In which abdominal regions does the liver lie?
Right hypochondriac region, epigastric, extends slightly into left hypochondriac region.
What ligament divides the liver into anatomical left and right lobes?
What structures surround the caudate lobe?
IVC and a fossa created by the ligamentum venosum.
Where is the caudate lobe located?
Visceral surface of right lobe, upper aspect.
What structures surround the quadrate lobe?
The gall bladder and a fossa created by the ligamentum teres.
What structure gives the impression on the visceral surface of the left lobe?
It is the gastric impression, so the stomach.
What 2 impressions are there on the visceral surface of the right lobe?
The renal impression from the right kidney and the hepatic impression from the hepatic flexure.
What structures are found at the porta hepatis?
The portal triad - common hepatic duct, hepatic artery and the hepatic portal vein. Nerves and lymph vessels too.
What structure lies most anterior in the portal triad and which most posterior?
The common hepatic duct lies the most anteriorly. The hepatic portal vein is the most posterior (DAV).
What is Calot’s triangle?
An anatomic space bordered by the inferior border of the liver superiorly, the cystic duct laterally and the common hepatic duct medially.
What nerves innervate the liver?
Parasympathetic and sympathetic stimulation comes from the celiac plexus. The anterior vagal trunk also gives rise to a hepatic branch.
What kinds of proteins does the liver synthesise?
- Plasma proteins.
- Clotting factors.
- Complement factors.
What are the main functions of Albumin?
- Maintains capillary oncotic pressure.
2. Allows binding and transport of large hydrophobic compounds e.g. bilirubin, hormones, fatty acids.
Why might liver failure result in oedema?
Liver failure may mean less albumin is produced and so you get hypoalbuminaemia. This means the capillary oncotic pressure is reduced and H2O accumulates in the interstitial space - oedema.
Why are complement factors important?
They form an important part of the immune system that responds to pathogens.
What is transamination?
The transfer of an alpha-amino group from an amino acid to a keto-acid.
What enzymes catalyse transamination and where are they found?
Aminotransferases, found in the cytosol and mitochondria.
What is anabolic nitrogen balance?
A positive balance; nitrogen intake is greater than nitrogen loss.
What are the products of transamination?
An alpha-keto acid that can go on to the krebs cycle, and glutamate.
What is oxidative deamination?
Amino acid catabolism that results in the liberation of the amino group as free ammonia.
What is the catalyst in oxidative deamination?
Where does the ammonia from oxidative deamination go on to?
The urea cycle.
What is nitrogen balance?
A measure of the equilibrium of protein turnover; nitrogen balance = nitrogen intake - nitrogen loss.
What is catabolic nitrogen balance?
A negative balance; nitrogen loss is greater than intake.
How much nitrogen should an adult intake daily?
0.8g/Kg body weight.
What is the glucose-alanine cycle?
A series of reactions in which amino groups and carbons from muscle are transported to the liver.
Glucose-alanine cycle: What reactions take place in muscle?
Glucose is converted to pyruvate via glycolysis. Pyruvate is then converted into alanine via transamination (glutamate -> alpha ketogluterate).
Glucose-alanine cycle: What reactions take place in the liver?
Alanine is converted to pyruvate via oxidative deamination. NH3 from this reaction goes on to the urea cycle. The pyruvate is converted into glucose via gluconeogenesis.
Where does Arginine come from for the urea cycle?
Diet or protein breakdown.
What is the product(s) of the urea cycle?
Briefly describe the urea cycle.
Arginine is converted to Ornithine and Urea is produced. Ornithine is converted into Citrulline using ammonia and CO2. Citrulline is converted into Arginine using ammonia.
What does 1 turn of the urea cycle consume?
3 ATP and 4 high energy nucleotides.
If you’re deficient in the enzymes involved in the urea cycle what might happen?
Ammonia levels in the blood will increase.
What is the danger of ammonia levels in the blood being too high?
Increased ammonia crosses the blood-brain-barrier. It is converted to glutamate and so you get a decrease in alpha-ketogluterate. This means less oxaloacetate and so the Krebs cycle stops resulting in cell damage and neural cell death.
Why might increased ammonia levels mean the Krebs cycle stops?
The ammonia is converted into glutamate, this means less oxaloacetate is produced and so the Krebs cycle stops - cell damage and death.
What is the absorptive state of glucose regulation?
- Ingested nutrients are absorbed from the GI tract into the blood.
- Some nutrients are catabolised and used and the remainder are stored for future use.
