Liver Flashcards
What does the liver metabolise?
- carbohydrates
- protein
- aldosterone
- Insulin
- bilirubin
- steroid hormones
DRUGS !!!!!
List the 6 main synthetic functions of the liver?
- proteins
- clotting factors
- fibrinogen
- cholesterol
- 25-OH of vitamin D
- glucose from fat and protein
What are the 5 main functions of the liver?
- Immunological (Kupffer cells)
- Storage (fat soluble vitamins)
- Glucose homeostasis
- Clearance of drugs/bilirubin/toxins
- Production of bile
What are the classes of Liver disease?
Can be:
- Cholestatic
- hepatocellular
They can overlap and both can lead to fibrosis and cirrhosis
What is cholestasis liver disease?
- Disruption of bile ducts
Intrahepatic: biliary ductules
Extrahepatic: mechanical obstruction
Ultimately you get impaired biliary excretion and reduced absorption of fatty substances.
Accumulation of bile salts can lead to damage of hepatocytes.
What is hepatocellular disease?
- Injury to hepatocytes
- Fatty infiltration (steatosis)
- Inflammation (hepatitis)
- Necrosis
what is fibrosis and Cirrhosis?
- Extensive hepatocyte damage (active deposition of collagen = formation of scar tissue = fibrosis)
- Cirrhosis = scar tissue takes over most of the liver.
Acute vs. Chronic liver disease
Acute - onset of symptoms does not exceed 6 months.
Acute liver failure - hyperacute, acute or subacute, depending on time from jaundice to encephalopathy.
Chronic - persists for more than 6 months, permanent structural changes following long standing cell damage.
Compensated vs. Decompensated
What are the normal bilirubin levels? What’s it function?
- Bilirubin (5-20 micromol/L)
- Product of RBC breakdown
- Attached to albumin
- transformed into a water-soluble conjugate which is excreted via the bile into the intestine.
Jaundice when bilirubin > 50 micromol/L
Liver function test
Transaminase enzymes
AST (0-40 iu/L)
ALT (5-30 iu/L)
— Levels increase in viral hepatitis, alcohol related liver injury, drugs, sepsis
Liver function tests
ALP and y-GT
Alkaline phosphatase (30-120 iu/L)
y-Glutamyltransferase (5-55 iu/L) = increased by enzyme inducers e.g. alcohol
Other tests that can tell us about liver function
- Albumin (35 - 50g/dL) = long half life (20-26 days)
- PT (10-14 secs)/ INR = short half-life (2-3 days)
PT/INR increase in acute and chronic liver disease
What is the Child’s Pugh scoring system ? And what does it take into account ?
Used to assess the prognosis of chronic liver disease.
Takes into account:
Bilirubin Albumin PT/INR Ascites Encephalopathy
What are the other investigations needed to assess liver function?
Liver ultrasound CT scan ERCP and MRCP MRI Fibroscan Liver biopsy MELD
-Never take LFTs in isolation !
What is Jaundice? How does it occur ?
Pre-hepatic jaundice - the disruption occurs before the bilirubin has been transported from the blood to the liver (sickle cell anaemia)
Intra-hepatic - disruption occurs inside the liver (Gilbert’s syndrome and cirrhosis)
Post-hepatic - disruption prevents the bile from draining out of the gallbladder (gallstones or tumours)
What is ascites?
Accumulation of fluid in the peritoneal cavity = swollen abdomen
- underfill = reduction circulating plasma volume
- overflow = increased plasma volume
- peripheral artery vasodilation
Ascites treatment ?
Diuretics:
- spironolactone
- Amiloride
- Furosemide
Fluid/sodium restriction
Paracentesis - drain fluids
Transjugular intrahepatuc portosystemic shuts (TIPS)
ASCITES monitoring
Monitor
- electrolytes
- daily weight
- fluid chart
- avoid high Na contents preparation
Hepatic encephalopathy
- Neuropsychiatric changes including changes in mood and behaviour, confusion, poor sleep rhythm, delirium and coma.
- due to accumulation of toxins, increased permeability of BBB, increased levels of neurotransmitters.
Hepatic encephalopathy treatments
Lactulose
Rifaximin
Metronidazole
Neomycin
Variceal bleeding and portal hypertension
Portal hypertension is caused by increased resistance to flow.
Collateral vessels form enabling the blood to bypass the liver
Variceal bleeding treatments
Terlipressin (potent splanchnic vasoconstrictor)
Somatostatin and analogues (causes selective vasoconstriction and reduces portal pressure on the portal blood flow).
