Liver Flashcards
What does the liver metabolise?
- Carbohydrates
- Proteins
- Fat
- Steroid hormones
- Insulin
- Aldosterone
- Bilirubin
- Drugs and toxins
What does the liver synthesise?
- Proteins
- Clotting factors
- Fibrinogen
- Cholesterol
- 25-OH of vitamin D
- Glucose from fat and protein that it breaks down
- Production of bile
What are the liver immune cells called?
Kupffer
What does the liver store?
Fat soluble vitamins A, D, E, K, B12 and folic acid
What is bilirubin and what is the normal range?
- Product of RBC breakdown
- 5-20 micromol/L
- Transported to the liver in the serum attached to albumin, and transformed into a water-soluble conjugate which is excreted via the bile into the intestine
At what level of bilirubin is clinical jaundice?
> 50 micromol/L
In what situations doe bilirubin levels increase?
Levels increase in liver damage, haemolysis and cholestasis (reduction in bile flow)
What is ALP and what is the normal range?
Alkaline phosphatase
- 30-120 iu/L
- Found in liver, bone, intestine and placenta so not liver specific
If ALP is raised, what could that indicate?
- Levels increase in cholestasis, liver disease, damage to biliary tree
- If raised alone could be due to other reasons e.g. Paget’s Disease
What is GGT and what is the normal range?
- 5-55 iu/L
* Found in liver and binary epithelial cells, pancreas, kidneys, prostate, intestine
GGT can be increased without any liver damage. What could be the reason behind this?
Levels increase by enzyme inducers of GGT e.g. cancer, alcohol without there being damage to liver
What is albumin and what is the normal range?
- 35-55 g/L
- Produced by the liver
- Long half life (20-26 days)
- Protein that keeps fluid from leaking out of blood vessels
What could a decreased level of albumin lead to and mean?
Can lead to oedema
Decreased in chronic liver disease and when someone is malnourished
What could an increased prothrombin time/INR indicate?
- Clotting factors produced by the liver
* Increases in acute and chronic liver disease
What is an important thing to consider about LFTs in diagnosing liver dysfunction?
They are non specific
Generally, if there are 2 x upper limit of normal and you need at least 2 factors However, even in end stage liver disease, LFTs can come back normal because there are not enough hepatocytes working properly to produce some of those enzymes
You can also get impaired LFTs with no liver dysfunction e.g. infection
What are inherited and metabolic disorders causing liver disease?
Wilson’s disease- cannot excrete copper
Glycogen storage disease
What are signs and symptoms of chronic liver disease?
- Abdominal pain
- Tremor
- Jaundice
- Encephalopathy- confused, agitated
- Blood results - raised LFTs
- Spider naevi
- Pale
- Low BP
- Increased HR
What treatment is given in alcohol withdrawal and why?
- Pabrinex – bright yellow
* To prevent Wernike’s encephalopathy to happen, vitamin deficient due to poor diet and malabsorption in intestinal mucosa due to alcohol consumption
* Cells are damaged in intestine when you drink which are involved in metabolising vitamin B, so you become vitamin deficient which can cause motor and sensory problems
* Thiamine (B1) deficiency
* Two pairs of Pabrinex TDS IV (two pairs of ampoules) - Chlordiazepoxide
* Long acting BDZ 25-50mg every 2 hours PRN
* Slower onset of action so less likely to be addicted
* Don’t want to stop straight away as they will get tremors and seizures could happen and there is an algorithm for this
If the patient does not have enough clotting factors due to hepatic dysfunction, how would you give Pabrinex and why?
- Do not give IM Pabrinex, only IV:
Patient is coagulopathic as they do not have enough clotting factors- IM would give them a haematoma and would be very uncomfortable. Needs to be giving slowly because can get an allergic like reaction if given too quickly
What is Wernike’s encephalopathy and what causes it?
Learning and memory impaired, mortality risk. Caused by biochemical lesions of the CNS after exhaustion of B-vitamin reserves
If Werenike’s is not managed. what could it lead to?
Korsakoff’s syndrome, a chronic memory disorder
Why do you give a longer acting BDZ in alcohol withdrawal?
Slower onset of action and less likely to be addicted
What is the PK of BDZ in terms of metabolism?
