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LMP301 > LMP301 Lecture 15: Liver Diseases > Flashcards

LMP301 Lecture 15: Liver Diseases Flashcards

1
Q

The liver has a small ___ and a big ____

A

left lobe

right lobe

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2
Q

Under the liver lies the…

A

gall bladder

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3
Q

___ brings blood from GI to the liver

A

hepatic portal vein

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4
Q

the hepatic vein flows into the…

A

superior vena cava

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5
Q

___ eliminates bile from liver

A

bile tract

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6
Q

____ mL of blood flow into the liver every minute. This is ___ of the CO

A

1300

1/4

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7
Q

___ constitutes 75% of the blood supplied to the liver

A

hepatic portal vein

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8
Q

___ constitutes 25% of blood supplied to the liver

A

hepatic artery

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9
Q

what carries blood directly to the liver?

A

hepatic artery

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10
Q

what indirectly carries blood to the liver?

A

hepatic portal vein (goes through stomach & intestines)

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11
Q

The liver is arranged into…

A

lobules

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12
Q

lobules are shaped like…

A

hexagon

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13
Q

the middle of a lobule is the…

A

central vein

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14
Q

what cells make up the liver?

A

hepatocytes

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15
Q

things from the central vein drain into ___ (connected by ___)

A

bile duct

bile canaliculus

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16
Q

Kupffer cells

A
  • phagocytic cells in sinusoids
  • remove foreign antigens
  • antigen-antibody complex
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17
Q

what can be found on the outside of the lobule?

A
  • hepatic artery
  • hepatic portal vein
  • bile duct
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18
Q

the hepatic portal vein drain into ___ (connected by ___)

A

central vein

sinusoid

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19
Q

hepatic artery flows into…

A

sinusoid

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20
Q

define: sinusoid

A
  • space in the liver that contains O rich blood from hepatic artery & nutrient rich blood from portal vein
  • also contains Kupffer cells
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21
Q

hepatocytes

A
  • major cells in liver

- site of metabolic & synthetic functions

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22
Q

Ito / stellate cells

A
  • normally store fat

- can produce collagen

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23
Q

which liver cells play an important role in liver pathology?

A
  • Kupffer cells

- Ito cells

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24
Q

liver physiology (4)

A
  1. energy metabolism / catabolism
  2. synthetic functions
  3. excretory & secretory functions
  4. other
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25
Q

what is metabolized in the liver?

A
  1. carbohydrate metabolism (glycogenolysis, gluconeogenesis)
  2. protein metabolism (protein catabolism in AA)
  3. lipid metabolism (FFA metabolism)
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26
Q

what is synthesized in the liver?

A
  1. serum proteins
  2. coagulation factors
  3. lipids
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27
Q

serum proteins synthesized in the liver

A
  • albumin
  • a-1-antitrypsin
  • hormone binding proteins
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28
Q

coagulation factors synthesized in the liver

A
  • fibrinogen
  • prothrombin
  • clotting factors
  • antithrombin
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29
Q

lipids synthesized in the liver

A
  • cholesterol
  • apolipoproteins
  • triglycerides
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30
Q

besides it’s main purpose, what other function do materials synthesized from the liver serve?

A

we can examine these in the body to see if there is something wrong with the liver

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31
Q

what is secreted by the liver?

A
  • bile acis

- bilirubin

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32
Q

what is excreted by the liver?

A
  • hormones
  • drugs
  • activated clotting factors
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33
Q

what are the “other” functions of the liver?

A
  1. detoxification
  2. storage
  3. immunological role
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34
Q

liver detoxification

A

breaks down toxic substances & drugs

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35
Q

liver storage

A
  • glycogen
  • vit A & vit D
  • vit B12
  • iron
  • copper
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36
Q

immunological role of liver

A

RES: reticuloendothelial system

  • has immune cells that remove antigens
  • Ag-Ab complex (Kupffer cells)
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37
Q

bilirubin is the breakdown product of…

A

RBC metabolism

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38
Q

breakdown of RBC and the formation of bilirubin happens in the…

A

spleen

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39
Q

enzyme: heme -> biliverdin

A

heme oxygenase

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40
Q

enzyme: biliverdin -> bilirubin

A

biliverdin-IXa reductase

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41
Q

difference between biliverdin and bilirubin

A
  • NADPH reduced to NADP+
  • the H goes onto a N in bilirubin
  • bilirubin has 1 more H than biliverdin
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42
Q

RBC can be broken down to…

A
  • heme group

- globin structure -> AA or recycled

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43
Q

What happens to the iron in the heme group?

