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)
