Liver Function Flashcards
What are the features of sinusoidal capillaries
arge intracellular gaps allowing movement of proteins and cells across endothelial lining, which allows transport between blood and hepatocytes via space of Disse
How are hepatocytes specialised to to exchange solutle between space of disse and bile canaliculi
Hepatocytes contain microvilli to increase SA for exhange from blood
they have special transportrs for uptake, metabolise and excrete range of solutes:
NTCP- bile acid transporter
OST-organic solute transporter
MATE1- organic cation transporter
BSEP- bile salt export pump
BCRP- drug transporter
How are lipids transported in body
diety fats and lipids get put into chylomicrons, which are hydrolyzed by lipoprotein lipase (LPL) to triglyerides when they touch endothelial walls to release FA and glycerol to be stored in adipocytes of skeletal muscle. The remaining chylomicron remnants bind to endothelial cells in liver sinusoids. The apolipoprotein-E on surface of chylomicron remnants, which trigger clearance of plasma liproteins.
How is cholesterol metabolised
sliver secretes very-low density lipids (VLDL) into blood, which are converted to IDL. IDL can then be taken up by liver to make more VLDL or stays in circulation where it is converted to cholesterol-rich LDL. LDL is taken up by LDL-R on hepatocytes via internalisation un clathrin-coated pits into endosome where vesciles fuse with lysosomes. In the lysosomes HMG-CoA reductase degrades LDL to melvalonate, which then converted to free cholesterol in cytoplasm.
Statins will inhbit HMG-CoA
How is protein metabolism
Transamination
AA converted to keto acids by aminotransferase (ALT,AST) and in a side reaction the NH2(amine group) is removed from AA and incorparted into α-ketogutaric acid to form glutamate.
Deamination
Glutamate dehydrogenase, will convert glutamate back into α-ketogutaric acid and ammonia
Urea Cycle
occurs in liver mitochondria where ammonia is converted to carbamyle phosphatase via carbomyl phosphatase synthase (require ATP). Carbamyle phosphatase with orthinine makes citrilline, which is converted to aspartate, which is converted to arginine. Arginine is then converted bac into orthinine but as a by-product Urea is formed and excreted into blood.
How can ketoacidosis occur
During starving/fasting states, lack of insulin or unresponsiveness insulin-dependent cells to insulin means only glucagon dominates causing lots of reactions including lipolysis. As a result of lipolysis reactions lots of Acely- CoA is made, which undergoes ketogenesis to form ketone bodies such as acetate and β-hydroxybutyrate. These then go into blood stream increase H+ ion conc of plasma, causing decrease pH causing metabolic acidosis, which causes vomitting, increase urine output (dehydration) and fall into coma
What is billirubin metabolism
Breakdown of RBC:
globin component broken down into AA
Heme component broken down into iron (taken to liver) and protoporphyrin. This is converted to unconj billirubin (billivirdin) and bound to albumin to be taken to liver. Hepatocytes convert billivirdin to conj billirubin via uridine glucoronyl transferease (UGT), which is stored in bile caniculi. Intestinal bacteria convert CB to urobilligin, which is then either oxidsed to stercobillin (brown colour of faeces) or urobillin (yellow of urine)
Alcohol metabolism
ethanol metabolised via alcohol dehydrogenase, cytochrome P-450 (particularly CYP2E1 isoform) isoenzymes or catalase to form acetaldehyde, which is converted in mitochondria to ALDH and Acetic acid
Effects of alcohol metabolism
Alcohol dehydrogenase uses up NAD+ therefore increases NADH. NAD+ is depleted so less hepatic fatty acid oxidsation occurs , which leads to fat accumulation in liver
Acetaldehyde toxicitiy
CYP2E1 produces ROS and lipid peroxidation causing cell damage
What is liver cirrhosis
triggers stellate cells to assume myofibroblast phenotype causing them to deposit collagen in space of Disse causing compression of sinusoidal capillaries causing increase blood flow resistance through sinusoids to hepatic vein causing portal hypertension. this then causes build up of pressure in splanchnic circulation triggering NO release so vasodialates splanchnic arterooles causing great blood vol in splanchnic circulation, so less blood reaches IVC. Decrease MAP detected by barroreceptors causing incease SNS actvity in kidneys increasing Na+ reabsorbtion and activates RAAS, which increases blood vol and thirst. This increses blood vol, so can handle large scale water loss to peritoneal cavity… ASCITES
deposition of collagen blocks fenstrations in sinusoidal capillaries so albumin cannot move into circulation causing hypoalbminemia. This increases fluid filteration across hepatic and intestinal cappilaries into peritoneal space causing increase fluid vol. This causes decrease blood vol then decrease MAP so decrease siusoidal and intestinal pressure
morphology of cirrhosis
characterized by tansformation of liver into regenrative parenchymal nodules surrounded by fiborus bands