A

sequestered / recycled

  • transported by tranferrin
  • stored by ferritin
44
Q

heme group can be broken down to…

A
  • Fe

- biliverdin

45
Q

to travel in the blood, bilirubin has to be bound to…

A

carrier protein (albumin)

46
Q

what happens to bilirubin after it leaves the spleen?

A

Binds with albumin and travels to the liver

47
Q

what happens to bilirubin in the liver?

A

conjugated with glucoronides to make it soluble (bilirubin diglucoronide)

48
Q

enzyme: bilirubin -> bilirubin diglucoronide

A

UDP-glucoronyltransferase

49
Q

route of excretion for bilirubin diglucoronide

A

canaliculis -> bile duct

50
Q

what are the forms of bilirubin? (2)

A
  1. unconjugated bilirubin

2. conjugated bilirubin

51
Q

which form of bilirubin is found in plasma?

A

unconjugated

52
Q

which form of bilirubin is soluble?

A

conjugated

53
Q

how to make unconjugated bilirubin soluble?

A

bind reversibly to carrier protein

54
Q

what conjugates bilirubin, and where is it done?

A

UDP-glucuronyltransferase

in the liver (ER)

55
Q

Where can conjugated bilirubin be found?

A

in bile

56
Q

what general things can lead to liver disease?

A
  1. infections
  2. toxins
  3. genetics
  4. (auto)immune
  5. neoplastic (cancer)
57
Q

example of liver infection

A

viral hepatitis

58
Q

example of liver toxins

A
  • alcoholic hepatitis

- medications / drugs

59
Q

define: hepatitis

A

inflammation of the liver

60
Q

example of liver genetic problems

A
  • hemochromatosis

- Gilbert’s sydrome

61
Q

example of liver immune diseases

A
  • autoimmune hepatitis

- 1* biliary cirrhosis

62
Q

example of liver neoplastic diseases

A

hepatocellular carcinoma

63
Q

hepatocellular carcinoma

A

most common type of liver cancer

64
Q

autoimmune hepatitis

A

body’s immune system attacks the cells of the liver

65
Q

Gilbert’s sydrome

A

Increased bilirubin due to reduced UDP-glucoronyltransferase (bilirubin cannot be excreted)

66
Q

1* biliary cirrhosis

A

Destruction of small bile ducts in the liver, causing bile buildup in the liver

67
Q

define: cirrhosis

A

end-stage consequence of liver injury

- fibrosis & conversion of normal liver tissue to structually abnormal nodules

68
Q

define: fibrosis

A

the thickening and scarring of connective tissue, usually as a result of injury.

69
Q

what is the mechanism leading to cirrhosis?

A

acute liver injury –> hepatocytes undergo necrosis / apoptosis –> loss of liver function

70
Q

what can be apoptotic stimuli? (2)

A
  • oxidative stress

- activation of death receptors

71
Q

which is less messy: apoptosis or necrosis?

A

apoptosis -> all degradation occurs within the intact membrane of the cell

72
Q

what happens after a cell receives apoptotic stimulus?

A
  • activation by TNFa

- disruption of mitochondrial membrane (can’t produce power for cell)

73
Q

what happens after TNFa is activated (for apoptosis)?

A

activation of capsases –> controlled intracellular degradation

74
Q

what happens after the mitochondrial membrane is disrupted (for apoptosis)?

A

activation of BCL-2 and cytochrome C –> activation of capsases –> controlled intracellular degradation

75
Q

what are signals that cause necrosis?

