Normal Liver Physiology Flashcards
Where is the liver located, how much does it weigh + how much of the cardiac output does it receive?
Right upper quadrant of abdomen
Weighs ~1.4kg
Receives ~25% of cardiac output
Where vessels does the liver get its blood supply from?
Venous flow from hepatic portal vein (~70% supply)
Arterial flow from hepatic artery
What 2 vessels make up the hepatic portal vein?
Splenic vein
SMV
What is the splanchnic circulation?
Includes blood flow from stomach, SI, LI, pancreas, spleen + liver
Portal vein carries venous blood draining from all of these organs except the liver itself (part of systemic circulation)
How is the liver organised?
- 8 functional segments having own division of hepatobiliary tree
- Segments further divided into individual lobules
- Lobule organized into plates of hepatocytes lying in case of reticuloendothelial cells
- Vascular spaces between plates = sinusoids
- Hepatic vein + artery mix in lobules to bath it in mixed blood supply e.g. freshly absorbed nutrients + drugs
What are the 2 ways in which substances can leave the liver?
Blood from sinusoid either drained into central vein then the portal vein to get into the circulation and be excreted by the kidney for e.g.
OR
Large drug metabolites exported on opposite side of hepatocyte across bile canaliculi membrane into bile duct, emptied into SI going via gallbladder secreted into bile
What are the 3 zones of the liver?
Zone I periportal hepatocytes: most oxygenated (nearest hepatic artery), specialize in oxidative metabolism, gluconeogenesis + urea synthesis
Zone II
Zone III pericentral hepatocytes: least oxygenated, specialize in drug metabolism, glycolysis + lipogenesis
What are the 5 major cell types of the liver?
Hepatocytes (60% of liver function)
Chloangiocytes
Reticuloendothelial cell meshwork includes:
Endothelial cells
Kupffer cells
Lipocytes (stellate cells) in Space of Disse
The liver performs > 500 functions. What are some of them?
Drug metabolism + detoxification Energy metabolism + substrate interconversion Synthesis of plasma proteins Production of bile Immune function Cholesterol processing Excretion of bile Storage of vitamins + minerals
Energy metabolism + substrate interconversion if a function of the liver. How is the liver involved in this?
Carbohydrate metabolism: glycogenolysis, gluconeogenesis, glycogen synthesis, glycolysis, citric acid cycle + FA synthesis
Lipid metabolism: ketogenesis + triglyceride synthesis from FAs
Protein metabolism: Deamination + urea formation
What types of plasma proteins does the liver synthesize?
Major ones e.g. albumin
Haemostasis/fibrinolysis factors
Carriage/binding proteins e.g. transferrin, SHBG + TBG
Pro-hormones + apolipoproteins
What haemostasis/fibrinolysis factors does the liver synthesize?
Coagulation factors e.g. fibrinogen
Coagulation inhibitors e.g. a1-antitrypsin
Fibrinolysis e.g. plasminogen
The liver is the major site of __ ____
Drug metabolism
What do Kupffer cells in the liver do?
They are tissue macrophages (immune function) located in hepatic sinusoids attached to the endothelial cell lining. They ingest bacteria by phagocytosis + inflammatory mediators.
Where is bile produced, stored + secreted?
Produced in liver
Stored + concentrated in gallbladder
0.7-1.2 L/day secreted by liver into the bile canaliculus, into the main bile duct + goes to the duodenum
Whatt does the hormone secretin do in the control of bile secretion?
Acts on exocrine pancreas to stimulate secretion of HCO3- ions into the pancreatic duct
Acts on liver to stimulate it to produce bile
What does the hormone cholecystokinin (CCK) do in the control of bile secretion?
Acts on exocrine pancreas to create secretory components e.g. a range of enzymes
Acts on gallbladder causing it to contract + release concentrated bile down bile duct into duodenum
Where is secretin and CCK secreted?
Wall of duodenum secretes them into the blood when food enters the stomach
What are the 6 major components of bile?
