone
Lap - chole +/- intraoperative cholangiogram
IV abx - e.coli - co-amox
primary sclerosing cholangitis what is it epi assoc pres severity ix mgmt comps poor outcome factors
chronic diffuse inflam
+ fibrosis of intra + extrahepatic bile ducts leading to multifocal biliary strictures
small
epi
men>w
assoc
risks - UC in 80%, increased risk of colon cancer - yrly colonoscopy
HCC
pres Asymptomatic + abnormal LFT hepatomegaly Jaundice/pruritus RUQ pain Fever, wt loss, fatigue, sweats
severity
childs-pugh - BRAIN
ix
difficult differential - MRCP (shows beaded appearance), liver biopsy - perductal onion skin fibrosis, Degeneration of ducts + ductal + periportal triad inflammatory cell infiltrate and scarring leading to disappearance of bile ducts and periportal cholestasis
Bloods - LFTs (elevated alk phos, ggt, raised trans)
raised immunos - IgG, IgM, hypergammaglobulnaemia, autoantibodies: p-ANCA
mgmt acute bact - ?cipro chronic - dominant stricture = balloon dilate or ?resect - cholangio urso reduce CRC yearly surveillance pruritic? cholestyramine if cholestatic - supplement diet with DEAK fat soluble vits avoid alc liver transplant if cirrhotic
comps
cholangiocarcinoma, gallstones, GB polyps/cancer
colorectal cancer
cirrhotic liver
prog 12-17
poor outcome factors: age bilirubin albumin varices dom stricture extra hepatic changes
benign biliary stricture
causes
mx
surgery/injury panc gallstone intervention cholangitis mx ERCP - dilation or removable metal or plastic stents
biliary dyskinesia
like biliary colic but without any gallstones chronic acalculus cholecystitis women >50 RUQ after fatty foods HIDA scan helpful
treat with lap chole (85% cure)
path chronic cholecystitis
systematic approach to AXR
- projection - standard is AP with patient supine
- patient details + date of film
- technical adequacy - entire abdomen? includes hemidiaphragms to symphysis pubis/hernial orifices
- obvious abnormalities
- systematic review
A - assess the bowel:
large bowel - diameter <6cm large bowel <9cm caecum + wall thickness
small - diameter <3cm + wall thickness
(should be hard to see if theyre normal)
B - check for pneumoperitoneum - riglers, subdiaphragmatic, visible falciform ligament, triangular lucent areas, hyperlucency of the liver, football sign
C - obvious abnormality of liver, gallbladder, spleen eg radio-opaque gallstones
D - assess renal tract - ?calculi
E - vascular structures - aorta, iliac vessels - vascular calcification, aneurysm
F - assesses imaged skeleton
G - comment on iatrogenic abnormalities - surgical clips, stents
summary - present findings, review previous imaging, provides differentials, suggest further approp ix or mgmt
when is an AXR indicated and why?
bowel obstruction, perf, exclusion of toxic megacolon
much higher amounts of radiation than CXR and really cant see a lot
acute pancreatitis patho causes pres classification diagnosis ix severity criteria mgmt comps
patho
inflam process with cascade release of inflam cytokines (TNF alpha, IL2, IL4) and pancreatic enzymes (trypsin/lipase etc) causing autodigestion of organ.
gallstones block bile duct, back log in panc duct, periductal necrosis
causes -GET SMASHED Gallstones - most likely in women Ethanol - most likely in men Trauma Steroids Mumps Autoimmune Scorpion sting - trindiad hyperlipidaemia, hypotherm, hypercalc ERCP Drugs - azathiprine, diuretics, NSAIDs
pres
severe epigastric pain radiating to back relieved by sitting
anorexia
n + v
fever, dehydration, hypotension, tachy - SEPTIC SHOCK
abdominal guarding
1-3% have haemorrhagic panc - grey-turners sign - left flank ecchymosis, cullens sign periumbilical ecchymosis
abdo rigidity
classification
- oedematous -70% - phlegmon formation + multiple transient fluid collections
- severe/necrotising - 25% - sterile or infected, pseudocyst formation (periductal or perilobular)
- haemorrhagic 5%
diagnosis
2/3 hx (pain), amylase x3 of normal (+raised lipase, more panc specific), imaging (CT) pathology (loss of fat planes/panc oedema and swelling +/- fluid loculations)
ix ABG FBC - leukocytosis CRP >200 = necrosis LFT AST:ALT >3, raised bili hypocalc hyperglyc U+E - raised urea plain erect AXR - panc calcification CXR - exclude perf, ?ARDS CT with contrast - diagnostic USS - swollen pan + glasstones ERCP?