What is the post-absorptive state of glucose regulation?
- Nutrients are no longer absorbed from the GI tract.
- Nutrient stores must supply the energy requirements of the body.
Name 4 mechanisms of producing glucose in order to maintain blood glucose levels.
What is the most common substrate for gluconeogensis?
How many ATP molecules are consumed per molecule of glucose formed in gluconeogenesis?
What is Ferritin?
The storage form of iron. Main source is found in the liver.
What are the fat soluble vitamins?
Where is vitamin A stored? How long can stores last?
Stored in Ito cells in space of Disse. The stores can prevent deficiency for 10 months.
How long can liver storage of vitamin D last?
What is the function of vitamin D?
Increases calcium reabsorption from the intestinal tract.
What is the function of vitamin E?
What is the function of vitamin K?
Necessary for the production of clotting factors.
What is the function of vitamin B12?
Promotes growth and RBC formation and maturation.
What might happen if you’re deficient in intrinsic factor?
Less B12 is absorbed and so you may develop pernicious anaemia.
How much glycogen is stored in the liver?
200g (150g in muscle).
What is the importance of glycogen stores?
Storage form of glucose. Ensures blood glucose levels are maintained.
Name 3 types of lipoprotein and state where they’re formed.
- HDL - formed in the liver.
- LDL - formed in the plasma.
- VLDL - synthesised in hepatocytes.
What is the function of lipoproteins?
To transport cholesterol through the blood.
What cholesterol is ‘good cholesterol’?
Give 3 functions of lipids.
- Energy reserves.
- Structural - part of cell membrane.
- Hormone metabolism.
Triacylglycerols are incorporated with cholesterol and apolipoproteins to form what?
What is the function of lipoprotein lipase?
Hydrolyses triglycerides in lipoproteins into 3 fatty acids and glycerol.
Briefly describe the mechanism of fat catabolism?
- CoA binds to the end of a fatty acid chain: fatty acyl CoA.
- ATP -> AMP + 2Pi.
- Fatty acyl CoA is a substrate for beta-oxidation.
- Acetyl CoA is split off from FA and 2H+ are transferred to coenzymes.
- H+ enter OP and another CoA attaches to repeat the cycle.
What is the function of hepatic lipase?
It is expressed in the liver and adrenal glands. It converts IDL (intermediate density lipoprotein) into LDL.
Approximately how much bile does the liver produce daily?
What stimulates CCK?
The presence of lipids in the duodenum.
What does CCK induce?
Gall bladder contraction and the release of bile. The sphincter of Oddi opens.
Where are bile salts reabsorbed?
In the terminal ileum.
What circulation returns bile salts to the liver?
What is the first phase of pancreatic secretion?
The buffer phase.
Exocrine pancreas: what is secreted in the buffer phase? What is its function?
HCO3- rich secretion. This protects the duodenal mucosa from gastric acid and buffers material entering the duodenum to a suitable pH for enzyme action.
What is the second phase of pancreatic secretion?
The enzyme rich phase.
Exocrine pancreas: what is secreted in the enzyme phase?
Pancreatic digestive enzymes. These enzymes are needed for the digestion of foodstuffs.
Briefly describe the mechanism of HCO3- secretion.
HCO3- is exchanged for Cl- at the luminal membrane through CFTR channels. H+ is then secreted into blood.
What hormones stimulate HCO3- and enzyme secretion?
- Secretin induces the release of HCO3-.
2. CCK induces the release of enzymes.
What hormone inhibits secretion?
What is the epithelium lining of the biliary tree?
Simple cuboidal epithelium.
What ducts terminate at the ampulla of Vater?
The pancreatic duct and the common bile duct.
What structure lies at the junction between the right mid-clavicular line and the right costal margin?
The gall bladder.
What 2 main products can Haem be broken into?
Biliverdin and Fe2+.
What enzyme converts biliverdin to unconjugated bilirubin.
What is the function of glucuronosyltransferase?
It transfers glucuronic acid to unconjugated bilirubin to form conjugated bilirubin.
What protein does unconjugated bilirubin bind to and why?
- It isn’t H2O soluble therefore it binds to albumin so it can travel in the blood to the liver.
What does conjugated bilirubin form?
What is responsible for the conversion of conjugated bilirubin into urobilinogen?
What can urobilinogen form?
- It can go back to the liver via the enterohepatic system.
- It can go to the kidneys forming urinary urobilin.
- It can form stercobilin which is excreted in the faeces.
If you have acute pancreatitis where may pain radiate to?
