Dr Allister J Grant Consultant Hepatologist University Hospitals Leicester NHS Trust

Dr Allister J GrantConsultant Hepatologist

University Hospitals Leicester NHS Trust

Anatomy &Physiology

Anatomy &Physiology

Anatomy &Physiology

Hepatic Artery

IVC

Splenic Vein

SMVGallbladder

Portal Vein

CBD

Anatomy &Physiology

Liver Functions

Nutrition/Metabolic– stores glycogen (glucose chains)– releases glucose when if no insulin– absorbs fats, fat soluble vitamins– manufactures cholesterol

Bile Salts– lipids derived from cholesterol– dissolves dietary fats (detergent)

Bilirubin– breakdown product of haemoglobin

Liver Functions

Clotting Factors– manufactures most clotting factors

Immune function– Kupfer cells engulf antigens (bacteria)

Detoxification– drug excretion (sometimes activation)– alcohol breakdown

Manufactures Proteins– albumin– binding proteins

Symptoms

Early disease• asymptomatic• fatigue, malaise• anorexia, nausea• jaundice• pruritis• easy bruising and

bleeding• abdominal pain

Cholestatic patients• fatigue, malaise• anorexia, nausea• jaundice• +++ pruritis• +++ grey or clay-

coloured stools

Disease Progression

Acute Liver Failure

• <6 weeks duration

• Jaundice• Encephalopathy• Cerebral Oedema• Acute Renal Failure• Acidosis• Hypoglycaemia• MOF

Chronic Liver Disease

• >6 months

Cirrhosis leading to

• Recurrent decompensation– Ascites– Portal Hypertension (variceal

bleeding)– Encephalopathy

• Low albumin/Malnutrition• Hepatorenal syndrome• Hyponatraemia• Hepatoma

Disease ProgressionL

iver

fu

nct

ion

100%

Cirrhosis

Liver Failure

Years

A

B

C

Causes of Chronic Liver disease

• Viral• Hepatitis B• Hepatitis C

• Autoimmune Hepatitis

• Metabolic• NASH• Amyloid

• Alcoholic Cirrhosis

• Inherited• Haemochromatosis• Wilsons Disease -1 Antitrypsin Deficiency

• Biliary Disease• PBC• PSC• Secondary sclerosing

cholangitis• Caroli’s syndrome

Signs of Chronic Liver Disease

• None• Asterixis/Flap• Relative hypotension• Oedema• Jaundice/No jaundice• Large/Small liver• Splenomegaly• Gynecomastia• Testicular atrophy-loss of secondary sexual

characteristics

Cirrhosis

Expanded Portal Tracts(Blue)

Decompensation in Cirrhosis

Means the development of-

Ascites

Hepatic Encephalopathy

Portal hypertension (variceal haemorrhage)

Decompensation in Cirrhosis

Means the development of-

Ascites

Hepatic Encephalopathy

Portal hypertension (variceal haemorrhage)

The Development of Ascites

50% of compensated cirrhotics develop ascites over 10yrs

50% of cirrhotics with ascites will die within 2 yrs

(50% 2yr rule for OLTx assessment)

The Development of Ascites

Peripheral arterial dilatation

Reduced effective blood volume

Activation of renin-angiotensin-aldosterone systemSympathetic nervous systemADH

Na retention &Water retention

Low urinary NaDilutional hyponatraemia

AscitesSchrier et al Hepatol 1988

Plasma volume expansion

NaCl

Ascites and Oedema

Decompensation in Cirrhosis

Means the development of-

Ascites

Hepatic Encephalopathy

Portal hypertension (variceal haemorrhage)

Encephalopathy

• Grade 1» Constructional apraxia» Poor memory – number connection test» Agitation/ irritability» Reversed sleep pattern

• Grade 2» Lethargy, disorientation» Asterixis

• Grade 3» Drowsy, reduced conscious level

• Grade 4» Coma

Causes of EncephalopathyINCREASED AMMONIAGENESIS

Increased substrate (protein) for ammoniagenesis

– Increased protein intake– Gastrointestinal bleeding– Constipation– Dehydration

Increased substrate (urea) for ammoniagenesis

– Renal failure

Increased catabolism of protein

– Infection– Hypokalemia– Sepsis

DECREASED HEPATOCELLULAR FUNCTION

– Worsened intrinsic liver disease– Hypoxia – Anaemia – Development of hepatocellular carcinoma – Dehydration – Hypotension – Sepsis– Drug toxicity – Superimposed viral hepatitis

Causes of Encephalopathy

INCREASED PORTOCAVAL SHUNTING

– Portal vein thrombosis – Transjugular intrahepatic portosystemic shunt formation – Surgical shunt formation – Spontaneous shunt formation

PSYCHOACTIVE DRUG USE

– Benzodiazepines – Ethanol – Antiemetics– Antihistamines – Others

Causes of Encephalopathy

Decompensation in Cirrhosis

Means the development of-

Ascites

Hepatic Encephalopathy

Portal hypertension (variceal haemorrhage)

Portal Circulation

Oesophageal varices

Prognosis

1 Year Survival

– Child Pugh A 80 - 100%

– Child Pugh B 60 - 80%

– Child Pugh C 35 - 45%

Management of Bleeding Varices

• Prevention

• Resuscitation

• Endoscopy - Band LigationSclerotherapy

• Pharmacotherapy- Terlipressin

• Balloon Tamponade

• TIPS

Management of Bleeding Varices

• Prevention

• Resuscitation

• Endoscopy - Band LigationSclerotherapy

• Pharmacotherapy- Terlipressin

• Balloon Tamponade

• TIPS

Fluid Management

• Crystalloid

• Colloid

• Blood

• Platelets

• FFP

• Vitamin K

Management of Bleeding Varices

• Prevention

• Resuscitation

• Endoscopy - Band LigationSclerotherapy

• Pharmacotherapy- Terlipressin

• Balloon Tamponade

• TIPS

Oesophageal varices

Oesophageal varices

Bleeding Gastric Varices

Variceal Bander

Variceal Band Ligation

Management of Bleeding Varices

• Resuscitation

• Endoscopy - Band LigationSclerotherapy

• Pharmacotherapy- Terlipressin

• Balloon Tamponade

• TIPS

PharmacotherapyTerlipressin vs. Balloon Tamponade

Mortality

Terlipressin vs. Endoscopic TherapyMortality

Favours Terlipressin Favours Tamponade

Management of Bleeding Varices

• Resuscitation

• Endoscopy - Band LigationSclerotherapy

• Pharmacotherapy- Terlipressin

• Balloon Tamponade

• TIPS

Sengstaken-Blakemore Tube

Complication of SBT

Management of Bleeding Varices

• Resuscitation

• Endoscopy - Band LigationSclerotherapy

• Pharmacotherapy- Terlipressin

• Balloon Tamponade

• TIPS

The End“All right, let's not panic.

I'll make the money by selling one of my livers.I can get by with one “

Doh!