LMP301 Lecture 15: Liver Diseases Flashcards Preview

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Flashcards in LMP301 Lecture 15: Liver Diseases Deck (106)
1

The liver has a small ___ and a big ____

left lobe
right lobe

2

Under the liver lies the...

gall bladder

3

___ brings blood from GI to the liver

hepatic portal vein

4

the hepatic vein flows into the...

superior vena cava

5

___ eliminates bile from liver

bile tract

6

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

1300
1/4

7

___ constitutes 75% of the blood supplied to the liver

hepatic portal vein

8

___ constitutes 25% of blood supplied to the liver

hepatic artery

9

what carries blood directly to the liver?

hepatic artery

10

what indirectly carries blood to the liver?

hepatic portal vein (goes through stomach & intestines)

11

The liver is arranged into...

lobules

12

lobules are shaped like...

hexagon

13

the middle of a lobule is the...

central vein

14

what cells make up the liver?

hepatocytes

15

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

bile duct
bile canaliculus

16

Kupffer cells

- phagocytic cells in sinusoids
- remove foreign antigens
- antigen-antibody complex

17

what can be found on the outside of the lobule?

- hepatic artery
- hepatic portal vein
- bile duct

18

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

central vein
sinusoid

19

hepatic artery flows into...

sinusoid

20

define: sinusoid

- space in the liver that contains O rich blood from hepatic artery & nutrient rich blood from portal vein
- also contains Kupffer cells

21

hepatocytes

- major cells in liver
- site of metabolic & synthetic functions

22

Ito / stellate cells

- normally store fat
- can produce collagen

23

which liver cells play an important role in liver pathology?

- Kupffer cells
- Ito cells

24

liver physiology (4)

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

25

what is metabolized in the liver?

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

26

what is synthesized in the liver?

1. serum proteins
2. coagulation factors
4. lipids

27

serum proteins synthesized in the liver

- albumin
- a-1-antitrypsin
- hormone binding proteins

28

coagulation factors synthesized in the liver

- fibrinogen
- prothrombin
- clotting factors
- antithrombin

29

lipids synthesized in the liver

- cholesterol
- apolipoproteins
- triglycerides

30

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

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

31

what is secreted by the liver?

- bile acis
- bilirubin

32

what is excreted by the liver?

- hormones
- drugs
- activated clotting factors

33

what are the "other" functions of the liver?

1. detoxification
2. storage
3. immunological role

34

liver detoxification

breaks down toxic substances & drugs

35

liver storage

- glycogen
- vit A & vit D
- vit B12
- iron
- copper

36

immunological role of liver

RES: reticuloendothelial system
- has immune cells that remove antigens
- Ag-Ab complex (Kupffer cells)

37

bilirubin is the breakdown product of...

RBC metabolism

38

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

spleen

39

enzyme: heme -> biliverdin

heme oxygenase

40

enzyme: biliverdin -> bilirubin

biliverdin-IXa reductase

41

difference between biliverdin and bilirubin

- NADPH reduced to NADP+
- the H goes onto a N in bilirubin
- bilirubin has 1 more H than biliverdin

42

RBC can be broken down to...

- heme group
- globin structure -> AA or recycled

43

What happens to the iron in the heme group?

sequestered / recycled
- transported by tranferrin
- stored by ferritin

44

heme group can be broken down to...

- Fe
- biliverdin

45

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

carrier protein (albumin)

46

what happens to bilirubin after it leaves the spleen?

Binds with albumin and travels to the liver

47

what happens to bilirubin in the liver?

conjugated with glucoronides to make it soluble (bilirubin diglucoronide)

48

enzyme: bilirubin -> bilirubin diglucoronide

UDP-glucoronyltransferase

49

route of excretion for bilirubin diglucoronide

canaliculis -> bile duct

50

what are the forms of bilirubin? (2)

1. unconjugated bilirubin
2. conjugated bilirubin

51

which form of bilirubin is found in plasma?

unconjugated

52

which form of bilirubin is soluble?

conjugated

53

how to make unconjugated bilirubin soluble?

bind reversibly to carrier protein

54

what conjugates bilirubin, and where is it done?

