1parts of the portal triad
hepatic artery (HA), brings fresh oxygenated blood from the aorta
portal vein (PV) blood from intestines, nutriets, toxins
bild duct (BD) takes bile produced from hepatocytes and takes to gallbladder and duodenum
2Two types of liver cells
parenchymal and non-parenchymal
3parenchymal cells
perform most of the biosynthetic and metabolic functions of the liver
4non-parenchymal cells
include kupffer cells, macrophages that perform phagocytic activity
stellate or ito cells, fat and retinol storage
endothelial cells, filtration
5At what point does an aminotransferase level become concerining
if the value is greater than 3x the normal level, it could be a sign of liver injury
6Bilirubin direct measurement
amount that reacts in one minute without ethanol
7bilirubin total measurement
amount that reacts in 30 minutes with ethanol
8bilirubin indirect measurement
difference of direct and total
9what does direct bilirubin approximate?
conjugated bilirubin
10what does indirect bilirubin approximate?
unconjugated bilirubin
11What does an increase in aminotransferases (ALT, AST) suggest?
injury to hepatocites
12What does an increase in alkaline phosphatases suggest?
Liver obstruction
13What does an increase in bilirubin suggest
improper excretory function (improper elemination of bile, which stores bilirubin)
14Total bilirubin normal serum value
1.1 mg/dl
15Conjugated bilirubin normal serum value
0.4 mg/dl
16Unconjugated bilirubin normal serum value
0.7 mg/dl
17Transaminases normal serum value
40 IU/L
18ALT and AST elevation will often occur after a major injury to the liver, however
just because the levels go down doesn't mean that the injury has been healed, often there is an initial spike as they are released after injury, and then levels rapidly drop as the liver is unable to produce more.
19Clotting factors that determine prothrombine time are short lived, meaning PT a good diagnostic tool for
fulminant hepatic failure (sudden), and acute alcoholic hepatitis
20Normal value of prothrombin time
11-14 seconds
21what is considered an abnormal prothrombine time?
a prolongation of 2 or more seconds
22alkaline phosphatase (ALP) is synthesized in
bile duct epithelial cells. However levels can also be increased with increased bone readsorption, and is produced by kidneys, instines, and the placenta during pregnancy, so not a very specific liver marker.
23GGT has high sensitivity to hepatobiliary disease, but is not very specific to the liver. This makes it helpful for
confirming hepatic origin of ALP elevation
24What is Hy's Law
indicator that there is drug-induced liver injury, which has a fatality rate of 10-50% without liver transplant.
253 components of Hy's Law
3x or greater elevation in ALT or AST
2x or greater elevation in TBL (total billirubin)
No other explanation for the increase in these values, such as hepatitis A, B, or C, or other preexisting or acute liver disease
26What microRNAs may be used to evaluate liver injury?
miR-122 and miR-192 appear to be potentially sensitive and specific markers of livery injury, with a short half life after being release from dying hepatocytes.
27What is HMGB-1 used for?
Considered a mechanistic biomarker. When elevated levels are found, you know there is not only liver injury, but liver injury involving activated immune cells.
28What is cyrokeratin-18 (CK-18) fragments used for?
During apoptosis of liver cells, CK-18 is cleaved, leaving CK-18 fragments in the plasma. Therefore, if elevated levels are found, you know there is liver injury being caused by high levels of apoptosis cell death. Mechanistic biomarker.
29What is GLDH used for?
It is a mitochondrial enzyme in the liver, that when released in high levels to the bloodstream suggests loss of mitochondrial integreity or "mitotoxicity".
30Canalicular Cholestasis
bile duct obstruction
31cholangiodestructive cholestasis
damage of biliary epithelial cells
32periportal
near portal triads
33midzonal
intermediary region