The Liver Flashcards
what is the gross anatomy of the liver?
Largest solid organ - grows to fit your metabolic requirement
Located in the abdomen in the upper right quadrant
It is closely associated with other abdominal organs (particularly intestines)
Composed of 2 lobes separated by Falciform ligament
what is the hepatic hilum?
Hepatic hilum: anatomical region where bile ducts, hepatic arterial branches, portal vein branches, lymphatics and nerves enter or leave the liver.
what is the structure of the anterior and posterior view of the liver?
what 3 factors could variations in the liver be due to?
Genetic variation: (no consequences)
Hereditary anatomical displacement of liver
Accessory lobes → no consequence
Internal factors:
Portal thrombosis: blockage or narrowing of the portal vein by a blood clot – the piece of the liver destined to receive this blood supply will die
Cardiac cirrhosis: hepatic disorders that occur due to cardiac dysfunction
Liver fibrosis: Scaring of liver - liver is no longer smooth but knobbly)
Liver atrophy
External factors:
Impression effects due to the diaphragm, tight belts/corsets, coughing/emphysema
Riedels and accessory lobes, clefts or fissures
Lobular atrophy: Portal thrombosis or cancer can result in one area of the liver having an interrupted blood/biliary drainage in or out which results in a loss of function and atrophy of that area.
what is bile and where does it drain into?
Bile is made in the liver by hepatocytes (epithelial cells)
This bile then moves via the common hepatic duct –> Cystic duct into gallbladder
Bile is then secreted from the gallbladder into the duodenum when necessary.
Cholecystokinin stimulates the gallbladder to contract and release stored bile into the intestine
When you eat: the detection of products of digestion in the intestine e.g. peptides, triggers release of sphincter muscle and contraction of gallbladder to introduce bile down common bile duct into intestine to help emulsify and absorb fat.
when do people with gall stones feel pain?
People with Gall stones experience pain after eating as this is when Gall bladder contracts on the gall stones within the Gall bladder.
describe the dual blood supply of the liver?
The liver receives venous blood directly from the intestine via the portal vein (supplies 75%)
The blood Contains:
Food materials for processing
Nutrients, glucose and lipids
Bacterial bi products
Tumours commonly metastasise from the colon to the liver because of the hepatic portal system
The liver also receives arterial blood via the hepatic artery (25%)
Supplies oxygenation
25% of the total cardiac output enters the liver - as liver is a very metabolic organ
Therefore, traumatic wound to the liver e.g. stabbing makes you bleed out very quickly
The blood then enters the liver → mixes in the sinusoids (capillary bed) → drains via hepatic veins into IVC near the right atrium.
how many segments can the liver be divided into?
why is this useful in surgery?
The liver can be divided into 8 segments.
Each of these segments have their own blood supply and bile duct (i.e., an independent system)
This is useful in surgery:
Tumour treated by chemotherapy to reduce their size and can then be removed without compromising the blood supply to the remainder of the liver. The liver can regenerate tumour free
Each segment is then divided into lobules/acini (functional units of the liver)
Lobules are composed of hepatocytes, sinusoidal channels, inlet + exit blood vessels and bile canaliculi
how does the liver regenerate?
Liver Regeneration:
The hepatocytes can regenerate.
The liver also contains resident stem cell populations that become activated in the context of injury and go on to regenerate the liver.
what is bile canaliculi?
Bile Canaliculi: thin tubes that collects bile secreted by hepatocytes. The bile canaliculi then empty into a series of progressively larger bile ductules and ducts which eventually become common hepatic duct.
describe the CT makeup of the liver
The liver is surrounded by a thick matrix rich capsule that protects the outside of the liver from traumatic injury. (Shiny Surface)
The liver has a lot of connective tissue within it:
Connective tissue surrounds the portal tract and blood vessels within the liver
Portal tracts (consist of a bile duct, portal vein, and arteriole) surrounded by a collagenous matrix.
Reticular network (image below): Network of reticular fibres around hepatocytes which allows then to orientate themselves and grow in appropriate channel
ECM of CT contains:
Collagen mainly produced by stellate cells
Glycoproteins which allow the cells to connect to ECM via surface molecules called integrins.
