liver disease Flashcards
Causes of high BR
gallstones - obstructive
haemolysis
hepatitis
alcoholic liver
anatomy of liver
o Centre of liver lobule – portal tracts (hepatic artery, bile duct, portal vein) at corner of hexagon, centre have central vein -> hepatic vein
o Hepatocytes – brick like cell – blood flow through sinusoid from the portal tract – exit through the central vein
divide the hepatocytes into 3 groups - 1 around portal tract, 2 midzone, 3 around central vein
endothelial cells lining the sinusoid have big spaces - blood can go to the hepatocytes
between the endothelial cells and the hepatocytes have the space of Disse - where stellate cells sit
how does the hepatic portal vein tie up with the function of the liver
o Hepatic portal vein come from gut – liver clear up gunky blood – 1st pass metabolism, clean blood through central vein to the heart
causes of high BR and investigations to determine them
Prehepatic – haemolysis = making more BR – FBC and film
Hepatic – repeat LFT
Post-hepatic – obstructive jaundice - AlkPhos usually goes up in obstructive
what is the van den Bergh reaction
measures serum bilirubin via fractionation A direct reaction measures conjugated bilirubin. The addition of methanol causes a complete reaction, which measures total bilirubin (conjugated plus unconjugated); the difference measures unconjugated bilirubin (an indirect reaction).
describe paediatric jaundice
might be normal - usually is, but should be unconjugated and due to liver immaturity, coupled with a fall in Hb early in life
• If it doesn’t settle, other rare causes should be
looked for including hypothyroidism, other
causes of haemolysis (including a Coombes
test or DAT), and the unconjugated bilirubin
will be useful.
describe phototherapy
Converts bilirubin into two other compounds,
lumirubin and photobilirubin which are
isomers that do not need conjugation for
excretion.
helps clear BR in normal paediatric jaundice
describe Gilberts disease
common dont need to worry autosomal recessive 50% carry the gene BR rise with fasting all LFTs normal shouldn’t biopsy people because cant be other things and there are risks
gilberts: •50% of us carry the gene •What will the population prevalence (as a percentage (%) of the full syndrome be given that half of us carry the gene?
probability both parents carry the gene: 25%
therefore probabilty of child having disease is 6%
•5-6% of the population have the disease
•1 in 20
•(15 in 300)
diagnostic test for Gilberts - not done anymore
induce liver enzymes - give phenobarbitone and BR levels fall
mechanism of Gilberts
UDP glucuronyl transferase activity reduced to 30% = slow down clearance of BR = higher level of BR, especially when fast Unconjugated bilirubin tightly albumin bound and does NOT enter urine
what do you look at to assess liver function
Liver makes clotting factors and albumin – so PT, PTTK, BR and albumin quite representative, albumin slow to change
But prothrombin time changes rapidly – so best for liver function
what do you look at liver enzymes for
ALT and AST – enzymes leak out, nothing to do with function. In different hepatocytes in different zones – pattern recognition
ALT – responsible for gluconeogenesis
Alk Phos high in post-hep – affect tracts – so assume more alk phos in this area
LFTs and paracetamol OD
damage liver = large ALT and AST leak out – sky high but diesnt correlate. PT correlates – goes up, if PT is sec goes up by >1sec every hr – need to be thinking of ringing liver unit, might need transplant. If PT stay the same can keep in normal hospital
ddx: •Aged 35 •Chronic alcohol intake •Often appeared drunk to A + E •Nausea, abdo pain and jaundice. •LFTs abnormal: Bilirubin 90
•Pre hepatic (Gilberts, haemolysis) - exclude early
•Viral hepatitis
•Alcoholic hepatitis (hurts)
•Cirrhosis
alcoholic fatty liver
•Post hepatic: Gallstones (painful), pancreatic
ca. (painless)
what is suggested: Aged 35 •Chronic alcohol intake •Often appeared drunk to A + E •Nausea, abdo pain and jaundice. •LFTs abnormal: Bilirubin 90 •Alk Phos 200 (NR <130) •AST 1500 (<50); ALT 750 (<50)
AST and ALT very high •Suggest hepatocyte damage •Alk Phos marginal: •Excludes obstructive jaundice. therefore ddx: o Viral hepatitis – check viral tures – more likely to have viral if you drink alcohol, common o Autoimmune hepatitis o Alcoholic hepatitis
