liver Flashcards
what divides the left and larger right lobe
falciform
fibrous protective lining
external Glisson’s capsule
metabolic function carbohydrate
hormonally regulated glucogeogenesis glycolysis glycogenesis glycogenolysis
fat metabolism
breakdown and synthesis
processing chlomicron remnants
lipoprotein HDL and cholesterol synthesis
ketogenesis
protein metabolism
synthesis plasma proteins - albumin
transamination/deamination amino acids
converts ammonia to urea
hormone metabolism
deactivates
insulin
glucagon
ADH
steroid hormones
hormone metabolism
activates
conversion T3 to T4
vitamin D to calcidiol
functions storage
vitamin ADEK - fat soluble
vitamin B12
iron, copper
glycogen
functions synthesis of proteins
for liver and for export clotting factors (II, VII, IX, X) proteins C and S albumin complement proteins apolipoproteins carrier proteins
functions protection
Kupfer cells
production immune factors
functions detoxification
endogenous substances - bilirubin
exogenous substances - drugs, ethanol
phases 1
oxidation reduction hydrolysis increases drug polarity new chemically reactive group permits conjugation cytochrome P450
phase 2
conjugation further increases polarity adds endogenous products results in inactive products glucuronidation
drug metabolism excretion
renal faeces - bile lungs sweat/tears milk, saliva
ALT
alanine aminotransferase liver enzyme high conc. within hepatocytes increased levels in blood following hepatocellular injury marker for hepatocellular injury
AST
aspartate aminotransferase
similar to ALT but less specific
enzyme in liver, heart, skeletal muscle, kidneys, brain, RBC
may be elevated in liver injury
may be elevated in MI, pancreatitis, haemolytic anaemia, renal or MSK disease
AST>ALT may suggest muscle source for enzymes
ALP
alkaline phosphatase
enzyme present in liver, bile duct, bone, placenta
altered levels - biliary obstruction, liver disease, bony mets, primary tumours, bone fractures, oseomalacia, vitamin D deficiency, hepatitis, cirrhosis, hyperthyroidism, hyperparathyroidism, renal osteodystrophy, pregnancy
GGT
gamma glutamyltransferase
enzyme present in liver/bile duct, kidneys, pancreas, gallbladder, spleen, heart, brain
altered levels - biliary obstruction, liver and pancreas disease, CV disease, alcohol
GGT and ALP elevated
biliary epithelial damage and bile flow obstruction
GGT and alcohol
elevated by large alcohol intake
may also be increased by drugs
AST
chronic liver disease
AST>ALT
cirrhosis and acute alcoholic hepatitis
AST level increase
20x normal in viral hepatitis, muscle trauma, surgery, drug induced hepatic trauma
10-20x alcoholic cirrhosis or MI
5x chronic cirrhosis
mildly raised steatosis, liver mets and PE
albumin
synthesised in functioning liver
maintains IV osmotic pressure
levels may famm due to - cirrhosis, inflammation , albumin loss due to protein losing enterpathies, nephrotic syndrome
prothrombin time
time taken for blood to clot
in absence of secondary causes, increased PT can indicate liver disease
reduced production of clotting factors increases PT
bilirubin
breakdown product of haemoglobin
conjugated when taken up in liver
jaundice >60mmol/l
unconjugated insoluble - no effect on urine
conjugated passes to liver causing darker urine
if bile and lipases can’t reach bowel from blockage, fat not absorbed and stools pale and bulky
pre-hepatic jaundice
excessive red cell breakdown overwhelms liver decreased conjugated, increased unconjugated
normal urine
normal stool
hepatocellular jaundice
liver looses conjugating ability cirrhosis compresses biliary tree can be mixed conjugated and unconjugated dark urine normal stool
post-hepatic jaundice
obstruction biliary drainage but bilirubin still conjugated in liver
dark urine
pale stool
Gilbert’s syndrome
mild disorder of bilirubin processing in liver
mutation decreases activity of liver enzyme that processes bilirubin
autosomal dominant or recessive
increased unconjugated bilirubin in blood with normal LFTs
usually asymptomatic
jaundice may appear due to illness, alcohol, stress
haemolytic anaemia
abnormal breakdown of red blood cells
fatigue, SOB
jaundice
many causes
hepatocellular jaundice
acute - poisoning (paracetamol), infection (hepatitis), liver ischaemia
chronic - alcoholic fatty liver disease, NASH, cirrhosis, chronic infection, primary biliary cholangitis, pregnancy, autoimmune hepatitis, PSC, haemochromatosis, Wilson’s diease
