liver
largest solid internal organ; RUQ; 2.5% of body weight and approximately 25% of cardiac output
hepatocytes, sinusoidal endothelial cells, Kupffer cells, hepatic stellate cells, cholangiocytes
major cell types of the liver
glucose regulation, protein synthesis, immune surveillance, drug and toxin metabolism, hormone regulation, bile acid synthesis and secretion
key functions of the liver
hepatic artery
25% oxygen rich
portal vein
75% nutrient rich, oxygen poor
portal
gateway between intestine and systemic blood
space of disse
contains stellate cells and lymph drainage
hepatic artery and portal vein -> sinusoids -> central vein -> hepatic veins -> inferior vena cava
hepatic blood flow pathway
basolateral surface
faces sinusoids/blood
apical surface
faces bile canaliculi
tight junctions
prevents bile leakage
smooth ER
detoxification and metabolism
rough ER
protein synthesis
mitochondria
high ATP demand
stored glycogen, iron, B12, and lipids
additional functions of the liver
Kupffer cells
resident macrophages
stellate cells
quiescent vitamin A storage; activated after injury, deposit collagen, fibrosis/cirrhosis
glycogenesis
stores glucose as glycogen
glycogenolysis
releases glucose during fasting
gluconeogenesis
synthesize glucose from amino acids and other precursors
lipids
convert excess glucose -> triglycerides -> VLDL; produce cholesterol, uptake of LDL, synthesis of HDL
cholesterol
produced for membranes, hormones, vitamins, and bile acids
HDL
synthesized for reverse cholesterol transport
amino acids
metabolized for gluconeogenesis substrate supply; synthesize proteins, breakdown plasma and metabolic proteins
plasma proteins (albumin), coagulation factors, complement proteins, carrier proteins, antioxidants and regulatory proteins, thrombopoietin
major hepatic protein products
water, bile salts, phospholipids, bilirubin, excreted toxins
what makes up bile composition
hepatocytes
location for bile synthesis
cystic duct of gallbladder
storage of bile
toxic ammonia -> water soluble urea
ammonia detoxification process
hepatic encephalopathy
result of hyperammonemia
lactulose
reduces pH and ammonia absorption, increases stool nitrogen excretion
reduce neurotoxicity
goal of managing hyperammonemia
heme -> biliverdin -> UBil + albumin -> liver -> conjugated with glucuronide -> excreted in bile
bilirubin metabolism
albumin
bound to UBili to transport to liver
glucuronide
essential for conjugation and excretion of bili
urobilinogen
gives stool its brown color
hemolysis
increased unconjugated bilirubin cause
bile duct obstruction
increased conjugated bilirubin cause
liver failure
increased conjugated and unconjugated bilirubin cause
cytochrome P450
phase 1 drug metabolism enzyme
phase 1 drug metabolism
oxidation reduction and hydrolysis; may activate prodrugs or create toxic metabolites
phase 2 drug metabolism
conjugation with glucuronic acid, sulfate, acetyl groups; increases water solubility (renal excretion); detoxification of previous intermediates
polymorphisms
fast vs slow metabolizers
enzyme induction vs inhibition
factors of major drug to drug interactions
first pass effect
oral drug metabolizers before systemic circulation; reduce bioavailability
sublingual, IV, and transdermal
which drugs bypass the liver