Physiology and Pharmacology of the Liver Flashcards

1
Q

what are the three main metabolic functions of the liver

A

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

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2
Q

describe the processes the liver undertakes when metabolising carbohydrates

A

gluconeogenesis, glycogenolysis,

glycogenesis

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3
Q

what does the liver synthesise after the metabolism of fat

A

lipoproteins, cholesterol and triglycerides, phospholipids

ketogenesis (starvation)

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4
Q

what is involved in the liver metabolising proteins

A

deamination of amino acids- conversion of amino ammonia to urea

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5
Q

what is the role of the liver in hormone metabolism

A

major site of degradation for:

  • insulin
  • steroid hormones
  • glucagon
  • ADH
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6
Q

what is normal thyroid hormone dependant on

A

hepatic formation of the more active T3 from T4

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7
Q

what does the liver activate Vit D into

A

25(OH)D

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8
Q

what does the liver store

A

Vit A, B12, E, D & K

copper, iron (heme synthesis)

glycogen

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9
Q

what does the liver coagulate

A

Factor II, VII, IX, X

protein C & S

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10
Q

what is albumin and how is it related to the liver

A

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

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11
Q

how is the liver protective

A

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

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12
Q

what happens to bile between meals

A

stored and concentrated in gall bladder

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13
Q

what happens to bile during a meal

A

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)

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14
Q

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

A

CCK and vagal impulses

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15
Q

via what does the sphincter of oddi open

A

CCK

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16
Q

what does bile do

A

helps on the digestion and absorption of fats (emulsification)

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17
Q

secretions from what produce bile

A

hepatocytes and bile duct cells (cholangiocytes)

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18
Q

what are the components of bile

A

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)

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19
Q

what might excess cholesterol precipitate into

A

microcrystals that aggregate into gall stones

20
Q

what is cholelithiasis

A

the formation of gall stones

21
Q

what is bilibrubin

A

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

22
Q

what happens when bilirubin is present in excess

A

jaundice

23
Q

what is the best treatment for symptomatic gall stones

A

laparoscopic cholecystectomy

24
Q

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

A

ursodeoxycholic acid

25
Q

why shouldn’t morphine be used to treat biliary colic

A

as constricts sphincter of oddi and raised intrabiliary pressure

26
Q

what are alternative analgesics for biliary colic

A

buprenorphine and pethidine

27
Q

what drugs are used to relieve biliary spasms

A

atropine

glyceryltrinitrate

28
Q

what is enterohepatic recycling

A

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

29
Q

name three bile acid sequestrants (resins)

A

colesevelam, colestipol, colestyramine

30
Q

what do bile acid sequestrants do

A

no digested or absorbed by the gut - act by binding bile acids preventing their absorption

as a result lower plasma cholesterol

31
Q

how do resins lower cholesterol

A

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

32
Q

what are resins used in

A

hyperlipidemia, cholestatic jaundice

33
Q

what are the negatives of resins

A

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

34
Q

what is the role of drug metabolism

A

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

35
Q

what may change when a drug is converted into a metabolites

A

converted from inactive pro-drug to active

gain activity

have unaltered activity

posses a different type or spectrum of action

36
Q

what organs are involved in drug metabolism

A

mainly liver

also GI tract, lungs and plasma

37
Q

what is a xenobiotics

A

substance not naturally made in the body

38
Q

what usually happens in the first phase of drug metabolism

A

oxidation, reduction, hydrolysis

39
Q

what is the purpose of the first phase of drug metabolism

A

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

40
Q

what happens in phase two of drug metabolism

A

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

41
Q

what are the cytochrome P450 family of monooxygenases

A

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

42
Q

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

A

3- gene family
A- gene subfamily
4-individual gene

(classified based on amino acid sequence similarities)

43
Q

what are the main gene families in the human liver

A

CYP1, CYP2, CYP3

44
Q

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

A

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

45
Q

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

A

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