SPR L19 Pathophysiology of Cirrhosis and Liver Failure Flashcards Preview

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Flashcards in SPR L19 Pathophysiology of Cirrhosis and Liver Failure Deck (29):
1

Learning Outcomes

(for general perusal)

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Give a summary of Liver Function

Protein metabolism 

Carbohydrate metabolism

Hormonal Control of metabolism

Lipid metabolism

Bile formation 

Hormone and drug metabolism

Immunological Functions

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Liver Function

Outline the Protein Metabolism that occurs in the liver

  • Protein synthesis
    • albumin
    • clotting factors
    • transporter proteins
  • Amino acid synthesis and breakdown
    • transamination and deamination
    • NH3 to urea

4

Liver Function

  1. Outline the Carbohydrate metabolism that occurs in the liver
  2. Outline the hormonal control of metabolism that takes place in the liver

1. glucose homeostasis

  • glucose uptake and release
  • glycogen synthesis and breakdown
  • gluconeogenesis

2. see picture

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Liver Function

Give an overview of the lipid metabolism that takes place in the liver

  • lipoprotein synthesis and breakdown
  • fatty acid synthesis and breakdown
  • triglyceride synthesis and breakdown
  • cholesterol synthesis
  • cholesterol esterification

6

Liver Function 

Give a summary of the metabolic interactions that take place in the liver

See picture

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Liver Function 

Give a summary of the bile formation that takes place in the liver

  • Bile acid/bile salt synthesis and secretion
    • enterohepatic re-circulation
  • Bile pigments
    • bilirubin uptake and conjugation
    • urobilinogn synthesis in bowel
    • re-absorption and hepatic/renal excretion
  • Lecithin
  • HCO3-

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Liver Function 

Give a summary of the Hormone and Drug Metabolism that takes place in the liver

  • Mainly inactivation 
  • Vitamin D Activation

9

Liver Function 

Give a summary of the Immunological Functions of the liver

Küppfer cells

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Main causes of cirrhosis and liver disease

Acute or chronic hepatitis and Cirrhosis

What are the main causes?

  • Alcohol
  • Infections (particularly viral)
  • Drugs/poisons (eg paracetamol)
  • Biliary tract obstruction and biliary sclerosis
  • Fatty liver disease

(Many others)

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Pathophysiology: consequences of liver disease

  1. How is protein metabolism altered?
  2. How is Amino Acid synthesis and breakdown altered?

1. Abnormal protein metabolism:

  • Reduced protein synthesis
    • hypoalbuminaemia
      • contributes to ascites and oedema
    • reduced clotting factors
      • clotting defects
      • prolonged prothrombin time

2. 

Reduced removal NH3

  • hepatic encephalopathy (usually with portal   hypertension or fulminant liver failure)
  • reduced [urea]

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Pathophysiology: consequences of liver disease

What are the consequences for carbohydrate metabolism?

hypoglycaemia

13

Pathophysiology: consequences of liver disease

What are the consequences for lipid metabolism?

  • Abnormal lipid metabolism:
    • lipid levels raised, particularly with obstructive jaundice
    • increased free cholesterol: esterified cholesterol
      • altered red cell membranes

14

Pathophysiology: consequences of liver disease

What are the consequences for bile acid/ bile salt secretion?

 

  • Biliary obstruction/ileal resection: fat malabsorption
    • steatorrhoea
    • fat soluble vitamin deficiency (A, D, E, K)
  • Inadequate bile pigment excretion:
    • Pre-hepatic jaundice (eg haemolytic)

      • unconjugated bilirubin in blood

    • Hepatic jaundice (eg acute hepatitis)
      • mixed (conjugated and unconjugated) bilirubin in blood
    • Post-hepatic jaundice (obstructive)
      • conjugated bilirubin in blood and urine (dark)
      • reduced urobilinogen/stercobilinogen in stools (pale)

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Pathophysiology: consequences of liver disease

Give examples of causes of inadequate bile pigment excretion?

 

 

(see picture)

  • Biliary obstruction/ileal resection: fat malabsorption
    • steatorrhoea
    • fat soluble vitamin deficiency (A, D, E, K)
  • Inadequate bile pigment excretion:
    • Pre-hepatic jaundice (eg haemolytic)

      • unconjugated bilirubin in blood

    • Hepatic jaundice (eg acute hepatitis)
      • mixed (conjugated and unconjugated) bilirubin in blood
    • Post-hepatic jaundice (obstructive)
      • conjugated bilirubin in blood and urine (dark)
      • reduced urobilinogen/stercobilinogen in stools (pale)

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Pathophysiology: consequences of liver disease

What are the problems in hormone and drug metabolism caused by liver disease?

  • increased oestrogen levels
    • gynaecomastia, testicular atrophy in men
  • amenorrhoea in women
  • prolonged drug half-life

17

Pathophysiology: consequences of liver disease

How is secondary hyperaldosteronism brought about in liver disease?

 

What is there a susceptibility to with liver disease?

