Tim BadcockFY1 Colorectal surgery

21/10/13

Plan• Introduction to the liver• Definition• Clinical Scenario• Presentation• Aetiology• Complications• Investigations• Management• Prognosis

Introduction to the liver5 Functional

domains4 lobes3 vascular2 important

ligaments1 Biliary tree

5.Domains• Synthetic

– Albumin– Clotting factors (1972)

• Metabolism– CYP350 drugs– Gluconeogenesis/glycogenesis/glycogenolysis– Homeostasis– Iron, copper, vitamin K

• Vascular• Immunological

– Kuppfer cells beside sinusoids• Biliary tree

– Bilirubin– Left/right hepatic = common hepatic duct– Common hepatic + bile duct = common bile duct– Common bile duct + pancreatic duct

4. LobesLeftRightCaudateQuadrate

3. Vascular structuresHepatic portal vein (80%) Hepatic artery (18%)Hepatic vein (2%)

2. LigamentsFalciform (developmental structure of liver,

umbilical vein) Venosum (ductus venosus)

1. Biliary tree

1

87

56

9

3

4

2

Definition• Acute/chronic, organ system, key

characteristics• A chronic reduction in hepatic function

characterised by poor synthetic, metabolic, and immunological functions and vascular compromise associated with ascites and portal hypertension.

• Also associated with acute decompensation events characterised by acute haemorrhage, severe abdominal infection, neurological impairment and oedema

TimingHyperacute (<1week)Acute liver failure (7-28 days)Fulminant liver failure

(1 month-6 months)Chronic (>6 months)

Clinical scenario• 54 year old gentleman presents to his GP with

increasing swelling of his abdomen and feet over the last 2 months. He has been increasing tired over this time and feels nauseous and is off his food. His wife has commented that his eye have turned yellow over the last few days. He works in a warehouse and smokes 10 cigarettes a day. He admits to drinking 4 cans of lager a night. His wife says he drinks at least 8 cans a night and a bottle of whiskey a week. He noticed that he bled profusely when he cuaght himself on a baked beans can

Case study On examination he has pale white nails and a

slghtly bent 4th finger. He has man boobs. He is jaundiced but has no hepatic flap and is orientated in time, place and person. His abdomen is distended but soft and non-tender. There is no palpable organomegaly but there is shifting dullness. A raised JVP is noted on hepatic compression

Presentation• Synthetic

– Albumin – ascites, infection– Clotting - variceal bleed, haematemesis, meleana

• Metabolism• Bilirubin – jaundice• CYP450 drugs – variable INR, toxicity

• ODEVICES = inhibitor• PCBRAS – inducer

• Hepatic encephalopathy• Hypoglycaemic• Hormones – high oestrogen• Syndromes

SyndromesAutoantibodies against hepatocytes. Often young women

with other autoimmune conditions. RUQ pain and jaundiceα1- antitrypsin deficiency (early severe fibrosis)Primary biliary cirrhosis (AMA, young women

autoimmune)Primary sclerosing choloangitis (ANA,Haemochromatosis – early onset jaundice, bronze

diabetesWilson’s disease – Keyser-Flescher, serum

caeruloplasminGilbert Syndrome (UDP glucoronyl transferase, early

mild jaundice)Crigler Nijjar syndrome (severe early, kernicterus)

PresentationVascular

Hepatomegaly (RUQ pain)SplenomegalyHaematesis (oesophageal varices)Meleana

ImmunologicalSpontaneous bacterial peritonitis

Biliary treeJaundice

Pre-hepatic (dark stools)

Hepatic (dark urine, normal/pale stools)

Obstructive (dark urine, pale stools)

Urobilinogen/stercobilinogen

Signs

Aetiology• Alcoholic liver disease• Non-alcoholic fatty liver disease• Viral liver disease• Primiary biliary sclerosis, Primary sclerosing

cholangitis, Wilson’s, HH etc• Hepatocellular Carcinoma (rare, UC)• Metastasis (common)/ Pancreatic cancer

(rare) • Cryptogenic Liver Cirrhosis

PathophysiologyChronic inflammatory (swelling, fatty infiltraton,

cytoplasm granulation)Eosinophil and macrophage invasionLytic necrosisFibrosis and contractureLoss of liver architecture

SinusoidsAciniiPortal triad

Alcoholic fatty liver diseaseHigh calorie intake in alcoholFat droplets deposit in hepatocytesEthanol directly affects cell membrane

stability as does aldehydeChronic necrosis of cells with fibrosis

Later becomes small cirrhotic liver

Non-alcoholic fatty liver disease5% population, asymptomaticSeen on US abdo/biopsy

Diabetes MellitusMetabolic syndrome (HTN,

hypercholesteraemia, diabetes)Pregnancy (high oestrogen)Idiopathic

Oxidative stress and steatohepatitis

Hepatitis B & CHepatitis B & CHepatitis B & CHepatitis B & CHepatitis B Hepatitis C

Virus DNA RNA

Spread Blood, sexual Blood

Presentation Fever, malaise, anorexia, nausea, arthralgia, jaundice, RUQ pain

Usually asymptomatic early on

Investigation See below. Biopsy Anti-HCV, HCV DNA. Biopsy.

