The liver Flashcards
Where is the liver?
In the right upper quadrant.
It is held in place by intraabdominal pressure.
The gallbladder is at the back underneath.
The kidneys and bladder are also underneath.
It shares a blood supply with the small intestine.
What is the structure of the liver?
It has right and left lobes, which are separated by the falciform ligament.
In the centre of each lobe is a central canal, which has the hepatic vein, from the inferior vena cava.
Hepatocytes and sinusoids branch from the central canal.
What is the blood supply of the liver?
The portal tracts lie at the periphery of each lobule and contains a bile duct, branch of portal vein and hepatic artery.
The hepatic artery brings in oxygenated blood from the lungs.
The portal vein has nutrient-rich blood from the intestines.
These then mix in the sinusoids.
What is the outside of the liver?
The liver is covered in a fibroconnective tissue capsule - the capsule of Glisson.
This is covered in peritoneum.
Thin connective tissue septa enter the organ and dividie it into lobes and lobules form the capsule.
What are genetic variations in liver anatomy?
Hereditary anatomical displacement, accessory lobes
What are internal factors causing variations in liver anatomy?
Portal thrombosis - blood clot, cardiac cirrhosis, fibrosis and atrophy.
What are external factors causing variations in liver anatomy?
Impression effects - diaphragm, tight belts, coughing, Riedel’s and accessory lobes an clefts or fissures.
How is the liver connected to the gallbladder?
The liver secretes substances into the blood and bile.
The bile is stored in the gall bladder in between meals, then released during meals in the cystic duct, which drains into the common bile duct then enters the small intestine duodenum.
Its entry is controlled by the Sphincter of Oddi.
What triggers the gall bladder?
Food stimulates CCK release from I cells which triggers contraction of the gall bladder forces the bile into the common bile duct, and the smooth muscle in the sphincter of Oddi relaxes, which opens the sphincter so bile goes into the duodenum.
What are the functional bits of the liver?
The liver is divided into 8 segments, which all have separate blood supplies and drainage.
Each segment is divided into lobules and acinus, the functional units of the liver.
These are composed of hepatocytes, sinusoids, blood vessels and bile canaliculi.
What is the capsule of Glisson made from?
The connective tissue is made of ECM materials, mainly collagens 1,2,3,4,5,6 and produced by stellate cells.
Has a long half life.
Glycoproteins link cells to the collagen.
What is the function of the capsule of Glisson?
It is important in health and disease.
It protects the liver from injury.
It has niches for orientation and growth of cells.
What is cirrhosis?
Scarring causes disruption of the architecture and therefore function.
F0 is a healthy liver, F4 requires a liver transplant.
In F4, the liver is mostly filled by scarring, and there are not enough healthy cells to function properly - decompensation.
What are hepatocytes?
The main cell type in the liver, perform most of the function.
There are less in a diseased liver and with age.
They are big because of their large function, and do not turn over often because of the large energy requirement.
What is the structure of hepatocytes?
Polarised epithelial cells - the function changes across the liver.
Hepatocytes near the blood supply have structures for removing things from the blood and structures for secreting into the blood.
How is the liver specialised for storage?
The liver stores carbohydrates as glycogen.
The ER synthesises proteins and carbohydrates and are found near the blood supply so the products are secreted straight into blood supply.
What are at the sides of hepatocytes?
There are tight junctions which holds the liver together.
There is also the beginning of the canaliculus in which bile is produced and drained into.
What is biliary epithelium?
Barrier cells, or cholangiocytes.
Polarised epithelial cell.
Has a dense basement membrane due to bile being caustic (corrosive).
The main function is transport and secretion.
What do barrier epithelia do?
Form the bile canalicular and bile channels which go to the gall bladder.
The beginning of the bile canaliculus matures into a larger duct, which is lined by cholangiocytes to protect the liver from bile.
It then matures into a big duct which connects to the common bile duct.
They can modify the bile through secretions, pH, concentration.
How do biliary epithelium vary in size?