describe hepititis A
o Faecoorally transmitted
o Eat bad food
o Don’t feel ill
o Excrete virus in faeces at 3-4wks and become ill
o Then recover with IgM – jaundice but recover
o No carrier form – either die (not fatal, but if malnourished – die), or cure – cant have again, have IgG
describe Hepititis B
o Not spread by mouth – blood transfusion, sharing needles
o If inject self with Hep B – virus replicate
o Incubation for a month, then start to make virus replicate
o Surface ag and core (e Ag) – they multiply in blood
o Immune system makes Ab to different parts of virus
o Against e Ag – e decline
o Still infective – making surface ag
o Then pt will have e Ab – if find e Ab – means been exposed to live virus, never vaccinate with this
o Then make surface Ab
o Vaccine has pure surface Ag – engineered/purified – all have anti-HBs (if just s – likely vaccinated, if both – exposed)
o A lot of people never clear the virus – make Ab to E, but always chronic ag – infectious forever, unless they have treatment
o Illness often subclinical – don’t know they’re carriers – individuals still infective
defining histological features of alcoholic hepatitis
- liver cell damage, swollen hepatocytes (mallory hyaline is pink uniform substance due to hepatocyte damage)
- inflammation - neutrophils and lymphocytes
- fibrosis, collagen around the hepatocytes
associated histological features of alcoholic hepatitis
- fatty change
* megamitochondria - alcohol damage mitochondria – mechanism of damage to hepatocytes
why do you see bile in hepatitis liver biopsy
disturbance to bile flow because of damage to the hepatocytes = cholestasis
quality of bile produced not as good
high BR
what is NASH
Non-Alcoholic Steato-Hepatitis
Raised BMI and insulin resistance and t2dm
Need clinician to say history to see if NASH or alcohol
management of alcoholic hepatitis
Supportive. •Stop alcohol. •Nutrition: •Vitamins - pabrinex (esp B1, thiamine) •Occasionally steroids - controversial, probably more harmful than beneficial
what is caused by B1 (thiamine) deficiency
Beri-Beri
what do these signify: •Multiple spider naevi •Dupuytren’s contracture •Palmar erythema •Gynaecomastia
Signs of chronic stable liver disease - pt is well in self
need to stop alcohol to stop the progression to chronic liver disease - pt would be unwell
what causes varicose veins in abdo
visible vein – end up being caput medusae but not yet
because of Pressure in umbilical vein
Suggests portal hypertension
before born umbilical vein went to liver, had ductus venosus - took blood from liver to umbilicus
if chronic portal htn, pressure in liver opens up the vessels surrounding - blood gets to the abdo wall, then finds a low pressure system and grows those veins
if have varicose vein on abdo wall other likely finding
Not hepatomegaly – because vein drains into portal vein connects into splenic vein
Pressure up because liver gets smaller and cirrhosed because kill hepatocytes
Spleen gets big because pressure goes up
if have scrotal oedema and shifting dullness what has developed
ascites – fluid in the abdomen from portal hypertension
diagnosis if have visible veins, splenomegaly, ascites
portal HTN
o Caused by cirrhosis
o In hexagons – blood got to get to central veins
o If kill hepatocytes
o In regeneration – form a nodule – grow into a round blob – damaged architecture
o Pressure rises
what has happened if pt with portal htn comes in vomiting blood and what would you do
– vein in oesophagus thickened = bleed – no muscle in wall = massive GI haemorrhage – so need to move quickly – press on bleeding vessel
o Go to casualty – NG tube with balloon down – pull up – balloon will press on vessels – when no endoscopist around
what if a pt comes in with chronic liver disease, and is found to have a flapping tremor
now in liver failure
o In trouble – cant synthesise clotting factors, albumin falls – retain salt because kidney notice drop in pressure, failed BR and ammonia clearance, encephalopathic because toxins irritate brain – flapping tremor – die
cirrhosis post mortum
• Pale, rather than red, because full of fat
• Made up of lots of nodules – regenerative hepatocytes which are damaged by alcohol
• Pale is regenerating hep
• Can see clearly because of fibrosis around them
Whole liver involved.