severity three main scoring tools: abbreviated glasgow scoring system >3 = ITU/anaesthetic review: PANCREAS P=pa02 <8kpa Age = >55 yrs Neutrophils >15x10-9 calc <2mmol/l raised urea >15mmol/l elevated enzymes LDH >200IU/l or AST>600IU/l albumin <32g/l sugar - serum glucose >15mmol/l
ranson criteria
balthazar score - CT severity index score
mgmt
pain control - pethidine or buprenorphine ± IV benzodiazepines (morphine spasms ampulla)
ABCDE
IV fluids, catheterise
severe - insulin, calcium correct, no abx unless culture postive/cholangitis (usually cef/met if +)
TP nutrition - NBM + NG tube >48hrs for gut rest + antiemetics
observes for internal necrosis (pancreas dissolving
gallstones out <2w after discharge - 18% remission
comps SIRS - systemic inflam response syndrome Pro-inflammatory state that does not include a documented source of infection. two or more of: temp <36 or >38 hr >90 rr >20 WCC >12x10-9 MODS - Multiple Organ Dysfunction Syndrome (MODS) Sequalae of above causing loss of body homeostatic mechanisms panc necrosis panc abscess ascites pulm oedema shock death
chronic panc def causes ddx types pres ix mgmt comps
irreversible fibrosis following necrosis of panc paranchyma - calc + dilation of ducts
abnormal bicarb excretion
causes alc!!! can cause chronic panc directly smoking meds - aza, tetracy, oestrogens idiopathic/tropical AD CF autoimmune (IgG4) - japan (may also have raised ANA, RF) - reversible + steroid responsive hypercalc - PTH
ddx
carcinoma of panc
types
large duct = dilatation and dysfunction of large ducts + diffuse calc + steatorrhoea - men
small = no calc or steat, women
pres
episodes of exacerbation or cont pain
still epigastric radiating to back relieved by sitting forward
n +v
anorexia
exocrine dysfunction - malabsorption with weight loss, diarrhoea, steatorrhoea and protein deficiency
endocrine dysfunction - diabetes
ix
Bloods: FBC, U+E, Cr, LFT, Ca (cause), amylase (normal), glucose, HBa1C (raised)
Secretin stimulation test: causes pancreas to release bicarb to neutralise stomach acid -> +ve result if over 60% exocrine function lost
Malabsorption tests: serum trypsinogen/faecal elastase
Imaging:
CT for atrophy, duct dilatation or calcification
MRCP (magnetic retrograde cholangiopancreatography)
?Endoscopic ultrasound
mgmt
Manage pain and malabsorption
Pain - simple + opiate (normally tramadol) - risks opioid dependence and gastroparesis
Malabsorption - replace pancreatic enzymes
+ Alcohol advice + low fat diet/gallstones treatment/diabetes treatment
comps pain - local inflam/duct obstruction with stones bile duct stricture nutrition endocrine - diabetes cancer
autoimmune pancreatitis - IgG4
panc cancer
survival
5 year survival 3%
what is painless jaundice a major red flag for
panc cancer
it gets missed cos people have USS and cant see panc well on USS cos of stuff in the way eg stomach that has gas in it.
wilson's disease inheritance mech genes onset features ix mgmt
AR
mech
disorder of biliary excretion of copper
Wilson’s ATP-ase normally moves copper across cell membranes in hepatocytes leading to incorporation into caeruloplasmin. This is deficient in Wilson’s leading to copper retention in liver and basal ganglia.
genes
ATP7B gene on chromosome 13
onset - young adult with liver abnormalities or movement disorders
features
LIVER - acute liver failure, chronic hepatitis + cirrhosis @ younger
PSYCH - severe dep 50%
NEURO - asymmetrical tremor, ataxia, mask-like faces, clumsiness, excess salivation, dysarthria (speech probs), choreiform movement - parkinsonian @older
OPTHALMOLOGICAL - kayser-fleischer ring 95% + sunflower cataracts
OTHER - haemolytic anaemia, renal tubular acidosis, oesteopenia, blue nails
ix copper-studies - low serum caeruloplasmin, high 24 hour urine copper excretion, high free copper slit-lamp - opth liver biopsy - copper MRI head - density at basal gang
mgmt
chelation agents - penicillamine (oral) or trientine - binds to copper for excretion in urine
zinc compounds - stop absorption of copper
avoid - mushrooms, liver, choco, nuts
monitor hepatic + renal fucntions, FBC + clotting
avoid alc + hepatotoxic drugs
liver failure when 4 characteristics + why classification causes ix gen mgmt
when
This occurs when liver loses the ability to regenerate.
4 characteristics + why:
- hepatic encephalopathy - In liver failure ammonia builds up in circulation and crosses BBB. Astrocytes clear this turning glutamate to glutamine. Glutamine excess causes fluid shift to cells -> cerebral oedema.
Altered mood, drowsiness, restless, coma - jaundice - build up of unconjugated bilirubin
- abnormal bleeding - factor 1972 (10, 9, 7, 2 with vit k) fibrinogen (factor 1)
- ascites - shifting dullness, fluid thrill, hypoalbuminaemia
ix FBC - thrombocytopenia LFTs bilirubin ammonia glucose - low copper studies paracetamol/tox creatinine PT/INR blood cultures - susceptible to infection - sepssi leading cause of death viral serology - ABCE, EBV, CMV doppler USS -ascites, occluded hepatic vein ?budd chiari ?CT/MRI ?CT head
gen mgmt consider transplant early - scores - MELD / UK MELD child-pugh - BRAIN B = bilirubin high R = refractory ascites A = albumin low <28 INR = >1.7 eNcephalopathy A = <7, B = 7-9, C = >9 specific management for cause: paracet = NAC ammonia = lactulose + neomycin raised ICP = IV mannitol AKI - haemodialysis bleeding - FFP, platelets, IV vit K
comps
infection/sepsis - spont bact peritonitis, pneumonia
cerebral oedema
haemorrhage from oesophageal varices
hepatic encephalopathy when precipitants features grading ix mgmt
when
50% of patients with cirrhosis
feature of decompensated cirrhosis
precipitants AKI infection constipation sedatives diuretics GI bleed TIPPS
features
confusion, altered GCS (see below)
asterix: ‘liver flap’, arrhythmic negative myoclonus with a frequency of 3-5 Hz
constructional apraxia: inability to draw a 5-pointed star
grading
0 - minimal changes in memory/intelligence
1 - irritable, change in mood
2 - confusion, drowsiness, gross deficits in mental ability, inappropriate behaviour
3 - somnolent but rousable, unable to perform mental tasks, marked confusion, occasional fits
4 - coma
ix
arterial/serum ammonia
EEG - triphasic waves
MRI/CT for other causes of encephalopathy
mgmt
avoid sedatives + diagnose early
decrease nitrogen load - lactulose removes nitrogen from gut
neomycin - abx lowers nitrogen forming gut bacteria
rifaximin - given as secondary prophylaxis of hepatic encephalopathy
hepatorenal syndrome
what is it
criteria
mgmt
what is it
A complication of end-stage liver disease (40%) e.g. cirrhosis with ascites and acute liver failure
Impaired renal function often precipitated by events lowering BP spotted by juxtaglomerular apparatus e.g. spontaneous bacterial peritonitis, GI bleed, pneumonia. Splanchnic vasodilation drops BP, activates SNS and RAAS, which causes renal vasoconstriction but not enough to counterbalance effects of splanchnic vasodilation
