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GI > Cholesterol and Bile Acid Metabolism > Flashcards

Cholesterol and Bile Acid Metabolism Flashcards

1
Q

The major components of bile include

A

Bile acids, phospholipids, and cholesterol

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2
Q

Contains bilirubin, electrolytes such as Na+, K+, and HCO3-, and small amounts of proteins

-Also copper

A

Bile

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3
Q

Bile has two fundamental functions. What are they?

A
  1. ) Lipid digestion and absorption

2. ) Excretion of cholesterol and bilirubin

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4
Q

Fatty acids in the duodenum stimulate the release of

A

CCK

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5
Q

Leads to the contraction of the gall bladder and the relaxation of the sphincter of Oddi to release bile into the duodenum

A

CCK

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6
Q

Are amphipathic, i.e. they have both hydrophobic and hydrophilic properties

A

Bile Salts

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7
Q

The hydrophilic parts of bile are the two or three

A

OH groups and a negative charge

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8
Q

While superficially similar to cholesterol, the additional hydroxyl groups are all

A

Below the plane of the ring

-methyl groups are above

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9
Q

Hence the amphipathic nature to these compounds, which plays into their role as

A

Detergents in the digestion process

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10
Q

Bile acids facilitate lipid digestion through emulsification of fat and formation of

A

Micelles

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11
Q

Transport the digested products of triacylglycerides (monoglycerides and free fatty acids), which are rather insoluble to the brush borders of epithelium for absorption

A

Bile salt micelles

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12
Q

Plays an essential role in liver homeostasis

A

Liver

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13
Q

A 27-carbon hydrophobic four-ringed compound that is an essential component of cell and organelle membranes

A

Cholesterol

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14
Q

Cholesterol is particularly abundant in the CNS in

A

Myelinated sheaths

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15
Q

Because of its insolubility in water, cholesterol is transported in the plasma as a component of

A

Lipoproteins

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16
Q

Cholesterol is not transported as free cholesterol but rather as an

A

Esterified version (i.e. w/ a fatty acid attached)

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17
Q

Cholesterol is the precursor of other important products as well, including the steroid hormones and the

A

Bile acids

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18
Q

The cardiac pathologies associated with cholesterol stem from the regulation of its abundance in the serum, packaged in

A

Lipoproteins

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19
Q

A hydrophobic compound and therefore does not exist dissolved in the aqueous environment of blood as a free compound

A

Cholesterol

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20
Q

The body’s supply of cholesterol, derived from the diet and from de novo synthesis, is always transported in the blood packaged into

A

Lipoproteins

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21
Q

Most of the cholesterol in a lipoprotein is located where?

A

Buried in interior in esterified form

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22
Q

Apart from its roles in cell and organelle membranes, cholesterol is the starting substrate in which three principal biosynthetic pathways?

A
  1. ) Steroid hormones
  2. ) Vitamin D
  3. ) Bile salts
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23
Q

Bile salts help to excrete the end product of heme degredation which is called

-gives feces a dark color

A

Bilirubin

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24
Q

In humans, the ring structure of cholesterol can not be metabolized to

A

CO2 and H2O

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25
Q

Synthesis and subsequent excretion of bile acids in the feces represent the only significant mechanism for the elimination of excess

A

Cholesterol

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26
Q

Once transported to the intestine for elimination, some of the cholesterol is modified to coprostanol and cholestenol by

A

Gut Bacteria

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27
Q

Together with cholesterol, make up the bulk of neutral fecal sterols

A

Coprostanol and cholestenol

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28
Q

The only mechanism the body possesses to eliminate cholesterol is via the bile acids in the feces and by secretion of cholesterol into the bile, which transports it to the intestine for

A

Elimination

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29
Q

The liver synthesizes which two primary bile acids from cholesterol?

A
  1. ) Cholic acid

2. ) Chenodeoxycholic acid

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30
Q

When these primary bile acids are secreted into the lumen of the intestine, a portion of each is dehydroxylated by gut bacteria at

A

C-7

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31
Q

This dehydroxylation creates the two secondary bile acids called

A

Deoxycholic acid and lithocholic acid

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32
Q

Thus how many bile acids are there?

