Liver Function & Disease Flashcards
Portal vein
brings nutrients & 75% of blood supply
Hepatic artery
brings 02 & supplies 25% of blood to liver
Hepatocytes
80% of liver space, do liver jobs & also facilitate regeneration
Kupffer cells
macrophages that line sinusoids, phagocytic cells engulf bacteria, toxins, debris etc
Stellate cells
contain lipid droplets, when they are activated the lipids begin to deposit in the sinusoid & fibrotic tissues -> cirrhosis
Liver functions (4)
excretory & secretory
synthesis
detoxification & drug metabolism
storage
waste products & where they go
bilirubin, bile acids, cholesterol, bile pigments & other wastes get excreted in the bile that goes to the gall bladder & then small intestine
Heme degradation
heme from hemoglobin is degraded to biliverdin & then to bilirubin
this is insoluble & cannot be removed by kidneys
unconjugated bilirubin transporter
albumin to the liver sinusoidal spaces
location of bilirubin conjucation & carrier
bilirubin is carried by ligandin in hepatocytes to ER where bilirubin is conjugated
conjugation enzyme for bilirubin
UPD-glucuronyl transferase
conjugated bilirubin path
water soluble & most leaves the hepatocyte via bile ducts to go to gall bladder -> common bile duct -> small intestine
help in the emulsification of fats & broken down by gut bacteria to form urobilinogen then urobilin
reabsorbed urobilinogen goes where?
reabsorbed urobilinogen from the small intestine can go from the plasma to the urine through the kidneys
major exit route for bilirubin
mostly out via feces
Malloy-Evelyn
uses diazo reaction & 50% methanol accelerator to measure serum/plasma bilirubin
cannot use plasma specimen bc alcohol will precipitate proteins
Jendrassik-Grof
uses diazo reaction & caffeine-benzoate-acetate accelerator to measure serum/plasma bilirubin
total bilirubin
includes conjugated bilirubin & unconjugated bilirubin
conjugated bilirubin methods
does not use caffeine or alcohol (only measures what is already soluble)
reasons why J-G method is preferred
not affected by pH
insensitive to 50x change in protein
maintains optical sensitivity even @ low [bilirubin]
minimal turbidity & relatively constant serum blank
not affected by hemoglobin up to 759mg/dl
specimen for bilirubin
free of hemolysis & lipemia
KEEP AWAY FROM LIGHT
how does the liver stabilize glucose concentrations
absorbs glucose for own use
circulates glucose for peripheral tissues
stores glucose as glycogen
can make glucose from non-CHO sources
lipid synthesis by liver
makes VLDL, cholesterol
removes lipids from circulation= chylomicrons & HDL
protein synthesis by liver
synthesizes proteins other than immunoglobulins
makes coag proteins, albumin, globulins etc
stores amino acids for use or degradation
Liver detoxification
liver 1st pass effect allows liver to remove toxic/foreign compounds before they enter blood & circulate
removes bilirubin & ammonia
uses oxidation, reduction, hydrolysis, hydroxylation, carboxylation, demethylation via CYTOCHROME p-450 isoenzymes
jaundice
observable when bilirubin >3.0 mg/dl
prehepatic : increased RBC breakdown; major increase in unconjugated
hepatic- usually increase in conjugated
post hepatic- usually obstruction of bile duct (both elevated)
Gilbert’s disease
not pathologic, elevation in unonjugated bilirubin
intermittent increase in unonjugated bili in ABSENCE OF HEMOLYSIS
reduction of UDP-glucuronyl transferase activity ~30%
Crigler-Najjar syndrome
2 types of UDP defect
type1: no UDP enzyme: fatal
type2: partial absence of enzymes
Dubin-Johnson syndrome
increased conjugated bilirubin
defect in MDR2/cMOAT or liver ability to remove & excrete conjugated bilirubin & cannot leave the liver
Rotor syndrome
unknown defect
increase in conjugated bilirubin
hepatic jaundice
post hepatic jaundice
often due to biliary obstruction: gallstones/tumors
labs: increase total bili & increased unconjugated bili
cirrhosis
scarring of liver tissues so that blood flow & liver function are blocked
causes of cirrhosis
alocholism, chronic hep C, other chronic hep autoimmune hep drugs toxins Wilson's disease hemochromatosis galactosemia
Lab results for Reye’s syndrome
increased total bili,
3x increase in ammonia
3x increase in AST & ALT
Enzyme used to detoxify alcohol
alcohol dehydrogenase (ADH) & Acetaldehyde dehydrogenase
lab results for alcoholic fatty liver
increased AST, ALT GGT
lab results for alcoholic hepatitis
increased AST, ALT, GGT, Bilirubin,
decreased albumin
prolonged prothrombin time
Drugs of concern for liver damage
acetaminophen (Tylenol), tranquilizers, some antibiotics, anti-neoplastic drugs, lipid lowering meds, anti-inflammatory drugs
liver function labs
bilirubin AST, ALT, ALP, GGT, LD >3 ALP is extrahepatic Albumin, alpha-globulins, gamma globulins, coag proteins, IgG & IgM ammonia levels hepatitis antigens & antibodies
AST & ALT
increase a lot in liver disease, use serial measurements
less increase in liver obstruction
ALP
located in bile canaliculi
intrahepatic <3x separate increases from bone ALP
5’NT
increase in liver not bone