The connective tissue produced has a half-life of 30 days.
Hydroxyproline is produced as a metabolite so can be used to measure rate/extent of breakdown
describe the structure of a liver lobule
Hexagonal in shape
Hepatic artery and portal vein (arterial and venous blood supply) and Bile ducts (where bile produced by hepatocytes leaves the liver to go to gall bladder) is found at the exterior of the hexagon.
This region is known as the portal tract.
The arterial and venous blood then mixes in the sinusoid, here it is exposed to the cords of hepatocytes on either side
Blood then drains from the liver via the central vein vessels which is found in centre of lobule - hepatic vein
how many zones is a liver lobule divided into?
Lobule divided into three zones
Zone 1: Periportal area – where nutrient and O2 blood comes in
Zone 2 – Intermediate zone
Zone 3 – Near the central vein where blood leaves
Cells closer to the zone 3 are more hypoxic (lack oxygen) than ones near where blood comes in. Hepatocytes with enzymes for drug metabolism are found here.
what does a healthy hepatocyte look like?
Cords of hepatocytes (rectangles) seen on right.
Sinusoidal channel (middle region) where blood mixes and comes into contact with hepatocytes.
how does fibrosis and cirrhosis lead to disruption of lobular architecture?
Connective tissue builds up as the liver gets injured and then expands to fill up space that would normally be filled by hepatocytes.
F1-4 is a system of grading severity:
F0 is normal liver
F1- the beginning of liver disease (starting to see some degree of expansion of CT)
F2 – CT expanding into normal area of hepatocytes
F3 – CT starts to join up
F4 - (cirrhosis) Islands of hepatocytes separated from each other by connective tissue. This compromises liver function as there is not enough normal liver left.
Staging effects treatment strategy
what are hepatocytes?
Main functional cells of the liver (60-65% of liver tissue)
Large Polarised polyhedral epithelial cells:
The upper and lower surfaces of the cell are called the sinusoidal plane (part of cell that is facing blood supply)
These region as where there is the machinery for:
absorbing material from circulation is located
Secreting carbohydrates (Glycogen broken down to release Glucose) and proteins that are made by liver into the circulation.
On the lateral surface of the cell, you can see cell junctions:
Desmosomes hold hepatocytes together
Tight junctions (occluding junctions) make sure the bile canaliculi are tightly sealed to ensure bile (made in hepatocytes) secreted into them does not leak out and damage adjacent hepatocytes
Low mitotic index: They cells are very complex so the cells don’t divide and die very often (long life and slow turnover) as it takes a lot of energy to produce the cells.
If you stain liver tissue you won’t see many proliferating cells.
what is Biliary epithelium (cholangiocytes)?
1-3% of liver tissue
Cholangiocytes: Polarised cuboidal/columnar epithelial cells
Form ducts of increasing size to collect canalicular bile and eventually transport it to the gall bladder.
Have dense basement membrane and tight junctions between cells to keep bile in the duct
Function: have transport and secretion properties to allows them to modify the contents of bile and excrete waste materials into it.
what is Endothelium?
adaptation?
Endothelium:
Simple Squamous epithelial cells
Line the hepatic vasculature (blood vessels)
Special functions:
Protect the parenchyma from blood cells, bacteria + viruses
They also allow for selective transport of materials into the liver tissue as necessary.
They also allow for products produced by hepatocytes e.g. protein and waste products of the liver cells to cross over and enter the blood.
Regulation of leukocyte traffic → WBCs entering tissue when appropriate
Regulation of coagulation
Adaptation:
Anti-thrombogenic surface → prevents blood clotting
what are kupffer cells?
function?
Kupffer cells:
Hepatic macrophages located within sinusoids
They have very active receptor-mediated endocytosis
Very motile – whiz up and down sinusoids.
Functions:
Phagocytosis – clear bacteria and debris from the microcirculation of the liver
Can produce cytokines, present antigens and stimulate immune responses → 1st to response to danger
Secrete mediators which regulate microcirculation
Removal of endotoxin
what are Stellate cells (lipocytes)?
function?