criteria - diagnosis of exclusion
Cirrhosis with ascites, Cr > 133 micromol, no shock, no hypovolaemia, no nephrotoxics
mgmt
General:
Admit to HDU + monitor fluids (urine output), treat infections + stop nephrotoxics/diuretics
Specific:
Splanchnic vasoconstrictors e.g. terlipressin with albumin - increases blood pressure and GFR + TIPS (transjugular intrahepatic shunt) - reduces ascites in portal HTN
cirrhosis def patho causes rf pres ix classification mgmt comps
def diffuse hepatic process characterised by fibrosis + conversion of normal liver architecture to nodules. final histological pathway for wide variety of liver pathology. can cause increased resistance in vessels = portal HTN
patho
Cytokines activate stellate cells at space of disse
Normal matrix replaced by collagen and fibronectin
Loss of fenestration/sinusoid and impaired function
causes
Common: alcohol, hep B/C, NAFLD and NASH - non-alcoholic fatty liver/steatohepatitis
rf
Alcohol, hepatitis, older age, obesity, T2DM
pres
occurs when 80% of parenchyma destroyed so may be asymp (40%)
vague - fatigue, anorexia, nausea, weight loss
if decompensated - oedema, ascites, brusing, poor mem, bleeding, SBP
clinical signs - FLAPS - finger clubbing, leukonychia, asterixis, palmar erythema, spider naevi, scratch, + jaundice, dupuytren’s contracture
OTHERS - hepatomeg, gynaecomastia (increased production androstenedione by adrenals and conversion to oestrogen), hypogonadism (toxicity of alcohol/iron)
ix
LFT
albumin - low
FBC - ?anaemia ?low platelets (hypersplenism), macrocytosis (alc)
U+E - hepatorenal syndrome
coag screen
ferritin
viral screen - B/C
NASH - Fasting glucose, insulin, triglycerides and uric acid levels
met - A1AT level, caeruloplasmin, urinary copper, fasting transferrin saturation
AAb screen - AMa
image - USS, CXR
GOLD STANDARD - biopsy - histology - loss of hepatic archiecture, bridging fibrosis, nodular regeneration or Fibroscan - transient elastography and acoustic radiation force impulse imaging - measures stiffness of liver
classification
child-pugh for cirrhosis - BRAIN = 5-6 A, 15-20 yr life expectancy, 7-9 B 4-14 yr, 10-15 C 1-3 yrs
MELD
mgmt delay progression, treat cause + comps adequate nutrition no alc review meds vaccinate for hep A, flu, penumococcal transplant
monitoring oesophageal varices + HCC alpha-fetoprotein - tumour marker for hepatocellular carcinoma and should be checked every 6 months as screening with USS. high protein low sodium diet MELD every 6 months consider liver transplant
comps
Malnutrition
Portal Hypertension, Varices and Variceal Bleeding
Ascites and Spontaneous Bacterial Peritonitis (SBP)
Hepato-renal Syndrome
Hepatic Encephalopathy
Hepatocellular Carcinoma
portal HTN what is it causes pathophys effect on circulation signs ix mgmt comps
what is it
Abnormally high pressure in hepatic portal vein (significant if hepatic venous pressure gradient >10mmHg)
causes
PREHEP - Portal vein thrombosis, splenic vein thrombosis, extrinsic compression e.g. tumour
HEP - Cirrhosis, hepatitis, schistosomiasis, granuloma (sarcoid)
POSTHEPATIC - Budd-Chiari, RHF/CHF, constrictive pericarditis
pathophys
PHTN from increased vascular resistance/increased blood flow
Raised pressure opens venous collaterals connecting portal to systemic system:
- Gastro-oesophago junction
- Anterior abdominal wall via umbilical vein (caput medusae)
- Anorectal junction
- Retroperitoneum
- ileocaecal junction
Portosystemic shunts may cause encephalopathy due to toxins bypassing liver
effect on circ
PHTN and cirrhosis produce hyperdynamic circulation (bounding pulse, low BP): splanchnic vasodilatation, increased cardiac output, arterial hypotension and hypervolaemia
There is salt and water retention, ascites and hyponatraemia
signs
Ascites, splenomegaly, dilated umbilical veins
*Haematemesis/melaena -> bleeding varices
Signs of cirrhosis/liver failure
ix AUSS for liver/spleen/ascites Doppler ultrasound - blood flows Spiral CT for portal vasculature Endoscopy for oesophageal varices Portal pressure by hepatic venous pressure gradient (normal < 5, varices > 10)
mgmt
Treat cause ± liver transplantation
Reduce portal venous pressure (beta blockers ± nitrates or shunts TIPS)
Non specific beta blockers e.g. carvedilol
TIPS for ascites, or refractory oesophageal varices or gastric varices
comps
Varices bleeding
Ascites complications (SBP, hepatorenal)
Pulmonary complications (portopulmonary hypertension, hepatopulmonary syndrome: hepatic dysfunction, hypoxaemia and extreme vasodilation)
budd-chiari syndrome what is it association pres ix mgmt
what is it
rare syndrome with obstruction of hepatic veins
association
genetic
myeloproliferative disorders (+hypercoagulable state, TB, tumour)
pres
sudden RUQ pain + rapidly developing ascites + hepatomegaly + jaundice + renal involvement (50%)
ix
doppler USS
mgmt
treat cause
if associated with chronic inferior vena cava thrombosis begin warfarin, treat ascites e.g. TIPS
liver cancer types causes pres screening diagnosing/ix mgmt prog prevention
types
10% are primary, 90% are secondary cancers (stomach, colon, lung, breast)
80% of primary are HCC, 20% are cholangiocarcinoma (flukes, PSC, biliary cysts, early jaundice)
70-90% have chronic liver disease
causes
90-95% of HCC patients have cirrhosis
Worldwide - HBV, Europe - HCV (5% annual risk)
Alcoholism, HH, PBC, metabolic syndrome
pres
Anorexia, wt loss, night sweats, RUQ pain + symptoms of liver disease/cirrhosis/failure
cholangiocarcinoma - presents with painless jaundice - similar to panc cancer
screening
Screen high risk i.e. HBV ± cirrhosis and HCV/alcoholic cirrhosis
6-12 monthly USS + AFP (alpha fetoprotein levels >400 n.b. If <4cm may be normal)
diagnosis
Focal liver lesion in someone with cirrhosis
>2cm mass on USS + Alpha FetoProtein raised in HCC, CA19-9 in cholangiocarcinoma
CT/MRI for staging
ix
LFT consistent cirrhosis,
clotting abnormalities,
low albumin,
CXR for raised right hemidiaphragm/lung mets
For cholangiocarcinoma - GB biopsy with ERCP
mgmt
Treat complications of cirrhosis or liver failure
Surgical resection (appropriate if no cirrhosis), ablation (e.g. alcohol injection, radiofrequency ablation), systemic chemotherapy (HCC relatively chemo resistant), liver transplant (sometimes), kinase inhibitors - sorafenib
prognosis
Median survival is 6 months, if early stage then 5 year survival can be 50%
Death from cachexia, variceal bleeding
prevention
HBV vaccine,
reduced alcohol,
screen those with cirrhosis
alcohol metabolism
alcohol converted to acetaldehyde by alcohol dehydrogrenase. this increases NADH and causes lipid peroxidation. NADH increase causes oxidative stress and lipogenesis. lipogenesis inhibits gluconeogensis and causes fatty liver.
