(SYNOPTIC) Liver Disease & Management Flashcards

1
Q

What percentage of the liver is comprised of hepatocytes?

A

60%

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2
Q

How many blood supplies does the liver have?

A

2

Hepatic artery (from heart)
Portal vein (blood from the bowel)
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3
Q

What are the functions of the liver?

A

(1) Metabolism
(2) Synthesis
(3) Immunological
(4) Storage
(5) Secretion
(6) Homeostasis

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4
Q

What are some examples of substances metabolised in the liver?

A
  • Products of digestion
  • Bilirubin
  • Steroid hormone
  • Insulin
  • Aldosterone
  • Vitamin D
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5
Q

What is synthesised in the liver?

A
  • Plasma proteins
  • Clotting factors
  • Cholesterol
  • Urea (from amino acids)
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6
Q

What is stored in the liver?

A
  • Fat soluble vitamins
  • Glycogen
  • Blood reservoir
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7
Q

What is secreted in the liver?

A

Bile + bile salts

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8
Q

What is the function of the liver in homeostasis?

A

Glucose regulation

Conversion of glucose to glycogen

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9
Q

What are some potential causes for chronic liver disease?

A
  • alcohol
  • NAFLD/ NASH
    ø Non-alcoholic fatty liver disease
  • immune/ autoimmune
  • drugs
  • malignancy
  • HCV/ HBV
    ø Hep C + Hep V
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10
Q

What are some potential causes for acute liver disease?

A
- HAV/ HBV/ HEV
  ø 3rd trimester of pregnancy
- Drugs
- TPN
- Infection, e.g. malaria
- Ischaemia
- Alcoholic hepatitis
- Acute fatty liver of pregnancy
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11
Q

What increases risk of non-alcoholic fatty liver disease?

A
  • T2DM
  • Obesity
  • Dyslipidaemia
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12
Q

What may be the first presentation of NAFLD?

A

Cirrhosis

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13
Q

What is the non-pharmacological management of NAFLD?

A
  • Weight loss
  • Healthy diet
  • Exercise
  • Smoking/ alcohol cessation
  • 2-3 cups of black coffee daily
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14
Q

What is the pharmacological management of NAFLD?

A
  • Statins

- Treat HTN/ T2DM

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15
Q

What co-morbidities can make a HepC (HCV) infection worse?

A

(1) HIV
(2) Underlying cirrhosis
(3) Liver transplant
(4) Lifestyle

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16
Q

What is the process of chronic liver disease development?

A

(1) Insult
- e.g. toxin/ virus
(2) Hepatitis or steatohepatitis
(3) Reversible
- if cause is stopped, e.g. alcohol cessation
(4) If insult is not removed
(5) Fibrosis
- scarring + thickening of smooth muscle
(6) Cirrhosis

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17
Q

What is the general classification of liver disease?

A

(1) Compensated
- Asymptomatic due to medication/ sufficient healthy liver tissue for normal function
(2) Decompensated
- Symptomatic

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18
Q

What is a liver function test?

A

Used to identify patients struggling with liver/ biliary tract disease

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19
Q

What is a downside of liver function tests when checking for liver disease?

A

Some LFTs reflect liver DAMAGE rather than function

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20
Q

What results from a liver function test are considered a cause for concern?

A

3 times the upper limit of normal

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21
Q

How should a liver function test be used?

A

(1) Look for trends

(2) Do not use in isolation

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22
Q

What would a liver function test (LFT) show in acute hepatocellular damage?

A
HIGH - plasma ALT
HIGH - plasma AST
HIGH - bilirubin (unconjugated)
PROLONGED - prothrombin time
NORMAL - albumin
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23
Q

What would a liver function test (LFT) show in chronic hepatocellular damage?

A

NORMAL - ALT
NORMAL - AST
LOW - albumin
PROLONGED - prothrombin time

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24
Q

What would a liver function test (LFT) show in cholestasis (blockage of bile duct)?

A

HIGH - plasma ALP

HIGH - bilirubin (conjugated)

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25
Q

What other investigations can be done alongside a liver function test (LFT)?

A

(1) Ethanol
(2) Drug history
(3) FBC
(4) Clotting
(5) U+Es
(6) Liver ultrasound
(7) Biopsy
(8) Liver screen
- if obstruction ruled out
- check for viral causes

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26
Q

How is acute liver failure graded?

