Liver failure Flashcards
What causes jaundice?
BILIRUBIN:
- more than 30 micromoles/L=yellow sclera and mucous membranes(eyes)
- more than 34 micromoles/L =yellow skin
CHOLESTASIS:
-slow/cessation of bile flow=retention of contents of bile including bilirubin
What are the 3 types of jaundice?
Pre-hepatic Jaundice
Intrahepatic Jaundice
Post-hepatic Jaundice
What are the 4 main cause of Pre-hepatic jaundice?
1) Haemolysis(as when RBCs breakdown they release bilirubin):
- Haemolytic anaemia
- toxins
2) Massive transfusion -where the transfused erythrocytes are short lived
3) Large Haemotoma reabsorption- this is broken down and this leads to high bilibrubin
4) Ineffective erythropoiesis
What are the causes of post hepatic jaundice?
(also called obstructive jaundice)
interruption to drainage of bile containing conjugated bilirubin caused by:
- GALLSTONES blocking the common bile duct
- CANCER in the head of the oancreas
What are causes of Intra-hepatic Jaundice?
Autosomal recessive disorders in the liver:
- GILBERTS SYNDROME-decreased bilirubin uptake into liver =more unconjugated bilirubin in blood (5%)
- CRIGLER-NAJAR SYNDROME-decreased conjugation of Bilirubin=gets into blood stream=can cross blood brain barrier(can happen in infants)
- DUBIN JOHNSON +ROTOR SYNDROME-decreased Bilirubin secretion into bilary canaliculi
Intrahepatic Cholestasis:
- decreased bilirubin output
- sepsis, TPN , drugs
Liver Failure
What is the differnece between conjugated and non-conjugated bilirubin
Conjugated is not toxin
-conjugated is made in the liver when unconjugated bilirubin binds to gucoronic acid
What si the pathophysiology of liver failure?
- When rate of hepatocyte death> regeneration
- combination of apoptosis and necrosis
- can lead to death and coma
What are the twon types of liver failure?
ACUTE LIVER FAILURE:
- fuliment hepatic failure=rapid development (less than 8 weeks)
- impaired synthetic function
- encephalopathy
- previously normal liver of well compensated liver disease
CHRONIC LIVER DISEASE:
- over years
- cirrhosis
What are the common causes of acute liver failure in the west and east?
In the West:Toxins
- too much paracetomal
- Amanita Phalloides(mushrooms)
- Bacillus cereus(bacteria)
In the east:inflammation
- Exacerbation of chronic Hepatitis B(hong kong)
- Hepatitis E(India)
What are other rare causes of acute liver disease?
Diseases of Pregnancy:
-AFLP, HELLP syndrome, hepatic infarction, HEV, Budd-Chiari
Idiosyncratic drug reactions:
- Single agent-isoniazid, NSAIDS, valproate
- Drug combinations- amoxicillion/ clavulonic acid, trimethoprim/sulphamethoxazole, rifampicin/isoniazid
Vascular disease:
- ischaemic hepatitis
- post-OLTx
- hepatic artery thrombosis
- post arrest
- VOD
Metabolic causes:
- Wilsons diseases(deposition of too much copper)
- Reye’s syndrome(if kids take aspirin after flu or chickenpox)
What are the causes of chronic liver failure(Cirrosis)?
INFLAMMATION:
-chronic persistant viral hepititis
Alcohol abuse
SIDE EFFECTS OF DRUGS:
- folic acid antagonists
- phenylbutazone
CARDIOVASCULAR CAUSES:
-decreased venous return=right heart failure = knok on effect on liver
INHERITED DISEASES:
- glycogn storage diseases
- wilsons disease
- Galactosaemia
- Haemochromatosis
- alpha 1 antitrypsin defficiency
NON-ALCOHOLIC STEATOHEPATITIS(NASH):
-fatty liver
AUTOMIMMUNE HEPATITIS:
-PBC, PSC
Describe the development of chronic liver disease?
