dr allister j grant consultant hepatologist university hospitals leicester nhs trust

Dr Allister J GrantConsultant Hepatologist

University Hospitals Leicester NHS Trust

Anatomy &Physiology

Hepatic Artery

IVC

Splenic Vein

SMVGallbladder

Portal Vein

CBD

Anatomy &Physiology

Liver FunctionsNutrition/Metabolic

– stores glycogen (glucose chains)– releases glucose– 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

Disease ProgressionAcute 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 ProgressionLi

ver f

unct

ion

100%

Cirrhosis

Liver Failure

Years

A

B

CD

24♀ 48hours post POD • ALT 13000• Alb 35• Bili 40

• Cr 160• Urea 24

• INR 3.0• PT 33

• Glc 3.6

• Ph 7.1• PCO2 3.2• PO2 12.4• BE -6

ALF• Treat the underlying cause• Resuscitate - Central access early • Give N-Ac regardless of cause• Monitor for hypoglycaemia• Monitor coagulopathy• Antibiotic prophylaxis• Stress Ulcers• Early elective ventilation for encephalopathy• Nutrition• Acidosis/ Renal Impairment

• Early referral to Hepatology / discuss with Birmingham Liver Unit

Mrs W• 48 year old ♀ admitted from a surgical clinic with

jaundice and unwell

• Unwell for 6 wks after holiday in Mexico

• Hx of xs alcohol 30u/wk

• No previous jaundice

• USS normal size liver and spleen – biliary tree normal

OE

• Jaundice• Drowsy• Agitated/Irritable• Doesn’t obey

commands• No stigmata of CLD• Asterixis

No spleenNo ascites

Mrs W

• U&E normal

• ALP 107• ALT 736• Bili 363• Alb 24

• FBC Normal

• INR 3.7

Causes of Acute Liver Failure

• Drugs• Paracetamol (UK)• INH• Halothane• Ecstacy

• Viral• Hepatitis A• Hepatitis B• Hepatitis E• Non-A Non-B

• Wilsons Disease

• Autoimmune Hepatitis

• Reye’s Syndrome

• Cardiovascular• Ischaemic hepatitis• Budd Chiari

• Acute Fatty Liver of Pregnancy

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

Cirrhosis

Expanded Portal Tracts(Blue)

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• Impotence

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

General ManagementAscites and Oedema

• Salt restriction

• Diureticsspironolactonefrusemide

• Water restriction if sodium < 125 mmol

• Paracentesisdiagnostic (SBP, tumour)therapeutic (20% Alb)

• DAILY WEIGHTS!

Decompensation in Cirrhosis

Means the development of-

Ascites

Hepatic Encephalopathy

Portal hypertension (variceal haemorrhage)

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

General ManagementEncephalopathy

Minimize effects of liver disease

Treat precipitants• sepsis• GI bleed• medications (over-diuresis)

Avoid sedatives, hypnotics, opiates

Lactulose to ensure BO 2x/day

Metronidazole/ neomycin

Decompensation in Cirrhosis

Means the development of-

Ascites

Hepatic Encephalopathy

Portal hypertension (variceal haemorrhage)

Portal Circulation

Oesophageal varices

Management of Bleeding Varices

• Prevention

• Prophylactic Antibiotics

• Resuscitation

• Endoscopy - Band Ligation Sclerotherapy

• Pharmacotherapy- Terlipressin

• Balloon Tamponade

• TIPS

Management of Bleeding Varices

• Prevention

• Prophylactic Antibiotics

• Resuscitation

• Endoscopy - Band Ligation Sclerotherapy

• Pharmacotherapy- Terlipressin

• Balloon Tamponade

• TIPS

Fluid Management

• Crystalloid• Colloid• Blood• Platelets• FFP• Vitamin K

Management of Bleeding Varices

• Prevention

• Prophylactic Antibiotics

• Resuscitation

• Endoscopy - Band Ligation Sclerotherapy

• Pharmacotherapy- Terlipressin

• Balloon Tamponade

• TIPS

Oesophageal varices

Bleeding Gastric Varices

Variceal Bander

Variceal Band Ligation

Management of Bleeding Varices

• Resuscitation

• Endoscopy - Band LigationSclerotherapy

• Pharmacotherapy- Terlipressin 2mg qds i.v

• Balloon Tamponade

• TIPS

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!