Oxidative stress and lipid peroxidation lead to hepatocyte injury and impair carb and protein metabolism
Increasing NADH:NAD ratio leads to increased hepatic fatty acid synthesis with decreased oxidation
steatosis/steatohepatitis (NAFLD/NASH) def categories pathophys aetiology epidemiology pres diagnosis initial ix mgmt comps AST:ALT ratio
def Accumulation of fat in the liver. If this is associated with inflammation it is called steatohepatitis (or NASH - non-alcoholic steatohepatitis)
categories
alcohol-related fatty liver disease and non-alcoholic fatty liver disease. its alcohol when their consumption is more than >2U/day w and >3U/day men
pathophys
Accumulation of triglycerides and lipids in hepatocytes
Result of defective fatty acid metabolism, excess intake, mitochondrial damage (alcohol)
RF obesity poor diet/low activity levels T2DM high cholesterol middle age smoking high blood pressure
causes metabolic syndrome PCOS alcohol excess starvation HBV/HCV metabolic disorders - wilsons medication - amiodarone, tamoxifen, glucocorticoids, methotrexate
epi
NAFLD - 20%
NASH - 5%
fatty liver in 90% of heavy alcohol users
pres
steatosis - asymp (some potentially hav fatigue/RUQ pain)
advanced - symps of cirrhosis - ascites, oedema, jaundice
hepatomeg
diagnosis
biopsy - cells swollen with fat - steatosis at zone 3, in steatohepatitis + inflammation ie mononuclear cell infiltrate, centrilobular hepatocyte necrosis and mallory bodies (dense eosinophilic cytoplasmic inclusions)
initial ix
USS - echogenic liver
ELF - enhanced liver fibrosis blood test - not always available
bloods for cause (baso non-invasive liver screen):
- LFTs - ALT>AST, rasied GGT if alc, 50% normal
FBC - macrocytosis in alc
fasting lipids, fasting glucose - metabolic syndrome
viral serology
caeruloplasmin + iron studies
autoimmune- ANA, ASMA raised in NASH
NALFD fibrosis score
fibroscan
mgmt abstinence from alc diet - high protein weight loss reg exercise + control co-morb eg BP, diabetes, lipids treat cause refer hepatologist if failure/cirrhotic
comps
progression to cirrhosis, liver failure, HCC
AST:ALT Ratios
In steatosis ratio is <1
In alcoholic liver disease ratio is >2 (but ALT > 500IU/L -> other cause)
name two benign cancers of the liver
haemangioma
focal nodular hyperplasia
alcoholic hepatitis triad
fever
mallory bodies
steatosis
metabolic syndrome
what is it
features
associations
group of chronic health conditions relating to processing and storing energy that increase risk of heart disease, stroke and diabetes.
features
obesity
abnormal glucose tolerance
dyslipidaemia
associations
NAFLD
stages of NAFLD
- Non-alcoholic Fatty Liver Disease
- Non-Alcoholic Steatohepatitis (NASH)
- Fibrosis
- Cirrhosis
name the autoantibodies to check in a non-invasive liver screen
Antinuclear antibodies (ANA) Smooth muscle antibodies (SMA) Antimitochondrial antibodies (AMA) Antibodies to liver kidney microsome type-1 (LKM-1)
alcoholic fatty liver disease stepwise progression recommended units + how to work them out screening questions comps of alc signs ix gen mgmt
stepwise
alcohol related fatty liver
alcoholic hepatitis
cirrhosis
unit
14 units/w m + w - spread evenly over 3 or more days and not more than 5 units in a day.
volume x percent of alc / 1000
screening qs
CAGE
C – CUT DOWN? Ever thought you should?
A – ANNOYED? Do you get annoyed at others commenting on your drinking?
G – GUILTY? Ever feel guilty about drinking?
E – EYE OPENER? Ever drink in the morning to help your hangover/nerves?
AUDIT - alcohol use disorders identification test
comps Alcoholic Liver Disease Cirrhosis and the complications of cirrhosis including hepatocellular carcinoma Alcohol Dependence and Withdrawal Wernicke-Korsakoff Syndrome (WKS) Pancreatitis Alcoholic Cardiomyopathy
signs Jaundice Hepatomegaly Spider Naevi Palmar Erythema Gynaecomastia Bruising – due to abnormal clotting Ascites Caput Medusae – engorged superficial epigastric veins Asterixis – “flapping tremor” in decompensated liver disease
ix FBC LFTs - gamma GT specifically, ADT:ALT >3 strongly suggestive of acute alc hepatitis clotting U+E USS - echogenicity CT/MRI **liver biopsy - gold standard
gen mgmt
stop drinking alc permanently
detox regime
nut support - vitamins, espesh thiamine + high protein
steroids (pred) - improve short term outcomes
treat comps - PHTN, varices, ascites, hep enceph
referral for transplant - must abstain from alc for 3 months prior to referral
hepatitis histology findings
Lobular disarray Inflammatory cell infiltrate Zone 3 necrosis Bile duct proliferation @chronic = lymphoid follicles at portal tract - classical
pathophys of hepatitis
Replication of virus at hepatocytes and secretion into bile
Liver inflammation and necrosis caused by immune response
hepatitis A virus type spread via culprits incubation where? course of illness pres ix mgmt travellers
virus type
small RNA - picoRNAvirus
spread via
faeco-oral
culprits
food handlers
shellfish
travellers
incubation
2-6 weeks
where?
