LFTs

ALT & AST

Hepatocellular damage

ALP & GGT

Bile duct damage Cholestasis ALP - bone & plancenta

Albumin & clotting factors

Loss of liver synthetic function

Summary
Unconjugated Br: conjugation failure Conjugated Br: excretion failure postconjugation Urinary urobilinogen: Br passing into bowel

Pre-hepatic jaundice
Unconjugated hyperbilirubinaemia Other LFTs usually normal Increased production
Haemolysis Br production exceeds conjugation capacity Excess Br reuxes into blood

No hepatocyte damage No obstruction to Reduced conjugation drainage Drugs e.g. ABx Gilbert syndrome

Gilbert syndrome
Reduced expression of UGT1A1 Mutation in promotor sequence Enough action normally Stress normally reduces UGT1A1 expression
Jaundice with sepsis

Fasting/illness/Sx raised unconjugated only

All else normal

Intrahepatic jaundice
Conjugated hyperbilirubinaemia
Usually Unconjugated if severe hepatocyte loss

Conjugated Br in blood
Water soluble Into urine Dark urine

Br still into bowel

Urinary urobiliogen present Normally pigmented stool

Br released with necrosis

AST/ALT raised

Causes of intrahepatic jaundice

Acute liver failure
Paracetamol poisoning Alcoholic liver disease NAFLD

Decompensated cirrhosis Infectious: A-E viruses Metabolic

Autoimmune hepatitis Biliary:

PBC PSC

Drugs

Post-hepatic jaundice
Back pressure
Reux into blood

Conjugated hyperbilirubinaemia
Dark urine

Less into bowel

No urinary urobilinogen Reduced stercobilinogen: pale stools

Raised Br Massively raised ALP & GGT Mildly raised ALT & AST
Bile toxic to hepatocytes Collateral damage

Dilated ducts on USS

Causes of post-hepatic jaundice

In lumen:
Gallstones

Outside wall:
Cancer of pancreatic head Lymphadenopathy

In wall:
PSC Cholangiocarcinoma Stricture

Stones in gallbladder
Contraction of GB on stone
Biliary colic (Or if in GB) Worse with fatty meals

Obstructs outow to gall bladder

Static bile infected Cholecystitis
Acute Chronic

Gallstones, GB & CBD

Biliary colic

In GB or cystic duct

Acute cholecystitis In GB neck

Cholangitis In CBD + infection

Biliary colic

Generally well Intermittent RUQ pain

Around to back & R. shoulder

After (fatty) meals Rapid onset

Biliary colic

Essentially normal exam No peritonitis USS: stones in gallbladder

Not seen on XR

Acute cholecystitis

Generally UNwell

N&V, anorexia, fever WCC

Continuous RUQ pain Quite rapid onset

Acute cholecystitis

Ill patient Murphys sign positive Mildly raised LFTs Stone in GB neck GB oedema

Cholangitis

VERY unwell - Charcot's triad: 1. RUQ pain 2. Obstructive jaundice 3. Rigors

Quickly deteriorated

Cholangitis

Raised LFTs

Bilirubin (direct) = conjugated ALP

Other investigations MRCP ERCP: intervention

USS: Stone in CBD/ampulla of Vater Dilated CBD (>6mm) or intrahepatic ducts

Courvoisier's law
Palpable gallbladder in presence of jaundice is usually not due to gallstones Stones - chronic cholecytitis - cannot dilate Tumour: pancreatic or bile duct (cholangiocarcinoma)

Cirrhosis
Pathological term
Architectural disruption Fibrosis Regenerative nodules

Chronic damage
Inammation (Not acute)

Causes of cirrhosis
Metabolic
Alcoholic liver disease NAFLD Other

Biliary:
PBC PSC

Drugs

Hepatitis viruses B & C Autoimmune hepatitis

Cirrhosis
Decompensation

Portal hypertension

Hepatic failure

Features of chronic liver disease

Portal hypertension
Porto-systemic anastamoses: Oesophgeal varices Splenomegaly & hypersplenism Thrombocytopenia Haemorrhoids Caput medusae Portal gastropathy Ascites Paracentesis Spironolactone Risk of spontaneous bacterial peritonitis Portal vein thrombosis Hepato-renal syndrome

Varices
Beta-blockers Monitoring OGD Banding / sclerotherapy

Causes of ascites
Malignant Hydrostatic pressure: cardiac, hepatic Hypoalbuminaemia Inflammatory (infective) Iatrogenic

Compensated cirrhosis
Sufficient function to meet demands No features of failure May have portal hypertension Stimulus for decompensation E.g. bleed, infection, alcohol

Hepatic failure
Encephalopathy Coagulopathy Hypoglycaemia Jaundice Worsening ascites Infection Hypoalbuminaemia

Hepatitis viruses
A & E
Acute only Faeco-oral transmission

C
Chronic only Blood transmission
Iatrogenic IVDU

B
Acute or chronic Acute blood/sex Chronic perinatally
High risk chronicity Low risk acute illness

D
Acute or chronic Only in presence of B

Bile duct disease

Primary biliary cirrhosis
Intrahepatic only Autoimmune - AMA+ Granulomas

Primary sclerosing cholangitis

Intra- & extra- hepatic Inammation & strictures of ducts Not classic AID

Both to cirrhosis

Hepatitis B serology
HBsAg = current infection Anti-HBs Ab = previous infection or immunised HBeAg = current infection and replicating Anti-HBeAg = response to infection

Hepatitis B serology: patterns

HBsAg+, HBeAg+ = active, replicating infection HBsAg+, anti-HBeAg+ = chronic, inactive infection Anti-HBsAg Ab+, anti-HBeAg Ab+ = previous infection Anti-HBsAg Ab+ = immunised

Metabolic disease
Wilsons disease Copper accumulation ATP27B mutation Cannot excrete from hepatocytes Cirrhosis Neurological damage Haemolysis Renal failure Alpha-1-antitrypsin deciency Inactivates neutrophil enzymes Accumulation of incorrectly folded enzyme in liver
Inammation cirrhosis

Absence of enzyme in lung

Emphysema Neutrophil elastases

Haemochromatosis
Mutation in HFE gene Excessive iron absorption Liver cirrhosis Diabetes & other endocrinopathy Cardiomyopathy Oestoarthritis

Paracetamol OD
150mg/Kg (or 12g) for severe damage Or a significant amount over a longer period Initially: asymptomatic 12-24hr: N&V 24-48hr: asymptomatic 48-72hr: RUQ pain, ALF renal failure