2˚ hyperaldosteronism

  • increased renal secretion of renin
  • reduced hepatic aldosterone breakdown
    • Na+/H2O retention (ascites)

 

 

Increased susceptibility to infection

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Pathophysiology: cirrhosis and portal hypertension

What are the main pathophysiological changes seen?

  • hepatomegaly
  • increased portal venous pressure (portal hypertension)
    • increased portal vascular resistance
      • increased vasoconstrictor activity
      • fibrosis
  • increased pressure in ‘portal’ capillary beds and organs
  • increased pressure in systemic veins (portosystemic   anastamoses)

19

Pathophysiology: cirrhosis and portal hypertension

What does portal hypertenison contribute to?

Direct

  • splenomegaly

    • splenic v.
  • ​ascites
    • splanchnic capillaries

p-s anastamoses

 

  • oesophageal varices (haematemesis/melaena)
    • left gastric v. to oesphageal v.
  • haemorrhoids
    • superior to middle and inferior   rectal vv
  • caput medusae
    • paraumbilical to epigastric vv.

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Pathophysiology: cirrhosis and portal hypertension

  1. ​What are the features of porto-systemic encephalopathy?
  2. What are the features of hepto-renal syndrome?

  1. porto-systemic collaterals by-pass hepatic de-toxification, gastro-intestinal bleed increases protein loading

2. 

  • renal failure with no renal disease
  • portal-hypertension or fulminant hepatic failure
    • splanchnic pooling of blood
    • renal vasoconstriction

21

Symptoms and signs of chronic liver disease-failure

List these

  • jaundice
  • right hypochondrial pain
  • abdominal distension (ascites)
  • ankle swelling (fluid retention/ hypoalbuminaemia causing oedema)
  • haematemesis and melaena (GIT bleeding)
  • pruritis due to cholestasis
  • gynaecomastia, loss of libido and amenorrhoea (endocrine dysfunction)
  • confusion and drowsiness (portosystemic encephalopathy)

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Investigations for liver disease

What investigations should be carried out?

Blood Tests

Urine Tests

Imaging

Liver Biopsy

23

Investigations for liver disease

Blood Tests, Urine Tests, Imaging, Liver Biopsy

What blood tests can be carried out?

  • Liver 'function' tests
    • Synthetic function: serum albumin and prothrombin time
    • Excretory function: serum bilirubin
      • unconjugated v. conjugated
  • Liver biochemistry:
    • Markers of liver cell damage:
      • serum aspartate and alanine (more liver specific) aminotransferases
    • Markers of cholestasis:
      • serum alkaline phosphatase, γ-glutamyl transpeptidase
  • Viral markers
  • Additional blood investigations: haematological, biochemical, immunological, markers of liver fibrosis and genetic analysis.

24

Investigations for liver disease

Blood Tests, Urine Tests, Imaging, Liver Biopsy

  1. What are the markers of liver cell damage?
  2. What are the markers of cholestasis?

  1. serum aspartate and alanine (more liver specific) aminotransferases
  2. serum alkaline phosphatase, γ-glutamyl transpeptidase

25

Investigations for liver disease

(Blood Tests, Urine Tests, Imaging, Liver Biopsy)

Why are the following carried out?

  1. Urine tests
  2. Imaging
  3. Biopsy

  1. for bilirubin and urobilinogen
  2. to define gross anatomy
  3. for histology.

26

Principles of management of chronic liver disease

What is one of the main principles of management? ​

What might this involve?

Treat major complications

eg. Gastrointestinal bleed

  • control bleeding (Sengstaken tube)
  • restore blood volume
  • check prothrombin time
  • sclerotherapy
  • proton pump inhibitors may help prevent gastric bleeding

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Principles of management of chronic liver disease

What is one of the main principles of management of encephalopathy?

  • restrict protein intake (<40 g/day; reduced nitrogenous toxins)
  • limit absorption toxins from GIT (eg antibiotics,   lactulose)
  • liver transplant

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28

  1. What is Fulminant liver failure?
  2. What is a key feature?
    1. What is this due to?
  3. What is the clinical course?

  1. Encephalopathy developing rapidly after 1st symptoms (<8 weeks)
  2. cerebral oedema and raised intracranial pressure
    1. probably 2˚ to high levels of toxins           cellular swelling (cytotoxic)                   breakdown of blood brain barrier (vasogenic)     hypoalbuminaemia may exacerbate oedema
  3. Rapid deterioration in symptoms/multi-organ failure
  • CVS (hypotension)
  • lungs
  • kidneys

29

Management fulminant liver failure

(summary of this condition in picture)

  1. How is the cerebral oedema managed?
  2. What is used to reduce risk of gastric blled?
  3. How can the coagulopathy be treated?
  4. How can the hypoglycaemia be treated?
  5. What else needs to be treated?
  6. What may be considered?

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  1. Osmotic diuresis with mannitol. Hyperventilation may help (reduced PCO2 causes   vasoconstriction)
  2. PPI
  3. Vit K, platelets, fresh frozen plasma
  4. IV dextrose
  5. Treat infections
  6. Liver transplant

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