Sit between endothelium + hepatocytes
Perisinusoidal fat/retinoid storing cells
Star shaped morphology with multiple membrane processes and branching structure -> make contact with other cells
Function:
Regulate diameter of sinusoid (vascular tone)
Can transform to fibroblast-like morphology in disease and cause fibrosis in chronic injury
Change nature + become more proliferative
Secrete more ECM
what is the Production of bile function of the liver?
0.5 L produced per day by hepatocytes → stored in gall bladder
Bile is released from the Gall Bladder into the intestine on demand to helps to emulsify fat and allow us to take up fat soluble vitamins (A,D,E,K)
Bile is also an important excretion route for non-water soluble molecules that can’t be excreted via the kidneys(non-water soluble drugs, cholesterol, bilirubin)
Bile acid is then actively reabsorbed from the ileum and sent back to liver in the portal circulation to recycle it.
what is the Immune function of the liver?
Protection of liver against pathogens arriving in the blood
This includes blood from periphery and blood from the GIT which could be full of pathogens e.g. bacteria in something you have eaten.
Phagocytosis of old or dying cells
Induction of tolerance → helps you decide what is ok to keep in the body
E.g. if you have a chicken sandwich you don’t want to raise an immune response due to proteins in chicken so the liver has a tolerising immune population in the liver that ignored chicken protein.
A lot of the immune cells are found around the portal area (blue circle). You can see their nuclei. They look out for harmful substances in the blood.
what are the Elimination/Detoxification functions of the liver?
what are CYPs?
Elimination:
Any compound that needs to be removed from the body (e.g. alcohol, medication,) is first sent to the liver.
Liver Metabolism which converts it into a water soluble product:
Phase 1 metabolism: oxidation to make substance water soluble (by cytochrome p450)
Phase 2 metabolism: conjugation of molecule to make water soluble
The water-soluble product then excreted:
Urinary excretion
Biliary excretion
CYPs are also responsible for bioactivation of some compounds
CYPs are the major enzymes involves in drug metabolism and deactivation – either directly or by facilitated excretion from the body.
Levels of CYPs vary with age, gender, individual and cell/organ (or even area in organ)
These factors are important in dosing of drugs that need to be bioactivated in blood – give elderly person different dose than young person due to different level of these enzymes.
what are the stages of liver disease?
describe the consequences of End Stage Liver Disease (Cirrhosis)
Cirrhosis can cause life threatening complications.
Patients will liver cirrhosis will either die due to liver failure or due to the consequence of liver cirrhosis.
Consequences of Cirrhosis include portal hypertension:
When you have extensive liver fibrosis it makes the blood pressure in the blood vessels draining from the intestine to liver very high (portal hypertension) due to increased vascular resistance in the cirrhotic liver.
This causes renal failure
It can also cause oesophageal Varices: This is where there are enlarged blood vessels in the oesophagus which are prone to rupture. If they rupture in a patient with impaired liver function, the blood wont clot, so you lose blood very quickly due to rupture which can be life threatening.
Splenomegaly – enlargement of the spleen.
Also because of the increase blood pressure in the abdomen you end up forcing tissue fluid into the abdomen. This is called ascites. This then has to drained.
Ascites is the abnormal build-up of fluid in the abdomen
what is non-alcoholic fatty liver disease?
Being overweight or obese put you at risk of developing non-alcoholic fatty liver disease
Non-alcoholic fatty liver disease is characterised as the presence of fatty accumulation > 5% of the liver’s weight is fat.
This can then progress down the line, eventually get to cirrhosis
This disease ranges from just fat to hepatitis to hepatitis and fibrosis.
Puts you at risk of developing primary liver cancer just like all chronic liver disease
You also get a lot of systemic consequences as the liver has a very important role in digestion e.g.
how does alcohol affect the liver?
Alcohol can cause death of hepatocytes.
However it is the inflammatory response to death of hepatocytes and presence of alcohol metabolites which causes chronic injury.
what are the common pathways that drive development of fibrosis the liver?
Regardless of what causes initial injury (virus, alcohol, obesity) you can progress along spectrum..
You get: acute hepatitis –> chronic hepatitis (activates wound healing which causes scaring and fibrosis) Liver fibrosis –> Liver cirrhosis –> which then maybe eventually lead to liver cancer
what are the future targets for managing liver disease?
