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Flashcards in Liver Disease Deck (35):
1

Main functions of the liver

Central to maintenance of homeostasis
Storage
Clearance
Filtration
Secretion
Excretion
Synthesis
Metabolism

2

Methods of detoxification

Destroys endogenous and exogenous substances
Destroys cellular debris
Deamination of amino acids
Removal of bilirubin
Hormone deactivation

3

Features of acute liver disease

Less than six months duration
Often resolves spontaneously, self limiting
Rapid decline in liver function
May be asymptomatic
100% association with encephalopathy and coagulopathy
Can result in acute liver failure

4

Features of chronic liver disease

Over six months duration
Often symptomatic
Secondary to long-standing cell damage
Permanent structural change
Loss of normal liver architecture
Cirrhosis- fibrous scars, divides the liver into nodules

5

Causes of liver disease

Viral infection- Hepatitis A-E
Alcohol
Non-alcoholic fatty liver disease
Non-alcoholic steatohepatitis
Cholestasis (intra-hepatic, extra-hepatic)
Immune disorders
Vascular abnormalities
Metabolic disorders
Genetic disorders

6

Features of viral infection

Hep A- faecal contamination of food or drink
Hep B- blood/blood contamination
Hep C- blood/blood contamination
Hep D- have to have Hep B to get Hep D
Hep E- faecal contamination of food or drink

7

Causes of liver disease- alcohol features

Single most significant cause of liver disease in the Western World
Eventually leads to cirrhosis
Fibrous tissue in liver increases resistance to blood flow from the portal system resulting in portal hypertension
As liver cell death continues, leads to liver failure
Rate of progression (and regression) linked to further alcohol consumption

8

Drug related liver disease- type A

Dose related
Withdrawal of precipitating drug results in reversal
e.g. paracetamol, tetracyclines, methotrexate

9

Drug related liver disease- type B

Idiosyncratic (related to a drug property)
Hypersensitivity or metabolic

10

Symptoms of liver disease

Non specific symptoms- weakness, fatigue, general malaise
Poor nutrition status- weight loss, anorexia, loss of muscle bulk
Abdominal discomfort/ pain
Tenderness over liver
Jaundice

11

Cutaneous symptoms of liver disease

Hyperpigmentation
Scratch marks
Spider naevi
Non-specific- palmar erythema, Dupuytren's contracture, finger clubbing

12

Abdominal signs of liver disease

Distension
Hepatomegaly (increase in liver size)
Splenomegaly (increase in splen size)
Umbilical and paraumbilical veins

13

Jaundice

Does not automatically mean liver disease
Yellowing of skin and sclerae
Hepatocellular- drugs, hepatitis, tumour
Cholestatic- obstruction
Prehepatic- increased blood breakdown

14

Pruritis

Deposition of bile salts in the skin
Concentration does not correlate with severity
Most debilitating in cholestatic conditions
Obstruction relieved by endoscopy, radiology, surgery
Pharmacological treatment favoured for other causes

15

Portal hypertension

Increase pressure in portal venous system leads to collateral vein formation and shunting of blood to systemic circulation
Contributes to formation of ascites and development of encephalopathy
Complications- variceal bleed

16

Ascites

Accumulation of fluid within the abdominal cavity
Caused by central hypovolaemia, reduced serum albumin, portal hypertension and splanchnic artery vasodilation

17

Clotting abnormalities

Hepatocyte failure causes defective synthesis of clotting factors I and V, leading to increased tendency to bleed
Also leads to defective bile salt excretion, malabsorption of vitamin K and defective synthesis of II, VII, IX and X

18

Sexual characteristics

Endocrine changes most common in alcoholic liver disease
Thought to be due to poor metabolism of oestrogen
Males- testicular atrophy, female body hair, gynaecomastia
Females- menstrual irregularity, reduced fertility

19

Biochemical investigations

Simple, inexpensive, easy to perform
Useful to monitor disease progression or response to therapy
Enzymes- hepatocellular or cholestatic
Bilirubin
Synthetic function- clotting time

