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Hugh's MD1 Abdominal > Liver Metabolism > Flashcards

Liver Metabolism Flashcards

1
Q

What colour is P450?

A

Red because of the iron protoporphyrin molecule which hemoglobin also has

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1
Q

Why doesn’t phototherapy work for older people?

A

Their skin is too thick for the light to penetrate

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1
Q

What is haemoglobin with Fe3+ called?

A

Methaemoglobin

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2
Q

What type of enzyme are P450?

A

Monoxygenase

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2
Q

How does a bruise appear after 5-10 days?

A

Greenish/yellowish - due to biliverdin

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2
Q

What makes conjugated bilirubin soluble?

A

Hydrophilic glucuronate

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3
Q

What is the implications of substances inducing its P450?

A

Can lead to the development of resistance to the drug or

Some people may be poor metabolises of a drug

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3
Q

How does a bruise appear after 1-2 days?

A

Bluish-purple/blackish

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3
Q

How can you treat Crigler-Najjar syndrome?

A

Fluorescent light therapy

Liver transplant

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3
Q

What is the major colourant of faeces?

A

Stercobilin

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4
Q

How does a bruise appear after 10-14 days?

A

Yellow-brown or light brown (bilirubin)

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6
Q

How do mitochondria appear when centrifuged?

A

A straw to red colour

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6
Q

What is special about CYP2D6?

A

It metabolising aprox. one quarter of all pharmaceuticals

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6
Q

What is the function of the mononuclear phagocyte system?

A

Destruction of old RBCs and WBCs

Formation of plasma proteins

Formation of antibody

Formation of bile pigment

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7
Q

What are the implications of low hemopexin?

A

Haemolytic anaemia

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8
Q

In general, how do cytochromes carry O2?

A

Fe2+ <> Fe3+

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10
Q

How are different P450 systems named?

A

CYP [number][letter][number]

CYP means cytochrome P450

And the latter are for family, subfamily and form respectively

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11
Q

How is urobilinogen made?

A

By the action of commensals in the gut

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13
Q

Which disease is aflatoxin associated with?

A

Kwashiorkor

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13
Q

What percentage of RBC turn over occurs outside the spleen?

A

10%

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14
Q

What does haem oxygenase resemble?

A

Globin

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15
Q

How long due RBCs last in the blood stream?

A

120 days

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15
Q

What does haemolytic crisis result in?

A

Anaemia

Jaundice

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16
Q

What happens to benzopyrene?

A

Can either be inactivated and safely secreted or

Activated into a carcinogen

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17
Q

What converts haem into biliverdin?

A

haem oxygenase

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19
Q

What determines whether the liver or the immune system will deal with a foreign substance?

A

The liver handles molecules <5000 molar mass

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21
Q

What is the role of Fe2/3 in the P450 cycle?

A

Take and pass e- to make the ROS

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23
Q

Why is it called the P450 system not enzyme?

A

Because two enzymes are required for the process to occur

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24
Q

How much urobilinogen is excreted through the kidney?

A

1%

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25
Q

What is a cause of haemolytic disease in newborns?

A

Maternal ab crossing the placenta and reacting with foetal RBCs

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27
Q

What is the ROS created in the P450 cycle?

A

Peroxide

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27
Q

What role does albumin play in haem metabolism?

A

Carries unconjugated bilirubin to the liver

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28
Q

What is haem first converted into?

A

Biliverdin

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28
Q

What is the mononuclear phagocyte system?

A

Immune cell mediated system consisting of monocytes, macrophages, and to a lesser extent T and B cells in the lymph nodes, spleen and liver.

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28
Q

What is the function of cMOAT?

A

Transport conjugated bilirubin from hepatocytes into liver canaliculi

29
Q

What is commonly added to substrates?

A

-OH group

30
Q

Where is EPO synthesized?

A

The kidney

31
Q

What is the function of P450 reductase in the P450 cycle?

A

Facilitate the supply of electrons from NADPH to O

31
Q

What is makes up the structure of bilirubin?

A

4 pyrrole rings

33
Q

What are microsomes?

A

The *in vitro *isolated form of P450 cytochromes

34
Q

What enzyme is required for the conjugation of bilirubin?

A

UDP glucuronyl transferase

34
Q

What carries iron to the liver/bone marrow after RBC destruction?

