Physiology and Pharmacology of the Liver

Question 1

what are the three main metabolic functions of the liver

Answer 1

carbohydrate metabolism, fat metabolism and synthesis of metabolic products, protein metebalism

Question 2

describe the processes the liver undertakes when metabolising carbohydrates

Answer 2

gluconeogenesis, glycogenolysis,

glycogenesis

Question 3

what does the liver synthesise after the metabolism of fat

Answer 3

lipoproteins, cholesterol and triglycerides, phospholipids

ketogenesis (starvation)

Question 4

what is involved in the liver metabolising proteins

Answer 4

deamination of amino acids- conversion of amino ammonia to urea

Question 5

what is the role of the liver in hormone metabolism

Answer 5

major site of degradation for:

• insulin
• steroid hormones
• glucagon
• ADH

Question 6

what is normal thyroid hormone dependant on

Answer 6

hepatic formation of the more active T3 from T4

Question 7

what does the liver activate Vit D into

Answer 7

25(OH)D

Question 8

what does the liver store

Answer 8

Vit A, B12, E, D & K

copper, iron (heme synthesis)

glycogen

Question 9

what does the liver coagulate

Answer 9

Factor II, VII, IX, X

protein C & S

Question 10

what is albumin and how is it related to the liver

Answer 10

is a plasma protein made by the protein that is raised if the liver is damaged

Question 11

how is the liver protective

Answer 11

produces immune factors

kupffer cells (liver phagocytes) digest/destroy cellular debris (RBCs) and any invading bacteria

detoxification of endogenous (e.g. DNA from viruses) and exogenous (drugs, alcohol) substances

Question 12

what happens to bile between meals

Answer 12

stored and concentrated in gall bladder

Question 13

what happens to bile during a meal

Answer 13

chyme in duodenum stimulates gall bladder smooth muscle to contract, sphincter of oddi opens and bile spurts into the duodenum via cystic and common bile ducts (mixed with bile from liver)

Question 14

via what does chyme stimulate the contraction of gall bladder smooth muscle

Answer 14

CCK and vagal impulses

Question 15

via what does the sphincter of oddi open

Answer 15

CCK

Question 16

what does bile do

Answer 16

helps on the digestion and absorption of fats (emulsification)

Question 17

secretions from what produce bile

Answer 17

hepatocytes and bile duct cells (cholangiocytes)

Question 18

what are the components of bile

Answer 18

bile acids (cholic and chenodeoxycholic) form bile salts with Na+ and K+

water and electrolytes

lipids and phospholipids

cholesterol

IgA

bilirubin

(plus some metabolic wastes and drug products)

Question 19

what might excess cholesterol precipitate into

Answer 19

microcrystals that aggregate into gall stones

Question 20

what is cholelithiasis

Answer 20

the formation of gall stones

Question 21

what is bilibrubin

Answer 21

breakdown product of the porphyrin component of haemoglobin- pigment rendering urine yellow and faeces brown

Question 22

what happens when bilirubin is present in excess

Answer 22

jaundice

Question 23

what is the best treatment for symptomatic gall stones

Answer 23

laparoscopic cholecystectomy

Question 24

what treatment may be suitable for gall stones where there is unimpaired gall bladder function with small/ medium sized radiolucent (transparent to x rays) stones

Answer 24

ursodeoxycholic acid

Question 25

why shouldn't morphine be used to treat biliary colic

Answer 25

as constricts sphincter of oddi and raised intrabiliary pressure

Question 26

what are alternative analgesics for biliary colic

Answer 26

buprenorphine and pethidine

Question 27

what drugs are used to relieve biliary spasms

Answer 27

atropine | glyceryltrinitrate

Question 28

what is enterohepatic recycling

Answer 28

when more than 95% of bile salts are reabsorbed by active transport in the terminal ileum (>5% entering duodenum are lost in faeces)

Question 29

name three bile acid sequestrants (resins)

Answer 29

colesevelam, colestipol, colestyramine

Question 30

what do bile acid sequestrants do

Answer 30

no digested or absorbed by the gut - act by binding bile acids preventing their absorption as a result lower plasma cholesterol

Question 31

how do resins lower cholesterol

Answer 31

promote hepatic conversion of cholesterol into bile acids- increase in LDL receptor activity of liver cells increases the clearance of LDL cholesterol from the plasma

Question 32

what are resins used in

Answer 32

hyperlipidemia, cholestatic jaundice

Question 33

what are the negatives of resins

Answer 33

unpalatable and inconvenient (large dose required), GI SE, deficiency of fat soluble vitamins

Question 34

what is the role of drug metabolism

Answer 34

convert parent drugs to more polar metabolites that are not readily reabsorbed by the kidney facilitating excretion conversion to metabolites that are usually pharmacologically less active than the parent compound

Question 35

what may change when a drug is converted into a metabolites

Answer 35

converted from inactive pro-drug to active gain activity have unaltered activity posses a different type or spectrum of action

Question 36

what organs are involved in drug metabolism

Answer 36

mainly liver also GI tract, lungs and plasma

Question 37

what is a xenobiotics

Answer 37

substance not naturally made in the body

Question 38

what usually happens in the first phase of drug metabolism

Answer 38

oxidation, reduction, hydrolysis

Question 39

what is the purpose of the first phase of drug metabolism

Answer 39

makes drug more polar, adds a chemically reactive group permitting conjugation

Question 40

what happens in phase two of drug metabolism

Answer 40

conjugation- addition of an endogenous compound increasing polarity- then excretion

Question 41

what are the cytochrome P450 family of monooxygenases

Answer 41

haem proteins in the ER of liver hepatocytes (and elsewhere) that mediate oxidation reactions (phase 1) of many lipid soluble drugs

Question 42

what do the number and letters following CYP meand (e.g. CYP3A4)

Answer 42

3- gene family A- gene subfamily 4-individual gene (classified based on amino acid sequence similarities)

Question 43

what are the main gene families in the human liver

Answer 43

CYP1, CYP2, CYP3

Question 44

what causes a patient to go into a coma in severe hepatic failure

Answer 44

detoxification of NH3 to urea (removed by kidneys) does not happen so NH3 blood levels rise

Question 45

what are two treatments used for high NH3 blood levels and how do they work

Answer 45

lactulose (semisynthetic disaccharide of fructose and lactose) - not digested/absorbed in ileum - breakdown products in colon are acidic, reduce pH - converts ammonia produced by bacteria to ammonium which is not absorbed antibiotics (neomycin, rifaximin) minimally absorbed, suppress colonic flora to inhibit ammonia-generation