20

Other investigations

Laboratory investigations- Hep A, B and C virology, immunoglobulins, lipid profile etc.
Imaging- ultrasound- preliminary assessment; CT and MRI- precise definition of abnormalities
Biopsy- gold standard for establishing diagnosis and assessing severity

21

Treatment of pruritis

Anion exchange resins e.g. colestyramine, colestipol- bind bile acids and prevent reabsorption, side effects: GI, fat and vitamin malabsorption, poor adherence due to palatability
Counselling- take interacting drugs one hour before or four hours after colestyramine, benefits may take up to one week to become apparent
Antihistamines
Arsodeoxycholic acid
Topical therapies e.g. calamine lotion

22

Treatment of ascites

Aim is to mobilise intra-abdominal fluid
Simple measures include reducing sodium intake and fluid restriction
Moderate to severe ascites requires diuresis or paracentisis (using needle to pull blood out)

23

Pharmacological treatment of ascites

Diuretics
Spironolactone is first line agent- blocks sodium reabsorption in kidney tubules, 50-400mg daily, titrate slowly, causes gynaecomastia and hyperkalaemia, add furosemide if severe, acre to avoid excessive diuresis

24

Paracentisis

Used in refractory ascites, combined with albumin administration, does not affect mechanisms responsible for fluid accumulation, repeated every 2-4 weeks in outpatient setting

25

TIPS

Transjugular Intrahepatic Portosystemic Shunt
Prevents recurrence in refractory ascites, shunt stenosis is common, bypasses liver to reduce pressure on circulation

26

Treatment of encephalopathy

Reversible neuropsychiatric condition- lack of awareness, altered mental state, disorientation, coma
Complex aetiology- portosystemic shunting, metabolic dysfunction, alteration of BBB, ammonia heavily implicated
Precipitated by GI bleeding, spontaneous bacterial peritonitis, drugs- remove if present

27

Pharmacological treatment of encephalopathy

Lactulose- acidifies colonic contents, leading to ionisation of nitrogenous products and therefore reduction in absorption, 30-40ml/day titrated to achieve 2-3 soft stools per day, causes bloating and diarrhoea
Antibiotics- metronidazole reduces ammonia production by GI bacteria

28

Treatment of clotting abnormality

Phytomenadione IV (vitamin K)- 10mg daily for 3 days, oral not as effective as IV therefore not used
Not effective in patients with significant disease
Also avoid NSAIDs, aspirin and anti-coagulants

29

Treatment of varices

Shunting of portal blood to systemic circulation- pre-existing vessels dilate, active angiogenesis
Initial treatment- stop immediate bleeding, treat hypovolaemic shock, aim to prevent recurrent bleeding

30

Immediate treatment of varices

Terlipressin (vasopressin analogue): systemic vasoconstrictor, infused for 2-5 days

31

Prevention of varices

Band ligation: long term non-selective B blockers e.g. propanolol, decrease PHT by splanchnic vasoconstriction and decrease portal blood flow

32

Acute Liver Failure

Rapid deterioration in liver function in a previously healthy individual, most common cause is a paracetamol overdose
Complicated to manage: CNS, CV and renal systems affected, infection and bleeding can be life threatening

33

Paracetamol and the liver

Most common agent of intentional self harm, 20-30 tablets consumed within 24 hours can result in severe hepatocellular necrosis
Saturation of glutathione pathway

34

Paracetamol toxicity

0-24 hours: asymptomatic or non-specific signs
24-48 hours: RUQ pain, jaundice, deranged bloods
>72 hours: jaundice, somnolence, liver failure
Results in: cerebral oedema, shock, sepsis, renal failure

35

Prescribing considerations

Impaired drug metabolism- main route of elimination for many drugs, liver disease must be severe for clinically relevant changes to occur, care with rifampicin and fusidic acid
Hypoproteinaemia- albumin produced in the liver, affects highly protein bound drugs
Impaired clotting- clotting factors synthesised in the liver, increased sensitivity to oral anticoagulants
Hepatic encephalopathy- many drugs can impair cerebral function, care with sedative drugs, opioids, diuretics that decrease K+