A

Transferrin

36
Q

How many genes for P450s have been identified?

A

57

37
Q

What does the P in P450 stand for?

A

Pigment

39
Q

What colour bilirubin?

A

Yellow

40
Q

At defect in what causes Crigler-Najjar disease

A

UDP glucuronyl transferase

41
Q

What reaction does P450 typically catalyse?

A

RH + NADPH + O2 + H+ > ROH + NADP+ + H2O

42
Q

What happens when bilirubin is exposed to light? What are the implications of that?

A

Double bonds isomerize making it more soluble.

Phototherapy can be used to treat jaundice

43
Q

Where does aflatoxin come from in the diet?

A

Aspergillus fungus on corn or peanuts

43
Q

What are the 3 signs of RBC aging?

A

Loss of sialic acid residues from glycophorin

Phosphatidylserine flips to the other side of the membrane

Oxidative damage eg Heinz bodies

45
Q

What initiates P450 reaction cycle?

A

A substrate binding to P450

47
Q

Where does the P450 process typically occur?

A

Smooth ER of hepatocytes

48
Q

What is the purpose of the P450 cycle?

A

Create a ROS next to the substrate

49
Q

What happens to free haemoglobin if haptoglobin is depleted?

A

It is excreted in the urine

50
Q

What is the function of hemopexin?

A

It carries free haem to the liver

51
Q

How many RBCs are made per second?

A

2 million

52
Q

What is Crigler-Najjar syndrome caused by?

A

Mutation causing inactivation of glucuronyltransferase

54
Q

Where is bilirubin usually produced?

A

Spleen

55
Q

How long does it take reticulocytes to mature into RBCs?

A

1 day

57
Q

How is the lifespan of RBCs calculated?

A

Tagging them with radioactive chromiun

59
Q

What provides the electrons in the P450 cycle?

A

NADPH

60
Q

What is kernicterus?

A

Neurotoxic damage due to high levels of bilirubin in the children

61
Q

Where in the spleen does RBC breakdown occur?

A

Red pulp

62
Q

Do reticulocytes have nuclei?

A

No

63
Q

Why are P450 types specific to certain substrates?

A

The binding cleft must be specific for the substrate

64
Q

What percentage of the population doesn’t response to codeine?

A

10%

64
Q

What is the problem with high levels of bilirubin in children?

A

It’s neurotoxic

65
Q

What are the physiological consequences of haemolysis

A

Unconjugated hyperbilirubinaemia as the liver’s capacity to metabolise Hb is saturated

Increase stercobilin in stool and urobilinogen in urine

Reticulocytosis

66
Q

How much of the circulating blood are reticulocytes?

A

1%

67
Q

In what form is bilirubin reabsorbed in the gut for excretion through the kidneys

A

Urobilinogen

68
Q

What are some causes of hyperbilirubinaemia

A

Bile duct obstruction

Severe liver failure due to cirrhosis

Dubin-Johnson syndrome

69
Q

What colour is urobilinogen?

A

Colourless

71
Q

What converts biliverdin to bilirubin?

A

Biliverdin reductase

73
Q

Which cell breaks down senescent RBCs?

A

Macrophages

74
Q

What do mitochondria use P450 for?

A

Oxidising steroids

75
Q

What is Dubin-Johnson syndrome caused by?

A

A genetic defect in cMOAT

76
Q

What is haptoglobin?

A

Plasma protein that binds to haemoglobin for RBCs that break down outside the spleen.

77
Q

What are the two forms of bilirubin?

A

Conjugated (direct)

Uncojugated (indirect)

78
Q

Where are P450 cytochromes located within cells?

A

ER

Mitochondria

80
Q

What happens to the haptoglobin-haemoglobin complex?

A

Removed with the mononuclear phagocyte complex mostly in the spleen

81
Q

Why must there be many different type of P450?

A

Because they are specific to different substrates

82
Q

Which P450 is deficient in individuals that have difficulty converting codeine to morphine?

A

CYP 2D6

83
Q

What is the outcome of the ROS reacting with the substrate?

A

-OH added most commonly

Sometimes can cause others eg epoxide

84
Q

What types of molecules does albumin bind?

A

Hydrophobic

85
Q

What is are the implications of low haptoglobin in the blood?

A

High levels of haemolysis is occurring

Hugh's MD1 Abdominal (21 decks)

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