Liver Disease [McNeish} Flashcards
List the 4 major functions of the liver
Metabolism & digestion
Immunity
Detoxification
Storage of energy & nutrients
Explain first pass metabolism
Via portal vein (from GI to liver)
Concentration of orally-administered drug is greatly reduced before it reaches the systemic circulation
List 4 physiological features of the liver
Multi-lobed organ
Large blood supply
Hepatocytes line the sinusoids
How the liver is made up of lobes
The liver is a multi-lobed organ
Each lobe operates independently of each other so the liver therefore has a high capacity to regenerate
Describe the structure of the lobes in the liver
Each lobe consists of many lobules
Lobules are the functional unit, each has its own blood supply
Vein-like structures inside (sinusoids) = increased surface area
Hepatocytes (liver cells) line the sinusoids
What are hepatocytes?
Liver cells
What are the vein-like structures inside of the liver lobules called?
Sinusoids
What fluid does the liver make?
The liver makes bile fluid and stores it in the bile duct
What is the role of bile fluid?
Bile neutralises stomach acid and is a major way of fatty acid transport
Some drugs and waste products are stored in the bile to be excreted
List 5 symptoms of liver disease
Jaundice - caused by high bilirubin levels
Ascites = build up of fluid around the abdomen
Pruritus = severe itching of skin
Changes in urine/faeces colour - to do with bilirubin conjugation
Cutaneous signs = spider-like structures of burst blood vessels under the skin
What are liver function tests (LFTs)?
Generally blood tests
Mainly look at liver enzymes and proteins
Normal ranges vary - possible to have abnormal results and a functional liver
Name 5 LFTs
ALT (alanine transaminase) and AST (aspartate transaminase) GGT (gamma glutamyltransferase) Bilirubin (high levels) Albumin (synthesised by the liver) Clotting - prothrombin
How do the tests for ALT and AST work?
ALT & AST are found in hepatocyte cells
Increased levels of both indicate an inflamed hepatocytes
However, AST is highly expressed in muscles so could also indicate muscle damage
How do tests for GGT work?
Can be a very good indicator of liver disease however it is very heavily affected by alcohol
Increased ALP & GGT may indicate blocked bile ducts
How do tests for bilirubin work?
Bilirubin = breakdown product of haemoglobin
Liver is supposed to conjugate bilirubin - make more soluble so it can be excreted in urine
Indicator of poor liver function if high level of bilirubin but low level of conjugated bilirubin
How do tests for albumin work?
Albumin is synthesised by the liver
Carries bilirubin to the liver to be conjugated
If a decrease in albumin causes fluid retention = clear indicator of liver disease
How do tests for clotting (prothrombin) work?
Prothrombin = clotting factor, altered by absorption of fat-clotting vitamin K
Prothrombin time = 12-16 seconds (how long it takes for blood to clot)
Longer time = reduction in clotting factors
PT test may also be called an INR test (international normalised ratio) = 1.0-1.3
What are ALT & AST?
Aminotransferases - liver enzymes
Inflammation indicators - damaged hepatocytes release them into the bloodstream
ALT more specific to the liver as AST may indicate muscle damage
What is the relevance of the AST:ALT ratio?
> 2 indicates alcoholic liver disease
List 3 further tests which can be used to investigate whether the liver is damaged
Liver biopsy
Imaging
Laparoscopy/endoscopy
Explain the use of a liver biopsy to diagnose liver damage
Invasive
Histology and pathology performed
Most reliable diagnostic tool for confirming liver damage
Explain the use of imaging to diagnose liver damage
Generally ultrasound - often prior to or with a biopsy
CAT scan
How can liver disease be defined as acute or chronic?
By the time course or damage type
Describe acute liver disease
Self-limiting episode
History of disease
Describe chronic liver disease
Long term damage to the liver
>6 month episode
Potential for permanent structure change
- alcohol cirrhosis, non-alcoholic fatty liver disease (NAFLD)
What does “acute on chronic” mean?
Sudden deterioration in ‘stable’ chronic patient
Name the 2 types of damage that the liver can suffer from
Cholestatic
Hepatocellular
Explain what cholestatic damage to the liver is
Bile flow is reduced or blocked to the duodenum and gall bladder
Increased levels of ALP, GGT, bilirubin, bile acids and cholesterol
Explain what hepatocellular damage to the liver is
Damage to hepatocytes by inflammatory processes
ALT & AST released by damaged hepatocyte cells - therefore serum levels may be elevated
What can both types of liver damage (cholestatic & hepatocellular) lead to?