% Chronic 5-10% 85%

Treatment Supportive. Chronic: antivirals (nucleoside analogues). Transplant

Nucleoside analogues, protease inhibitors (anti-retroviral). Liver transplant

HbcAg = core antigen = replicatingHBeAg = pre-core antigen = current infectionHBsAg = surface antigen = acute/chronicHBV DNA = infectious

Anti-HBc = active infectionAnti-HBe = latent infection if HBeAg +ve

vaccinated if HBeAg -ve

ComplicationsPortal hypertensionDiabetesSpontaneous bacterial peritonealHepatic encephalopathyLiver transplantMalnutritionRenal failure

Portal hypertensionOesophageal varices (azygous veins)Rectal varices (inferior rectal veins)Caput medusae (umbilical veins)Budd-Chiari syndrome (hepatic vein thrombosis)

TIPSS (transjugular intrahepatic portosystemic shunt)

OGD +/- Variceal banding, stent, sclerotherapyMassive haemorrhage protocol

DiabetesPoor glucose storageBronze diabetes

Diabetic therapyDietary modification

Spontaneous bacterial peritoneal8% ascitesSevere abdominal painSeverely unwell

Ascitic tapPeritoneal lavageIntravenous antibioticsLiver transplant

Hepatic encephalopathy Increased ammonia from bacterial activity on protein in faeces Liver bypass (TIPSS) Haemorrhage

Foetor hepaticus Hepatic flap (asterix) Decreased mental capacity e.g. Constructional apraxia

West Haven Criteria Grade I altered mood/behaviour Grade II reduced consciousness Grade III Stupor Grade IV Coma

Enemas, lactulose, niacin, IV fluids

Liver transplantEnd stage liver failureSBPCongenital syndromes

Strict criteria for transplant

Long term immunosuppresants (azathioprine, ciclosporin)

Avoid alcohol

MalnutritionEncourage highest possible protein intakeHigh calorie intakeAvoid alcoholChlordiazepoxideAcamprosateDisulfiram

Renal failureIncreased vascular pressure from portal

hypertension into splenic and renal veinsDiabetic nephrotic syndrome – minimal

changeHepatorenal syndrome – low oncotic pressure

triggers peripheral hypovolaemia, neuropepetide Y and RAAS activation leads to constriction of afferent and dilatation of efferent arterioles leading to renal hypoperfusion

InvestigationsBiological

BedsideBloodsImagingSpecial

PsychologicalAlcohol addictionDepression

SocialUnemploymentSupportive housing

Biological Bedside

Observations (BP, pyrexia, BM) ECG ABG GCS/West Haven

Bloods FBC (anaemia, WCC) U&Es (urea, creatinine) LFTs (all important) Clotting (intrinsic and

extrinsic) CRP (infective) Cholesterol (fatty) HbA1c Gamma GT (alcohol) Antibodies

• Imaging• US Abdomen• CT abdomen• CT angiography• CXR• ERCP

• Special• Drugs e.g. paracetemol• OGD (varices)• Hepatitis

screen/leptospirosis• Ascitic tap• Liver biopsy (cancer,

severity)• PET scan (mets)• Colnoscopy (ulcerative

colitis)

Liver function testsTotal protein = albumin + globinsAlbumin – long term syntheticBilirubin – bile production/retention, Gilberts/Crigler

Nijjar, Sickle cell, Iatrogenic - carbimazoleALP – bile duct inflammation + bone +

hyperoestrogenic states, drugsALT – hepatocyte inflammaion + thyroid

dysregulation + coeliac + exercise

Clotting – INR, APTTExtras – amylase, gGT, paracetemol (NAC)

Acute ManagementPersonal Alcohol abstinence Fluid restriction 10% dextrose infusion/sliding scale Raise head of bed

Medical Jaundice – urseodoexycholic acid ,

colystyramine reduces pruritus Alcohol complications - Pabrinex

(IV/PO), chlordiazepoxide Ascites – Diuretics, Paracentesis, NG

feeding Ulceration – omeprazole Bleeding – vitamin K/octaplex Wilsons’s - penicillamine

• Hepatic encephlopathy – laxatives, antibiotics, IV fluids (avoid NaCl), mannitol

• SBP – antibiotics e.g. tazocin

Surgical• TIPSS• Peritoneal lavage/ascitic tap

Chronic managementPersonal Alcohol abstinence Optimise nutrition Low salt diet

Medical Jaundice – urseodoexycholic acid , Ascites – Diuretics Hepatic encephlopathy – laxatives, Autoimmune – steroids Renal failure - Haemodialysis Rastionalise pharmacy Omeprazole

Surgical• TIPSS• Liver transplantation

Multidisciplinerary Team• GP• Psychiatrist• Gastroenterology• Social services• Physiotherapy• Dietician• Specialist nurses

Prognosis5 year survival rate is 50%Post-transplant 5 year survival 65%

Prognosis

References Kumar and Clarke, Clinical Medicine Oxford Clinical Handbook of Medicine Washington Hepatitis Study NICE guidelines albumen dialysis NICE guidance living donor liver transplant Review article: the modern management of hepatic

encephalopathy by Bhajaj Netters anatomy Child-Pugh scoring article by Child and Pugh BMJ learning – liver disease module Doctors

Consultant S Ramcharan, M Osborne, Dr Gelsthorpe Reg. K McArdle, J. Barnes SHO T. Nash

THANK YOUAny questions?