A

Four

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33
Q

What is more soluble, primary bile acids or secondary bile acids?

A

Primary

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34
Q

The initial products of bile-targeted cholesterol metabolism in the liver

A

The primary bile salts cholic acid and chenodeoxycholic acid

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35
Q

Their synthesis from cholesterol is a multi step process; the rate limiting step being catalyzed by

A

7a-hydroxylase (CYP7A)

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36
Q

Hydroxylates cholesterol at the 7 position to form the primary bile acids

A

CYP7A

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37
Q

This enzyme is found only in the liver and it is localized to the ER

A

CYP7A

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38
Q

When bile acids accumulate, synthesis is reduced by a negative feedback mechanism that decreases the expression of

A

CYP7A

39
Q

Induces bile acid synthesis by activating cholesterol 7a-hydroxylase in some but not all species

A

Cholesterol accumulation

40
Q

The most abundant bile acids in the human bile are

A

Chenodeoxycholic acid and cholic acid

41
Q

The pKa of bile acids is approximately

A

6

42
Q

Therefore, in the contents of the intestinal lumen, which normally have a pH of 6, approximately 50% of the molecules are present in the protonated form and 50% are ionized, which form

A

Bile Salts

43
Q

The ionized form of bile acids

A

Bile salts

44
Q

Before the primary bile acids are secreted into the canalicular lumen they are conjugated via amide linkages of

A

Glycine or taurine to the rings carboxyl group

45
Q

This amide linkage produces the primary bile salts

A

Glycocholic acid and taurocholic acid

46
Q

Have pKa values that are much lower than the pH of the intestinal lumen, therefore a higher percentage of the molecules is present in the ionized form

A

Glycocholic acid and taurocholic acid

47
Q

These modifications help to further enhance their hydrophilicity as well as decrease their

A

Cytotoxicity

48
Q

The conjugated bile acids are the major solutes in

A

Human Bile

49
Q

During the enterohepatic recycling of bile acids, the structure is altered by bacterial enzymes in the

A

Distal intestine

50
Q

First, intestinal bacteria deconjugate the bile salts, removing the

A

Glycine and Taurine

51
Q

The 7-hydroxyl group of C7 is also attacked by

A

Anaerobic bacteria in the colon

52
Q

The secondary bile acids may be reconjugated in the liver, but they are not

A

Rehydroxylated

53
Q

Therefore, more than 95% of the biliary bile acids in healthy humans are

A

Cholic acid, chenodeoxycholic acid, and deoxycholic acid

54
Q

Virtually all of the biliary bile acids are in the

A

Conjugated form

55
Q

On the other hand, fecal bile acids are almost entirely

A

Unconjugated

56
Q

Fecal bile acids consist primarily of the dehydroxylated bile acids

A

Deoxycholic acid and lithocholic acid

57
Q

Implies the movement of bile acids from the liver to the small intestine and back to the liver

A

Enterohepatic circulation

58
Q

The bile acid pool contains about

A

2-4g of bile acid

59
Q

This pool is recycled via the enterohepatic circulation on the order of six to ten times each day, so that how much bile enters the duodenum during a 24 hr. period?

A

15-30g

60
Q

Of the total bile salt pool, how much is excreted in feces per day?

A

0.2-0.6 g per day

61
Q

Bile acids traverse the hepatocyte and are actively secreted into canalicular bile, completing the

A

Enterohepatic Cycle

62
Q

Ileal bile salt transport is highly efficient (about 95%), but approximately 0.2-0.6 g of bile salts escapes the

A

Enterohepatic cycle each day

63
Q

This loss of bile acids in the feces represents the body’s sole mechanism for elimination of the four-membered ring originally derived from

A

Cholesterol

64
Q

In the liver, bile acids are efficiently transported from portal blood by the

A

Na+-taurocholate cotransporting polypeptide (NTCP)

65
Q

These bile salts are then resecreted across the canalicular membrane by the

A

Bile salt export pump (BSEP)