A

sudden acute stress:

  • hypoxia
  • infection
  • chemical injury
  • physical injury
76
Q

what happens after a cell receives necrosis stimulus?

A
  1. cell / mitochondrial swelling
  2. membrane disruption
  3. leakage of cellular contents, nuclear disintegration
  4. active Kupffer & immune cells
  5. inflammatory response
77
Q

What happens if there is sustained inflammation to the liver (chronic)? [cirrhosis pathway]

A
  1. ito cells activate
  2. deposit matrix proteins (glycoproteins, collagen, elastin) in sinusoid
  3. fibrosis (due to disruption of liver structure)
  4. cirrhosis
  5. liver failure
78
Q

What happens if there is sustained inflammation to the liver (chronic)? [fatty liver pathway]

A
  1. ito cells activate
  2. deposit matrix proteins (glycoproteins, collagen, elastin) in sinusoid
  3. ito cells deposit fat everywhere in liver
  4. fatty liver
79
Q

consequences of cirrhosis (3)

A
  1. portal hypertension
  2. decreased hepatic function
  3. liver failure
80
Q

portal hypertension

A

blood can’t get into liver from the hepatic portal vein

81
Q

decreased hepatic function

A
  • synthetic / excretory
  • metabolic / catabolic
  • detox
82
Q

what is examined when assessing liver function?

A
  • status of hepatocyte?
  • things still being synthesized?
  • metabolic capacity?
  • excretory function?
83
Q

What are the membrane bound liver enzymes?

A

ALP

GGT

84
Q

What are the cytosolic liver enzymes?

A

AST
ALP
GGT (some)

85
Q

which liver enzyme is found in mitochondria?

A

ASTm

86
Q

normal ratio of AST:ALT

A

1:1

ALT usually a bit more

87
Q

acute injury: AST:ALT ratio

A

1:1

Both increased

88
Q

chronic injury: AST:ALT ratio

A

AST > ALT

  • decreased production of ALT
  • ASTm from mitochondria is leaked out
89
Q

what causes AST > ALT

A
  • alcoholic hepatitis

- chronic liver disease

90
Q

what is used to examine hepatocellular injury?

A

AST:ALT

91
Q

what is used to examine biliary tract injury?

A

ALP and GGT

92
Q

when is GGT elevated?

A
  • biliary tract injury
  • cholestasis
  • acute hepatitis
93
Q

cholestasis

A

little or no bile is secreted or the flow of bile into the digestive tract is obstructed

94
Q

cholestasis stimulates synthesis of ____ by hepatocytes

A

ALP

95
Q

When is ALP elevated?

A
  • biliary tract obstruction
  • cholestasis
  • 1* biliary cirrhosis
  • biliary atresia
96
Q

biliary atresia

A

congenital form: bile duct is blocked or absent

acquired type: autoimmune disease

97
Q

biliary tract injury causes…

A

elevated ALP and GGT levels

98
Q

increase in unconjugated bilirubin indicates…

A
  • increased hemolysis
  • inability of hepatocytes to remove bilirubin from blood
  • cannot conjugate bilirubin
99
Q

increase in conjugated bilirubin indicates…

A
  • cannot secrete

- biliary tract obstruction

100
Q

hemolytic jaundice results in increased levels of ____ bilirubin

A

unconjugated

101
Q

what is seen at the liver for hemolytic jaundice?

A
  • more in blood
  • more excreted
    ratio is still the same, but everything is increased (not a liver problem)
102
Q

biliary obstruction results in increased levels of ____ bilirubin

A

conjugated bilirubin

103
Q

what is seen at the liver for biliary obstruction?

A
  • conjugated bilirubin cannot be excreted into canaliculus

- backup into hepatocyte and blood stream

104
Q

jaundice is very harmful to ___

A

babies

bilirubin deposits in brain tissue and may cause brain damage

105
Q

babies have high ___ compared to adults

A

hematocrit
AST
ALT

106
Q

when do levels of AST and ALT become concerning in infants?

A

> 100

LMP301 (18 decks)

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