• Nodules of regenerating hepatocytes
• Fibrosis
• Shunting of blood
describe shunting of blood in liver failure
– blood cant get through liver = portal htn = not good for body or liver. Blood now bypassing liver – so liver cant get what it needs, or do the homeostatic func = encephalopathy
defining features of cirrhosis
Whole liver involved.
• Nodules of regenerating hepatocytes
• Fibrosis
• Shunting of blood
histology of alcoholic liver disease
signs of fatty liver on own, or heptatis on own or cirrhosis on own or more commonly all together
what are the causes of cirrhosis
Fatty liver disease ( alcoholic and nonalcoholic) - micronodular
• Viral hepatitis ( Hepatitis B, C and D) –
macronodular
Haemochromatosis (iron overload)
Wilson’s Disease ( copper overload)
Primary Biliary Cholangitis
Primary Sclerosing Cholangitis.
how does shunting effect the liver
• Normally blood from hep vein and port artery – to cenyral vein – through sinusoid
o In cirrhosois – blood not coming in because of the shunting so liver doesn’t function
• Summary of EtOH
progression of alcohol’s effect on liver
o Admission with sever pain and alcoholic hepatitis – recover when stop drinking
o Chronic stable liver disease – see signs, chronically drinking a lot but well
o Portal HTN – cause of death is vom blood vol because tear varicies
o Liver failure – present with liver flap
sites of porto-systemic anastomosis
o Portal vein meets the systemic circulation:
o Oesophagus varicies
o Rectum varicies
o Umbilical vein recanalising
o Rectal varices
o Can put shunt into spleen (spleno-renal shunt) to lower the pressure between portal vein and hepatic vein – reduce pressure and reduce risk of bleeding but make liver failure worse – encephalopathy
what do scratch marks suggest
suggests that jaundice that they have is because of obstruction of the bile ducts
o Make think post-hepatic
o Obstruct the bile duct (head of panc cancer/gallstones) – might get enlarged gall bladder if not caused by stone
o Bile and bile salts that come into duct are absorbed by enterohepatic circ
o Bile salt – emulsify fat and enable absorption of fat and salts
o If obstruct duct – bile salts cant get into stool so also end up in skin = itchy
o In hep – bile salts will go into gut = not itchy
describe stercobilinogen
BR get into gut - bacterio convert to stercobilinogen
this is reabsorbed in gut and peed out as urobilinogen
if block bile duct so BR cant get to bacteria - stop making stercobilinogen and so urobilinogen = dark urine and pale stools
US guided biopsy results of cancer
determine if primary hepatic - in which case produce bile
or secondary - if adenocarcinoma (glands and mucin) secondary pancreatic cancer
spindly tumour - tumour of connective tissue
melanin - met from malignant melanoma
need to do stains to see where coming from
what is Courvoisier’s law
gall bladder is palpable in panc cancer – stretch and full of fluid
not in gallstones - – thick, small and fibrosed gallbladder so not palpable – incapable of being enlarged
investigation for obstructive jaundice
Ultrasound abdomen
•Dilated bile ducts
•Probable metastatic disease
post mortum of liver cancer
- Multiple firm white tissue – irregular borders, invade locally
- Invade by circ by met
- Met are multiple, primary are single
histology of adenocarcinoma
eg panc mets
• Tumour making glands and secreting mucin
alcohol withdrawal
If heavy alcoholic and stop drinking = terrible tremors, and withdrawal symptoms – some people physically dependant on it = give chlordiazepoxide
distinguish between NAFLD and FASH
NAFLD means all fattly liver disease not due to alcohol, ie due to insulin. NASH is hepatitis subset of NAFLD
