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PM2B Autumn Amy L > Liver Disease [McNeish} > Flashcards

Liver Disease [McNeish} Flashcards

1
Q

List the 4 major functions of the liver

A

Metabolism & digestion
Immunity
Detoxification
Storage of energy & nutrients

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2
Q

Explain first pass metabolism

A

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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3
Q

List 4 physiological features of the liver

A

Multi-lobed organ
Large blood supply
Hepatocytes line the sinusoids

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4
Q

How the liver is made up of lobes

A

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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5
Q

Describe the structure of the lobes in the liver

A

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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6
Q

What are hepatocytes?

A

Liver cells

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7
Q

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

A

Sinusoids

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8
Q

What fluid does the liver make?

A

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

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9
Q

What is the role of bile fluid?

A

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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10
Q

List 5 symptoms of liver disease

A

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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11
Q

What are liver function tests (LFTs)?

A

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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12
Q

Name 5 LFTs

A 
ALT (alanine transaminase) and AST (aspartate transaminase)
GGT (gamma glutamyltransferase)
Bilirubin (high levels)
Albumin (synthesised by the liver)
Clotting - prothrombin
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13
Q

How do the tests for ALT and AST work?

A

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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14
Q

How do tests for GGT work?

A

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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15
Q

How do tests for bilirubin work?

A

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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16
Q

How do tests for albumin work?

A

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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17
Q

How do tests for clotting (prothrombin) work?

A

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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18
Q

What are ALT & AST?

A

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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19
Q

What is the relevance of the AST:ALT ratio?

A

> 2 indicates alcoholic liver disease

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20
Q

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

A

Liver biopsy
Imaging
Laparoscopy/endoscopy

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21
Q

Explain the use of a liver biopsy to diagnose liver damage

A

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

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22
Q

Explain the use of imaging to diagnose liver damage

A

Generally ultrasound - often prior to or with a biopsy

CAT scan

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23
Q

How can liver disease be defined as acute or chronic?

A

By the time course or damage type

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24
Q

Describe acute liver disease

A

Self-limiting episode

History of disease

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25
Q

Describe chronic liver disease

A

Long term damage to the liver
>6 month episode
Potential for permanent structure change
- alcohol cirrhosis, non-alcoholic fatty liver disease (NAFLD)

26
Q

What does “acute on chronic” mean?

A

Sudden deterioration in ‘stable’ chronic patient

27
Q

Name the 2 types of damage that the liver can suffer from

A

Cholestatic

Hepatocellular

28
Q

Explain what cholestatic damage to the liver is

A

Bile flow is reduced or blocked to the duodenum and gall bladder
Increased levels of ALP, GGT, bilirubin, bile acids and cholesterol

29
Q

Explain what hepatocellular damage to the liver is

A

Damage to hepatocytes by inflammatory processes

ALT & AST released by damaged hepatocyte cells - therefore serum levels may be elevated

30
Q

What can both types of liver damage (cholestatic & hepatocellular) lead to?

A

Fibrosis (scarring)

31
Q

What can chronic injury (leading to early fibrosis) be caused by?

A

Alcohol
Viral infection
NASH (non-alcoholic steatohepatitis)

32
Q

What does the change from early fibrosis to cirrhosis indicate?

A

Loss of liver function

33
Q

What does cirrhosis indicate for the future of the liver?

A

Irrepairable damage

34
Q

What is early fibrosis?

A

Beginning of scarring

35
Q

Can cirrhosis be reversed?

A

Yes

Regression then resolution

36
Q

What further consequences can develop from cirrhosis?

A

Hepatocellular carcinoma = liver cancer

Liver transplant

37
Q

How does alcoholic fatty liver disease cause damage?

A

Generation of ROS (reactive oxygen species) leads to inflammation - causes damage
Most common cause of cirrhosis but generally reversible

38
Q

What are the 3 recognised stages of alcoholic liver disease causing cirrhosis?

A

Alcoholic fatty liver disease
Alcoholic hepatitis
Cirrhosis

39
Q

Explain the stage of alcoholic liver disease

A

Normally asymptomatic, can occur rapidly

Can be reversible by taking a break from alcohol

40
Q

Explain the stage of alcoholic hepatitis

A

Mainly due to chronic use of alcohol over a long period

Progression can be halted by stopping drinking

41
Q

Explain the stage of cirrhosis caused by alcoholic liver disease

A

Unlikely to survive more than 5 more years unless patient stops drinking

42
Q

Describe the management of alcoholic liver disease

A

Stop drinking alcohol

Diazepam = treats symptoms of alcohol withdrawal

43
Q

What is non-alcoholic fatty liver disease commonly caused by?

A

Obesity

44
Q

What are the 4 stages of non-alcoholic fatty liver disease?

A

Fatty liver - asymptomatic, may be detected by LFTs
NASH (non-alcoholic steatohepatitis) = inflammation, possibly pain
Fibrosis
Cirrhosis = degeneration of cells, inflammation, extensive scarring

45
Q

Name 3 classes of patient which are at risk of developing non-alcoholic fatty liver disease

A

Diabetes type II
Obese
Hypertension

46
Q

What is the recommended therapy for NAFLD/NASH?

A

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

47
Q

What are the 3 types of hepatitis?

A

A, B & C

48
Q

Profile Hepatitis A

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

49
Q

Profile Hepatitis B

A

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

50
Q

Profile Hepatitis C

A

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

51
Q

What are the symptoms of a paracetamol overdose?

A

Initially asymptomatic

Then nausea, vomiting, fatigue

52
Q

How is paracetamol overdose treated?

A

Acetylcysteine treatment IV

100% effective when given within 8 housrs of OD

53
Q

Name 2 drugs that should be avoided being given to patients with liver disease

A

Rifampicin and Fusidic acid

Excreted unchanged by the liver

54
Q

How does liver disease affect what a patient can be prescribed?

A

Liver disease seriously affects the metabolism and duration of drugs

55
Q

What makes it more likely for patients with liver disease to experience problems?

A

If the patient experiences jaundice, ascites, portal hypertension

56
Q

How does liver disease affect hepatic blood flow

A

Liver disease slows hepatic blood flow

57
Q

How can hepatic blood flow affect the dose of a drug administered?

A

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

58
Q

What is Hypoproteinemia?

A

Low blood protein

Symptom of another disease

59
Q

What are the consequences of hypoproteinemia for albumin?

A

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

60
Q

What are the consequences of hypoproteinemia for clotting factors?

A

Reduced clotting factors

Therefore increased sensitivity to anticoagulants e.g. warfarin

61
Q

How does hypoproteinemia affect fluid retention?

A

Increases fluid retention and ascites

PM2B Autumn Amy L (14 decks)

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