A

(1) Hyperacute
- 6-7 days
(2) Acute
- 8-28 days
(3) Subacute
- 29-84 days

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27
Q

In which liver failure grade(s) is cerebral oedema rare?

A

Subacute

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28
Q

In which liver failure grade(s) is cerebral oedema common?

Hyperacute/ acute/ subacute

A

(1) Hyperacute

(2) Acute

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29
Q

What is the prognosis for each liver failure grade?

A

Hyperacute - moderate
Acute - Poor
Subacute - Poor

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30
Q

What is used to grade chronic liver disease?

A

(1) Child’s Pugh Score

(2) MELD
- Model for end-stage liver disease
- OR UKELD

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31
Q

What are the grades for chronic liver disease using the Child’s Pugh Score?

A

(1) A 5-6 points COMPENSATED
(2) B 7-9 MODERATE
(3) C 10-15 ADVANCED

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32
Q

What is the MELD score used for?

A

Determining the mortality of end-stage liver disease

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33
Q

What are some common symptoms of liver disease?

A

(1) Jaundice - yellowing of eye
(2) Spider nevi in upper chest
(3) Ascites - accumulation of fluid in peritoneal cavity
(4) Clubbing of nails
(5) Dilated abdominal veins
(6) Ankle oedema
(7) Bleeding tendency due to decreased prothrombin time

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34
Q

Which blood vessel brings blood to the liver from the heart?

A

Hepatic artery

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35
Q

Which blood vessel brings blood to the liver from the bowel?

A

Portal vein

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36
Q

How many general functions of the liver are there?

A

6

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37
Q

What are the general functions of the liver?

A

(1) Homeostasis
(2) Storage
(3) Metabolism
(4) Immunological
(5) Secretion
(6) Synthesis

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38
Q

Name some causes of chronic liver disease.

A
  • Alcohol
  • NASH/ NAFLD
  • Drugs
  • Malignancy
  • Autoimmune
  • HCV/ HBV
  • Metabolic, e.g. haemochromatosis
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39
Q

Name some causes of acute liver disease.

A
  • Drugs
  • TPN
  • Ischaemia
  • Infection
  • Alcoholic hepatitis
  • Acute fatty liver of pregnancy
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40
Q

What is non-alcoholic fatty liver disease?

A

A range of liver diseases

From simple fatty liver -> Non-alcoholic seato-hepatitis -> Fibrosis/ cirrhosis

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41
Q

What are some risk factors for NAFLD?

A
  • Diabetes
  • Obesity
  • Dyslipidaemia (metabolic syndrome)
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42
Q

What is the non-pharmacological management for NAFLD?

A
  • Weightloss
  • Healthy diet
  • Exercise
  • Stop smoking/ alcohol
  • 2-3 cups of black coffee daily
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43
Q

What is the pharmacological management for NAFLD?

A
  • Treat BP
  • Treat diabetes
  • Statins
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44
Q

What patient groups are at higher risk of Hepatitis B?

A
  • IV drug users
  • Casual sex
  • Close family members
  • Babies born to infected mothers
  • HCPs
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45
Q

What are the stages of progression of chronic liver disease?

A

(1) Insult
- e.g. toxin/ virus

(2) Hepatitis/ steatohepatitis

(3) Reversible
- liver is regenerating

(4) Insult not removed

(5) Fibrosis
- thickening + scarring

(6) Cirrhosis
- chronic liver disease

46
Q

What is compensated chronic liver disease?

A

Asymptomatic

Sufficient meds/ tissue to continue normal function

47
Q

What is decompensated chronic liver disease?

A

Symptomatic

48
Q

What result of a LFT is considered to be cause for concern?

A

3x upper limit of normal

49
Q

What LFT results would be expected in acute hepatocellular damage?

A
  • Large rise in ALT + AST
  • 2y rise in unconjugated bilirubin
  • Prolonged PT
  • Normal albumin
50
Q

What LFT results would be expected in chronic hepatocellular damage?

A
  • Fairly normal ALT + AST
  • Prolonged PT
  • Low albumin
51
Q

What LFT results would be expected in cholestasis?

