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pharmacology > Hepatic system > Flashcards

Hepatic system Flashcards

1
Q

Describe the structure of the liver.

A

4 lobes: 2 major (left and right) - largest and 2 minor (caudate and quadrate)

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2
Q

Describe the Glisson’s capsule.

A
  • Well defined thin capsule of connective tissue
  • Rich in nerve endings
  • Covered by a single layer of mesothelium
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3
Q

Where is the gallbladder?

A

Lodged within recess under right lobe

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4
Q

State the function of the liver.

A

An exocrine gland - bile secretion

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5
Q

What is a liver lobule?

A

Basic functional unit of liver

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6
Q

What are hepatocytes?

A

Specialised epithelial cells

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7
Q

Which two vessels does the liver receive blood from?

A
  • Hepatic portal vein
  • Hepatic artery
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8
Q

Describe the hepatic portal vein.

A
  • Not a true vein: conducts blood to liver and not directly to the heart
  • Nutrient rich blood from digestive tract and spleen
  • Filters toxins delivered from digestive tract
  • 75% blood supply to liver
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9
Q

Describe the hepatic artery.

A
  • Oxygenated blood from aorta
  • 25% blood supply
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10
Q

What does the liver lobule have instead of capillaries?

A

Endothelium-lined spaced called sinusoids

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11
Q

Which artery and vein discharge into the sinusoids?

A
  • Hepatic artery
  • Portal vein
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12
Q

What are sinusoids partly lined with and what is their function?

A
  • By phagocytes
  • Destroy bacteria, worn out blood cells
  • Hepatic stellate cells
  • Pericytes found in space of Disse
  • Retinoid storage (in lipid droplets)
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13
Q

Approximately how much of the hepatocyte surface area faces sinusoid and what is the advantage of this?

A

~70%
- Maximises blood exchange

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14
Q

State the functions of the liver.

A
  • Xenobiotic detoxification and metabolism
  • Decomposition of erythrocytes and excretion of bilirubin
  • Bile Production
  • Cholesterol synthesis and Lipogenesis
  • Carbohydrate Metabolism
  • Protein synthesis:
    Albumin (major osmolar component of blood serum)
    Coagulation
  • Hormone production:
    Thrombopoietin (regulates platelet production by bone marrow)
  • Angiotensin (raises blood pressure following renin activation)
  • Storage of:
    Glycogen
    Vitamins A, D, E, K (fat soluble), B12 (water soluble)
    Iron, Copper
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15
Q

Describe carbohydrate metabolism

A
  • Liver receives glucose and other monosaccharides from the blood plasma
  • Converted to glucose 6-phosphate and other intermediates of glycolysis
  • Stored as glycogen (Glycogenesis), converted to FA or degraded
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16
Q

When does the liver secrete glucose?

A
  • When there is a major decline in blood glucose level
  • Glucose derived from glycogen store (Glycogenolysis)
  • Liver glycogen declines to zero in periods of starvation > 1day
  • If glycogen exhausted – Gluconeogenesis
17
Q

What is the cori cycle?

A

Lactate (anaerobic glycolysis) transported to the liver,
converted into glucose

18
Q

What is the alanine cycle?

A

Degradation of proteins - amino groups transferred
to pyruvate, giving rise to alanine, transported to the liver and carbon skeleton converted into glucose

19
Q

Describe glucose regulation.

A
  • After meals glucose mainly stored as glycogen in liver
  • When more energy needed
    between meals, glycogen, fat & protein (last) are broken down & liver makes glucose.
  • Hormones (insulin, glucagon, adrenalin, cortisol) signal change from storage to synthesis.
20
Q

Describe lipid metabolism.

A
  • Liver converts glucose via acetyl-CoA into fatty acids
  • Retrieves fatty acids from lipids supplied with chylomicrons from intestine
  • Converted into neutral fats and phospholipids, soluble forms
  • VLDL are formed (transport of fatty acids to other tissues)
21
Q

What is cholesterol used for?

A
  • The synthesis of bile acids, cell membranes, hormones
22
Q

What happens to excess cholesterol?

A

Converted into bile acids or excreted with the bile.

23
Q

What are bile acids?

A

Steroids synthesised in the liver from cholesterol
- Amphipathic (have a polar and an apolar side); act as detergents
- Linked to amino acid to from BILE SALTS

24
Q

What does bile contain?

A

organic and inorganic (bile salts) components

25
Q

Describe the production of bile.

A
  • Produced by hepatocytes and passes into bile canaliculi
  • Bile canaliculi carry bile back to the portal triad (opposite direction to blood)
26
Q

Describe the role of bile in lipid digestion.

A

Bile facilitate solubilisation of dietary lipids during
digestion by micelle formation (promoting intestinal absorption of lipids)

27
Q

Describe bilirubin metabolism in the liver?

A
  • Uptake of Bilirubin by hepatocytes:
  • Bilirubin dissociates from albumin & enters hepatocytes
  • Bilirubin conjugated with two glucuronic acids by UDP-
    glucuronyl transferase (bilirubin diglucuronide)
  • Conjugated bilirubin transported into bile canalculi and bile.
  • Process energy dependent and impaired in liver diseases
  • Intestinal bacteria degrade bilirubin to urobilinogen
  • 80% oxidised to stercobilin and excreted in faeces
  • 20% enters extrahepatic circulation and excreted in urine
28
Q

What does the liver act as?

A
  • Liver acts as gatekeeper between circulation and absorbed substances
  • Liver principal site of metabolism
29
Q

What is the first pass effect?

A

Substance absorbed from GI tract passes through liver

30
Q

Describe the phase 1 reaction of drug metabolism.

A
  • Convert parent compound into a more polar (hydrophilic) metabolite by
    adding or unmasking functional groups (-OH, -SH, -NH2, -COOH, etc.)
  • Often metabolites are inactive; may be sufficiently polar to be excreted
31
Q

Describe phase 2 reactions of drug metabolism.

A
  • Conjugation with endogenous substrate to increase aqueous solubility
  • Conjugation with glucoronide, sulfate, acetate, amino acid etc.
32
Q

Describe transaminase enzymes - liver function assessments?

A
  • Alanine aminotransferase (ALT)
  • Increased when cells of the liver are inflamed or undergo cell death
  • Rises dramatically in acute liver damage, such as viral hepatitis
  • Aspartate aminotransferase (AST)
  • Raised in acute liver damage; less specific for liver disease
33
Q

Describe cholestatic enzymes - liver function assessments.

A
  • Alkaline Phosphatase (ALP):
    Raised in biliary tract damage and inflammation
  • Gamma-Glutamyl Transferase (GGT):
    Produced by the bile duct (sensitive marker for cholestatic damage)
    Raised in alcohol toxicity
34
Q

Describe a foetal and newborn liver?

A
  • First trimester, liver main site of RBC production. By 32 weeks BM has
    taken over task
  • Low bilirubin glucuronyl transferase at birth (adult levels by 4 weeks)
  • Paediatric Jaundice
35
Q

Describe the liver in childhood.

A
  • Liver produces insulin-like growth factor-1 (IGF-1), hormone plays role in
    childhood growth
36
Q

Describe the liver in old people.

A
  • Oxidative capacity of liver decreases with age
  • Reduced metabolism: longer drug exposures and reduced toxin clearance
37
Q

What are the mechanisms of drug induced liver injury?

A
  • Direct hepatocyte damage
  • Mitochondrial toxicity
  • Metabolite activity
  • Cholestasis

pharmacology (40 decks)

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