- Bile salts (bile acids conjugated with taurine)
- Lecithin (phospholipid)
- HCO3- + other salts
- Cholesterol
- Bile pigments + small amounts of other metabolic end-products
- Trace metals
In terms of bile production, what do hepatocytes secrete?
Bile salts
Cholesterol
Lecithin
Bile pigments
In terms of bile production, what do cholangiocytes secrete?
Bicarbonate
Water
How is bile synthesized?
14 reactions that occur within 4 organelles of the hepatocyte:
- Liver converts cholesterol to primary bile acids
- Primary bile acids solubilized via conjugation to taurine or glycine
- Conjugated bile salt is exported from hepatocyte across canaliculus membrane via bile canaliculus
- Go down bile duct into duodenum where they can carry out functions
What happens after bile salts are released into the SI?
95% are continuously recycled via the enterohepatic circulation + returned to the liver for reuse
5% are lost in faeces (liver will synthesize new bile salts to replace these)
What happens to bile salts when they are recycled?
75% recycled as intact bile salts
25% deconjugated by bacteria in terminal ileum + colon to yield primary bile acids (some are dehydroxylated by bacteria to secondary bile acids) which are then recycled + reconjugated in liver to form bile salts again
How is excess cholesterol removed from the liver (which has not been used for bile acid production)?
Can be removed directly from hepatocytes from bile canaliculus down SI to be lost in the faeces
What are the 4 functions of bile salts?
- Emulsification of dietary lipids, rendering them accessible to pancreatic lipases
- Elimination of cholesterol
- Prevention of cholesterol precipitation in the gallbladder (prevents stone formation)
- Facilitation of absorption of fat-soluble vitamins
What is cholesterol?
Lipid molecule that has many important functions
15% comes from diet + 85% is synthesized within body (mostly in liver)
What are the 4 functions of cholesterol?
- Plasma membranes
- Component of bile salts
- Precursor for steroid hormones
- Myelin (neuronal axonal “wrapping”)
How is cholesterol transported in the body?
Transported in plasma in complexes with lipoproteins (mainly synthesized in liver)
What roles does the liver have in cholesterol processing?
Converts Acetyl CoA to cholesterol
Synthesizes lipoproteins that transport cholesterol in plasma
Exports it via circulation to body cells for synthesis of key products e.g. steroid hormones
Exports it to liver for synthesis of bile salts by secreting it into bile
Exports excess via liver into bile for faeces excretion
What vitamins + minerals are extracted from the blood, stored in the liver + released when needed?
Fat soluble vitamins A, D, E + K
Minerals: iron + copper
What are the steps of bilirubin formation and how does it progress through the body to be excreted?
- Breakdown of haem in the spleen + bone marrow = unconjugated bilirubin
- Binds albumin in blood to be carried to hepatocytes in liver
- Conjugated to glucuronic acid to form conjugated bilirubin (water soluble)
- Excreted into bile canaliculus + into bile
- Released into SI where bacterial proteases convert it to urobilinogen
- 10% go back to liver via portal vein then goes into blood to the kidneys to be excreted as urine
- 90% lost in faeces
Bilirubin is the main __ ___
Bile pigment (NOT the same as bile salts or bile acids)
Why can cholesterol be precipitated in the gallbladder to forms stones?
Because its insoluble which is why bile salts solubilise it to prevent this precipitation + stone formation
How are bile salts + acids transported into or out of the hepatocyte?
Because there are large molecules they cannot just pass across the membrane of the hepatocyte so need special transporter molecules to move in/out of hepatocyte + bile canaliculus (use different sets of transporters)
What is the function of HCO3- + other salts?
Neutralize acid in duodenum
What is the function of albumin?
Maintains colloid/osmotic pressure of plamsa
Transport of components in blood as its sticky + keeps things soluble e.g. FA, steroids, vitamins + bilirubin
What carrier protein carries iron around in the blood?
Transferrin
What do SHBG + TBG stand for and what do they carry in the blood?
Sex Hormone Binding Globulin carries sex hormone
Thyroid-Binding Globulin caries thyroid hormone
Why are lipocytes of the liver important in disease process?
In the development of cirrhosis, they start to secrete collagen changing the liver architecture