A
  • Rise in ALP

- Rise in conjugated bilirubin

52
Q

What is cholestasis?

A

Blockage of the bile duct

53
Q

Name some other investigations that can be carried out to determine liver damage/ function, alongside LFTs.

A
  • Ultrasound of liver
  • Biopsy
  • Liver screen (if known no obstruction)
54
Q

What are the grades of acute liver failure?

A

(1) Hyperacute
(2) Acute
(3) Subacute

55
Q

How many grades of acute liver failure are there?

A

3

56
Q

What is the time from jaundice to encephalopathy in hyperacute liver failure?

A

6-7 days

57
Q

What is the time from jaundice to encephalopathy in acute liver failure?

A

8-28 days

58
Q

What is the time from jaundice to encephalopathy in subacute liver failure?

A

29-84 days

59
Q

In which grades of acute liver failure is cerebral oedema common?

A
  • Hyperacute

- Acute

60
Q

When does renal failure occur in hyperacute liver failure?

A

Early

61
Q

When does renal failure occur in acute liver failure?

A

Late

62
Q

When does renal failure occur in subacute liver failure?

A

Late

63
Q

What is ascites?

A

Abnormal fluid buildup in the abdomen.

64
Q

In which acute liver failure types is coagulation disorder considered marked?

A

Hyperacute and acute

65
Q

What is the prognosis of hyperacute liver failure?

A

Moderate

66
Q

What is the prognosis of acute liver failure?

A

Poor

67
Q

What is the prognosis of subacute liver failure?

A

Poor

68
Q

What is the Child’s Pugh Score used for?

A

Grading of chronic liver disease (cirrhosis)

69
Q

How is cirrhosis graded?

A

(1) Child’s Pugh Score

(2) MELD/ UKELD

70
Q

Name some symptoms of liver cell failure.

A
  • Coma
  • Spider nevi
  • Gynecomastia
    ø enlargement of male breasts
  • Jaundice
  • Ascites
  • Loss of sexual hair
  • Testicular atrophy
  • Bleeding tendency
    ø decreased prothrombin
  • Anaemia
  • Ankle oedema
71
Q

Name some symptoms of portal hypertension.

A
  • Oesophageal varices
  • Gastropathy
    ø melaena
  • Splenomegaly
  • Dilated abdominal veins
  • Ascites
  • Haemorrhoids (rectal varices)
72
Q

What are some causes of ascites?

A
  • Impaired aldosterone metabolism
  • Low albumin
  • Reduced renal blood flow
  • Portal hypertension
  • Increased hepatic lymph production
73
Q

Which drugs, generally, can exacerbate ascites and peripheral oedema?

A
  • NSAIDs
  • Salt
  • Saline
74
Q

What is the treatment for ascites?

A

(1) Fluid + salt restriction

(2) Spironolactone
- aldosterone antagonist

(3) Furosemide
- for peripheral oedema

(4) Paracentesis
- Removal of peritoneal fluid

(5) TIPSS
- connect portal vein to hepatic vein in the liver

(6) Peritoneo-venous shunt
- peritoneal fluid from peritoneum into veins

75
Q

What is hepatic encephalopathy?

A

Reversible changes in mental state

2y to failure of liver, due to inability to metabolise toxins

76
Q

What are the stages of hepatic encephalopathy?

A

(1) Forgetfulness/ confusion/ agitation
- >
(4) Coma + unresponsive to painful stimulus

77
Q

How many stages of hepatic encephalopathy are there?

A

4

78
Q

What is the treatment of hepatic encephalopathy?

A
  • Remove/ avoid precipitants
  • Reduce protein intake
  • Decrease bacterial ammonia production
  • Increase elimination of bacteria ammonia production
79
Q

What is the pharmacological treatment for hepatic encephalopathy?

A

(1) Lactulose
- prevents constipation, inhibits colonic bacteria

(2) Phosphate enemas

(3) Rifaximin
- poorly absorbed Abx, eliminates colonic bacteria

80
Q

What is pruritus?

A

Severe itching of the skin

81
Q

How does chronic liver failure cause pruritus?

A
  • Bile acid build up in the skin
82
Q

What is the pharmacological treatment for pruritus, secondary to liver failure?