UDP-glucuronyltransferase
in the liver (ER)

55

Where can conjugated bilirubin be found?

in bile

56

what general things can lead to liver disease?

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

57

example of liver infection

viral hepatitis

58

example of liver toxins

- alcoholic hepatitis
- medications / drugs

59

define: hepatitis

inflammation of the liver

60

example of liver genetic problems

- hemochromatosis
- Gilbert's sydrome

61

example of liver immune diseases

- autoimmune hepatitis
- 1* biliary cirrhosis

62

example of liver neoplastic diseases

hepatocellular carcinoma

63

hepatocellular carcinoma

most common type of liver cancer

64

autoimmune hepatitis

body's immune system attacks the cells of the liver

65

Gilbert's sydrome

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

66

1* biliary cirrhosis

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

67

define: cirrhosis

end-stage consequence of liver injury
- fibrosis & conversion of normal liver tissue to structually abnormal nodules

68

define: fibrosis

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

69

what is the mechanism leading to cirrhosis?

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

70

what can be apoptotic stimuli? (2)

- oxidative stress
- activation of death receptors

71

which is less messy: apoptosis or necrosis?

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

72

what happens after a cell receives apoptotic stimulus?

- activation by TNFa
- disruption of mitochondrial membrane (can't produce power for cell)

73

what happens after TNFa is activated (for apoptosis)?

activation of capsases --> controlled intracellular degradation

74

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

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

75

what are signals that cause necrosis?

sudden acute stress:
- hypoxia
- infection
- chemical injury
- physical injury

76

what happens after a cell receives necrosis stimulus?

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

77

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

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

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

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

consequences of cirrhosis (3)

1. portal hypertension
2. decreased hepatic function
3. liver failure

80

portal hypertension

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

81

decreased hepatic function

- synthetic / excretory
- metabolic / catabolic
- detox

82

what is examined when assessing liver function?

- status of hepatocyte?
- things still being synthesized?
- metabolic capacity?
- excretory function?

83

What are the membrane bound liver enzymes?

ALP
GGT

84

What are the cytosolic liver enzymes?

AST
ALP
GGT (some)

85

which liver enzyme is found in mitochondria?

ASTm

86

normal ratio of AST:ALT

1:1
ALT usually a bit more

87

acute injury: AST:ALT ratio

1:1
Both increased

88

chronic injury: AST:ALT ratio

AST > ALT
- decreased production of ALT
- ASTm from mitochondria is leaked out

89

what causes AST > ALT

- alcoholic hepatitis
- chronic liver disease

90

what is used to examine hepatocellular injury?

AST:ALT

91

what is used to examine biliary tract injury?

ALP and GGT

92

when is GGT elevated?

- biliary tract injury
- cholestasis
- acute hepatitis

93

cholestasis

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

94

cholestasis stimulates synthesis of ____ by hepatocytes

ALP

95

When is ALP elevated?

- biliary tract obstruction
- cholestasis
- 1* biliary cirrhosis
- biliary atresia

96

biliary atresia

congenital form: bile duct is blocked or absent

acquired type: autoimmune disease

97

biliary tract injury causes...

elevated ALP and GGT levels

98

increase in unconjugated bilirubin indicates...

- increased hemolysis
- inability of hepatocytes to remove bilirubin from blood
- cannot conjugate bilirubin

99

increase in conjugated bilirubin indicates...

- cannot secrete
- biliary tract obstruction

100

hemolytic jaundice results in increased levels of ____ bilirubin

unconjugated

101

what is seen at the liver for hemolytic jaundice?

- more in blood
- more excreted
ratio is still the same, but everything is increased (not a liver problem)

102

biliary obstruction results in increased levels of ____ bilirubin

conjugated bilirubin

103

what is seen at the liver for biliary obstruction?

- conjugated bilirubin cannot be excreted into canaliculus
- backup into hepatocyte and blood stream

104

jaundice is very harmful to ___

babies
bilirubin deposits in brain tissue and may cause brain damage

105

babies have high ___ compared to adults

hematocrit
AST
ALT

106

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

> 100