LMP301 Lecture 15: Liver Diseases Flashcards
The liver has a small ___ and a big ____
left lobe
right lobe
Under the liver lies the…
gall bladder
___ brings blood from GI to the liver
hepatic portal vein
the hepatic vein flows into the…
superior vena cava
___ eliminates bile from liver
bile tract
____ mL of blood flow into the liver every minute. This is ___ of the CO
1300
1/4
___ constitutes 75% of the blood supplied to the liver
hepatic portal vein
___ constitutes 25% of blood supplied to the liver
hepatic artery
what carries blood directly to the liver?
hepatic artery
what indirectly carries blood to the liver?
hepatic portal vein (goes through stomach & intestines)
The liver is arranged into…
lobules
lobules are shaped like…
hexagon
the middle of a lobule is the…
central vein
what cells make up the liver?
hepatocytes
things from the central vein drain into ___ (connected by ___)
bile duct
bile canaliculus
Kupffer cells
- phagocytic cells in sinusoids
- remove foreign antigens
- antigen-antibody complex
what can be found on the outside of the lobule?
- hepatic artery
- hepatic portal vein
- bile duct
the hepatic portal vein drain into ___ (connected by ___)
central vein
sinusoid
hepatic artery flows into…
sinusoid
define: sinusoid
- space in the liver that contains O rich blood from hepatic artery & nutrient rich blood from portal vein
- also contains Kupffer cells
hepatocytes
- major cells in liver
- site of metabolic & synthetic functions
Ito / stellate cells
- normally store fat
- can produce collagen
which liver cells play an important role in liver pathology?
- Kupffer cells
- Ito cells
liver physiology (4)
- energy metabolism / catabolism
- synthetic functions
- excretory & secretory functions
- other
what is metabolized in the liver?
- carbohydrate metabolism (glycogenolysis, gluconeogenesis)
- protein metabolism (protein catabolism in AA)
- lipid metabolism (FFA metabolism)
what is synthesized in the liver?
- serum proteins
- coagulation factors
- lipids
serum proteins synthesized in the liver
- albumin
- a-1-antitrypsin
- hormone binding proteins
coagulation factors synthesized in the liver
- fibrinogen
- prothrombin
- clotting factors
- antithrombin
lipids synthesized in the liver
- cholesterol
- apolipoproteins
- triglycerides
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
what is secreted by the liver?
- bile acis
- bilirubin
what is excreted by the liver?
- hormones
- drugs
- activated clotting factors
what are the “other” functions of the liver?
- detoxification
- storage
- immunological role
liver detoxification
breaks down toxic substances & drugs
liver storage
- glycogen
- vit A & vit D
- vit B12
- iron
- copper
immunological role of liver
RES: reticuloendothelial system
- has immune cells that remove antigens
- Ag-Ab complex (Kupffer cells)
bilirubin is the breakdown product of…
RBC metabolism
breakdown of RBC and the formation of bilirubin happens in the…
spleen
enzyme: heme -> biliverdin
heme oxygenase
enzyme: biliverdin -> bilirubin
biliverdin-IXa reductase
difference between biliverdin and bilirubin
- NADPH reduced to NADP+
- the H goes onto a N in bilirubin
- bilirubin has 1 more H than biliverdin
RBC can be broken down to…
- heme group
- globin structure -> AA or recycled
What happens to the iron in the heme group?
sequestered / recycled
- transported by tranferrin
- stored by ferritin
heme group can be broken down to…
- Fe
- biliverdin
to travel in the blood, bilirubin has to be bound to…
carrier protein (albumin)
what happens to bilirubin after it leaves the spleen?
Binds with albumin and travels to the liver
what happens to bilirubin in the liver?
conjugated with glucoronides to make it soluble (bilirubin diglucoronide)
enzyme: bilirubin -> bilirubin diglucoronide
UDP-glucoronyltransferase
route of excretion for bilirubin diglucoronide
canaliculis -> bile duct
what are the forms of bilirubin? (2)
- unconjugated bilirubin
2. conjugated bilirubin
which form of bilirubin is found in plasma?
unconjugated
which form of bilirubin is soluble?
conjugated
how to make unconjugated bilirubin soluble?
bind reversibly to carrier protein
what conjugates bilirubin, and where is it done?
UDP-glucuronyltransferase
in the liver (ER)
Where can conjugated bilirubin be found?
in bile
what general things can lead to liver disease?
