59 - Diseases of the hepatobiliary system Flashcards
Jaundice is visible when bilirubin is >?
> 40umol/l
Commonest sign of liver disease
Jaundice has 3 types
Pre-hepatic - too much bilirubin made e.g. haemolytic anaemia, Gilbert’s syndrome
Hepatic - too few functioning liver cells
Post hepatic - bile duct obstruct
Bilirubin pathway
Bilirubin produced by RBC breakdown = uncojugated
Metabolised in liver - conjugated and excreted in bile
Some bilirubin is re-absorbed from gut
Also bile salts
Pre-hepatic is…
unconjugated
Bound to albumin, insoluble, not excreted - less dangerous
Yellow skin/dark eyes ONLY
Hepatic is…
Conjugated
Soluble = yellow eyes and dark urine
Post hepatic is…
Conjugated - soluble, excreted but can’t get into gut
Yellow eyes, pale stool and dark urine
LFTs test what
ALT AST Alk Phos Bilirubin Albumin Clotting factors
ALT, AST
Leak from hepatocytes due to injury
Mild increase over time = chronic liver
Very high levels = severe acute
Alk Phos
Leak from bile ducts
High in obstructive jaundice and chronic biliary disease
Histopathological features in liver with obstructive jaundice
Bile in liver parenchyma - jaundice in skin
Increasing with time: portal tract expansion, oedema, ductular rxn, bile salts and copper can’t get out, which accumulates in hepatocytes
Where would obstructive jaundice occur?
Bile pigment forms bile plugs that block intracellular canaliculli.
Swelling and irregularity of hepatocytes + increased Kupffer cells phagocytosis increases the issue
Obstructive jaundice long term effects pathogenesis
The portal tract gets larger - due to swelling (oedema with tissue looking pale), then ductular rxn (more small bile ducts around periphery of tracts).
More inflammatory cells inc. neurophils. Over time, liver sorts itself out, but the features combine to have characteristic biliary Gestalt.
Jaundice - investigation
USS for dilated ducts
Only if no dilated ducts is biopsy done
Cause of most non-obstructive cases of jaundice
Acute hepatitis
what is hepatitis?
inflammation of liver - any liver disease not neoplastic
Acute hepatitis - clinical presentation
asymptomatic malaise jaundice coagulopathy encephalopathy death
Acute hepatitis - causes
any dmg to hepatocytes
inflammation - viral, drugs, autoimmune, unknown
toxic - e.g. -OH, drugs (paracetamol)
Injury and death of hepatocytes is called what on a slide
lobular disarray
severe acute hepatitis with confluent necrosis
severe end of spectrum acute hep
acute hepatitis with bridging necrosis
Between portal tract and hepatic vein is bridge
intermediate severity
Chronic hepatitis - causes
immunological
toxic/metabolic - fatty liver disease, -OH, non-alcoholic fatty liver disease (NAFLD), drugs
Genetic in born errors - Fe, Cu, alpha1antitrypsin
Biliary disease
Vascular disease
Chronic hepatitis - pathology
Injury to liver cells, inflammation, scar tissue and regeneration of hepatocytes
Chronic hepatitis - progression
Scarring gradually increases and starts to link vascular structure (bridging)
Transform liver tissue into separate nodules - end-stage cirrhosis
Viral hepatitides
Hepatotrophic viruses - A, B, C
D = delta, only in people with B
E = waterbourne, increasingly recognised in last few years - zoonosis
EBV
CMV
HSV - in immunocomp
Table of slide 24
worth looking at
-OH and liver
Spectrum of fatty change, alcoholic steatohepatitis and cirrhosis
Depends on dose and susceptibility
-OH and liver biopsy
Features of steatohepatitis if long term alcoholic liver disease
if fatty change this is reversible
Steatohepatitis
Van Gieson stain for collagen
Chicken wire appearance increases as well as portal tract fibrosis
-OHic characteristically very fibrotic with small nodules of hepatocytes
NAFLD stands for
Non-alcoholic fatty liver disease
NAFLD - presentation
steatosis
steatohepatitis
cirrhosis
HCC
NAFLD - associated with
metabolic syndromes: obesity, T2DM, hyperlipidaemia and some drugs
Hepatotoxic drugs -
Iatrogenic - induced inadvertently by a doctor, medical treatment or diagnostic procedures.
