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S1 Pharmacology > Hepatic System > Flashcards

Hepatic System Flashcards

1
Q

What is the largest gland + largest internal organ in the body ?

A
  • the liver
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2
Q

How many lobes does the liver contain ?

A
  • 4 lobes
  • 2 Major (Left & Right) -largest
  • 2 Minor (Caudate & Quadrate)
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3
Q

What is the liver covered by ?

A
  • a single layer of mesothelium
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4
Q

Where is the gall bladder located in relation to the liver ?

A
  • under the right lobe
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5
Q

What is one of the primary functions of the liver ?

A
  • Functions as exocrine gland – bile secretion
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6
Q

What is a liver lobule composed of ?

A

– Central terminal hepatic venule
– Interconnecting plates of hepatocytes
– Peripherally arranged portal triad (hepatic artery, portal vein and bile duct )

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7
Q

What are the hepatocyte zones ?

A
  • centrilobular, periportal, mid zone
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8
Q

What 2 vessels does liver receive its blood from ?

A
  • hepatic portal vein
  • hepatic artery
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9
Q

What is the function of the hepatic portal vein ?

A
  • blood to the liver, 75% blood supply to liver
  • nutrient rich blood from digestive tract and spleen
  • filters toxins from digestive tract
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10
Q

What is the function of the hepatic artery ?

A
  • Oxygenated blood from aorta
    • 25% Blood Supply
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11
Q

What are the sinusoids in the liver ?

A
  • endothelium lined spaces in lobule, replacing capillaries
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12
Q

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

A
  • lined with Kupffer cells (phagocytes)
  • function is to destroy bacteria + worn-out blood cells
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13
Q

What are hepatic stellate cells function + location ?

A

• Pericytes found in space of Disse (perisinusoidal space)
• Retinoid storage (in lipid droplets)

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14
Q

What does damage to hepatic stellate cells lead to ?

A
  • leads to transdifferentiation into proliferative fibrogenic myofibroblasts and liver fibrosis
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15
Q

What percentage of hepatocyte surface area faces sinusoid ?

A
  • 70% to maximise blood exchange
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16
Q

What percentage of hepatocyte surface area faces bile canaliculi ?

A
  • 15%
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17
Q

What happens to bile canaliculi in the liver ?

A
  • merge into bile ductless, running alongside portal veins
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18
Q

What are the main functions of the liver ?

A
  • Xenobiotic detoxification and metabolism
    • Decomposition of erythrocytes and excretion of bilirubin
    • Bile Production
    • Cholesterol synthesis and Lipogenesis
    • Carbohydrate Metabolism
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19
Q

What proteins does the liver synthesise ?

A
  • Albumin (major osmolar component of blood serum)
    • Coagulation factors : fibrinogen, prothrombin, factors (V, VII, IX-XI), antithrombin
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20
Q

What hormones does the liver produce ?

A

• Thrombopoietin (regulates platelet production by bone marrow)
• Angiotensin (raises blood pressure following renin activation)

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21
Q

What does the liver store ?

A

• Glycogen
• Vitamins A, D, E, K (fat soluble), B12 (water soluble)
• Iron, Copper

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22
Q

What happens when there is a decline in glucose level ?

A
  • glycogenolysis = glycogen —-> glucose
  • if glycogen exhausted = gluconeogenesis
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23
Q

What is the Cori cycle ?

A
  • lactate converted to glucose
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24
Q

what is the alanine cycle ?

A
  • Degradation of proteins - amino groups transferred to pyruvate
  • giving rise to alanine, which is transported to the liver
  • it’s carbon skeleton is converted into glucose
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25
Q

How does the liver convert glucose into fatty acids ?

A
  • via acetyl-CoA, which is then used to form fatty acids
26
Q

What does the liver do with fatty acids supplied from intestine ?

A
  • receives fatty acids from lipids in chylomicrons from intestine
  • converted into neutral fats and phospholipids
27
Q

What percentage of cholesterol is produced by the liver ?

A
  • 70%
28
Q

What is cholesterol used for ?

A
  • synthesis of bile acids
  • cells membranes
  • hormones
29
Q

What happens to excess cholesterol ?

A
  • converted into bile acids or excreted with the bile
30
Q

What are bile acids ?

A
  • steroids synthesised in the liver form cholesterol
31
Q

What does it mean when bile acids are amphipathic ?

A
  • have a polar and a polar side , act as detergents
32
Q

How do bile acids form bile salts ?