Endoscopic (band ligation/ sclerotherapy/ballon tamponade)
What is spider Naevi ?
Central red arteriole, representing the body of the spider.
Cause: failure to metabolise oestrogen
What is Pruritus? (Caused by liver disease)
Severe itching of the skin
What are the Factors effecting drug handling in liver disease?
- Patient factors (such as LFTs)
- Drug factors (PK/PD/side effects)
- Therapeutic effect
Child-Pugh scoring system is used to make recommendations in drug SPCs.
Increased bilirubin effect on drugs
- Reduces absorption for highly lipophilic drugs = reduced clinical effect.
- Biliary clearance will be reduced = this may affect drugs which are cleared by biliary system e.g. digoxin.
- Competition for protein binding sites (potential displacement of drug = enhancing clinical effect) such as warfarin and phenytoin.
Decreased albumin effect on drugs
Decreased protein binding =
Highly protein bound drugs - increase in “free” drug available to act = increased clinical effect.
INR/PT effect on drugs
Dose adjustment if prothrombin time > 130% normal
Effect of liver disease on metabolism
High extraction ratio drugs
= drugs that are highly first-pass metabolised.
Reduced hepatic blood flow = increased bioavailability
What are the caused of reduced hepatic blood flow?
Cirrhosis Portal vein thrombosis Cardiac failure Shock ( reduced BP) Portal systemic shunting
Pharmacodynamic
Patients may be at risk of:
- Increased toxicity
- Exaggerated response
- Reduced response
Route of administration for liver disease
Oral – generally preferred
Avoid modified release and long-acting preparations
Avoid IM if coagulopathy
Topical preparations – consider transdermal absorption
Topical preparations – may cause irritation
PR – consider presence varices/bleeding
Risk factors which may pre-dispose drug induced liver disease
- Gender (tends to be more common in females)
- Age
- Genetics
- Concurrent diseases e.g. obesity, diabetes, co-infection with HIV
- Polypharmacy
Intrinsic drug induced liver disease
Predictable Reproducible Dose dependent Tend to occur rapidly e.g. within hours Tend to cause necrosis, acute liver failure E.g. paracetamol overdose
Idiosyncratic drug induced liver disease
Not predictable
Not reproducible
Not dose dependent
Tend to take longer to occur – weeks to months
Can result from metabolic idiosyncrasy or immunoallergic reaction
Can cause any type of liver injury e.g. increased LFTs, jaundice, fever, rash, eosinophilia
E.g. NSAIDS (metabolic), carbamazepine (immunoallegic)
Drugs that can cause liver disease
Cholestasis – OCP, warfarin, azathioprine
ALF – allopurinol, NSAIDS, MDMA
Steatosis – amiodarone, steroids, TPN
Fibrosis and Cirrhosis – methotrexate
Vascular disorders – OCP, azathioprine
Symptoms of alcohol withdrawal
Marked tremor Fear and delusions Restlessness and agitation Fever Rapid pulse Dehydration Seizures Delirium tremens
Alcohol withdrawal treatment
combination sedatives and vitamin supplementation – Chlordiazepoxide + Pabrinex
- Benzos can be given e.g. Diazepam
- Shorter acting, e.g. Oxazepam or lorazepam, more suitable in patients with hepatic impairment
Acute Alcoholic Hepatitis treatments
- Prednisolone 40mg OD for at least 5-7 days.
Problem: increased risk infection and GI bleeding - Pentoxifylline (Oxpentifylline)
Non-selective phosphodiesterase inhibitor which inhibits TNFα. - Other anti-TNF agents – Infliximab, Etanercept
Management of Alcoholic Cirrhosis
- Diuretics for ascites
- Propanolol for portal hypertension
- Vitamin K for coagulopathy
- Antibiotics for spontaneous bacterial peritonitis
- Lactulose for hepatic encephalopathy (+ avoidance precipitants)
How to achieve abstinence?
Abstinence can be achieved by:
Psychological treatments
Pharmacological treatments
Combination of both
Agents available:
- Acamprosate
- Disulfiram (Antabuse)
- Naltrexone
key points
- Patients may present at any stage – need to understand degree underlying dysfunction
- Abstinence is key
- Appropriate use of benzodiazepines in management of withdrawal
- For AAH – in severe cases Prednisolone treatment should be used but stopped after 7 days if no fall in bilirubin