- infections
- toxins
- genetics
- (auto)immune
- neoplastic (cancer)
example of liver infection
viral hepatitis
example of liver toxins
- alcoholic hepatitis
- medications / drugs
define: hepatitis
inflammation of the liver
example of liver genetic problems
- hemochromatosis
- Gilbert’s sydrome
example of liver immune diseases
- autoimmune hepatitis
- 1* biliary cirrhosis
example of liver neoplastic diseases
hepatocellular carcinoma
hepatocellular carcinoma
most common type of liver cancer
autoimmune hepatitis
body’s immune system attacks the cells of the liver
Gilbert’s sydrome
Increased bilirubin due to reduced UDP-glucoronyltransferase (bilirubin cannot be excreted)
1* biliary cirrhosis
Destruction of small bile ducts in the liver, causing bile buildup in the liver
define: cirrhosis
end-stage consequence of liver injury
- fibrosis & conversion of normal liver tissue to structually abnormal nodules
define: fibrosis
the thickening and scarring of connective tissue, usually as a result of injury.
what is the mechanism leading to cirrhosis?
acute liver injury –> hepatocytes undergo necrosis / apoptosis –> loss of liver function
what can be apoptotic stimuli? (2)
- oxidative stress
- activation of death receptors
which is less messy: apoptosis or necrosis?
apoptosis -> all degradation occurs within the intact membrane of the cell
what happens after a cell receives apoptotic stimulus?
- activation by TNFa
- disruption of mitochondrial membrane (can’t produce power for cell)
what happens after TNFa is activated (for apoptosis)?
activation of capsases –> controlled intracellular degradation
what happens after the mitochondrial membrane is disrupted (for apoptosis)?
activation of BCL-2 and cytochrome C –> activation of capsases –> controlled intracellular degradation
what are signals that cause necrosis?
sudden acute stress:
- hypoxia
- infection
- chemical injury
- physical injury
what happens after a cell receives necrosis stimulus?
- cell / mitochondrial swelling
- membrane disruption
- leakage of cellular contents, nuclear disintegration
- active Kupffer & immune cells
- inflammatory response
What happens if there is sustained inflammation to the liver (chronic)? [cirrhosis pathway]
- ito cells activate
- deposit matrix proteins (glycoproteins, collagen, elastin) in sinusoid
- fibrosis (due to disruption of liver structure)
- cirrhosis
- liver failure
What happens if there is sustained inflammation to the liver (chronic)? [fatty liver pathway]
- ito cells activate
- deposit matrix proteins (glycoproteins, collagen, elastin) in sinusoid
- ito cells deposit fat everywhere in liver
- fatty liver
consequences of cirrhosis (3)
- portal hypertension
- decreased hepatic function
- liver failure
portal hypertension
blood can’t get into liver from the hepatic portal vein
decreased hepatic function
- synthetic / excretory
- metabolic / catabolic
- detox
what is examined when assessing liver function?
- status of hepatocyte?
- things still being synthesized?
- metabolic capacity?
- excretory function?
What are the membrane bound liver enzymes?
ALP
GGT
What are the cytosolic liver enzymes?
AST
ALP
GGT (some)
which liver enzyme is found in mitochondria?
ASTm
normal ratio of AST:ALT
1:1
ALT usually a bit more
acute injury: AST:ALT ratio
1:1
Both increased
chronic injury: AST:ALT ratio
AST > ALT
- decreased production of ALT
- ASTm from mitochondria is leaked out
what causes AST > ALT
- alcoholic hepatitis
- chronic liver disease
what is used to examine hepatocellular injury?
AST:ALT
what is used to examine biliary tract injury?
ALP and GGT
when is GGT elevated?
- biliary tract injury
- cholestasis
- acute hepatitis
cholestasis
little or no bile is secreted or the flow of bile into the digestive tract is obstructed
cholestasis stimulates synthesis of ____ by hepatocytes
ALP
When is ALP elevated?
- biliary tract obstruction
- cholestasis
- 1* biliary cirrhosis
- biliary atresia
biliary atresia
congenital form: bile duct is blocked or absent
acquired type: autoimmune disease
biliary tract injury causes…
elevated ALP and GGT levels
increase in unconjugated bilirubin indicates…
- increased hemolysis
- inability of hepatocytes to remove bilirubin from blood
- cannot conjugate bilirubin
increase in conjugated bilirubin indicates…
- cannot secrete
- biliary tract obstruction
hemolytic jaundice results in increased levels of ____ bilirubin
unconjugated
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)
biliary obstruction results in increased levels of ____ bilirubin
conjugated bilirubin
what is seen at the liver for biliary obstruction?
- conjugated bilirubin cannot be excreted into canaliculus
- backup into hepatocyte and blood stream
jaundice is very harmful to ___
babies
bilirubin deposits in brain tissue and may cause brain damage
babies have high ___ compared to adults
hematocrit
AST
ALT
when do levels of AST and ALT become concerning in infants?
> 100