In obstructive jaundice where would gallstones be located?
In the common bile duct.
What is pre-hepatic jaundice?
When a condition or infection speeds up the breakdown of red blood cells. This causes bilirubin levels in the blood to increase, triggering jaundice.
What conditions can cause pre-hepatic jaundice?
Malaria, sickle-cell anaemia, thalassaemia.
What is intra-hepatic jaundice?
When there is a problem in the liver – for example, damage due to infection or alcohol, this disrupts the liver’s ability to process bilirubin.
What can cause intra-hepatic jaundice?
HepatitisA/B/C, alcoholic liver disease, Gilbert’s syndrome, drug misuse.
What is Gilbert’s syndrome?
A genetic syndrome where the liver has problems breaking down bilirubin at a normal rate. The conjugated bilirubin is normal but the unconjugated bilirubin levels will be elevated.
What is post-hepatic jaundice?
When the bile duct system is damaged, inflamed or obstructed, which results in the gallbladder being unable to move bile into the digestive system.
What can cause post-hepatic jaundice?
Gall stones, pancreatic cancer, gallbladder cancer, pancreatitis.
What are xenobiotics?
Foreign chemical substances that are not normally found or produced in the body. Drugs are considered xenobiotics. They’re excreted in urine, bile, sweat and breath.
What is the importance of pharmacologically active compounds being lipophilic?
It enables them to pass through plasma membranes to reach metabolising enzymes.
At what pH are pharmacologically active compounds non-ionised?
How are pharmacologically active compounds transported in the blood?
Bound to plasma proteins.
Where are microsomal enzymes located?
Which type of enzymes can have their activity induced or inhibited?
What can induce or inhibit microsomal enzymes?
Drugs, food, age bacteria, alcohol.
Where are non-microsomal enzymes located?
Cytoplasm and mitochondria.
What reactions are non-microsomal enzymes involved in?
All conjugation reactions except glucuronidation!
What are the mechanisms for drug metabolism?
Phase 1 and phase 2 reactions. They usually occur sequentially. The aim is to make drugs more polar.
What is the aim of drug metabolism?
To make drugs more polar.
Where does drug metabolism mostly occur?
In the liver - where the enzymes are.
What is a phase 1 reaction?
- Non-synthetic catabolic reaction: oxidation, reduction and hydrolysis.
- Introduces a reactive group to the drug, this is the attack point for conjugation.
Phase 1 reactions: what can happen in an oxidation reaction?
- Hydroxylation (add OH group).
- Dealkylation (remove CH side chains).
- Deamination (remove NH).
- Hydrogen removal.
Phase 1 reactions: what can happen in a reduction reaction?
Add hydrogen, saturate unsaturated bonds.
Phase 1 reactions: what can happen in a hydrolysis reaction?
Split peptide and ester bonds.
What usually catalyses phase 1 reactions?
What type of enzyme is cytochrome P450?
Give examples of non-microsomal enzymes.
Oxidases, esterases, conjugases.
Flavoprotein: what is the role of FAD?
Accepts electrons from NADPH.
Flavoprotein: what is the role of FMN?
Electron donor to CYP’s.
What is a phase 2 reaction?
- Synthetic anabolic reactions: conjugation, glucuronidation etc.
- Usually inactivate products and increase hydrophilicity for renal excretion.
What enzyme catalyses glucuronidation reactions?
What kind of enzyme is Glucuronosyltransferase?
Is Glucuronosyltransferase involved in phase 1 or phase 2 reactions?
What other reaction is Glucuronosyltransferase involved in?
The conjugation of bilirubin.
What are sinusoidal macrophages called?
Where are Ito cells located?
In the space of Disse.
What is the epithelium lining of pancreatic ducts?
Simple cuboidal epithelium.
What week does the liver bud form?
What is the liver bud?
An endodermal outgrowth from the distal part of the foregut.
What part of the gut has dorsal and ventral mesentery?
When does bile production start?
What layers of the trilaminar disc is the primitive gut derived?
Endoderm and visceral mesoderm.
What does the liver divide the ventral mesentery into?
Lesser omentum and falciform ligament.
Pancreas development: What does the ventral bud go on to form?
The head and uncinate process.
Pancreas development: What does the dorsal bud go on to form?
Neck, body and tail.
Why are the SMA and SMV trapped between the head, neck and uncinate process of the pancreas?
Because the ventral bud rotates posteriorly behind the duodenum to fuse with the dorsal bud trapping the vessels in between.