1) Necrosis of hepatocyte
2) enzymes release that kick of cytokines
3) cytokines and cell debri activates Kupiffer cells that realease growth factors
4) This stimulates Ito fat cell(hepatic stellate cell)=production of myofibroblasts= increased deposition of cellular matrix
5) at the same time ctokines and cell debri both cause chemotaxis of inflammatory cells(monocytes-> macrophages) and macrophages = fibroblast proliferation=increased deposition of matrix
6) increased matrix =FIBROSIS= CIRRHOSIS
7) Cirrhosis= metabolic failure, cholestasis and portal hyper tension
What are normal liver functions and the consequences of Hepatocyte/liver failure whcih stop these functions?
Production of clotting factors-coagulation and bleeding
Protein synthesis-Ascites(decreased albumin), decreases clotting factors
Detoxification- encephalopathy and cerebral odeoma
glycogen storage-hypoglycaemia
immunological function and globin production-increased susceptibility to infection
Maintainence of homeostasis-circulatory collapse and renal failure
What is the funtion of albumin?
What does decreased albumin lead to?
- Albumin keeps fluid in your blood stream so it doesnt leak into other tissues
- less albumin production = fluid leak out of capillaries=plasma volume decrease=secondary hyperaldosteronism, hypokalaemia(decreased k+), alkolosis(excess alkaline in body fluids and tissue which can cause cramp and musle weakness)
less albumin=ASCITES(build upn of fluid in the abdominal cavity)
Which clotting factors do hepatocytes synthesis?
all except-von willebrand factor and factor VIIIC
What are the problems caused by cholestasis?
aggravates bleeding tendencies:
-decreases in bile salts=decrease in micelles and vit K absorption, decrease in y-carboxlation of VIT K DEPENDENT CLOOTING FACTORS(prothrombin(II), VII, IX, X)
What are the 5 mechanisms of Cholestasis?
- bilary canalicular dilation(bilary obstruction)
- decreased cell membrane fluidy due to increase in cholestrol=deformed brush borders
- Bilary transporters in the wrong place(basplateral side instread apical side where it should be pumping things into bile)
- tight juction permeability is increased
- mitochondrial ATP production decreased
What are the consequences of cholestasis?
ICTURUS- another name for jaundice
PRURITUS-itching often due to bile salts being deposited under skin
CHOLESTROL DEPOSITION
MALABSORPTION-due to bile defficiency
CHOLANGITIS
What can liver failure lead to?
Cholestasis
Portal hypertension
hypoalbuminia-less albumin
What is portal hypertension?
What problems does it cause?
Blood is supposed to go from portal vein to liver, but if it cant use this route it uses other vessels which are MUCH smaller =bad
Problems:
- Blood coming from the spleen cant enter liver=back pressure =SPLENOMEGALY(enlarged spleen)=THROMBOCYTOPENIA(reduction in platelets(thombocytes)
- OESOPHAGEAL VARICES
- combination of decreased clotting factors in liver failure, thrombocytopenia, varices, and small vessels carrying too much blood(ruptue) = SEVERE BLEEDING
- EXUDATIVE ENTEROPATHY-loss of albumin from the blood into large bowel=feeds bacteria =produces ammonia (toxic to the brain
What are the causes of portal hypertension?
Prehepatic:
-Portal vein thrombosis
Post-hepatic:
- right heart failure
- constrictive pericarditis
Intrahepatic:
-Presinousoidal-chronic hepatitis, PBC, granulomas(TB)
- sinusoidal-acute hepatitus, alcohol, fatty liver, toxins, amyloidosis
- Post sinosoidal- venous occulsive disease of venules and small veins, Budd-chiari syndrome
What are the consequences of portal hypertension?
increased portal vein pressure:
MALABSORPTION-as blood cant enter the liver
SPLENOMEGALY
VASODILLATORS-decrease blood pressure but this mean cardiac output increases to make up for this= HYPERPERFUSION(increased blood pressure ) in abdo organs= increased varices(enlarged swollen veins) as blood travels thorugh small alternative pathways
ENCEPHALOPATHY-toxins (ffa, biogenic amines, NH3) form intestines that are normally extracted from blood in portal vein by hepatocytes crossing the blood brain barrier
VARICES- thinwalled collateral vessels =bleeding
What are the causes for hepatic Encephalopathy?
