Liver Failure Flashcards
What is the normal plasma bilirubin concentration?
17 micromol/litre
At what concentration of plasma bilirubin will patients experience yellow sclera?
When the plasma bilirubin concentration increases above 30 micro mol/L
At what concentration of plasma bilirubin will patients experience yellowing of the skin alongside yellow sclera?
When the plasma bilirubin concentration increases above 34 micro mol/litre
What is cholestasis?
The slow cessation of bile flow
What does cholestasis normally result in?
Jaundice
What are the three types of jaundice?
- Pre-hepatic
- Intrahepatic
- Post Hepatic
What are the four most common causes of pre-hepatic jaundice?
- Haemolysis
- Massive transfusion
- Large intrathoracic haematoma
- Ineffective erythropoesis
What two things can cause an increase in haemolysis resulting in pre-hepatic jaundice?
- Haemolytic anaemia
- Toxins
How can blood transfusions lead to pre-hepatic jaundice?
Erythrocytes that have been transfused are short lived, and get broken down quickly compared to normal RBCs - therefore there is an excess of bilirubin leading to jaundice
How does a haematoma lead to increased risk of jaundice?
Body absorbs some of the haematoma, increasing the number of RBC’s and therefore increase amount of bilirubin in the blood
What are the four causes of intrahepatic jaundice?
- Decreased Uptake
- Decreased Conjugation
- Decreased Secretion
- Decreased Outflow
What is the name of the condition where you have a reduced uptake of bilirubin in the liver?
Gilberts syndrome
What is the name of the condition where you have a reduced conjugation of bilirubin in the liver?
Crigler-Najar syndrome
What is the name of the condition where you have a reduced secretion of bilirubin into the biliary cannaliculi?
Dubin-Johnson, Rotor syndrome
What are some causes of intrahepatic cholestasis (reduced outflow)?
Sepsis, drugs, total parenteral nutrition (IV food)
What are the two types of liver failure?
Chronic and Acute
What is the pathophysiology of liver failure?
When the rate of hepatocyte death is greater than regeneration
By what two mechanisms can hepatocytes die?
Apoptosis and Necrosis
What causes hepatocytes to die via apoptosis?
Paracetamol
What causes hepatocytes to die via necrosis?
Ischemia
What can liver failure lead to?
Coma and death due to multi-organ failure
What causes chronic liver disease?
Cirrhosis
What are the two types of Acute Liver Failure?
Fulminant and Subfulminant
What is meant by fulminant liver failure?
When the liver has failed very quickly (rapid degeneration in less than 8 weeks)
What is meant by subfulminant acute live disease?
When the liver progression has been less than 6 months
What is associated with fulminant liver failure
impaired synthetic function
encephalopathy - damage to brain
What can an increase in unconjugated bilirubin as seen in Crigler-Hajar syndrome lead to?
Brain damage in infants
What is the most common cause of liver failure in the west?
TOXINS
What is the most common cause of liver failure in the east?
inflammation
What three toxins can cause liver failure in the west?
- Paracetamol
- Amanita Phaliodes =death cap mushroom
- Bacillus cereus - a spore forming bacteria found in soil and food
Which strain of Hepatitis is generally found to cause liver failure in India?
Hepatitis E
Which strain of Hepatitis is generally found to cause liver failure in Hong Kong?
Hep B
What are 4 other causes of Acute Liver Failure?
- Pregnancy Diseases
- Idiosyncratic drug reactions
- Vascular diseases
- Metabolic Causes
What is a drug combination which can cause acute liver failure?
Amoxicilin and clauvonic acid =coamoxiclav
What is Wilson’s disease?
A metabolic cause of liver failure - where copper is deposited
Who does Reye’s syndrome most commonly affect?
Young children who have recently suffered from a recent viral infection
What are the five causes of chronic liver failure?
- Inflammation
- Alcohol Abuse
- Drug Side Effects
- Cardiovascular causes
- Inherited Diseases eg Wilsons
What is the most common inflammatry cause of chronic liver disease?
Chronic persistent viral hepatitis
The side effects of which drug can cause chronic liver failure?
Folic acid antagonists
The liver has many function, one being production of clotting factors. What can a distruption to this result in?
Coagulopathy and bleeding
The liver has many function, one being protein synthesis. What can a distruption to this result in?
Ascites
The liver has many function, one being Detoxification. What can a distruption to this result in?
Encephalopathy and cerebral oedema
The liver has many function, one being glycogen storage. What can a distruption to this result in?
Hypoglycaemia
The liver has many function, one Immunological funcion and globulin production. What can a distruption to this result in?
Increased suceptibility to infection
The liver has many function, one being maintainance of homeostasis. What can a distruption to this result in?
circulatory collapse, renal failure
How does liver failure lead to ascites?
- Liver failure leads to decreased protein synthesis
- Therefore albumin levels are lowered
- The fluid then leads out vasculature, resulting in a distended abdomen, full of fluid
What does a reduction in blood plasma volume as a result of ascites lead to?
- Low plasma volume = secondary hyperaldosteronism
- This results in too little K+ = hypokalaemia
- Alkalosis
Why does liver failure lead to increased risk of internal bleeding?
The liver makes all clotting factors, except VWF and 8
How does choleostasis aggrevate any bleeding tendancies?
- Cholestasis decreases bile salts which are needed for the absorption of fats and especially fat soluble vitamins like Vitamin K
- Therefore absorption is reduced
- Therefore decreased carboxylation of Vitamin K which clotting factors 2,7,9 and 10 are dependant on = GI Tract bleeding
What are the six mechanisms of cholestasis?
