PY511 > Liver pathophysiology > Flashcards

Liver pathophysiology Flashcards

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1
Q

What does “liver disease” refer to?

A

Any condition that causes damage to hepatocytes, bile ducts, or vascular structures of the liver, leading to impaired liver function.

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2
Q

What four major hepatic functions are essential for normal physiology?

A
  • Metabolic: glucose homeostasis, lipid metabolism, amino acid processing
  • Synthetic: albumin, clotting factors, transport proteins
  • Storage: glycogen, vitamins A, D, B12, iron
  • Excretory: bilirubin conjugation, bile production, drug elimination
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3
Q

Why are hepatic functions important when understanding liver disease complications?

A

Most complications occur because one or more of these key functions is lost or impaired.

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4
Q

What are the three major patterns of liver injury?

A
  • Hepatocellular
  • Cholestatic
  • Mixed
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5
Q

What characterises hepatocellular liver injury?

A
  • Direct hepatocyte damage
  • Inflammation and necrosis
  • Elevated transaminases (ALT, AST)
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6
Q

Give examples of hepatocellular liver injury causes.

A
  • Alcohol-related liver disease
  • Viral hepatitis (A, B, C)
  • Paracetamol toxicity
  • Ischaemic hepatitis
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7
Q

What characterises cholestatic liver injury?

A
  • Impaired bile flow
  • Accumulation of bile salts and bilirubin
  • Elevated alkaline phosphatase (ALP)
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8
Q

Give examples of cholestatic liver disease.

A
  • Gallstones
  • Primary biliary cholangitis (PBC)
  • Drug-induced cholestasis (e.g. flucloxacillin)
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9
Q

What characterises mixed liver injury?

A

Combination of hepatocellular and cholestatic features with variable enzyme patterns.

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10
Q

Give examples of mixed-pattern liver injury.

A
  • Drug-induced liver injury (DILI)
  • Sepsis-related hepatic dysfunction
  • Acute liver failure
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11
Q

How is liver disease classified based on time course?

A
  • Acute liver disease
  • Chronic liver disease
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12
Q

What defines acute liver disease?

A
  • Onset < 6 months
  • Sudden hepatocellular injury
  • Often reversible with treatment
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13
Q

What are common causes of acute liver disease?

A
  • Paracetamol overdose
  • Acute viral hepatitis (A, E)
  • Ischaemic liver injury
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14
Q

What is the prognosis of acute liver disease?

A

Variable: may resolve completely or progress to acute liver failure.

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15
Q

What defines chronic liver disease?

A
  • Disease duration > 6 months
  • Persistent inflammation and fibrosis
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16
Q

What are common causes of chronic liver disease?

A
  • Alcohol excess
  • MAFLD
  • Chronic viral hepatitis (B, C)
  • Autoimmune disease
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17
Q

What happens to chronic liver disease over time?

A
  • Progressive fibrosis
  • Architectural distortion
  • May develop cirrhosis
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18
Q

What metabolic liver disease is strongly associated with obesity and diabetes?

A

MAFLD (Metabolic dysfunction-associated fatty liver disease), previously NAFLD.

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19
Q

What metabolic conditions are linked to MAFLD?

A
  • Obesity
  • Insulin resistance
  • Type 2 diabetes
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20
Q

Which viral infections commonly cause liver disease?

A
  • Hepatitis A, B, C
  • Less commonly D and E
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21
Q

How are viral hepatitis infections commonly transmitted?

A
  • Blood exposure (needle sharing)
  • Blood transfusion
  • Unprotected sexual contact
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22
Q

What is drug-induced liver injury (DILI)?

A

Liver damage caused by medications or toxins.

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23
Q

Give examples of drugs that can cause liver injury.

A
  • Paracetamol
  • Methotrexate
  • Isoniazid
  • Amoxicillin-clavulanate
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24
Q

How does alcohol cause liver disease?

A

Through direct hepatotoxicity and inflammatory mechanisms leading to steatosis, alcoholic hepatitis, and cirrhosis.

