Liver failure

Question 1

What are the levels of bilirubin

Question 2

What is cholestasis

Question 3

What are the causes of jaudice

Answer 3

Pre-hepatic causes

• Haemolytic anaemia, toxins
• Massive transfusion - transfused erythrocytes short-lived
• Large haematoma resorption
• Ineffective erythropoiesis

Question 4

What are the causes of jaudice (Intrahepatic causes)

Answer 4

Intrahepatic causes

• specific defects
• decreased BR uptake - Gilberts syndrome 5% (autosomal recessive)
• decreased conjugation BR - Crigler-Najara syndrome - brain damage in infacts - nonhemolytic syndrome
• decreased secretion of BR into biliary canaliculi - dubin-johnson syndrome (AR benign causes increase conjugation)

rotor syndrome

Intrahepatic cholestasis (decreased outflow)

• Sepsis, TPN (Total Parenteral Nutrition) and drugs

Liver failure

Question 5

What is the pathophysiology of liver failure

Answer 5

When rate of hepatocyte death > regeneration

Combination of apoptosis or necrosis

• Apoptosis (acetaminophen = paracetamol)
• Necrosis (ischaemia)

Clinical result

Question 6

Types of acute liver failure

Answer 6

Fulminant hepatic failure = rapid development (<8wks) of severe acute liver injury

• imapired synthetic function (INR/PT, albumin)
• encephalopathy
• previously normal lvier or well compensated liver disease

Question 7

Common causes of acute liver failure

Answer 7

Toxins (West)

• Parac

Question 8

Other causes of acute liver failure

Answer 8

Disease of pregnancy (acute fatty liver of pregnancy, hemolysis elevated liver enzyme and low platelets, hepatic infarction, HEV, Budd-Chiari)

• Idiosynratic drug reactions (single agent, drug combinations
• Vascular disease - ischaemic hepatitis, hepatic artery thrombosis, post arrest,

Question 9

Chronic Liver failure causes

Answer 9

Inflammation - viral hepaptitis

Alcohol abus

Side effects of drugs - folic acid antagonist

Cardiovascular causes - decrease venous return - right heart failure

Inherited disease - glycogen storage disease, wilsons disease, galactosaemia, haemochromatosis, a1-antitrypsin defieincy

Non alcoholic steatohepatitis

Autimmune hepatitis (PBC, PSC)

Question 10

How does cirrhosis happen

Answer 10

Question 11

What are the hepatocyte functions

Answer 11

Metabolic and catabolic functions - synthesis and utilization of carbohydrations

Question 12

Consequences of Liver Failure

Answer 12

Production of clotting factors - coagulopathy and bleeding

Protein synthesis - ascites

Detoxification - encephalopathy and cerebral oedema

Glycogen storage - hypoglycaemia

Immunoligcal function and globulin production - increased susceptibility to infection

Maintenance of homeostasis - circulatory collapse and renal fialrue

Question 13

Why does decreased protein synthesis cause liver failure

Answer 13

Decreased albumin ( cannot keep fluid within vasculature) - ascites

Decrease plasma volume - hypokalaemia, alkalosis, secondary hyperaldosteronism

Decrease (cloti

Question 14

What is the consequence of cholestasis

Answer 14

Leads to liver damage

Aggravates any bleeding tendency

• Decreased bile salts
• decreased micelles and absorption of vit K
• decreased y-carboxylation of vit K dependent colotting factors (prothrombin 2, VII, IX and X)

Question 15

Causes of death due to liver

Question 16

Liver support devices

Answer 16

Artificial (MARS, bio-logic DT) - albumin exchange system - removing albumin bound toxins from blood

Boartifical (hepactocytes in culture)

Hepatocyte transplantation (inject hepatocyte/not effective)

Question 17

When do you need a liver transplant

Question 18

What are some supportive treatments that you can do

Answer 18

Encephalopathy - reduce protein intake( decrease ammonia), phosphate enemas/lactulose (to empty bowles)

Hypoglycaemia - infusion 10-50% dextrose

Hypocalcaemia - infuse calcium gluconate

Renal failure - haemofiltration

respiratory failure - ventilation

hypotension - albumin, vasoconstrictors

infection - antibiotics

bleeding - platelets, FFP, vit K

Question 19

Severity of liver failure

Answer 19

Question 20

How you get varices

Answer 20

Portal-systemic anastomoses

Question 21

How does cholestasis happen

Answer 21

Question 22

Cause of portal hypertension liver failure

Answer 22

Decreased lympahtic flow - ascites gets worse

Thrombocytopenia due to splenomegaly

oesophageal varicies

decreased active clotting factors, thrombocytopenia and varicies, severe bleeding

exudative enteropath y(lose

Question 23

Causes of protal hypertension

Answer 23

Increases vascular resistance

Prehepatic - PV thrombosis

Posthepatic - right heart failure, constrictive pericarditis

Intrahepatic - presinuosidal chronic hepatitis, PBC, granulomas - sinusoidal acute hepatitis, alcohol, fatty liver, toxins, posinusoidal - venous occlusive disease of venules and small veins, Budd-Chiari (obstruction of large HV - tumour or pressing)

Question 24

Portal Hypertension - consequences

Answer 24

Increase protein vein pressure

Mall absorption

Splenomeglay (anaemia and thrombocytopaenia)

Vasodilators (glucagon, VIP, substance P, prostacyclins)

Encephalopathy - toxins from intestine (NHS) normally extracted from portal blood by hepatocytes

Varices - thin walled collateral vessels

Question 25

What is encephalopathy

Answer 25

Apathy, memory gaps, tremor and liver coma

• Hyperammonaemia - GI bleeding and increased colonic proteins, liver can’t convert NH3 to urea
• Hypokalaemia - intracellular acidosis - activates ammonium formation - alkalosis

Tocins bypass leave - not extracted

False transmitters (e.g. serotonin) from aromatic amino acids result in increased liver failure

Transmitters - encephalopathy