In zone 1 - where the blood supply of the liver is, the ducts are small and few number.
Towards the edges of the liver the duct cells are bigger and more polarised.
What is endothelium?
The cells that line the blood vessels, a barrier between the blood and the tissue.
What is the function of the endothelium?
Exchange materials between the blood and tissues.
Protect the body of the liver (parenchyma) from blood cells, viruses, toxins and bacteria.
Selectively allow materials and cells through - filtration.
What is anti-thrombogenic surface?
The endothelium has an anti-thrombogenic surface which means there are no blood clots formed unless damage is detected.
Endothelium is involved regulation of coagulation.
What are the types of liver endothelium?
Lymphatic, venous, sinusoidal, arterial, all have similar function
Sinusoidal have more uptake and scavenging properties
Functions of endothelium: clear waste, dying cells, tumour cells.
How are endothelial cells for the immune response?
Endothelial cells regulate immune cell traffic into the liver tissue.
If a hepatitis virus is detected, the endothelium changes its nature to have molecules on its surface whcih pull lymphocytes to clear the virus.
What are Kupffer cells?
Immune cells located in the blood stream on top of the sinusoidal endothelium.
Clear debris from circulation
Secrete cytokines, growth factors for dilation and constriction, and things for signalling.
Endocytotic capability
What are stellate cells?
Or ito cells, or lipocytes.
function is liver fibrosis.
It sits on the back of blood vessels to regulate constriction and dilaton.
What are the functions of stellate cells?
Stores retinoid vitamins - vitamin A.
Stores lipocytes.
Regulates vascular tone.
In disease they proliferate and move around, produce connective tissue.
Inhibit clearance of connective tissue, results in accumulation of fibrotic matrix
What is the digestive function of the liver?
Carbohydrate and fat metabolism:
Excess sugar in bloodstream goes to liver and stored as glycogen in hepatocytes until needed, controlled by insulin.
Glycogen then converted back to glucose then secreted into bloodstream through epithelial cells.
What is the digestive function of the liver with other materials?
Liver can also remove lipids from circulation, use them for energy by beta oxidation or store until needed.
Storage of vitamin A in stellate cells, iron, copper stored in hepatocytes.
What is the cholesterol synthesis function of the liver?
The liver makes and regulates circulating cholesterol.
The rate limiting step of HMG-CoA to mevalonate, by HMG-CoA reductase, which then forms cholesterol takes place in the hepatocytes.
This step is inhibited by statins to slow down cholesterol synthesis.
What is the function of cholesterol?
Vitamin, steroids and hormone production.
What is bile?
Bile is made from hepatocytes and contains bilirubin pigment, salts, proteins and antibodies.
It is released into the small intestines for emulsifcation of fat.
Some is reabsorbed back into the liver.
It is required for excretion of non-water soluble molecules like cholesterol and bilirubin, and uptake of fat soluble vitamins.
What is the detoxification function of the liver?
Foreign compounds are made into water soluble products bile and urine.
Phase 1 metabolism is oxidation by P450 enyzmes.
Phase 2 is conjugation.
The levels of P450 vary with age, gender and between organs.
What are the synthetic functions of the liver?
Hepatocytes produce proteins:
Albumin - for transport, regulation of blood osmolarity.
Coagulation factors - fibronectin.
Plasminogen
a1-antitrypsin.
Transferrin
Hepcidin
What are liver function tests?
Measures the levels of bilirubin, total protein or albumin, or other proteins to indicate liver function.
How does the liver function change with age?
Decline in bilirubin.
Decline in liver P450.
Reduction in bile acid synthesis and flow.
Accumulation of oxidised proteins.
Decline in autophagy level
More senescent cells and scarring.
What are the morphological changes of the liver with age?
Dark colour due to accumulation of lipofuscin.
Loss of volume.
ECM deposition.
What is the immune function of the liver?
Protection against pathogens arriving in the blood.
The liver clears things from circulation.
Has innate immune cells which tolerise the liver and body against proteins that don’t need to worry about.