Canalicular dilation
↓ cell membrane fluidity
Deformed brush border
Biliary transporters
↑ tight junction permeability
↓ mitochondrial ATP synthesis
What are the consequences of cholestasis?
↑ BR → jaundice
Pruritus (itching)
Cholesterol deposition
Malabsorption
Cholangitis
What is a key physical sign that a patient might be presenting with cholestasis?
Scratch marks from pruritus = itching
Why does portal hypertension make ascites worse?
Because there is a reduction in lymphatic flow
What is the consequences of splenomegaly in portal hypertension?
Thrombocytopenia
What three factors contribute to severe bleeding due to portal hypertension?
- Reduction in active clotting factors
- Thrombocytopenia
- Varices
Describe the onset of exudative enteropathy
- Blood cannot get out small and large bowel
- Increase ascites
- Therefore loss of albumin from plasma
- This albumin is then favoured by bacteria in large bowel - bacteria feed on it
- This increases the liberation of ammonium which is toxic to the brain
What is the fundamental cuase of portal hypertension
Increased vascular resistance
What are the three classes of causes of portal hypertension?
- Prehepatic
- Post Hepatic
- Intrahepatic
What causes prehepatic portal hypertension?
Portal Vein thrombosis
What causes post hepatic portal hypertension?
Right heart failure
constrictive pericarditis
What are the three classes of portal hypertension?
Presinosoidal
Sinosoidal
Postsinusoidal
What can cause presinusoidal intrahepatic portal hypertension?
Chronic hepatitis, Primary Biliary Cirrhosis, schistosomiasis, TB
What can cause sinusoidal intrahepatic portal hypertension?
Alcohol, fatty liver, toxins, amyloidosis
What can cause postsinusoidal intrahepatic portal hypertension?
venous occlusive disease of veins and venules
What is Budd-Chiari Syndrome?
Obstruction of large hepatic veins
What are the five consequences of portal hypertension?
Malabsorption
Splenomegaly
Vasodilators
Encephalopathy
Varices
Describe how splenomegaly results in bleeding due to portal hypertension?
- Blood is trying to get out spleen via splenic arteries and veins but cannot
- Therefore blood pools and sequestrates
- First thing that gets used up are platelets = leading to thrombrocytopenia
- Therefore nothing to help clot blood so bleeding
Which vasodilators are released due to portal hypertension?
Glucagon, VIP, Substance P, prostacylins, NO
Portal hypertension causes vasodilators to be releases which decreases blood pressure. What is the effect of this?
Decreased blood pressure increases Cardiac Output
This results in the hyperperfusion of abdominal organs and worsens varices
How does encephalopathy get worsened by portal hypertension?
Toxins from the inestine release toxic substances like ammonia and ammonium
These would usually get removed in the liver, but blood cant reach liver due to portal hypertension, therefore stay in blood
Affects CNS
How does portal hypertension result in varices?
Since the main blood vessels have been blocked off, other thinner walled collateral vessels take on more blood and become swollen
What must you watch for with varices?
That they don’t rupture - this combined with thrombocytopenia from splenomegaly and loss of clotting factors = bleeding
What are the symptoms associated with encephalopathy?
Apathy, memory gaps, tremor, liver coma
Why does encephalopathy lead to hyperammonaemia?
Increased GI Bleeding due to less clotting factors increase colonic proteins - broken down into ammonium and ammonia which cannot be converted into urea by liver
How does hyperkalaemia lead to alkalosis?
→ intracellular acidosis → activates ammonium formation in proximal tubules → systemic alkalosis. .
Which toxins contribute to encephalopathy?
Amines, phenols, FFAs
What is the name given to substances made from aromatic amino acids in the brain which are increased in liver failure?
False Transmitters
What is an example of a false transmitter?
Serotonin
What is the most common place for portal-systemic anastomoses to occur as a result of varices?
Eosophageal tributaries of left gastric vein anastomose with tributaries of azygos vein
Where can portal-systemic anastomoses occur?
- gastric vein and azygos
- superior and middle + inferior rectal veins
- paraumbilical veins and superficial veins of anterior abdominal wall
How is the severity of liver failure assessed?
Child-Pugh Score
What are the five parameters of the child-pugh score?
Total Bilirubin
Serum albumin
INR
Ascites
Hepatic encephalopathy
What are the uses of the child-pugh score?
Tells you life-expectancy and the percentage peri-operative mortality
What are the supportive treatments for encephalopathy?
Reduce protein intake - decrease ammonia
phosphate enemas
no sedation
What is the supportive treatment to counteract hypoglycaemia?
Infusion of 10-15% dextrose
What is the supportive treatment to counteract hypocalcaemia?
10 ml 10% calcium gluconate
What is the supportive treatment to counteract renal failure?
Haemofiltration
What is the supportive treatment to counteract respiratory failure?
ventilation
What is the supportive treatment to counteract hypotension?
albumin
vasoconstrictors
What is the supportive treatment to counteract infection?
frequent cultures
Antibiotics
What is the supportive treatment to counteract bleeding?
Vitamin K
FFP
Platelets
What are the seven causes of death of liver failure?
AIRCROC
Acid-base and electrolyte disturbance
Infections (Bacterial and Fungal)
Renal failure
Circulatory instability
Respiratory failure
Odema (cerebral)
Coagulopathy
What are some liver support devices which are offered?
Artificial (MARS, Bio-Logic DT) - Albumin exchange system- based on selective removal of albumin-bound toxins from blood
Bioartificial (Hepatocytes in culture)
Hepatocyte transplantation
