Liver Flashcards
What protects the liver?
thoracic ribcage
What is the gross anatomy of the liver?
4 lobes - right, left, quadrate, caudate
right lobe is the largest
falciform ligament attaches it to the diaphragm, some ligaments attach it to other parts of the body
What is Calot’s triangle?
bound by cystic duct, bile duct and cystic artery
this space is dissected in cholecystectomy to identify safe window to expose the gall bladder
What is the functional anatomy of the liver?
Couinaud classification
8 functionally independent ‘Couinaud’ segments
- centrally (portal veins, hepatic artery and bile duct)
- peripherally ( hepatic vein)
- each segment resected without damaging remaining segments
- each receives own blood supply and venous drainage and segments can be resected without damage to others
What is the blood supply of the liver?
rich - 25% cardiac output
dual blood supply = blood supplying liver is poorly oxygenated compared to other tissues
- 20% arterial from L and R branch of hepatic artery
- 80% venous blood draining from gut through HPV
blood drains into IVC via hepatic vein
What is the microanatomy of the liver?
made of lobules
- 6 portal tracts/triads at each corner of hexagonal lobule linking to central vein
- acinus = elliptical or diamond shape divided into 3 zones
- HPV and artery combine to form a sinusoid which passes through the lobule and enters the central canal
What 2 hepatocytes are found in a lobule?
laterally - periportal hepatocytes
centrally - centrilobular hepatocytes
What 5 cells types are found in the liver?
hepatocytes - 80%
endothelial cells - lining blood vessels and sinusoids
cholangiocytes - bile duct epithelial cells
Kupffer cells - fixed macrophages (liver) (resident immune cells)
hepatic stellate cells - Vit A storage cells, can be activated to fibrogenic myofibroblastic phenotype in proinflammatory environment, located in the space of Disse, if hepatic infection can replace functional tissue with fibrotic tissue
How to distinguish between hepatocytes and stellate/Kuppfer cells?
hepatocytes - large, pale and rounded nuclei
Kupffer/stellate cells - flattened, dense nuclei that appear to be in sinusoids
How are hepatocytes arranges in parenchymal tissue?
coordinated in sheets radiating from the central vein to corners of hexagons
sinusoids located between the hepatocyte sheets
80% of liver mass
What are the 3 zones of the acinus?
periportal, transition, pericentral
- terminal acinus is located on the portal tract and each hepatic acinus is centred on line connecting 2 portal triads
- unit of hepatocytes are divided into zones depending on proximity to arterial blood supply
Zone 1 - closest to portal triad
Zone 3 - closer to central vein
What zone is most vulnerable to
ischaemia
viral hepatitis?
Zone 3
Zone 1 - more susceptible to insult because closest to portal triad
What is the function of Zone 1 ?
gluconeogenesis, FA oxidation, cholesterol synthesis
What is the function of Zone 3 ?
glycolysis, lipogenesis, P450 based drug detoxification
Describe bile flow?
produced by hepatocytes from RBC and cholesterol breakdown
bile flows along canaliculus to bile duct
What is the histology of non parenchymal cells?
- not organised into sheets that radiate from the central vein
- stellate cells (Vit A storage, ECM production - fibrogenesis)
- sinusoidal cells
- Kupffer cells (phagocytosis for RBC breakdown, secrete cytokines in proinflammatory environment to change HSC –> fibrogenesis and cirrhosis)
What is the structure of sinusoidal epithelial cells?
fenestrated to allow lipid and other large molecule movement to and from hepatocytes
For how long does liver store enough glucose?
24h
What is the function of the liver in the case of anaerobic respiration to produce lactate?
O2 is needed to pass glucose through TCA cycle, if none lactate is produced and passed to liver to be converted into pyruvate and undergo gluconeogenesis
Energy intensive (6ATP) needed so liver takes over
How does liver function affect marathon runners?
muscle and liver glycogen and glucose stores exhausted
fat doesnt product as much energy
What is the liver function in terms of processing AAs from the diet?
generates proteins that are secreted and needed by body (plasma protein, clotting factor, lipoprotein) - essential AAs
not all from diet some must be made by liver from AA that are essential to non-essential AAs
- transamination by transaminase
- alanine + a ketoglutarate –> pyruvate + glutamate
alanine (=essential AA), glutamate (non essential)
What non essential AAs made by
a keto glutarate
pyruvate
oxaloacetate
1- glutamate, proline, valine
- alanine, valine, leucin
- aspartate, methionine, lysine
What is the glucose alanine cycle?
muscle can use AAs to make glucose for energy but this is energy intensive
- convert pyruvate to glucose 6ATP
- remove nitrogen as urea from glutamate 4ATP - would produce NH3 which is toxic to body esp brain
so transfer this to liver
What are 4 AAs in higher [] than other 16?
glutamate most important - reversibly made to a keto, or to glutamine (N carrier most common free AA in blood plasma)
alanine is main AA released from muscle tissue in starvation - substrate for hepatic gluconeogenesis
alanine transamination need to maintain proper fasting blood glucose
also pyruvate, a-keto
What is triglyceride metabolism of liver?
Liver can convert excess glucose/AAs to fat for storage
Acetyl CoA x2 –> acetoacetyl CoA + acetyl CoA –> HMG-CoA which is cleaved to release acetoacetate and acetyl CoA
Liver can also make ketones as energy source which when in blood are broken down to acetyl CoA by tissue and used in TCA cycle
2 acetyl CoA –> acetoacetate
How does liver make lipoprotein?
glucose converted into glycerol, FAs, cholesterol
TAG + apoprotein, cholesterol, phospholipids –> lipoprotein
LDL - transport chol to tissue to make hormone, maintain cell membrane integrity, excess returns to liver and excreted in bile
VLDL - transport FA to adipose tissue for storage , high TAG component
HDL - empty, pick up excess chol, high protein
What is the function of the liver in ion storage?
- iron as ferritin available for erythropoiesis
- store fat soluble vitamins (ADEK) for 6-12mnths except Vit K where store is small (VitK needed for blood clotting)
What is the livers role in detoxification?
P450 enzyme
Phase 1 more hydrophilic
Phase 2 attach water soluble side chain to make less reactive