Fibrosis (scarring)
What can chronic injury (leading to early fibrosis) be caused by?
Alcohol
Viral infection
NASH (non-alcoholic steatohepatitis)
What does the change from early fibrosis to cirrhosis indicate?
Loss of liver function
What does cirrhosis indicate for the future of the liver?
Irrepairable damage
What is early fibrosis?
Beginning of scarring
Can cirrhosis be reversed?
Yes
Regression then resolution
What further consequences can develop from cirrhosis?
Hepatocellular carcinoma = liver cancer
Liver transplant
How does alcoholic fatty liver disease cause damage?
Generation of ROS (reactive oxygen species) leads to inflammation - causes damage
Most common cause of cirrhosis but generally reversible
What are the 3 recognised stages of alcoholic liver disease causing cirrhosis?
Alcoholic fatty liver disease
Alcoholic hepatitis
Cirrhosis
Explain the stage of alcoholic liver disease
Normally asymptomatic, can occur rapidly
Can be reversible by taking a break from alcohol
Explain the stage of alcoholic hepatitis
Mainly due to chronic use of alcohol over a long period
Progression can be halted by stopping drinking
Explain the stage of cirrhosis caused by alcoholic liver disease
Unlikely to survive more than 5 more years unless patient stops drinking
Describe the management of alcoholic liver disease
Stop drinking alcohol
Diazepam = treats symptoms of alcohol withdrawal
What is non-alcoholic fatty liver disease commonly caused by?
Obesity
What are the 4 stages of non-alcoholic fatty liver disease?
Fatty liver - asymptomatic, may be detected by LFTs
NASH (non-alcoholic steatohepatitis) = inflammation, possibly pain
Fibrosis
Cirrhosis = degeneration of cells, inflammation, extensive scarring
Name 3 classes of patient which are at risk of developing non-alcoholic fatty liver disease
Diabetes type II
Obese
Hypertension
What is the recommended therapy for NAFLD/NASH?
Currently no NICE guidelines on how to treat
Increase in exercise and improve diet
Treat underlying cause - better control of diabetes/hypertension/cholesterol
Avoid/reduce alcohol intake
What are the 3 types of hepatitis?
A, B & C
Profile Hepatitis A
Transmission = faecal-oral route (contaminated food, needles)
Symptoms = nausea, vomiting, mild fever
Acute, self-limiting (3-6 weeks)
No treatment required, however avoid alcohol while ill
Vaccination is available
Profile Hepatitis B
Transmission = contracted from infected blood products (sex, mother-baby during birth)
Symptoms = similar to hepatitis A, may take 1-3 months to present, blood test required for diagnosis
Some patients may progress to chronic hepatitis = further treatment with anti-viral drugs (20% may progress to cirrhosis)
Prevention = avoid high risk activities (needles, unprotected sex), vaccination for risk groups
Profile Hepatitis C
Caught from injected blood, rarely from unprotected sex
Generally asymptomatic/mild until chronic liver disease or cirrhosis
Diagnosis confirmed only from blood test
Treatment aims at achieving sustained viral clearance, anti-viral drugs
No vaccine
What are the symptoms of a paracetamol overdose?
Initially asymptomatic
Then nausea, vomiting, fatigue
How is paracetamol overdose treated?
Acetylcysteine treatment IV
100% effective when given within 8 housrs of OD
Name 2 drugs that should be avoided being given to patients with liver disease
Rifampicin and Fusidic acid
Excreted unchanged by the liver
How does liver disease affect what a patient can be prescribed?
Liver disease seriously affects the metabolism and duration of drugs
What makes it more likely for patients with liver disease to experience problems?
If the patient experiences jaundice, ascites, portal hypertension
How does liver disease affect hepatic blood flow
Liver disease slows hepatic blood flow
How can hepatic blood flow affect the dose of a drug administered?
Bioavailability of API is increased (less 1st pass metabolism) - dose may need to be reduced
Reduced 1st pass metabolism due to portosystemic shunting = liver bypassed by circulatory system
What is Hypoproteinemia?
Low blood protein
Symptom of another disease
What are the consequences of hypoproteinemia for albumin?
Low serum albumin
Albumin = main site of drug binding in plasma
Therefore low serum albumin = increased concentrations of free drug
Important for drugs that bind strongly to plasma proteins e.g. warfarin, phenytoin
What are the consequences of hypoproteinemia for clotting factors?
Reduced clotting factors
Therefore increased sensitivity to anticoagulants e.g. warfarin
How does hypoproteinemia affect fluid retention?
Increases fluid retention and ascites