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25
What autoimmune diseases affect the liver?
- Autoimmune hepatitis (AIH) - Primary biliary cholangitis (PBC) - Primary sclerosing cholangitis (PSC)
26
What genetic diseases cause liver injury?
- Wilson's disease (copper accumulation) - Haemochromatosis (iron overload) - α1-antitrypsin deficiency
27
What is the step-by-step progression from liver injury to cirrhosis?
1. Hepatocyte injury – necrosis or apoptosis 2. Inflammation – cytokine release (TNF-α, IL-6) 3. Stellate cell activation – myofibroblast transformation 4. Collagen deposition 5. Fibrosis formation 6. Cirrhosis with regenerative nodules
28
Why is fibrosis initially protective?
It walls off injured tissue and limits further damage.
29
Why does fibrosis become harmful in chronic disease?
It distorts hepatic blood flow, impairs sinusoidal exchange, and reduces functional liver mass.
30
What is fibrosis?
Collagen deposition with minimal architectural distortion.
31
Is fibrosis reversible?
Yes, if the underlying cause is treated.
32
What defines cirrhosis?
Extensive scarring, nodular regeneration, vascular distortion, and loss of normal liver architecture.
33
Is cirrhosis reversible?
No — irreversible structural damage.
34
What is the Metavir fibrosis staging system?
F0: No fibrosis F1: Portal fibrosis without septa F2: Portal fibrosis with few septa F3: Numerous septa without cirrhosis F4: Cirrhosis
35
Which Metavir stage represents irreversible disease?
F4 – Cirrhosis
36
What is the Child-Pugh score used for?
To assess cirrhosis severity and prognosis.
37
What five parameters are used in the Child-Pugh score?
- Total bilirubin - Serum albumin - Prothrombin time / INR - Ascites - Hepatic encephalopathy
38
How is the Child-Pugh score calculated?
Each parameter is scored 1–3 points and the total determines disease severity.
39
What are the Child-Pugh classes?
A: 5–6 B: 7–9 C: 10–15
40
What is the 1-year survival rate for each Child-Pugh class?
A: 84% B: 62% C: 45%
41
Why is the Child-Pugh score clinically important?
It guides surgical risk assessment, transplant listing, and drug dosing adjustments.
42
What causes impaired detoxification in cirrhosis?
Reduced metabolism of ammonia, bilirubin, drugs, and toxins.
43
What is portal hypertension?
Increased resistance to portal blood flow due to cirrhotic architectural distortion.
44
What complications result from portal hypertension?
- Varices - Splenomegaly - Ascites
45
What causes fluid dysregulation in cirrhosis?
- Hypoalbuminaemia - RAAS activation - Portal hypertension
46
What are the manifestations of fluid dysregulation in cirrhosis?
- Ascites - Peripheral oedema
47
What causes synthetic dysfunction in cirrhosis?
Reduced production of albumin, clotting factors, and transport proteins.
48
What causes jaundice in liver disease?
Reduced bilirubin conjugation and excretion.
49
What causes hepatic encephalopathy?
Accumulation of ammonia and neurotoxic metabolites crossing the blood–brain barrier.
50
What is compensated cirrhosis?
Liver disease where homeostasis is still maintained.
51
What symptoms may appear in compensated cirrhosis?
- Spider naevi - Palmar erythema - Mild biochemical abnormalities
52
What is the prognosis of compensated cirrhosis?
Median survival >12 years.
53
What is decompensated cirrhosis?
Stage where the liver can no longer maintain homeostasis.
54
What are the major complications of decompensated cirrhosis?
- Jaundice - Ascites - Variceal bleeding - Hepatic encephalopathy - Coagulopathy
55
What is variceal bleeding?
Life-threatening haemorrhage from portal hypertension-induced varices.
56
What causes coagulopathy in cirrhosis?
Reduced clotting factor synthesis causing prolonged INR and bleeding risk.
57
What is the prognosis of decompensated cirrhosis without transplantation?
Median survival ~2 years.
58
Why does liver disease cause hypoalbuminaemia?
Reduced hepatic albumin synthesis.
59
Why does cirrhosis impair hepatic blood flow?
Fibrotic tissue and regenerative nodules distort vascular architecture.
60
What is the key concept linking liver pathophysiology to pharmaceutical care?
Liver disease affects drug metabolism, clearance, protein binding, and bleeding risk, so drug dosing must be adjusted.
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