Liver and friends Flashcards
Name the 4 lobes of the liver
Left, right, caudate and quadrate
What are the 2 main ligaments in the liver and what are their attachments?
o Falciform attaches liver to anterior abdominal wall – contains ligamentum teres (remnant of umbilical vein)
o Coronary and triangular ligaments attach liver to superior abdominal wall
What are the 6 liver impressions on the visceral surface?
oesophageal, renal, colic, duodenal, gastric and gallbladder
What is Calot’s triangle?
(cystohepatic triangle): anatomical space bordered by cystic duct (inferior), common hepatic duct (medial) and inferior visceral surface of liver (superior)
What does Calot’s triangle contain?
contains cystic artery
What’s the portal system?
venous drainage from GI tract to liver via hepatic portal vein – dominant blood supply to liver
What are the 3 parts of the microscopic liver anatomy?
Lobules, acinus and sinusiods
What are the lobules of the liver?
Structural units of liver
Hexagonal shape with central vein
Portal triad at lobule corners: hepatic artery, hepatic portal vein, bile duct
What are the acinus of the liver?
Functional units of liver
Localised collection of hepatocytes around portal triad
What are the sinusoids of the liver?
Discontinuous capillary
Mixes oxygenated blood from hepatic artery with nutrient rich blood from hepatic portal vein
Go through the relationship position, the ducts and arterial supply of the pancreas
o Lies inferior to stomach and duodenum – head of pancreas in C shaped duodenal curve
o Pancreatic duct joins with common bile duct at ampulla of Vater
o Arterial supply: pancreatic branch of splenic artery
Which organs are retroperitoneal?
S = Suprarenal (adrenal) Glands
A = Aorta/IVC
D =Duodenum (except the proximal 2cm, the duodenal cap)
P = Pancreas (except the tail)
U = Ureters
C = Colon (ascending and descending parts)
K = Kidneys
E = (O)esophagus
R = RectumGo through the function and ducts of the gallbladder
o Peritoneal structure involved with storage and concentration of bile
o Cystic duct from gallbladder joins with common hepatic duct to form common bile duct
o Common bile duct empties into duodenum at major duodenal papilla – controlled by sphincter of Oddi
Name the fat soluble vitamins, where they’re found in food and their function in the body
o Vitamin A – retinal light adaptation (carrots)
o Vitamin D – increase intestinal calcium uptake (milk)
o Vitamin E – prevents RBC destruction (veg oil)
o Vitamin K – normal blood clotting (spinach)
Go through retinol metabolism
- Retinol absorbed by enterocytes
- Retinol esterified and incorporated into chylomicrons
- Chylomicrons travel through intestinal lymph to liver
- Retinol de-esterified and bound to retinol binding protein
- Retinol stored in lipid droplets of sinusoidal pericytes
Go through vitamin B metabolism
- Vitamin B binds to R protein released from salivary glands and stomach (protects Vit B from HCl)
- Pancreatic proteases free Vitamin B in duodenum
- Vitamin B binds to intrinsic factors (released from parietal cells)
- Vit B-IF complex absorbed in enterocytes of terminal ileum
- Vitamin B transported in blood to liver, then back to duodenum in bile – enterohepatic circulation
Go through vitamin D metabolism
- D3 (synthesised from sunglight) transported to liver and converted to intermediate
- Intermediate travels to kidney and converted to calcitriol
- Calcitriol binds to vitamin D receptors in target tissues
Go through iron metabolism
- Iron absorbed into enterocytes
- Some iron bound in enterocytic ferritin, the rest transported to blood via ferroportin
- Iron in blood bound to transferrin travels to liver
- Transferrin in hepatocytes and Kupffer cells stores iron in ferritin
- When hepatic iron stores are full, hepatocytes release hepcidin which inhibits ferroportin iron transport across enterocyte basolateral membrane
What is another name for vitamin A and B?
Retinol and folate
What’s the aim of drug metabolism?
• Most drugs actively absorbed by kidneys but lipophilic drugs not removed easily and so passively absorbed. Aim of drug metabolism is to make drugs more polar so they cannot get across membranes and thus are easily excreted
What’s the aim of a phase 1 reaction?
• Aim of phase 1 reaction is to make the drug more hydrophilic so that it can be excreted by the kidneys – and it does this by adding a hydroxyl group to the drug. Expose it it to a hydroxyl group or other reactive sites so it can be used for conjugation reactions (Phase II reactions)
What are non-synthetic catabolic reactions and what is their function?
oxidation, reduction and hydrolysis – introduces a reactive group to drug so there’s an attack point for conjugation
Name the different types of oxidation reactions
hydroxylation, dealkylation, deamination or hydrogen removal
What is a reduction reaction?
adding a hydrogen (saturate unsaturated bonds)
What is a hydrolysis reaction?
splitting amide and amino and ester to replace them with a HC bons
What is functionalisation?
• Adding a reactive group
What does functionalisation do?
• Makes drug more hydrophilic, more reactive, occurs in the liver and mainly catalysed by cytochrome P450
Where does metabolism mostly take place?
• Metabolism is mainly metabolised via a phase 2 reaction
What are xenobiotics?
foreign substances that are absorbed (skin, lungs, intestine) and are not used for energy purpose (like drugs)
What are the criteria for pharmacologically active compounds?
lipophilic (pass through plasam membranes), non-ionised at pH 7.4, bound to plasma proteins for blood transportation
Where are microsomal enzymes found and in what reaction are they used?
• Microsomal enzymes found in smooth ER – phase 1 reaction
Where are microsomal enzymes found, name examples and in what reaction are they used for?