Intrinsic hepatoxocity
e.g. paracetamol - every time, predictable
Idiosyncratic hepatoxicity
Rare, unpredictable - metabolic, immunological
Criteria for DILI
Onset of abnormal LFTs
50% reduction in LFTs after stopping drug
Alternative causes researched
Increase in LFTs by 100% if rechallenged
Slide 38
look at paracetamol mechanism toxicity
Paracetamol toxicity - treatment
IV - N-acetyl cystein
Restores - glutathione
Avoids liver cell damage
Cirrhosis - defined
Histologically as a diffuse hepatic process characterised by fibrosis and the conversion of normal liver architecture into structurally abnormal nodules
Cirrhosis - pathogenesis
Liver cells still present, but portal vein blood bypasses sinusoids so liver cell cannot perform functions. Pressure in liver increases = portal hypertension
Cirrhosis - causes
-OH
No-alcoholic steatohepatitis (metabolic syndrome)
Chronic viral hep - B, C
Autoimmune - primary biliary cirrhosis, primary sclerosing cholangitis
Metabolic - Fe, Cu, alpha1antitrypsin
Cirrhosis - complications
Structural changes, fibrosis -> portal hypertension, increased blood flow, stiff liver, pressure rises in portal vein —–> oesophageal varices
Liver cell failure
Excretion
Reticulo-endothelial cells - vulnerable to infection
Cirrhosis - liver cell failure complication
Fewer hepatocytes +/- blood bypass
Synthetic - oedema, bruising, muscle wasting
Detoxifying - drugs, hormones, encephalopathy
Ascites - low albumin, portal hypertension, hormone fluid retention (aldosterone)
Cirrhosis - excretion complication
Bile - jaundice
Bile salts - itching
Liver biopsy tests
Stage
Cause of disease
Current activity
Response to treatment
Alpha-1-antitrypsin deficiency
Abnormal anti-protease which cannot be exported from hepatocyte - PAS +ve globules in hepatocytes
Accumulates in liver cells and injures them - cirrhosis
Insufficient in blood failure to inactivate neurophil enzymes - emphysema
Haemochromotosis
Inborn error of iron metabolism - bronzed diabetes
Fe accumulates in liver - cirrhosis, pancreas - diabetes, skin - pigmented, joints - arthritis, heart - cardiomyopathy
Rx venesection to deplete iron stores to normal (take blood)
Also have high [transferrin] in serum
Wilson disease
Inborn error of copper metabolism
Copper accumulates in liver - cirrhosis, eyes - Kayser-Fleischer rings, brain - ataxia
Treatment to chelate copper and enchance its excretion
Systemic effects of liver failure
Ascites Muscle wasting Bruising Gynaecomastia Spider naevi
Caput medusae - varices from umbilical vein collaterals
Ascites is
Abnormal swelling due to fluid accumulating in the peritoneal cavity
Spider naevi is
Small clusters of dilated capillary vessel in the skin due to hormone imblaance
Caput medusae
Dilated veins radiating around the umbilicus in patients with severe portal hypertension due to recanalisation of the embryonic vitelline vein to the umbilicus
Portal hypertension - definition
Increased pressure in portal veins
Portal hypertension - main causes
Pre-sinusoidal, sinusoidal and post-sinusoidal
Portal hypertension - complications
Splenomegaly - low platelets
Oesophageal varices - haemorrhage
Piles - perianal varices (most aren’t due to portal hypertension)
Part of cause of ascites
Post-sinusoidal
Hepatic vein thrombosis = Budd Chiari syndrome
Sinusoidal -
Cirrhosis
Pre-sinusoidal
Portal fibrosis in cirrhosis
Non-cirrhotic portal hypertension caused by sarcoid, schistosomiasis, portal vein thrombosis