india
africa
far-east - related to socio-economic indicators
course of illness
self limiting, acute, no chronic phase
pres
prodrome - mild flu (VANFAM - vomiting, anorexia, nausea, fever, arthralgia, malaise) + lose taste for cigs
hepatitis phase - dark urine, pale stools, jaundice, abdo pain, itch, hepatomeg (this when its causes cholestasis)
recovery = 6 months
ix
viral serology - HAV IgM @3w from onset, HAV IgG - persists yrs
LFT - AST + ALT rise to >1000 (AST:ALT <1), rise in ALP + bilirubin
mgmt
supportive - fluids, antiemetics, rest
avoid alc
itch? cholestyramine
travellers
should have live attenuated vaccine
hep E virus type spread culprit incubation where course of illness pres ix mgmt prevention
virus type RNA virus (calcivirus)
spread
faeco-oral route
culprit pigs slaughterhouses vets contaminated drinking water
incubation
2-9 weeks
where
india
asia
course
acute
self-limiting
pres
similar to hep A
ix
viral serology - HEV IgM + IgG +/- viral PCR
mgmt
supportive
prevention
no vaccine
good hygiene + sanitation
hep B virus spread at risk incubation where course what do these indicate: HBsAg HBsAb HBcAg HBcAb HBeAg HBeAb pres ix - results at immune tolerant, clearance, surveillance + reactivation prevention mgmt - acute + chronic comps
virus
DNA
most common worldwide
spread
parenteral - blood or bodily fluid
vertical - up to 90% if HBeAg+ve (10% if negative)
Horizontal: sexual (more than HCV), IVDU, blood products, dialysis, toothbrush
at risk
IVDU, health workers, sex workers, prisons *HIGHLY INFECTIOUS
incubation
60 to 90 days
where
SSAfrica
Asia (10% may be infected)
course
acute
may go chronic if it persists after 6 months
what do these indicate:
HBsAg - surfce antigen, current infection (may be produced at vaccine)
HBsAb - surface antibody, immunity post infection/vaccine
HBcAg - core antigen, diagnostic purpose
HBcAb - core antibody, indicates exposure but doesnt differentiate acute, chronic or cleared (however IgM = recent infection, IgG = recovered or chronic infection)
HBeAg - when virus is actively replicating, indicates someone is infectious
HBeAb - evidences immune response to above
HBcAg (IgG) + HBsAb = past HBV infection
HBcAg (IgG) + HBsAg = chronic HBV infection
pres
ACUTE
Prodromal: VANFAM + disinclination to smoke
Hepatic: RUQ pain + hepatomegaly + jaundice (50%) - darkening urine and lightening stools
Occasionally may lead to fulminant hepatic necrosis - marker is increasing INR and requires transplant
CHRONIC >6m active infection (HBsAg)
May lead to fibrosis, cirrhosis and *HCC
Fatigue, anorexia, nausea and RUQ pain ?signs of chronic liver disease
ix
PCR HBV (for response to therapy and viral replication)
Viral serology including HDV serology (5% HBV have HDV)
FBC, LFT, clotting, ferritin, AA screen, caeruloplasmin
Screen for liver cancer (USS, AFP) + Hep C/A + HIV
immune tolerant = normal ALT, HBeAg +ve, HBV DNA high
clearance = ALT high, HBeAg +/-, HBV DNA low
surveillance = ALT normal/slightly raised, HBeAg mostly -ve, HBV DNA low
reactivation = ALT high, HBeAg -ve, HBV DNA high
prevention blood screening safe sex vaccinate (partners + at risk groups) educate -transmission
mgmt -
ACUTE
symptomatic relief
bed rest
stop smoke + alc
antipyretics
fluids
cholestyramine
notify PHE
refer to gastro, hepatology, ID for specialist mgmt
test for potential comps - fibroscan + USS
CHRONIC
48 week course of injected pegylared interferon alpha
second line = tenofovir or entecavir oral daily, + 6m screen for HCC
comps Fulminant hepatic failure Relapse - chronic hep = ground glass hepatocytes on light micro Cirrhosis HCC Concurrent HCV/HIV (increases progression to cirrhosis) glomerulohephritis polyarteritis nodosa cryoglobulinaemia
hep B serology quiz: what would be postive if you had: acute HBV chronic cleared vaccination
acute HBcAb IgM HBcAb IgG HBsAg HBeAg HBV DNA - high/low
chronic HBcAb IgG HBsAg HBeAg +/- Anti-HBe +/- HBV DNA - low/high
cleared/recovery
HBcAb IgG
Anti-HBs
Anti-HBe +/-
vaccination
Anti-HBs
describe some extra -hepatic manifestations of hep B
Polyarteritis nodosa (PAN): found in 10-30%. Systemic vasculitis of medium and small vessels. Characterised by small aneurysm formation that can rupture. Multi-system disease affecting skin, joints, GI tract, kidneys and more.
Glomerulonephritis: More common in children. Causes a range of glomerulonephritides including membranous, mesangiocapillary and focal proliferative. For more information see notes on glomerulopathies.
Mixed cryoglobulinaemia: systemic inflammation due to cryoglobulins in the serum, which are immunoglobulins that precipitant at low temperature. Associated with digital ulcers, Raynaud’s, purpura and peripheral neuropathy. More common in hepatitis C.
Papular acrodermatitis: seen in young children. Typically presents with an eruption of a erythematous, symmetrical, maculopapular rash on the thighs, buttocks, outer arms and face. Non-itchy
what stage of immune response do you treat Hep B? and why?
what is the aim of treatment
immune clearance and immune escape (reactivation)
as that is when ALT is high
aim = control viral replication and reduce inflammation to decrease cirrhosis and HCC
what is given in the Hep B vaccine?