66
Q

In the terminal ileum, bile salts are efficiently absorbed in by the

A

Apical Sodium Bile acid Transporter (ASBT)

67
Q

In the terminal ileum, they are efficiently absorbed in by the apical sodium bile acid transporter (ASBT) and transported out by the basolateral

-returns bile salts to liver in portal circulation

A

Heteromeric transporter, OSTα-OSTβ

68
Q

A small percentage of the bile salts are not reabsorbed and are modified from primary bile acids to secondary bile acids by anaerobic bacteria present in the

A

Colon

69
Q

These secondary bile acids are either passively absorbed from the colon or they are

A

Excreted in feces

70
Q

Represents one of the most common surgical problems worldwide and is especially prevalent in most western countries

A

Cholelithiasis (or gallstones)

71
Q

In the U.S. alone, gallstones are present in 8-20% of the population by the age of 40 and are more likely to develop in women than in men by a ratio of about

A

2-3:1

72
Q

What are the three varieties of gallstones?

A
  1. ) Cholesterol stones (75%)
  2. ) Pigmented stones (15-20%)
  3. ) Mixed
73
Q

The most common type of gall stone is the

A

Cholesterol stone

74
Q

Arise from the crystallization of calcium bilirubinate

A

Pigmented stones

75
Q

Increased red blood cell destruction (hemolysis) and abnormal metabolism of hemoglobin (liver disease) cause

A

Pigmented stones

76
Q

Tend to form when there is stasis of bile, impaired gallbladder motility, and an imbalance in the bile content

A

Gallstones

77
Q

(1) certain genetic factors, including LITH genes,
(2) hepatic hypersecretion of biliary cholesterol,
(3) gallbladder hypomotility,
(4) rapid phase transitions of cholesterol in bile from liquid to solid state, and
(5) certain intestinal factors

Are factors that result in

A

Cholesterol stones

78
Q

Certain genetic factors such as LITH genes increase risk for

A

Cholesterol stones

79
Q

Normally, a delicate balance exists between the levels of

A

Bile acids, phospholipids, and cholesterol

80
Q

When this balance is disrupted, especially when there is supersaturation with cholesterol, there is predisposition for the development of

A

Cholesterol gallstones

81
Q

This is because when cholesterol supersaturates, it tends to

A

Crystallize

82
Q

In Admirand’s Triangle. The small, blue area is the only area where cholesterol is

A

Completely soluble

83
Q

Refers to the blockage of any duct that carries bile from the liver to the gallbladder or from the gallbladder to the small intestine

A

Bilary obstruction

84
Q

The clinical setting of cholestasis or failure of biliary flow may be due to biliary obstruction by mechanical means or by metabolic factors in the

A

Hepatic cells

85
Q

Common to both obstructive and non obstructive cholestasis is the accumulation of bile pigment within the

A

Hepatic Parenchyma

86
Q

Elongated green-brown plugs of bile are visible in dilated bile canaliculi. Rupture of canaliculi leads to extravasation of bile, which is quickly phagocytosed by

A

Kupffer cells

87
Q

Droplets of bile pigment also accumulate within hepatocytes, which can take on a fine, foamy appearance, so called

A

“Feathery degeneration”

88
Q

Bile deposits as conjugated bile plugs in the

A

Draining ductules

89
Q

Bind bile acids in the intestine, resulting in interruption of the reabsorption of bile acids (which is usually 90 percent efficient), thus promoting their excretion

A

Bile acid sequestrants (BAS or bile acid resins (BAR))

90
Q

Used in the treatment of hypercholesterolemia because the removal of bile acids relieves the inhibition on bile acid synthesis in the liver, thereby diverting additional cholesterol into that pathway

A

BAS and BAR

91
Q

The available bile acid sequestrants include

A

Cholestyramine, colestipol, and colesevelam

92
Q

Certain soluble fibers (psyllium, pectin, wheat dextrin, and oat products) reduce serum levels of

A

Cholesterol

93
Q

May interfere with micelle formation in the proximal small intestine, resulting in decreased absorption of cholesterol and fatty acids

A

Soluble fibers

GI (59 decks)

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