BDZs are highly lipophilic and undergoes extensive liver metabolism, with most forming active metabolites
When would a shorter acting BDZ be appropriate in alcohol withdrawal?
Significant hepatic impairment as they may not be able to break down a longer acting one
e.g. Lorazepam or ozaxepam as they do not have active metabolites
Name some short acting BDZs and what wouldn’t be used in liver impairment?
Oxazepam or lorazepam
- Diazepam can be accumulated in liver impairment due to reduced metabolism so not used that much
When the patient is discharged after alcohol withdrawal, what formulation are they switched to?
IV to oral
What are the signs of alcohol withdrawal?
- Tremor
- Fear
- Rapid pulse
- Dehydration
- Seizures
What treatment should be given for hepatitis and what additional medication would you need to add in?
- Settling inflammation of the liver- prednisolone 40 mg OD for 5-7 days. Then you measure the Lille Score (calculates different liver function tests and if it has dropped below a certain threshold, then it has shown it has workedà then carry on for a month
- To switch off inflammatory component
- However, at risk of infection e.g. fungal and GI bleeding (so add in PPI)
What pharmacological management do you need to consider with a liver impairment patient after treating their immediate condition?
- Do an OGD (endoscopy in oesophagus) to check for varices
- Diuretics for ascites
- Propranolol for portal hypertension
- Vitamin K for coagulopathy
- ABX for bacterial peritonitis (infection of the ascitic fluid)
- Lactulose for hepatic encephalopathy
- ? Transplant
- May have complications related to alcohol - pancreatitis
What are the pharmacological and non-pharmacological treatments for abstinence?
- Psychological and drug treatments
- Disulfiram
- Naltrexone
- Acamprosate – huge tablets, problem with adherence
How does acamprostate work and what is the dose?
Any side effects?
- Derivative of taurine
- Stimulates GABA-ergic neurotransmission and antagonises effect of excitatory amino acid neurotransmission
- 666mg TDS with food for 1 year (2 tablets)
- Renally excreted and not metabolised by the liver
- Crosses BBB
- No sedative effects and minimal abuse potential
How does disulfiram work and any side effects?
- Irreversibly inhibits acetaldehyde dehydrogenase therefore leading to increased levels of acetaldehyde à hangover effect
- Initially 800mg OD then reduce by 200 mg a day to maintenance of 100-200 mg OD
- Duration varies
- Nausea, flushing, sweating for up to 30 minutes when you take alcohol. This effect may last up to 14 days post discontinuation
- Metabolised by the liver and renally excreted
- Side effect- hepatotoxicity so don’t like to use it in chronic liver disease patients
- Interacts with phenytoin
How does naltrexone work? Any side effects?
- Opiate antagonist to decrease alcohol craving
- 50mg OD
- IM preparation available
- Liver metabolised and renally cleared
- Side effect – hepatoxicity
Why could a platelet count be low in Chronic liver disease?
Lots of pressure in portal vein and cirrhosis-
blood flow is not going through to the liver so blood goes back to the spleen.
Starts to accumulate blood and platelets cannot be made properly. Spleen gets larger
What are the signs and symptoms of a variceal bleed?
- Pale- low Hb
- Low BP
- Tachycardia
- Passing fresh blood
How does liver disease lead to bleeding varices?
- Cirrhosis of the liver causes an increase in the intrahepatic vascular resistance due to architerctural distortion and deficiency of nitrix oxide.
- Portal hypertension results from a combination of increased intrahepatic resistance (decreased outflow) and splanchnic arteriolar vasodilation (increased inflow)
- Varices form in the oesophagus and stomach by dilation of preexisting vesseld and active angiogensisis.
They increase in size with the severity of portal hypertension and can rupture and bleed when the pressure exceeds a max point
What treatments should be given to a variceal bleed patient before endoscopy to find out where the bleed is?
- Fluid resuscitation to see if BP increases
- Blood transfusion Hb 8-10 target
- Correct clotting- do not want them bleeding out whilst doing the endoscopy
Fresh frozen plasma if INR>1.5 Vitamin K and PPI - Due to high risk of infection, most patients started on broad spectrum ABX Ciprofloxacin/Piperacillin + tazobactam (Tazocin)
- Terlipressin to increase BP
Why would WBC be raised in liver disease?