Encephalopathy-brain disease/damage/malfunction
HYPERAMMONEAMIA-GI bleeding =increased protein in bowel=feeds bacteria = produces nitogen/ammonia
HYPERKALAEMIA-intracellular acidosis=activates ammonium formation in proximal tubes=systemic alkolosis OR hyperventilation of lungs=alkalosis
TOXINS(amines, phenyl, ffa)-bypass liver =not extracted from blood=go to brain=encephalopathy
FALSE TRANSMITTERS- toxins can cause production in serotonin and others from aromatic amino acids in the brain=increased liver failure=encephalopathy
What organs blood goes toward the portal vein which goes to the liver?
GI Tract, pancreas, spleen
everything else should be ging to the systemic venous system
What happens when organs that send blood to the liver via the portal vein cant do it via this vein?
there are some places where the portal blood supply anastomoses with the systemic venous supply- blood can go through these pathways and htis froms VARICES
What are the common portal-system anastomoses that form varices?
- eosophageal tributaries of the left gastric vein (from portal vein) connect to the tributaries of the azygous vein(conneceted to vena cava). This forms eosphageal VARICES(common place of bleeding)
- middle and inferior rectal veins anastomose with vena cave
- paraumbilial vein(normally closed) opens up and connects with superficial veins of anterior abdominal wall
What is hepatorenal syndrome?
kidney failure seen in people with severe liver damage
What causes hepatorenal syndrome?
liver disease=portal hypertension and decrease cardiac output=splenic artery vasodialation=decreased vascular resistance=acivation of vsoconstriction factors=renal vasoconstriction=renal failure
How do work out the severity of liver failure?
CHILD PUGH SCORE:
assesses 5 parameter and then gives it a score
What is a clinical sign of liver failure?
ASTERIXIS-tremour of the hand when wrist is extended
-known as ‘liver flap’
What is the treatment for each of the problems involved in liver failure?
ENCEPHALOPATHY:
- Reduce protein intake
- give phosphate enemas/lactulose (clear bacteria)
- no sedation
HYPERGLYCAEMIA:
-IV glucose(10-50% dextrose)
HYPOCALCAEMIA:
10ml of 10% calcium gluconate
RENAL FAILURE:
-haemofiltration
RESPIRATORY FAILURE:
-ventilation
HYPOTENSION:
- albumin
- vasoconstrictors
INFECTION:
-frequent blood tests
BLEEDING:
- vit K
- FFP (fresh prozen plasma)
- Platelets
What are causes of death fron people with liver falure?
- Bacterial and fungal infections
- circulatory instability
- cerebral odema
- renal failure
- respiratory failure
- acid-base and electrolyte ditubance
- coagulopathy
What are alternative treatments if the normal treament doesnt work?
- Artificial albumin exchange system(MARS)-removal of albumin from the blood based on albumin bound toxins
- Bioartificial-diffusing blood through hepatocyte cultures
Hepatocyte(liver ) transplant
What are the indications you need a liver transplant?
Cirrosis-58%
cancer-14%
cholestatic disease-10%
acute liver failure -8%
Metabolic disease-6%
others(buud chiari, beneign liver tumours, polycystic liver disease)-4%
In a liver transplant which vessels do you have to cut?
- divide inferior vena cave under the liver as is goes in and above the liver as it leaves
- portal vein
- hepatic duct
- cystic duct
- common hepatic duct
and then you replace the liver and rejoin the vessels
What is the survival rate if you have a liver transplant?
What is the chance of disease reoccuring?
5 years(60-80%)
no recurrence but pateint will require lifelong immuno-supressants
