59 - Diseases of the hepatobiliary system Flashcards by David Thomas

Jaundice is visible when bilirubin is >?

> 40umol/l

Commonest sign of liver disease

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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

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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

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Pre-hepatic is…

unconjugated

Bound to albumin, insoluble, not excreted - less dangerous

Yellow skin/dark eyes ONLY

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Hepatic is…

Conjugated

Soluble = yellow eyes and dark urine

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Post hepatic is…

Conjugated - soluble, excreted but can’t get into gut

Yellow eyes, pale stool and dark urine

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LFTs test what

ALT
AST
Alk Phos
Bilirubin
Albumin
Clotting factors

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ALT, AST

Leak from hepatocytes due to injury

Mild increase over time = chronic liver

Very high levels = severe acute

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Alk Phos

Leak from bile ducts

High in obstructive jaundice and chronic biliary disease

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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

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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

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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.

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Jaundice - investigation

USS for dilated ducts

Only if no dilated ducts is biopsy done

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Cause of most non-obstructive cases of jaundice

Acute hepatitis

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what is hepatitis?

inflammation of liver - any liver disease not neoplastic

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Acute hepatitis - clinical presentation

asymptomatic
malaise
jaundice
coagulopathy
encephalopathy
death

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Acute hepatitis - causes

any dmg to hepatocytes

inflammation - viral, drugs, autoimmune, unknown

toxic - e.g. -OH, drugs (paracetamol)

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Injury and death of hepatocytes is called what on a slide

lobular disarray

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severe acute hepatitis with confluent necrosis

severe end of spectrum acute hep

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acute hepatitis with bridging necrosis

Between portal tract and hepatic vein is bridge

intermediate severity

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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

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Chronic hepatitis - pathology

Injury to liver cells, inflammation, scar tissue and regeneration of hepatocytes

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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