obstrctive jaundice
gallstones
strictures
tumours
congenital biliary atresia
chronic liver disease
> 6 months
present acutely or subclinical
progress to cirrhosis
signs and symptoms depend on underlying disease
insult to hepatocytes - recurrent inflammation - process of fibrosis - compensated cirrhosis - decompensated cirrhosis
decompensated cirrhosis
ascites
jaundice
variceal haemorrhage
hepatic encephalopathy
liver injury
hepatic stellate cells (HSC) in space of disse activated by injury and cause fibrosis
normally exist in quiescent state
change to activated state when liver is damaged
secrete fibrogenic factors that encourage portal myofibroblasts to produce collagen and thus cause fibrosis
responsible for regression
NAFLD
NAFL and NASH
first hit - excess lipid accumulation in liver
second hit - oxidation stress and lipid peroxidation, pro-inflammatory cytokine release, lipopolysaccharide, ischaemia-reperfusion injury
associated with metabolic syndrome
NAFLD history
fatigue
LUQ pain
alcohol, drugs, sexual activity
obesity
NAFLD diagnosis
usually detected incidentally
suspect if abnormal USS or LFT derangement for >3 months
biopsy
examine patient for signs of advanced liver disease
liver screen to rule out any other causes
NAFL simple steatosis
steatosis - fatty acid build up in cells no inflammation or fibrosis most common diagnosed ultrasound no liver outcomes increased CV risk treatment - weight loss, exercise
NASH
non alcoholic steatohepatitis steatosis and inflammation and scarring diagnosed liver biopsy risk of progression to cirrhosis mallory bodies ballooning treatment - weight loss, exercise
alcohoilc liver disease
increased release and synthesis of fatty acids and TAGs in hepatocytes
acetaldehyde responsible for damage
involves pro-inflammatory cytokines, oxidative stress, lipid peroxidation
ALD history
same questions as for NAFLD
there will be a clear history of alcohol excess
ensure you get an accurate picture of how much and how long
fever, N&V may be present in alcoholic hepatitis
ALD diagnosis
may be asymptomatic liver screen to rule out other causes LFTs USS, CT, MRI liver biopsy
ALD treatment
no alcohol
corticosteroids may be used in acute inflammation
transplant
ALD complications
acute liver failure cirrhosis hepatocellular carcinoma focal liver lesions hepatic encephalopathy oesophageal varices ascites thrombocytopenia malnutrition
cirrhosis
final common end point if liver disease
irreversible
bands of fibrosis separating regeneration nodules of hepatcytes
macronodular, micronodular ALD or mixed
pattern depends on what caused the cirrhosis
causes of cirrhosis
ALD NASH hep b and C autoimmune hepatitis cardiac cirrhosis
cirrhosis signs and symptoms
liver dysfunction - spider nevi, palmar erythema, gynecomastia, ascites, shrunken or enlarged liver, jaundice, abnormal bruising, intense itching, acute kidney injury, hypogonadism, encephalopathy
portal hypertension - splenomegaly, eosophageal varices, caput medusa, anorectal varices
unestablished cause - finger clubbing, Dupuytren’s contracture, weakness, fatigue, weight loss, anorexia
cirrhosis history
chronic alcohol abuse
NAFLD
chronic infection
autoimmune or inherited disorders
cirrhosis diagnosis
liver biopsy - regenerating nodules of hepatocytes, fibrosis/connective tissue between these nodules
liver screen to determine cause
LFTs
USS
compensated cirrhosis
asymptomatic stage
LFTs show damage
some back pressure signs may be visible to physician
palmar erythema, clubbing, gynaecomastia, hepato/splenomegaly
decompensated cirrhosis
symptomatic - ascites, jaundice, variceal haemorrhage, easy bruising, hepatic encephalopathy
grading cirrhosis
child-pugh score A - well compensated B - functional compromise C - decompensated MELD
cirrhosis management
cannot be reversed
healthy diet
no alcohol
increase calories - small frequent meals
cirrhosis symptom management
ascites - furosemide itch medication - colestyramine caution with paracetamol treat cause weight loss transplantation
liver transplant
event based
liver function based
quality of life
UKELD score
49 is minimum score to be considered to go on transplant waiting list
UKELD calculated using - INR, creatinine, bilirubin and sodium
ascites
cirrhosis causes portosystemic shunting, increases capillary hydrostatic pressure in splanchnic vessels
results in release of vasodilators to decrease pressure