HBsAg
3 doses at different intervals
Hep C virus spread at risk incubation where course pres extra-hepatic chance of end stage liver disease ix mgmt prog
virus
RNA (flavivirus) - 3rd largest cause of ESLD in UK following alc + NAFLD
spread
6 genotypes, in UK HCV1 (50%) or HCV2/3 (50%)
Parenteral - blood or body fluid, IV drug use, tattoos, *sexual transfer is much less common as is vertical (6%), blood, transfusion, needlestick (3%)
at risk IVDU blood transfusion pre 1991 health workers male >40, co-infected with HBV/HIV, alc
incubation
6-7 weeks
9 weeks for seroconversion
where
UK
middle east
course
acute or chronic - often asymp so found on routine blood tests
pres
85% asymp BUT more likely to progress to chronic
15% develop hepatic illness: malaise, nausea, RUQ pain + jaundice
chronic infection often not recognised for 20 yrs
extra-hep AI thyroid disease membranoproliferative glomerulonephritis sjorgrens cryoglobulinaemia
chance of ESLD
1/3 25 yrs
1/3 after
1/3 never
ix
HCV serology - (anti HCV Ab, IgM or IgG) +ve at 3 months in 90% but may take 9 months
PCR HCV RNA to confirm diagnosis (for ongoing/chronic infection) treat if detectable > 2 months
LFT (AST:ALT < 1) will fluctuate in chronic infection
HIV, HBV testing
Biopsy for degree of inflammation and fibrosis if HCV-PCR+ (*may measure fibrosis non-invasively with *FibroScan)
*HCV genotype + calc viral load
mgmt
Prevention: needle exchange, screen blood products, no vaccine, alcohol avoidance
Screen for HCC 6 monthly USS and AFP, also for cirrhosis - fibroscan
Treatment aims to prevent cirrhosis and HCC
ACUTE - self-limiting, wont know got it, no mgmt
CHRONIC
Specific treatment depends on serotype and degree of fibrosis:
aims to negative HCV RNA PCR 6 months after treatment (95%) i.e. a sustained virological response
currently a combination of protease inhibitors (e.g. daclatasvir + sofosbuvir or sofosbuvir + simeprevir) with or without ribavirin
direct acting antivirals are curative
prog
20% cirrhosis at 20 yrs
autoimmune hepatitis def patho type course pres ix associations mgmt comp
def Chronic disease of unknown cause characterised by hepatocellular inflammation, necrosis and autoantibodies (association with other AI disease)
patho
Hepatocyte expression of HLA antigens (B8/14,DR3,4,DW3) becomes focus of T-cell mediated AI attack. Lymphoid infiltration of portal tract and necrosis.
types
75% Type 1: ANA (anti-nuclear Ab), ASMA (anti-smooth muscle Ab) Adults
25% Type 2: ALKM-1 (anti-liver-kidney-microsomal), anti-LC-1 (anti-liver-cystolic) children
course
acute, severe (fulminant), asymp, or chronic
pres
subclinical - many present with cirrhosis
generic symps - prominent nausea, fatigue, myalgia, anorexia, arthralgia, wt loss
endo - skin rashes, amenorrhoea, oedema, chest pain
liver - pruritis, jaundice, RUQ discomfort
potentially - hepatomeg, juandice, spleno, ascites
ix
non-invasive liver screen
diagnostic - liver biopsy - Interface hepatitis with portal plasma cell infiltrate
raised IgG +ve autoantibodies
Serum protein electrophoresis and quantitive immunoglobulins (IgG polyclonal hypergammaglobulinaemia)
Raised alk phos, low albumin
FBC and blood film - leukopenia, normochromic anaemia
associated with
IBD, coeliac, proliferative glomerulonephritis, Grave’s, AI thyroiditis, T1DM
mgmt
immunosuppression (if AST > 5x, serum globulins > 2x or symptoms, established cirrhosis)
Prednisolone + azathioprine (good response at 80%) AZT - BM suppression
Monitor: 6M USS + AFP, liver biopsies, Hep A/B vaccination, liver transplant if end stage
comp
hyperviscosity syndrome IgG,
HCC
simple liver cyst
pres
ix
mgmt
pres
normally asymp
if large RUQ pain + bloating
causes
Mainly congenital, biliary epithelium, fluid continuously secreted therefore reaccumulate post aspiration
ix
USS/CT/MRI
mgmt
wait for spontaneous resolution or aspirate/sclerotherapy (injection of irritant salt soln causing collapse) if symptomatic
polycystic liver disease
causes/assoc
mgmt
Mainly congenital, associated AD PKD - kidney cysts often present before liver - similar management to simple
types of liver cyst
simple
polycystic liver disease
neoplastic
hydatid - tapeworm - echinococcus granulosus
liver abscess causes epi RF organisms infection route pres ix mgmt comps
causes
bacteria
parasite
fungus
epi
developed world = pyogenic (Single or multiple following abdominal infection (cholangitis, malignancy, diverticulitis, Crohn’s)
developing = amoebic
RF
immunocomp
liver surg
liver cirrhosis
organisms
amoebic - Entamoeba histolytica (12% of world pop Cx infected) R lobe 80% may present months after travel
pyogenic - staph aureus, e.coli
infection route
Faeco-oral, amoeba invade intestinal mucosa and pass to portal system
pres
RUQ pain (prominent in amoebic), tenderness, hepatomegaly
*Swinging fever (pyogenic may be pyrexia of unknown origin) + night sweats + wt loss
Nausea, vomiting, anorexia
Pain referred to R shoulder, *cough due to diaphragmatic irritation + reactive pleural effusion, jaundice
amoebic dysentery
ix
FBC - raised WCC, mild anaemia
Raised ESR
Abnormal LFT
Blood cultures - 50%
Stool microscopy and cultures - cysts or trophozoites of E.histolytica
CXR - right reactive pleural effusion, raised hemidiaphragm
USS/CT liver - show abscess and guide aspiration
Aspiration + culture
mgmt
ABX ± drainage + fluids + pain relief
pyogenic - IV third cephalosporin (or cipro + amox) + metronidazole (anaerobes) for ?12 weeks
Amoebic - metronidazole (good response 72 hours) + diloxanide furoate to clear intestinal amoebae
<5cm = needle aspiration, >5cm = percutaneous catheter drainage
comps
sepsis
rupture into pleural , peritoneal or pericardial space.