If it recognises bad things, can rapidly trigger anti-viral immune response.
What does the organ do in a double organ transplant?
The liver can become tolerised so the person won’t reject the liver.
It can also protect the second organ if it is from the same donor against rejection.
Why does liver disease go undetected?
The liver regenerates and has massive functional reserve.
Person won’t see loss of normal function if 25% of liver is removed, so don’t realise they have liver disease until it is extreme - cirrhosis, at risk of developing liver cancer.
What are the symptoms of cirrhosis?
Scarring:
Renal failure
Varices in oesphagus
Ascites
Splenomegaly
Portal hypertension
How do the symptoms of cirrhosis cause effects?
Hypertension in blood vessels to liver,
which causes altered blood flow to other organs.
Causes renal failure, splenomegaly, ascites, varices (bulge) in oesophagus - bleed easily, Sick liver doesn’t make coagulation factors. And hypertension forces tissue fluid into abdomen - ascites accumulation.
What are the main causes of cirrhosis?
Fatty liver disease and alcohol abuse.
What is viral hepatitis?
Viruses selectivity infect hepatocytes.
Hepatitis B and C are particularly damaging.
Hep B vaccines can help combat this, but can inadvertently causes hepatitis C and causes cirrhosis.
How does hepatitis occur?
Viruses selectively infect hepatocytes.
Very strong immune response causes severe hepatitis.
The immune system kills the infected hepatocytes.
Some viruses are cleared but some cause chronic infection and immune response, which drives fibrosis and end stage liver failure.
What is MALSD?
Metabolic associated liver disease.
Ranges from fat to hepatitis and fibrosis.
Caused by obesity, diabetes, dyslipidaemia, hypertension.
Can cause insulin resistance, lipotoxicity, oxidant stress, apoptosis, inflammation, scarring risk.
What is acute liver disease?
Can be caused by alcohol binge, or a bad drug reaction.
The injury is removed, and the liver regenerates.
But the injury can persist, e.g. chronic Hep C, where the immune response and inflammation becomes chronic and damages tissue, by activating stellate cells to cause scarring.
What is jaundice?
Yellow discolouration of the skin, eye and other tissues.
Due to a build-up of bilirubin in tissue fluids and bloodstream.
In excess of 2mg/ml.
How can jaundice be detected?
Increased levels of aspartate transaminases and alanine transaminases shows that the hepatocytes are damaged.
Alkaline phosphatase and gamma glutamyl transferase (gGT) also shows biliary disease.
Albumin levels would decrease.
How can jaundice be detected through antibodies?
Autoantibody levels might be increased, which target the biliary tree or hepatocytes.
In advanced liver disease, there may be altered white blood cell count.
Viral DNA or antibodies in the blood can indicate hepatitis virus.
How can jaundice be detected by metabolic indicators?
Metabolic liver disease, dyslipidaemia and type 2 diabetes can all indicate liver disease.
As tumours grow, tumour specific molecules like alpha feta protein increase, which indicates liver cancer.
What are technologies for detecting liver disease?
MRI or CT imagining to see the tumours.
Ultrasound using a fibroscan, the faster the sound waves bounce back the more scarred the liver is.
What is prothrombin time?
Can measure how fast the liver makes clotting factors by measuring how fast blood clots.
Increased prothrombin time shows the blood clotting is slow.
What is bilirubin?
A product of haem catabolism.
It comes from red blood cells, myoglobin, cytochromes and peroxidases.
It is an orange/yellow pigment.
Lots of bile is needed for excretion of substances and for digestion, some is lost by the faecal route.
So bile salts are recycled often in the day.
What do Kupffer cells do for bilirubin?
The macrophages break the RBCs into hem.
Heme is modified by heme oxygenase, to form green biliverdin. Fe2+ is kept, CO is removed.
Biliverdin is further reduced by biliverdin reductase to form the orange bilirubin.
How does bilirubin go to the liver?
Unconjugated bilirubin is not water soluble, so it is complexed to albumin so it can travel in the blood to the liver.