vasodilation causes decreased arterial blood volume
decreaed blood volume activates - RAAS, sympathetic system, ADH
leads to sodium and water retention by kidneys and renal vasoconstriction
ascites diagnosis
shifting dullness
USS
ascites treatment
treat underlying disease look for infection decrease salt intake no NSAIDs spironolactone first line loop diuretics paracentesis TIPSS or transplant
hepatorenal syndrome
kidney failure seen in those with severe liver damage
mechanism for ascites
can lead to kidney failure
look for altered liver function, abnormalities in circulation, kidney failure
treat - transplant and TIPSS
spontaneous bacterial peritonitis
bacterial infection in the peritoneum, despite the abscenece of an obvious source of infection
diagnosis - neutrophils >250
mild - co-trimaxazole PO
severe - piperacillin/tazobactam IV then step down to co-trimoxazole
IV albumin sometimes given
hepatic encephalopathy
urea cycle takes places in cytosol and mitochondrial matrix of liver cells
produces urea from ammonia, dissolved in blood, excreted via kidneys
liver failure causes hyperammonaemia - toxic to CNS
portosystemic shunting increases NH3 in blood
hepatic encephalopathy symptoms
liver flap confusion non-coordination/shaking drowsiness/coma slurred speech siezures cerebral oedema
hepatic encephalopathy treatment
lactulose
antibiotics - neomycin, rifaximin
acute liver failure
any insult to liver causing damage in previously normal liver
< 6 months
causing encephalopathy and impaired protein synthesis
acute liver failure clinical features
non jaundice lethargy, arhtlargia N&V, anorexia RUQ pain itch
acute liver failure diagnosis
physical exam - jaundice, ascites history infections, alcohol, pregnancy mental changes coagulopathy abnormal LFTs
acute liver failure investigations
alcohol drugs - paracetamol, over the counter, herbal, supplements possible toxins LFTs USS virology investigation of chronic liver disease rarely biopsy
acute liver failure treatment
rest 3-6 months recovery fluids no alcohol increase calorie intake regular observation monitor and supplement K, PO4, Mg
acute liver failure causes
viral hep A-E, CMV, EBV, toxoplasmosis drugs - paracetamol chock liver cholangitis alcohol malignancy Budd Chiari acute fatty liver of pregnancy cholestasis pregnancy
NSAIDs
decrease renal PGE synthesis
worsen renal impairment bu increasing renal vasoconstriction and sodium retention
increase risk of hepatorenal syndrome
opiates
increased levels in blood due to decreased metabolism
increases risk of respiratory depression
diuretics
furosemide - decreases IV volume, hypokalaemia, hepatorenal syndrome #thiazide - same as furosemide spiralactone - combats secondary aldosteronism
hepatitis A
most common viral hepatitis transmission faecal oral associated with poor sanitation and overcrowding high risk - gay men, PWID acute infection
hepatitis A clinical presentation
systemic upset - nausea and anorexia
jaundice, most infectious just before jaundice
hepatic jaundice
vomiting and altered mental state - hospital admission
enlarged liver, splenomegaly
hepatitis A investigations
hepatitis A IgM (HAV IgM)- acute infection
IgG - HAV = vaccinated
LFTs
serum bilirubin reflects the level of jaundice
serum AST and ALT rise before jaundice
hepatitis A management
stop alcohol consumption when acutely unwell
supportive treatment
hepatitis E
similar presentation to hepatitis A
more common in tropical countries
faecal oral transmission
contaminated drinking water
pregnancy associated with severe disease
acute infection, chronic infection in immunocompromised patients
hepatitis E clinical presentation
nausea and anorexia
jaundice
vomiting altered mental state
enlarged liver, splenomegaly
hepatitis E investigations
viral RNA (HEV RNA) can be detected by PCR in the stool or serum ELISA for IgG/IgM HEV
hepatitis E management
stop alcohol consumption
supportive treatment
hepatitis B transmission
bone - sex
baby
blood
if infected in infancy infection is more likely to become chronic
people with increased risk of hepatitis B
born in areas of high prevalence multiple sex partners men who have sex with men PWIDs children of infected mums
hepatitis B clinical presentation
children are more likely to develop chronic infection adults more likely to develop an acute infection may be asymptomatic similar to HAV illness may be more severe itchy rashes arthritis fever diarrhoea, abdo pain