retroperitoneal structures
SADPUCKER Suprarenal Aorta/IVC Duodenum (2+3) Pancreas Ureter Colon Kidney Esophagus Rectum
autoimmune panc immunoglob
IgG4
panc cancer types most common why worry RF
types
endo or exo
95% adenocarcinoma
most common
exo
90% of cancers are infiltrating ductal adenocarcinoma @head/neck/uncinate
90% of periampullary malignancies are pancreatic (10% distal common bile, ampulla, duod *these have a better prognosis as they present early with obstructive jaundice)
why worry
High mortality,
early metastasis (liver/peritoneum/lung)
late presentation - 11th cancer but 5th death
RF
Main: Smoking, alcohol, obesity + diet (low fruit veg), diabetes
Precursor: chronic pancreatitis
Family history pancreatic cancer + familial cancer syndromes (BRCA1/2, FAP, Lynch, MEN)
exocrine panc cancer pres ddx ix staging tumour types mgmt
pres
Early: vague - epigastric discomfort/dull backache
*painless, progressive, obstructive jaundice (⅔ are in the head of the pancreas)
Pancreatic pain (body/tail)
Obstructive jaundice (dark urine, pale stools, pruritus)
Weight loss, anorexia, steatorrhoea (loss of exocrine)
Palpable gallbladder (from retrograde flow) - Courvoisier’s sign *if it is painless it is unlikely to be gallstones
Stomach/duodenum compression -> gastric outlet obstruction -> nausea/vom
Advanced disease: rapid wt loss, persistent back pain, ascites, epigastric mass, Virchow’s node
Tousseau sign - migratory thrombophlebitis
ddx
Gallstones, PUD, hepatitis, liver abscess, pancreatitis (bile duct stricture)
assocs increasing age smoking diabetes chronic pancreatitis (alcohol does not appear an independent risk factor though) hereditary non-polyposis colorectal carcinoma multiple endocrine neoplasia BRCA2 gene KRAS gene mutation
ix
non-invasive liver screen
FBC - anaemia of Ca, LFT - for jaundice (bilirubin + ALP + GGT raised), serum glucose - hyperglycaemia
Tumour marker - CA19-9
Imaging: USS liver, bile duct, pancreas -> tumour mass + dilated bile ducts (double duct sign - simultaneous dilation of common bile duct and panc duct)
Abdominal CT (multiphase spiral/helical) for diagnosis and staging
ERCP visualises common bile duct and pancreatic duct (contrast)
T1 - limited to pancreas < 2cm
T2 - limited to pancreas > 2cm
T3 - beyond pancreas not to coeliac axis or SMA
T4 - to coeliac axis or SMA
tumour types
Solid - 90% ductal adenocarcinoma etc…
Cystic - serous cystic/mucinous cystic etc…
mgmt
Only 10-20% are resectable (often metastatic)
1. Whipple’s procedure -
proximal pancreaticoduodenectomy
2. Distal pancreatectomy for body/tail
Adjuvant chemotherapy 5-FU (flourouracil)
Unresectable: (IIB - 4 locally advanced to metastatic)
Bile duct stent (ERCP) for pruritus/jaundice, palliative chemo (suctal adenocarcinoma resistant)/radio
endocrine panc cancer classified as.. types assoc pres
classified as neuroendocrine tumours (PNET) which can be functional (hormone hypersecretion) or non-functional (majority eg MEN1) low grade, med or high
types
insulinomas (beta islet, 90% benign) and gastrinomas (>50%)
VIPoma (1/8th) - vasoactive intestinal polypeptide
glucagonoma (alpha islet)
assoc
75%of MEN1 (AD famililal cancer syndrome)
pres
insulinoma = confusion, sweating, dizziness, weakness, hypoglycaemia
gastrinoma = severe peptic ulceration/diarrhoea - zollinger-ellison (excess gastrin -> HCl)
VIPoma - profuse watery diarrhoea and hypokalaemia + achlorhydria (no HCl)
glucagonoma - DM, weight loss, necrolytic migratory erythema
non-functional - mass effect eg jaundice
describe the pres of these conditions biliary colic acute cholecystitis ascending cholangitis pancreatitis
biliary colic - RUQ pain
acute cholecystitis - RUQ pain + fever/WCC
ascending cholangitis - RUQ pain + fever/WCC + jaundice - charcot’s triad
pancreatitis - jaundice - raised biirubin, alk phos, GGT
NOTE - 70% are asymp
biliary colic due to pres ix mgmt
due to
temp obstruction of cystic or common bile duct
pres
sudden onset epi/RUQ pain radiation to intrascapular region, constant lasting 15mins-24 hours, relieved spont or with analgesia
jaundice - if stone moves to common bile duct
n+v due to GB distension
ix USS - 95% sensitice urinalysis CXR ECG for exclusion if unsure
mgmt
NON SURG
Note the patient is probably vomiting NBM (stop CCK release)
Good response of pain to parenteral opioids (pethidine) or ****PR diclofenac
>24 hours admit
Rehydrate IVI
Consider antibiotics IV (3rd gen ceph)
SURG
Laparoscopic cholecystectomy for removal of GB
Complications: fat intolerance, injury to bile duct
ascending cholangitis what is it pres patho organisms causes criteria ix mgmt comps
what is it
infection of bile duct
This is a medical emergency
pres
charcots triad 70% - RUQ +fever/chills + jaundice
reynolds pentad 20% - RUQ +fever/chlls + jaundice + altered mental state + hypotension/tachycardia
patho
Bile normally sterile. If CBD is obstructed, flow of bile is reduced leading to biliary stasis and infection. Infection may also be retrograde flow due to acute cholecystitis or ERCP (1%)
organisms
ecoli
klebsiella
enterococci
causes Obstruction of gallbladder (stones), ERCP, tumours (ca panc, cholangiocarcinoma), bile duct stricture
criteria have one of each of: (or suspect if have 2)
- systemic inflammation - fever >38
