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Phase 1 Medicine (Extra) > Liver > Flashcards

Liver Flashcards

1
Q

Why are pharmacologically active compounds lipophilic?

A

To be able to pass through plasma membranes to reach metabolising enzymes.

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2
Q

Are phase I or phase II reactions known as ‘functionalisation’?

A

Phase 1

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3
Q

Which ion do cytochrome p450 enzymes use to oxidise substances?

A

Fe2+

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4
Q

What is the overall equation for the reaction that occurs at a CYP enzyme in a type I drug metabolism reaction?

A

NADPH + H+ + O2 + R-H —> NADP+ + H2O + R-OH

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5
Q

Which phase (I or II) of drug metabolism is non-synthetic catabolic?

A

Phase I

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6
Q

Which phase (I or II) of drug metabolism is synthetic anabolic?

A

Phase II

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7
Q

What is UGT?

A

glucuronosyltransferase

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8
Q

What is UDPGA?

A

A co-enzyme/donor compound required to conjugate glucuronic acid.

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9
Q

What is formed in a paracetamol overdose?

How is this substance formed?

A

NAPQI

Produced when stores of glucuronic acid and sulphate are not sufficient to conjugate all the paracetamol.
Instead the paracetamol is oxidised.

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10
Q

What is the role of ADH (alcohol dehydrogenase)?

A

Converts ethanol to acetaldehyde.

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11
Q

What is the role of ALDH (aldehyde dehydrogenase)?

A

Converts acetaldehyde to acetate (in alcohol metabolism).

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12
Q

What is acetate converted into in alcohol metabolism?

A

CO2 and H2O

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13
Q

How is the absorption of iron controlled?

A

Active absorption in the duodenum responds to negative feedback.

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14
Q

What happens when there is sufficient concentrations of free iron in the blood?

A

Increased transcription of the gene coding for ferritin.

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15
Q

What happens when the concentration of free iron in the blood is low?

A

Production of ferritin decreases so unbound iron increases.

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16
Q

What protein binds iron in the blood?

A

Transferrin

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17
Q

How is iron stored in the body?

A

Bound in ferritin in liver kupffer cells.

18
Q

How is iron mostly excreted?

A

It is stored in ferritin in intestinal epithelial cells, and is released to be excreted when cells at the tips of the villi disintegrate.

19
Q

What are the four starling forces?

A

Capillary hydrostatic pressure
Interstitial hydrostatic pressure
Osmotic force due to plasma protein concentration (capillary oncotic pressure)
Osmotic force due to interstitial fluid protein

20
Q

Which clotting factors are not produced in the liver?

A

Calcium (IV) and von Willebrand Factor (VIII)

21
Q

What is a complement factor?

A

A plasma protein which sticks to pathogens and is recognised by neutrophils.
Helps mark pathogens to kill.

22
Q

Briefly describe the lysosomal pathway of protein degradation.

A

Carried out in reticuloendothelial system of the liver (sinusoidal epithelial cells, Kupffer cells, & pit cells).

Sinusoidal epithelial cells remove soluble proteins from the blood.

Proteins fused with lysosomes which contain lysosomal enzymes.

Kupffer cells work similarly but they phagocytose particulate matter.

23
Q

Briefly describe the Ubiquitin-Proteasome Pathway of protein degradation.

A

Degradation is a selective process.

Proteins targeted for degradation by attachment of ubiquitin peptide.

Peptide directs protein to complex called a proteasome.

Proteasome unfolds and breaks down protein.

24
Q

Define catabolism.

A

Breakdown of complex substances into simpler ones accompanied by the release of energy.

25
Q

What is the coenzyme involved in oxidative deamination?

A

NAD+

26
Q

How does glycogenolysis in muscle contribute to increasing blood glucose levels?

A

Glycogen hydrolysed to glucose-6-phosphate.

Glucose-6-phosphate undergoes glycolysis to produce pyruvate/ATP/lactate.

Lactate can be converted to glucose in the liver.

27
Q

What is the role of HDL (high-density lipoprotein)?

A

Removes excess cholesterol from blood and tissue.

Transports cholesterol to liver to be excreted as bile salts.

28
Q

What is the role of LDL (low-density lipoproteins)?

A

Deliver cholesterol to cells throughout the body.

29
Q

What is the role of VLDL (very low-density lipoproteins)?

A

Carries triglycerides from glucose in the liver to adipocytes.

30
Q

What is the role of lipoprotein lipase?

A

Hydrolyses triglycerides in lipoproteins into 2 free fatty acids and 1 glycerol molecule.

31
Q

What are the 6 major ingredients of bile?

A 
Bile salts
Lecithin (a phospholipid)
HCO3- and other salts
Cholesterol
Bile pigments
Trace metals
32
Q

Which cells in the liver secrete the HCO3- rich solution into bile, and what stimulates this?

A

Epithelial cells lining the bile ducts.

Secretin stimulates this.

33
Q

What vein drains the gall bladder.

A

There is no apparent venous drainage of the gall bladder.

34
Q

What are bile salts synthesised from?

A

Cholesterol

35
Q

What are mixed micelles in bile formed from?

A

Bile salts, cholesterol, and lecithin.

36
Q

How is cholesterol transported:

a) in blood
b) in bile

A

In blood: lipoproteins

In bile: mixed micelles

37
Q

How does the gall bladder concentrate bile?

A

Absorbs some NaCl and water into the blood.

38
Q

Which enzyme breaks down haem?

A

Haemoxygenase

39
Q

Is urobilinogen water or lipid soluble?

A

Lipid soluble.

It is transported back to the liver bound to albumin.

40
Q

How much urobilinogen is converted to urobilin and how much is converted to stercobilin?

A

10% urobilin

90% stercobilin

41
Q

How do gall stones form?

A

High concentration of cholesterol in the bile which crystallises out of solution.

42
Q

Which enzyme in the intestine activates trypsinogen to trypsin?

A

Enterokinase

Phase 1 Medicine (Extra) (7 decks)

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