liver-hap 2

Question 1

anatomy of liver

Answer 1

The liver lobule is the structural and functional unit of the liver. A portal triad of structures is situated at each of the 6 corners of the liver lobule, consisting of a branch of the hepatic artery which supplies O2 rich blood to the liver, a branch of the portal vein which carries nutrient rich blood from digestive viscera, and a bile duct which conducts bile used for fat emulsification to the gall bladder.

Question 2

1. The liver has a dual blood supply via two different circulatory routes: systemic circulation and hepatic portal circulation. Explain.

Answer 2

The liver is supplied by the hepatic artery (a branch of the aorta) and the hepatic portal vein (The vessel involved in the drainage of the capillary beds of the GI tract and spleen into the capillary bed of the liver).

Question 3

2. State four functions of the human liver, providing examples

Answer 3

Homeostasis: regulation of blood composition, including the amounts of sugar (glucostat), protein and fat entering the bloodstream.
Storage: glycogen, vitamins, minerals.
Synthesis: e.g. albumin (oncotic pressure) & globulins, complement system (immunity), clotting factors (hemostasis), angiotensinogen (BP regulation), cholesterol, lipoproteins, non-essential aa. Secretion: bile
Metabolism/ Clearance: hormones, nutrients and drugs.

Question 4

3. Explain the role of liver in drug metabolism including the first pass metabolism?

Answer 4

-The INITIAL drug metabolism in the 1st pass through the liver is referred to as the first pass metabolism.
Two phases of drug metabolism:
-Phase I Oxidative reactions: Catalysed mainly by Microsomal Cytochrome P450 (CYP)
-Phase II Conjugation: Polar groups are added to drug molecules forming water-soluble
Metabolites to be easily excreted.

Question 5

Some blood liver tests reflect liver function, others indicate liver cell injury. Explain

Answer 5

• Liver Enzyme tests: used as indicators of liver damage or injury
• Liver Function Tests: used to detect liver functions

Question 6

5. Where is bile stored and what is its function?

Answer 6

Bile is stored in the gall bladder; it helps carry away waste. Bile salts produce fat emulsification (breakdown) in the small intestine during digestion.

Question 7

Pharmacokinetics

Answer 7

Describes the physiological processes acting on a drug once it enters the body. (divided into 4 stages: absorption, distribution, metabolism and excretion)

Question 8

Bioavailability

Answer 8

The percentage of original drug dose that reaches systemic circulation unchanged.

Question 9

• Half-life:

Answer 9

the time it takes for the amount of drug in the body to decrease to half of the peak level it previously achieved

Question 10

• Minimum effective concentration (MEC):

Answer 10

The amount of a drug that is needed to cause a therapeutic effect

Question 11

• Onset of drug action:

Answer 11

Time taken until the drug reaches the MEC.

Question 12

Maximum plasma concentration (Cmax.):

Answer 12

Peak/maximum plasma concentration of drug reached after administration and absorption.

Question 13

• Steady state:

Answer 13

is reached when the rate of administration equals the rate of drug elimination.

Question 14

Describe the 2 phases of drug biotransformation (metabolism)

Answer 14

Phase I: Oxidative reactions: Catalysed mainly by a family of enzymes; Cytochrome P450 (CYP) monooxygenase system present in the liver microsomes.
Phase II: Conjugation: Polar groups are added to drug molecules forming water-soluble metabolites to be easily excreted.

Question 15

6. Morphine has a bioavailability of about 30%, Morphine is therefore usually given by intramuscular (IM) injection. Explain this statement

Answer 15

Because 70% is metabolized via 1st pass metabolism by the liver if taken orally. Therefore, it is given by intramuscular (IM) injection to bypass this mechanism.

Question 16

first pass metabolism- explained more dont need to learn so indepthly

Answer 16

Drugs given orally travel to the liver via the portal vein for metabolism by liver enzymes. This INITIAL metabolism is referred to as the first pass metabolism, decreasing the drug bioavailability (drugs taken orally have variable bioavailability). After passing through the liver the drug enters the circulation via hepatic veins -> IVC.
Drugs given sublingually: most of the dose will be absorbed by the sublingual vessels, thus escaping first pass metabolism in the liver and increasing the drug bioavailability

Question 17

7. What is the importance of drug binding to plasma proteins

Answer 17

• Facilitate the transport of lipid soluble drugs, as they do not dissolve in plasma.
• Protein binding stops drug being chemically reactive during transport. Once free, drug moves out of plasma to the target tissue and produces its therapeutic effect, then more drug unbinds from protein to become “free”.

Question 18

8. Define the volume of distribution (Vd), underlining its clinical implication

Answer 18

Vd is a theoretical volume which gives information on HOW the drug is distributed in the body.
*Clinical implications:High Vd indicates extensive tissue binding of the drug; wide distribution often accounts for many of the side effects of a drug.

Question 19

9. What is the significance of half-life?

Answer 19

Predicts the timing of subsequent drug doses

• Reflects drug elimination from the body
• prolonged t ½ indicates drug accumulation which may lead to toxicity, while shortened t ½ may lead to sub-therapeutic drug levels

Question 20

11. How might abnormal liver and kidney function affect drug handling?

Answer 20

a. Lower drug dose (as liver and kidney impairment interferes with drug elimination)
b. in case of impaired liver function: the usage of some drugs e.g. lipid soluble drugs should be avoided

Question 21

first pass metabolism

Answer 21

Occurs mainly in the LIVER or by bacteria in GI tract.

  It is the INITIAL metabolism that occurs to drugs given orally, 
  affecting their bioavailability. The drug travels FIRST to the 
  liver via the portal vein to be metabolised by liver enzymes
  before reaching the systemic circulation to exert its effect.

  Some drugs are so extensively metabolized, only a small
 amount of active drug remains, so these drugs must be given by 
 a different route or their dose must be increased.