In the hepatocytes, it is conjugated with glucoronic acid by UDP glucooronyltransferase.
Conjugated bilirubin is water soluble.
What can conjugated bilirubin do?
Conjugated bilirubin is excreted as bile from the bile duct.
Some bile is used to digest food and for lipid emulsification.
It can be metabolised by b-glucuronidase in the gut in bacterial or epithelial cells, to form urobilinogens.
Some urobilinogens are reabsorbed and sent back to the liver via the portal vein, some are excreted in urine.
What is haemochromatosis?
Increased serum ferritin suggests there is too much iron in the liver, which causes oxidative injury.
This damages the liver and leads to cirrhosis.
But there are specific gene mutations in haemochromatosis, so this can indicate if disease is this or something else liver related.
What are the different forms of jaundice?
Pre-hepatic upstream of liver
Intrahepatic - liver
Extrahepatic - downstream of liver
All linked to haem metabolism, which makes the pigments.
What is pre-hepatic jaundice?
The macrophages eat the RBCs as normal.
Levels of unconjugated bilirubin are elevated, which shows the issues are before the liver.
Associated with fragile RBCs rupturing - haemolysis.
There are normal AST/ALT and normal AP/gGT.
What are the causes of fragile RBCs?
Haemolytic anaemia - RBC destruction.
Paroxysmal nocturnal haemoaglobulinurea (PNS), genetic.
Sickle cell disease - genetic, variant haemoglobin,
Malaria.
Can have inherited diseases which alter the phospholipid membranes of RBCs.
What are the liver symptoms in anaemias?
Bilirubin causes gallstones - darker urine, elevated unconjugated bilirubin.
Enlarged liver - thrombisis, increased transaminases.
Iron overload due to high RBC turnover.
Splenomegaly.
Coagulation deficity.
MRI shows defections.
What is Gilberts’ syndrome?
A form of pre-hepatic jaundice.
Gene mutation in glucronyl transferase 1 gene, responsible for conjugating bilirubin.
Causes elevated unconjugated bilirubin, as UDP-glucoronyl transferase can’t glucuronate fast enough.
What is neonatal jaundice?
Common in babies
Delays in clearance of bilirubin from red blood cell breakdown.
Treated by phototherapy to remove bilirubin.
Only a concern if there is dark urine or it persists.
What is hepatic jaundice?
Jaundice due to liver injury.
Increased conjugated and unconjugated bilirubin in circulation.
Increased transaminases and bilirubin enzymes (gGT) in liver function tests.
Increased conjugated bilirubin due to the liver reserves of conjugated are released once hepatocytes start dying.
How does hepatitis cause hepatic jaundice?
Strong immune response to the virus kills hepatocytes and causes jaundice.
Hepatitis A and E from faecal route, not chronic
B is from sexual or blood route
B can be chronic, C is mostly chronic
Vaccines for A,E and B.
How do bile salts cause hepatic jaundice?
Cholestasis or interruption of bile flow due to damage to the liver, from:
Cancer, destruction of bile ductules from autoimmunity or drugs, or cholestasis secondary to injury, pregnancy or drug toxicity.
Why are there psychiatric symptoms in liver disease?
Deteriorating mental function and further bleeds in end stage liver disease because the liver clears breakdown products of proteins and ammonia.
Elevated levels of ammonia can travel to brain and cause astrocytes to swell and cause psychiatric symptoms.
What is post-hepatic jaundice?
Causes green plasma and urine.
Caused by obstruction of bile ducts.
This means the bilirubin is conjugated but cannot circulate.
The bile is not drained properly, can cause secondary injury.
Shows increased transaminases and biliary enzymes.
Caused by gallstones, cancers, compression.
What are gallstones?
Gallstones can block bile ducts and cause infections - cholangitis and jaundice.
It can be inherited, causing an imbalance in chemical constituents of bile, or from the diet.
What is pancreatic cancer?
Growth obstructs the bottom of the common bile duct.
Painless jaundice associated with weightloss.
Common in older patients.
Can also compress the ducts.