• Non-microsomal enzymes found in cytosol – phase 2 reaction (but also involved in all conjugation reactions except for glucoronidation. Examples: protein oxidases, esterases, amidases, conjugases (transferase), alcohol dehydrogenase, aldehyde dehydrogenase
Go through a phase 1 reaction
• Phase 1 reaction (cytochrome P450 responsible) – oxidation, hydrolysis, small hydrophilicity increase
Go through a phase 2 reaction
• Phase 2 reaction – glucoronidation (conjugation of substance with glucuronic acid) greatly increases hydrophilicity (water soluble = able to excrete) and in cytoplasm and mitochondria of hepatocytes. Uses glucuronosyltransferase enzyme.
What are the factors that can induce or inhibit metabolism?
rugs, food, age, bacteria and alcohol
Where is albumin produced?
Hepatocytes
What is the function of albumin?
o Maintains oncotic pressure (fluid distribution)
o Acts as carrier for hormones and molecules (like hormones, bilirubin, fatty acids, hormones and drugs (NSAIDS and warfarin)
o Mops up free radicals
Name the Starling forces that act to move fluid across the capillary wall
capillary hydrostatic pressure, interstitial hydrostatic pressure, osmotic force plasma protein, osmotic force interstitial fluid protein (all influence of pushing fluid out except osmotic force plasma protein
How can albumin levels decrease in the blood?
• Albumin level (highest protein in the blood) can decrease due to nephrotic syndrome or a haemorrhage
Which clotting factors do globulins produce?
• Globulins produce all clotting factors except calcium and von Willebrand factor (VIII)
What are complement factors?
• Complement factors – enhances immune system by stimulating release of cytokines
Go through protein degredation
o Lysosomal – Kupffer cells phagocytose unnecessary proteins
o Non-lysosomal (ubiquitin-proteasome pathway) – ubiquitin binds to protein for destruction, proteasome encases protein and destroys (amino acids can be recycled)
Go through the glucose/alanine cycle
- Alanine aminotransferase removes amine from glutamate and adds it to pyruvate to form alanine (transamination) and an alpha keto acid (used in Kreb cycle)
- Alanine is transported in blood to liver and broken down into pyruvate and an ammonia group
- Pyruvate is used for gluconeogenesis, and the ammonia group is incorporated into the urea cycle
What’s the function of the glucose/alanine cycle?
o Provides liver the necessary ingredients for gluconeogenesis and urea cycle
o Muscles don’t have to use energy to make glucose -> all energy can go to muscle contraction
Go through the urea cycle
- Ammonia and carbon dioxide combines to form carbomoyl phosphate
- Carbomoyl phosphate combines with ornithine to form citrulline
- Citrulline is converted to arginine and another ammonia group is incorporated
- Arginine is cleaved by arginase to form urea and ornithine
What are the energy requirements and by-products of the urea cycle?
• Urea cycle requires 3ATP and results in the excretion of 2 ammonia molecules
Go through chylomicrons and VLDL
o Chylomicrons are synthesised in enterocytes, VLDL’s are synthesised in hepatocytes
o Function – transport of triglycerides from liver to tissues
o Lipoprotein lipase strips triglycerides from VLDL and degrades them to glycerol and 3 fatty acids
o Components diffuse across cell membranes – used for energy or recycled into triglycerides (adipocytes)
What is LDL?
Produced by hepatic lipase in hepatocytes.
Transport cholesterol from liver to tissue cell membranes – taken up by endocytosis
What is HDL?
o Removes excess cholesterol from cells and returns to liver
o Excess cholesterol converted into bile salts and excreted (or involved in fat emulsification)
Go through beta oxidation
- Fatty acids diffuse across cell membranes
- Fatty acid combine with coenzyme A to form acyl coenzyme A – catalysed by acyl CoA synthase
- Acyl coA transported across mitochondrial membrane via cartinine shuttle
- Beta oxidation – 2 carbons removed from fatty acid produces acetyl CoA, NADH and FADH (Kreb cycle/oxidative phosphorylation)
What is hepatic lipid metabolism and relate this to ketoacidosis
• Hepatic lipid metabolism:
o High levels of fatty acid oxidation -> excess acetyl coA (too much for Kreb) -> increased ketogenesis
o 3 products – acetoacetate (converted immediately to acetone), acetone, hydroxybutyrate
o Regulation – high concentration of glycerol-3-phosphate = high levels of fatty acid oxidation, insulin inhibits fatty acid oxidation and glucagon activates it
o Ketoacidosis:
Diabetic = low insulin levels
Alcoholic = high glucagon levels
Ketones are strong acids -> lower blood ph -> oxygen cannot bind to haemoglobin as effectively
How are bile salts produced in the gallbladder?
o Bile salts primarily cholesterol and waste products that need to be excreted
o Bile produced in hepatocytes and transported in micelles through canaliculi (bile damages cell membranes)
o Actin filaments contract around canaliculi to move bile to hepatic ducts -> cystic duct -> gallbladder (Sphincter of Oddi is closed)
How are bile salts released from the gallbladder?
- Food enters duodenum and CCK is released
- Gallbladder contracts and Sphincter of Oddi opens
- Bile enters the duodenum and emulsifies fats
- Bile salts are reabsorbed in the terminal ileum – enterohepatic circulation
Go through the breakdown of bilirubin starting from biliverdin
- Kupffer cells break down haem to produce biliverdin
- Biliverdin converted to bilirubin and catalysed by biliverdin reductase
- Bilirubin released from Kupffer cells and travels in blood bound to albumin
- Hepatocytes conjugate bilirubin with glucuronic acid, catalysed by glucuronyl transferase
- Water soluble conjugated bilirubin is excreted in bile and unconjugated in duodenum
- Majority of bilirubin secreted as stercobilin or urobilin, some is recycled via enterohepatic circulation
