Liver Disease [McNeish} Flashcards by Amy Lockyer

List the 4 major functions of the liver

Metabolism & digestion
Immunity
Detoxification
Storage of energy & nutrients

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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

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List 4 physiological features of the liver

Multi-lobed organ
Large blood supply
Hepatocytes line the sinusoids

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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

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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

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What are hepatocytes?

Liver cells

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What are the vein-like structures inside of the liver lobules called?

Sinusoids

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What fluid does the liver make?

The liver makes bile fluid and stores it in the bile duct

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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

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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

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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

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Name 5 LFTs

ALT (alanine transaminase) and AST (aspartate transaminase)
GGT (gamma glutamyltransferase)
Bilirubin (high levels)
Albumin (synthesised by the liver)
Clotting - prothrombin

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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

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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

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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

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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

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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

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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

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What is the relevance of the AST:ALT ratio?

> 2 indicates alcoholic liver disease

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List 3 further tests which can be used to investigate whether the liver is damaged

Liver biopsy
Imaging
Laparoscopy/endoscopy

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Explain the use of a liver biopsy to diagnose liver damage

Invasive
Histology and pathology performed
Most reliable diagnostic tool for confirming liver damage

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Explain the use of imaging to diagnose liver damage

Generally ultrasound - often prior to or with a biopsy

CAT scan

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How can liver disease be defined as acute or chronic?

By the time course or damage type

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Describe acute liver disease

Self-limiting episode

History of disease

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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