S1 Pharmacology > Hepatic System > Flashcards

Hepatic System Flashcards

(60 cards)

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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
How does the liver convert glucose into fatty acids ?
- via acetyl-CoA, which is then used to form fatty acids
26
What does the liver do with fatty acids supplied from intestine ?
- receives fatty acids from lipids in chylomicrons from intestine - converted into neutral fats and phospholipids
27
What percentage of cholesterol is produced by the liver ?
- 70%
28
What is cholesterol used for ?
- synthesis of bile acids - cells membranes - hormones
29
What happens to excess cholesterol ?
- converted into bile acids or excreted with the bile
30
What are bile acids ?
- steroids synthesised in the liver form cholesterol
31
What does it mean when bile acids are amphipathic ?
- have a polar and a polar side , act as detergents
32
How do bile acids form bile salts ?
- linked to amino acids
33
What components are found in bile ?
- organic = bilirubin - inorganic = bile salts
34
Where is bile produced and how does it move within the liver ?
- produced by hepatocytes - Bile canaliculi carry bile back to the portal triad (opposite direction to blood)
35
How does bile aid in lipid digestion ?
- bile facilitates solubilisation of lipids by forming micelles which can be absorbed by the intestines
36
What happens to erythrocytes and the end of their life span ?
- phagocytosed haemoglobin released - blobs metabolised + amino acids recycled - iron bound to transferrin + returned to liver - Haem converted to bilirubin, bound to albumin
37
How is bilirubin metabolised in the liver ?
- 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
What role does the liver replay in biotransformation + metabolism ?
- acts as against gatekeeper between circulation + absorbed substances from the GI tract - metabolizing both natural and foreign substances (e.g., drugs).
39
What is the first pass effect in metabolism ?
- 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
What happens during phase I reactions of drug metabolism ?
- make parent compound more polar by adding or unmasking functional groups
41
What happens during phase II reactions ?
• Conjugation with endogenous substrate to increase aqueous solubility • Conjugation with glucoronide, sulfate, acetate, amino acid etc.
42
What is an example of a phase I reactions ?
- Oxidation Reactions (Cytochrome P450’s): - Oxygen incorporated into drug - Oxidation causes loss of part of drug
43
What are 2 examples of substrates for Cyt P450 isozymes ?
- caffeine - estradiol
44
What is an example of phase II reactions ?
- Glucuronidation- UDP-Glucuronosyltransferase:(-OH, -COOH, -NH2,-SH)
45
What is Hepatitis ?
- inflammation of liver
46
What is Cirrhosis ?
- formation of fibrous tissue in liver replacing dead cells
47
What is Haemochromatosis ?
- excessive iron accumulation and liver damage
48
What are Hepatic system cancers ?
- hepatocellular carcinoma - cholangiocarcinoma
49
What is Wilson’s disease ?
- hereditary disease causing copper retention
50
What is Biliary cirrhosis ?
- disease of small bile ducts
51
What is Gilbert’s syndrome ?
- genetic disorder of bilirubin metabolism
52
What is Jaundice ?
- Yellow coloured skin, nail beds & sclera caused by deposition of bilirubin due to hyperbilirubinemia
53
What is the role of Alanine aminotransferase (ALT) is liver function tests ?
- Increased when cells of the liver are inflamed or undergo cell death - Rises dramatically in acute liver damage, such as viral hepatitis
54
What is the significance of Aspartate aminotransferase (AST) in liver function tests?
- AST is raised in acute liver damage, but it is less specific for liver disease compared to ALT.
55
What does Alkaline Phosphatase (ALP) indicate in liver function assessment?
- Raised in biliary tract damage and inflammation, indicating issues with bile flow
56
What is the role of Gamma-Glutamyl Transferase (GGT) in liver function tests ?
- Produced by the bile duct (sensitive marker for cholestatic damage) - Raised in alcohol toxicity
57
How is bilirubin used in liver function assessments?
- measured in plasma total and direct (conjugated) forms - Urine may show urobilinogen and bilirubin levels, indicating liver or bile duct function.
58
What is paediatric jaundice and why does it occur?
- occurs in newborns due to low levels of bilirubin glucuronyl transferase in the liver, causing inefficient conjugation of bilirubin.
59
How does the liver function in childhood?
- liver produces insulin-like growth factor-1 (IGF-1), a hormone important for growth during this period.
60
What age-related changes occur in the liver during geriatrics?
- the liver’s oxidative capacity decreases, - leading to reduced metabolism, longer drug exposures, and decreased toxin clearance.
S1 Pharmacology
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