Liver Kupffer cells are not being produced properly so its own immune defence isn’t that good
How does terlipressin help to increase BP and what are the side effects?
- Synthetic analogue of vasopressin
- Splanchnic vasoconstriction (circulation of GI tract)
- 1-2 mg every 4-6 hours (continue until haemostasis and BP is achieved)
- Side effects- headaches, abdominal cramps and ischaemic colitis (but this can be monitored)
What alternative pharmacological treatment is there for acute variceal bleeding?
Somatostatin causes selective splanchnic vasoconstriction and reduces portal pressure and portal blood flow
Analogue of this is octreotide but there was no difference compared to placebo, and caused death
Why would you perform an OGD in a query variceal bleed patient?
To confirm bleed and locate it
What is sucralfate used for?
Used to coat ulcers to prevent those from bleeding
Why would you give lactulose in a variceal bleed patient?
Opens bowels as you don’t want to rupture the varices
What are the 4 procedures for variceal bleeds and which one is the most temporary measure?
- Band ligation
- Schlerotherapy
- Balloon tamponade- temporary measure
- TIPSS
What is band ligation?
Putting a tie around the enlarged veins so they cannot bleed and eventually will heal itself
What is schlerotherapy?
Burn the varices
What is balloon tamponade?
High complication
Put a balloon down and inflates, which mechanically presses on the veins to stop them bleeding
Temporary measure
What is TIPPS
Transjugular intrahepatic portosystemic shunt
Puts a shunt through so the blood only goes through the portal vein and not through tiny veins that will burst and bleed
What is the role of beta blockers in variceal bleed patients?
When would you initiate therapy?
What beta blockers could you use?
Treats portal hypertension
- Not started in acute phase due to low BP
- Start at lowest dose and titrate every 4-5 days
- Start when stable and any procedures have been done
- Need to monitor BP closely as it can drop back down again - systolic should not be <90mmHg and resting HR should not be <55 bpm
Non selective beta blocker - propranolol or carvedilol
- Splanchnic vasoconstriction (beta 2 blockade)
- Cardiac output results in reduced portal pressures (beta 1 blockage)
What does the Child Pugh score assess?
Assess prognosis of chronic liver disease
The liver produces all clotting factors apart from…?
Factor 8
What is paracentesis?
Drainage
What do you need to make sure you replace when draining ascitic fluid?
Albumin
What can ascites lead to?
Spontaneous bacterial peritonitis
What is ascites? How does it occur?
Accumulation of fluid in the peritoneal cavity leading to swollen abdomen
- Cirrhosis - portal hypertension
- Splanchnic arterial vasodilation
- Decrease in effective blood volume
- Stimulation of RAAS, sympathetic NS, arginine vasopressin
- Sodium and water retention
How is ascites managed?
- Drain if large volume
- Albumin given to replace nutrient that has been removed when ascites is drained
- Diuretic e.g. spironolactone, amiloride, furosemide
- Can be diuretic resistant
- Fluid and sodium restriction
- Drain if large volume
- TIPSS for stubborn/refractory ascites
What monitoring is required with ascites?
- Daily Us and Es
- Aim for 0.5-1kg/day weight loss
- Fluid chart (intake and output)
- Avoid high sodium contents
What are the complications associated with ascites?
- Hypo sodium
- Hyperkalaemia
- Muscle cramps
- SBP (infection)
- Hepatorenal syndrome
What is Spontaneous bacterial peritonitis and how is it diagnosed?
- Infection of ascitic fluid without any other source of sepsis around abdomen
- From gut/skin
- Ascitic tap to take portion of fluid and put it under microscope and count WBC count
- Neutrophil count > 250
- Mortality rate 40%
What is the treatment for spontaneous bacterial peritonitis?
3rd generation cephalosporins, co-amoxiclav, Piperacillin+Tazobactam
What is the prophylaxis for spontaneous bacterial peritonitis?
Norfloxacin or Ciprofloxacin
Life long
Should an episode of bacterial peritonitis be considered as an indication for liver transplantation assessment and why?
Yes due to the high mortality and poor one year survival (405)
What is a risk with Cephalosporin?
C Difficile
What is the MOA of pentoxifylline?
non-selective phosphodiesterase inhibitor which inhibits TNF alpha (pro-inflammatory cytokine)