hepatitis B investigations
hep B surface antigen (HBsAg) - in all infectious individuals
hep B e antigen (HBeAg) - highly infectious individuals
hep B virus DNA (HBV DNA) - highly infectious individuals
hep B c IgM - high titre: acute, low titre: chronic infection
hep B IgG - past exposure usually vaccine
anti-HBs (hep B surface antibody - HBsAb) - recovery/immunity to HBV, seen in vaccinated
hepatitis B prognosis
self resolving
most people full recovery
chronic infection prognosis depends on age
hepatitis B management
symptomatic
constant HBV marker monitoring
antivirals - antecavir, tenofovir, suppress not cure
controlling hepatitis B
vaccination
minimise exposure
post exposure prophylaxis
hepatitis D
a parasite of a parasite
only found in those with hepatitis B infection
exacerbates a hep B infection
hepatitis C
most common
bone -sex
baby
blood
no vaccine
acute infection - asymptomatic, mild flu and jaundice with raised amino transferases
chronic infection are more common - a result of asymptomatic acute infection
hepatitis C investigations
initially test for antibody - anti-HCV
HCV-RNA test positive after 1-8 weeks infection
anti-HCV usually positive after 8 weeks of infection - past or current infection
hepatitis C management
continually monitor HCV-RNA levels
almost half of those with acute HCV infection spontaneousy clear the virus within 6 months
if viral load falls treatment not required
viral load does not decrease - anti-viral therapy
chronic viral hepatitis
caused by HBV and HCV
spontaneous cure in chronic HBV is not uncommon
no spontaneous cure in chronic HCV
chronic hepatitis virus outcomes
20 years from initial infection to cirrhosis
30 years chronic infection hepatocellular carcinoma
a child with HBV infection acquired perinatally is far more likely to develop chronic infection
when to treat chronic viral hepatitis
HBV - raised ALT and high HBV DNA
HCV - chronic hep C is always treated right away
management of chronic HBV
perginterferon alpha-2a first line
tenofovir disoproxil second line
entercavir can be second line instead
management of chronic HCV
aiming for undetectable HCV RNA 12 weeks after treatment completion
specific treatment depends on disease progression
antivirals
regular screening for hepatocellular carcinoma
no alcohol
autoimmune hepatitis
755 cases occur in females - young females, oral contraceptives
T cells directed against hepatocyte surface antigen
type 1 - ages 10-20 and 45-70
type 2 - presents usually in young kids/adults
autoimmune hepatitis clincal features
hepatomegaly
jaundice
signs of chronic liver disease
may present similar to acute on hepatitis
autoimmune hepatitis investigations
raised LFTs antibodies type 1 - ASMA and ANA positive type 2 - LKM positive (ASMA and ANA negative) Igg will be raised liver biopsy to confirm disease severity
autoimmune hepatitis management
corticosteroids and azathioprine combined gradually reducing steroids
may eventually need a liver transplant
benign hepatic tumours
haemangioma
focal nodular hyperplasia
adenoma
liver cysts
haemangioma
most common liver tumour
hypervascular tumour
small mass contained within a capsule with clear borders
usually asymptomatic
haemangioma management
diagnosis
US - echogenic spot which is well demarcated
CT - venous enhancement from periphery to centre
MRI - high intensity area
no treatment
focal nodular hyperplasia
benign nodule formation on liver tissue - congenital vascular anomaly causing a hyperplastic response to abnormal arterial flow
classic description - central scar containing a large artery, radiating branches to the periphery
contains all liver ultra structure
most common in middle aged women
usually asymptomatic but may cause pain
FNH investigations
Us - nodule with varying echogenicity
CT - hypervascular mass with central scar
MRI - iso/hypo intense
FNA - normal hepatocytes and Kupffer cells
no treatment
no malignancy potential
isointense on sulphur colloid scan
hepatic adenoma
benign neoplasm composed of normal hepatocytes
more common in women, associated with contraceptive hormones, associated with anabolic steroids
usually asymptomatic, may be RUQ pain
can rupture causing haemorrhage
can undergo malignant transformation
hepatic adenoma investigations
US - filling defect CT - diffuse arterial enhancement MRI - hypo/hyper intense lesion FNA - may be required cold on sulphur colloid scan