What is the effect of starvation on the rate of protein metabolism?
The rate of protein metabolism increases. Protein in skeletal muscle is degraded into amino acids; these go on to gluconeogenesis.
In starvation why is it important that amino acids are formed from skeletal muscle degradation?
The amino acids can be used in gluconeogenesis to produce glucose.
What must be removed for amino acids to undergo catabolism?
The alpha-amino group.
What are the products of oxidative deamination?
- An alpha-keto acid -> krebs cycle
- Ammonia -> urea cycle.
What is the only amino acid to undergo rapid oxidative deamination?
Glucose-Alanine cycle: what is the process by which glucose gets converted into pyruvate in muscle?
Glucose-Alanine cycle: what is the process by which pyruvate gets converted into alanine in muscle?
Glucose-Alanine cycle: what is the process by which alanine gets converted into pyruvate in the liver?
Glucose-Alanine cycle: what is produced when alanine gets converted into pyruvate in the liver?
Ammonia which goes on to the urea cycle.
Glucose-Alanine cycle: what is the process by which pyruvate gets converted into glucose in the liver?
What is gluconeogenesis?
Generating new molecules of glucose from non-carbohydrate precursors.
What is the function of transferrin?
It transports iron in the plasma to bone marrow. Iron is then incorporated into new RBC.
What is the function of vitamin A?
- Lymphocyte production.
- Growth and reproduction.
- Maintains mucous membranes.
What hormone is responsible for triggering the release of bile?
CCK - triggered by the presence of lipids in the duodenum.
What is the effect on the efficacy of a drug if microsomal enzymes are induced?
The efficacy of the drug will reduce because the inducer will cause increased metabolism by microsomal enzymes.
What is aspirin hydrolysed into?
Salcylic acid and ethanoic acid.
What happens to aspirin in phase 2 metabolism?
It is conjugated with glycine or glucuronic acid and excreted in urine.
What is needed for intestinal absorption of vitamin K?
Bile salts - without these clotting factor production will be affected.
What happens in a glucuronidation reaction?
Glucuronic acid is added to conjugate a substrate. UDPGA is needed for this. Catalyst: glucuronyltransferase.
Give 2 functions of CCK.
- Stimulates contraction of the gall bladder -> release of bile.
- Causes relaxation of the sphincter of Oddi.
What cells in the spleen are responsible for RBC break down?
What are the products of heme breakdown?
- Fe2+ and CO.
What is the importance of the hepatocyte canalicular surface?
Permits the excretion of bile.
What is the purpose of conjugating bilirubin?
It increases its water solubility for excretion.
Give 2 functions of albumin.
- Maintains capillary oncotic pressure.
2. Binds and transports H2O insoluble compounds.
Give 4 risk factors for hepatitis B.
- Sharing needles.
- Unprotected sex.
- Having a job where you’re exposed to a lot of human blood.
- If you’re born to a hepatitis B positive woman.
A patient with jaundice has dark urine. What compound is present in increased levels?
A patient with jaundice has pale stools. What compound is absent?
What is the affect on conjugated and unconjugated bilirubin levels in someone with intrahepatic jaundice?
Increased unconjugated and normal conjugated.
What is the affect on conjugated and unconjugated bilirubin levels in someone with pre-hepatic jaundice?
Unconjugated is elevated and conjugated is slightly raised too. You also get slightly raised urobilinogen.
What is the affect on conjugated and unconjugated bilirubin levels in someone with post-hepatic jaundice?
Conjugated is elevated and unconjugated is normal. Urobilinogen is decreased/absent.
Urinary bilirubin will be raised.
What is the affect on the urine and stools in a patient with post-hepatic jaundice?
Urine will be dark and the stools will be pale.
What is the affect on the urine and stools in a patient with intra-hepatic jaundice?
Urine will be dark and stools will be normal or slightly paler.
What is the affect on the urine and stools in a patient with pre-hepatic jaundice?
Which enzyme converts alcohol to acetaldehyde?
ADH - alcohol dehydrogenase.
Which enzyme converts acetaldehyde to acetate?
ALDH - aldehyde dehydrogenase.
What are the consequences of being deficient in the enzymes required for the urea cycle?
NH3 levels would rise and would cross the BBB easily. NH3 would be converted into glutamate meaning you have less alpha ketoglutarate and so the Krebs cycle would be unable to function. This leads to cell damage and neural cell death.
What type of bonds are broken in a phase 1 drug hydrolysis reaction?
Amide and ester bonds.