LMP301 Lecture 15: Liver Diseases Flashcards
(106 cards)
1
Q
The liver has a small ___ and a big ____
A
left lobe
right lobe
2
Q
Under the liver lies the…
A
gall bladder
3
Q
___ brings blood from GI to the liver
A
hepatic portal vein
4
Q
the hepatic vein flows into the…
A
superior vena cava
5
Q
___ eliminates bile from liver
A
bile tract
6
Q
____ mL of blood flow into the liver every minute. This is ___ of the CO
A
1300
1/4
7
Q
___ constitutes 75% of the blood supplied to the liver
A
hepatic portal vein
8
Q
___ constitutes 25% of blood supplied to the liver
A
hepatic artery
9
Q
what carries blood directly to the liver?
A
hepatic artery
10
Q
what indirectly carries blood to the liver?
A
hepatic portal vein (goes through stomach & intestines)
11
Q
The liver is arranged into…
A
lobules
12
Q
lobules are shaped like…
A
hexagon
13
Q
the middle of a lobule is the…
A
central vein
14
Q
what cells make up the liver?
A
hepatocytes
15
Q
things from the central vein drain into ___ (connected by ___)
A
bile duct
bile canaliculus
16
Q
Kupffer cells
A
- phagocytic cells in sinusoids
- remove foreign antigens
- antigen-antibody complex
17
Q
what can be found on the outside of the lobule?
A
- hepatic artery
- hepatic portal vein
- bile duct
18
Q
the hepatic portal vein drain into ___ (connected by ___)
A
central vein
sinusoid
19
Q
hepatic artery flows into…
A
sinusoid
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
21
Q
hepatocytes
A
- major cells in liver
- site of metabolic & synthetic functions
22
Q
Ito / stellate cells
A
- normally store fat
- can produce collagen
23
Q
which liver cells play an important role in liver pathology?
A
- Kupffer cells
- Ito cells
24
Q
liver physiology (4)
A
- energy metabolism / catabolism
- synthetic functions
- excretory & secretory functions
- 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