A

(1) Chlorphenamine, be careful due to masking hepatic encephalopathy
(2) Menthol in aqueous cream

83
Q

How is VTE risk evaluated in liver failure?

A

PT

Prothrombin time

84
Q

Which administration route should be avoided in VTE, secondary to liver failure?

A

IM

Can lead to haematoma

85
Q

What is a variceal haemorrhage?

A

Bleeding of varices in GIT

86
Q

What causes a variceal haemorrhage?

A

(1) Decrease blood flow through liver
(2) Portal HTN (>12mmHg)
(3) Collateral vessels
(4) GIT varices

87
Q

What is DILI?

A

Drug induced liver injury

88
Q

What are the types of DILI?

A

(1) Type A - intrinsic

(2) Type B - idiosyncratic

89
Q

Describe Type A (intrinsic) DILI (drug induced liver injury)

A
  • Predictable
  • Dose related
  • Occurs rapidly
  • Causes necrosis/ acute liver
  • Can occur at lower doses if LD already
  • Direct toxicity of drug/ metabolite
  • Often identified in clinical trials
  • Reproducible in animal models
90
Q

Describe Type B (idiosyncratic) DILI.

A
  • Unpredictable
  • May/ may not be dose related
  • Tends to take longer to occur (weeks->months)
  • Often more frequent if pre-existing LD
  • Accounts for >90% of cases
91
Q

What website/ source can be used to identify causative agent(s) of drug-induced liver injury (DILI)?

A

LiverTox

92
Q

What drug class has the highest incidence for causing DILI?

A

Antimicrobials

93
Q

What drug class has the second highest incidence for causing DILI?

A

Herbal and dietary supplements

94
Q

Which metabolite of paracetamol is toxic?

A

NAPQI

95
Q

What is the antidote for paracetamol?

A

N-acetylcysteine

96
Q

What are inducers of P450 enzymes in the liver?

A
  • Carbamazepine
  • St John’s Wort
  • Phenytoin
  • Rifampicin
  • Ethanol
97
Q

What are inhibitors of P450 enzyme in the liver?

A
  • Erythromycin
  • Amiodarone
  • Protease inhibitors
  • Ciprofloxacin
98
Q

What are some prescribing tips for drugs and the liver?

A
  • Most drugs are safe in stable liver disease
  • Use older + more established drugs
  • Avoid drugs
  • Start with small dose and increase slowly
  • Choose best option and monitor clinical response
99
Q

Which analgesics should be actively avoided in hepatic impairment?

A

NSAIDs + COX2 inhibitors

100
Q

For which analgesics should there be caution when used in hepatic impairment?

A

Opioids

e.g. codeine is metabolised to active form in the liver

101
Q

Are tricyclic antidepressants suitable in hepatic impairment?

A

Yes, at low doses

102
Q

How should neuropathic pain be treated in hepatic impairment?

A

Gabapentin is suitable

103
Q

What should be the antidepressant choice in hepatic impairment?

A
  • Sertraline/ citalopram
  • TCAs should be avoided due to sedating effect
  • Mirtazepine is also suitable, due to low bleeding risk but has a sedating effect
104
Q

When should statins be avoided in hepatic impairment?

A

(1) Acute liver disease

(2) Decompensated chronic liver disease

105
Q

How can seizures from alcohol withdrawal be prevented?

A

Benzodiazepine

  • Chlordiazepoxide
  • Diazepam
  • Lorazepam
106
Q

What is chlordiazepoxide?

A

Anxiolytic + anticonvulsant

107
Q

When should a chlordiazepoxide dose be reassessed, when used in alcohol withdrawal?

A

If >3 PRN doses are required in 24hrs

108
Q

On a flexible chlordiazepoxide regimen, for alcohol withdrawal, what should the review criteria be?

A

Calculate every 2-4hrs depending on severity

109
Q

Is this drug long, intermediate, or short-acting? Diazepam

A

Long-acting

110
Q

Is this drug long, intermediate, or short-acting? Lorazepam

A

Short/ intermediate-acting

111
Q

Is this drug long, intermediate, or short-acting? Oxazepam

A

Short/ intermediate-acting

112
Q

Is this drug long, intermediate, or short-acting? Chlordiazepoxide

A

Long-acting