A
  • linked to amino acids
33
Q

What components are found in bile ?

A
  • organic = bilirubin
  • inorganic = bile salts
34
Q

Where is bile produced and how does it move within the liver ?

A
  • produced by hepatocytes
  • Bile canaliculi carry bile back to the portal triad (opposite direction to blood)
35
Q

How does bile aid in lipid digestion ?

A
  • bile facilitates solubilisation of lipids by forming micelles which can be absorbed by the intestines
36
Q

What happens to erythrocytes and the end of their life span ?

A
  • phagocytosed haemoglobin released
  • blobs metabolised + amino acids recycled
  • iron bound to transferrin + returned to liver
  • Haem converted to bilirubin, bound to albumin
37
Q

How is bilirubin metabolised in the liver ?

A
  • 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.
  • Intestinal bacteria degrade bilirubin to urobilinogen
  • 80% oxidised to stercobilin and excreted in faeces
    • 20% enters extrahepatic circulation and excreted in urine
38
Q

What role does the liver replay in biotransformation + metabolism ?

A
  • acts as against gatekeeper between circulation + absorbed substances from the GI tract
  • metabolizing both natural and foreign substances (e.g., drugs).
39
Q

What is the first pass effect in metabolism ?

A
  • after absorption from the GI tract, a significant portion of a substance may be metabolically inactivated in the liver before it reaches circulation, making dosage important.
40
Q

What happens during phase I reactions of drug metabolism ?

A
  • make parent compound more polar by adding or unmasking functional groups
41
Q

What happens during phase II reactions ?

A

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

42
Q

What is an example of a phase I reactions ?

A
  • Oxidation Reactions (Cytochrome P450’s):
  • Oxygen incorporated into drug
  • Oxidation causes loss of part of drug
43
Q

What are 2 examples of substrates for Cyt P450 isozymes ?

A
  • caffeine
  • estradiol
44
Q

What is an example of phase II reactions ?

A
  • Glucuronidation- UDP-Glucuronosyltransferase:(-OH, -COOH, -NH2,-SH)
45
Q

What is Hepatitis ?

A
  • inflammation of liver
46
Q

What is Cirrhosis ?

A
  • formation of fibrous tissue in liver replacing dead cells
47
Q

What is Haemochromatosis ?

A
  • excessive iron accumulation and liver damage
48
Q

What are Hepatic system cancers ?

A
  • hepatocellular carcinoma
  • cholangiocarcinoma
49
Q

What is Wilson’s disease ?

A
  • hereditary disease causing copper retention
50
Q

What is Biliary cirrhosis ?

A
  • disease of small bile ducts
51
Q

What is Gilbert’s syndrome ?

A
  • genetic disorder of bilirubin metabolism
52
Q

What is Jaundice ?

A
  • Yellow coloured skin, nail beds & sclera caused by deposition of bilirubin due to hyperbilirubinemia
53
Q

What is the role of Alanine aminotransferase (ALT) is liver function tests ?

A
  • Increased when cells of the liver are inflamed or undergo cell death
  • Rises dramatically in acute liver damage, such as viral hepatitis
54
Q

What is the significance of Aspartate aminotransferase (AST) in liver function tests?

A
  • AST is raised in acute liver damage, but it is less specific for liver disease compared to ALT.
55
Q

What does Alkaline Phosphatase (ALP) indicate in liver function assessment?

A
  • Raised in biliary tract damage and inflammation, indicating issues with bile flow
56
Q

What is the role of Gamma-Glutamyl Transferase (GGT) in liver function tests ?

A
  • Produced by the bile duct (sensitive marker for cholestatic damage)
  • Raised in alcohol toxicity
57
Q

How is bilirubin used in liver function assessments?

A
  • measured in plasma total and direct (conjugated) forms
  • Urine may show urobilinogen and bilirubin levels, indicating liver or bile duct function.
58
Q

What is paediatric jaundice and why does it occur?

A
  • occurs in newborns due to low levels of bilirubin glucuronyl transferase in the liver, causing inefficient conjugation of bilirubin.
59
Q

How does the liver function in childhood?

A
  • liver produces insulin-like growth factor-1 (IGF-1), a hormone important for growth during this period.
60
Q

What age-related changes occur in the liver during geriatrics?

A
  • the liver’s oxidative capacity decreases,
  • leading to reduced metabolism, longer drug exposures, and decreased toxin clearance.

S1 Pharmacology (29 decks)

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