- lab - high WCC/CRP - cholestasis - jaundice/ abnormal LFTs (alk phos/gamma gt)
- imaging - biliary dilatation, evidence of aetiology (stricture, stone, stent)
ix
as above
WCC/ESR/CRP, LFT
worry about sepsis, pancreas, AKI - U+E, amylase, blood cultures
imaging - KUB XR + AUSS + contrast CT (best method)
MRCP (non-calc biliary stone)
mgmt
fluid resus
correct coagulopathy
broad spec abx
if septic - o2 + fluids + BC + IVAbx ?metro + ceftriaxone
emergency biliary drainage via ERCP 24-48 hrs
comps Severe may cause: Septic shock AKI All other system dysfunction Liver abscess Liver failure
primary biliary cirrhosis/cholangitis def typical patient pres assoc AI ab ix dx criteria mgmt comp
def Slowly progressive AI disease causing destuction of small interlobular bile ducts (canals of Hering)
typical patient
50 yr old woman, sister had it aswell
90% women
pres asymp 25% suspect in causes of chronic cholestasis fatigue pruritis RUQ pain cholestatic jaundice O/E - may have hepatomeg, jaund, hyperpigmentation
assoc
sjorgrens
other AI - thyroid
AI ab
high cholesterol - xanthelasma
AMA - antimito ab
ix AMA FBC - ESR raised LFT - raised alk phos + gamma gt late rise in bili raised IgM TFT - strong assoc USS - rule out obstruction MRCP - rule out PSC fibroscan for cirrhosis liver biopsy - stage - non suppurative cholangitis of interlobular and septal bile ducts + granulomatous lymphocytic infiltration of portal triad
dx criteria
2 of:
- Biochemical evidence of cholestasis (raised alk phos)
- AMA
- Hist evidence of destruction interlobular bile ducts
mgmt
allievate symps + slow disease + only transplant is curative
prurits - cholestyramine or antihist
ursodeoxycholic acid slows disease prog
immunosuppression - methotrexate, steroids
oestrogens promote cholestasis so avoid OCP
comp
50% renal tubular necrosis
20% hypothyroidism
malabsorption of fats + steatorrhoea
PSC vs PBC
- which ducts
- sex
- familial assoc
- AAb
- assocs
- cure?
Both involve primary sclerosis of bile ducts:
- PSC affects intrahepatic and extrahepatic bile ducts
- PBC affects small interlobular bile ducts
Sex
- PSC occurs more in men,
- PBC occurs x10 in women
Both have x10 familial association
AAb
- PBC is an autoimmune condition with AMA antibodies
- PSC is an autoimmune condition with pANCA antibodies
Associations
- PSC is associated with UC and colon cancer
- PBC is associated with Sjogren’s and thyroid disease
Liver transplant is curable for both but there is significant recurrence
cholangiocarcinoma aka def where/type epi rf pres ix mgmt
aka
klatskins tumour
def carcinoma arising in any part of the biliary tree (may be intrahep)
where/type
90% ductal adenocarcinoma, 10% squamous cell carcinoma
Normally at bifurcation of right and left hepatic duct = perihilar region
Next near to ampulla of Vater
epi
v rare
SE asia due to liver flukes
RFs
Liver flukes, chronic UC with PSC
pres
Jaundice early in perihilar tumours, RUQ abdo pain (biliary colic) + jaundice + cholestasis + pruritus + hepatomegaly + wt loss + anorexia
- a palpable mass in the right upper quadrant (Courvoisier sign)
- periumbilical lymphadenopathy (Sister Mary Joseph nodes) and left supraclavicular adenopathy (Virchow node) may be seen
ix
LFT: cholestatic picture
Tumour marker CA19-9 and CEA but not AFP
USS/CT, MRI is optimal
mgmt
To treat it needs removal but only 33% are resectable at presentation
Aggressive surgical resection including liver resection ± liver transplantation
Symptom relief with stents and ERCP
Intrahepatic tumours have worst prognosis
cholestasis ix ddx q1 if jaundice not due to cholestasis what could it be? q2 dark urine not due to bilirubinuria? q3 pruritis not due to cholestasis? mgmt comps
ix
non-invasive liver screen
Cholestasis characterised by elevated serum bilirubin, elevated alkaline phosphatase (>3x), raised GGT compared to transaminase.
Serum concentration of conjugated bilirubin and bile salts
Low serum albumin in chronic disease
Hyperlipidaemia if ability to break down cholesterol
FBC
Anaemia suggests malignancy
Raised WCC suggests infection e.g. ascending cholangitis
Reticulocytosis suggests prehepatic jaundice
ddx
Obstructive cholestasis
- Gallstones + carcinoma head of pancreas (most common)
- Obstruct lumen: gallstones, parasite, post ERCP
- Obstruct within wall: sclerosing cholangitis, cholangiocarcinoma, congenital stricture (biliary atresia)
- Obstruct outside wall: pancreatitis, Ca HoP
Hepatocellular cholestasis
- Commonly cirrhosis and drug reactions (erythromycin, gold, anabolic steroids)
- Viral/alcoholic hepatitis
- Sclerosing cholangitis, primary biliary cirrhosis, A1AT
q1
*Unconjugated hyperbilirubinaemia (pre-hepatic)
q2
Haematuria
Dehydration
q3
Atopic disease
Drugs
Lymphoma
mgmt
manage cause
Biliary drainages, colestyramine, rifampicin, UDCA (ursodeoxycholic acid)
Involve dietician for fat soluble vitamins
comps
Retention of bile salts -> injury to cell membrane e.g. hepatic fibrosis/cirrhosis
Chronic cholestasis -> metabolic bone disease = hepatic osteodystrophy
Chronic cholestasis -> asthmatic wheeze unresponsive to normal treatment
drugs that cause jaundice
Haemolysis - antimalarials
Cholestasis - Gold salts, nitrofurantoin, statins, erythromycin, anabolic steroids, oestrogen COCP
Hepatitis - paracetamol, rifampicin, statins