hepatic adenoma treatment
stop taking contraceptives, hormone, anabolic steroids
males - surgical excision irrespective of size
females <5cm or reducing in size - annual MRI
females >5cm or increasing in size - sugical excision
malignant hepatic tumours
primary tumours are rare - hepatocellular carcinoma, fibro-lamellar carcinoma
secondary tumours are more common - multiple lesions, metastases - colon, pancreas, stomach, breast, lung
hepatocellular carcinoma
most common primary liver cancer
important risk factor is cirrhosis
carriers of HBV and HCV high risk of developing HCC
more common in males than females
hepatocellular carcinoma pathology
usually a single nodule but can be multifocal in rarer cases
it consists of cells resembling hepatocytes
metastasis can spread to bones, lungs, lymph nodes
clinical features of HCC
weight loss, malaise, fever, anorexia ache in RUQ worsening of pre-existing chronic liver disease ascites signs of cirrhosis hard enlarged RUQ mass liver bruit
investigating suspected HCC
serum alpha-fetoporotein may be raised but is normal in a third of cases
USS can show filling defects
CT to identify HCC
tumour biopsy is used less frequently
HCC treatment
resection is the first choice liver transplant local ablation TACE - transarterial chemoembolisation systemic therapies - sorafenib, kinase inhibitor
fibro-lamellar carcinoma
more common in younger patients
no correlation with cirrhosis
AFP isn’t raised
investigations - CT shows stellte scar with radial septa showing persistent enhancement
treatment - resection or transplant, TACE
cystic lesions
simple cyst
hysatid
polycystic liver disease
pyogenic or amoebic abscesses
simple cyst
liquid collection lined by epithelium
solitary - so no biliary tree
usually asymptomatic - RUQ pain, fever
simple cyst investigation
USS fist line
simple cyst treatment
asymptomatic no treatment
symptomatic/uncertain diagnosis surgical intervention required
hydatid cyst
caused by tapeworm echinoccocus granulosus
more prevalent in farming communities
cysts can erode into adjacent structures and vessels
asymptomatic - dull ache and swelling in right hypocondrium
hydatid cyst investigation
AXR - mauy show cyst calcification
US/CT
check for anti-echinococcus antibodies
hydtid cyst management
surgery is most common
albendazole - reduce size
drained using PAIR
polycystic liver disease
caused by embryonic ductal plate malformation
three types - von meyenburg complexes, polycystic liver disease, AD polycystic kidney disease
von meyenburg complexes
benign cystic nodules throughout liver
originate in the peripheral biliary tree
asymptomatic
polycystic liver disease presentation
abdominal pain
abdominal distention
may be atypical symptoms
may be signs of liver failure if there is severe disease
polycystic liver disease investigations
gene studies
CT
kidney function tests
polycystic liver disease treatment
aim to halt cyst growth
surgical - aspiration and liver transplantation
pharmacological therapy somatostatin analogues
liver abscess
can be pyogenic or caused by Protozoas
liver abscess presentation
high fever abdominal pain nausea and vomiting jaundice pleural rub in lower right chest malaise
liver abscess investigations
check for leucocytosis CXR - raised right hemi-diaphragm US CT echocardiogram
liver abscess management
initial empiric board spec antibiotics - amoxicillin, metronidazole, gentamicin IV
aspiration/drainage
operation if no clinical improvement
haemochromatosis
an inherited disease characterised by excess iron deposition in the liver as well as other organs
autosomal recessive inheritance pattern
symptomatic 20-40g
haemochromatosis clinical features
classic triad - bronze skin pigmentation, hepatomegaly, diabetes mellitus cardiac arrhythmias and heart failure liver fibrosis/failure joint pain hypogonadism
haemochromatosis investigations
serum iron elevated >30 in most cases
LFTs often normal
biopsy
MRI
haemochromatosis management
venesection
avoid iron rich food
Wilson’s disease
autosomal recessive disorder leading to reduced ceruloplasmin
defect in copper transorting and excretion into bile
Wilson’s disease symptoms
Kayser-fleisher rings
signs of liver disease
CNS issue - tremor, involuntary movements
Wilson’s disease investigations
urinary copper increased
serum copper and ceruloplasmin usually reduced
Wilson’s disease management
penicillamine
nausea, rash, haematuria
