Hepatobiliary System

Question 1

Describe location of liver with respect to surface landmarks

Answer 1

The top right border of the liver can be found inferior to the right nipple. The lower right border of the liver can be found just above the subcostal margin. It is contained within the thoracic cavity.

Question 2

Describe morphological anatomy of liver

Answer 2

Consists of a right lobe and left lobe with the diaphragm lining the superior surface of the liver. Falciform ligament runs medially to liver which is the anterior fold of the peritoneum and forms the ligamentum teres, ending in umbilical vein remnant which in embryonic development would join umbilical cord to falciform ligament and then left portal vein. The line dividing the left and right lobe is the middle hepatic vein which descends curving to the right – falciform ligament is not the dividing line.

Question 3

Describe vessels connected to the liver

Answer 3

Inflow include the hepatic artery (supplies 25% of blood) and portal vein (75%). Outflow includes the bile duct and 3 hepatic veins. The hepatic artery provides nutrients and oxygen to hepatocytes while portal vein’s blood flow is filtered.

Question 4

Describe functional anatomy of liver

Answer 4

The liver is divided into 8 segments where segment 1 is in front of the IVC behind the portal vein. Segments 1-4 then run in a clockwise direction from here on left side while 5-8 run in clockwise direction on right side.

Question 5

Describe the structure of a hepatic lobule

Answer 5

Hexagonal structural unit of liver tissue. Each corner consists of a portal triad and links with 3 other adjacent lobules. Centre of liver lobule is a central vein which collects blood from the hepatic sinusoids. This then drains into the hepatic vein from the central vein and finally into systemic venous circulation in inferior vena cava. The lobule contains rows of hepatocytes where each has a sinusoid-facing side & bile canaliculi-facing side. Sinusoid-facing side faces the blood vessel and collects material from inflow of blood. Bile-canaliculi side takes the nutrients from inflow of blood, processes it and shifts it to the biliary system.

Question 6

What is the portal triad?

Answer 6

1. Branch of hepatic artery - brings O2-rich blood into liver to support hepatocytes as they have a high energy demand
2. Branch of portal vein - Splenic vein joins superior mesenteric vein which forms the portal vein and so brings mixed venous blood from GIT (nutrients, bacteria & toxins) and spleen (waste products). Hepatocytes process nutrients, detoxify blood & excrete waste.
3. Bile duct - Bile produced by hepatocytes drains into bile canaliculi. This coalesces with cholangiocyte-lined bile ducts around lobule perimeter.

Question 7

What is the hepatic acinus?

Answer 7

Functional unit of the liver. Consists of two adjacent 1/6th hepatic lobules. Share 2x portal triads. Extend into hepatic lobules as far as central vein.

Question 8

What is the 3 zone model?

Answer 8

Blood enters hepatic sinus through the portal vein and drains out at central vein. Hence, hepatocytes near outer hepatic lobule(zone 1) receive early exposure to blood contents including good components like oxygen and bad components like toxins. Acinus split into 3x regions:
Zone 1 – O2 ↑, Toxin risk ↑
Zone 2 – O2 →, Toxin risk →
Zone 3 – O2 ↓, Toxin risk ↓

Question 9

What is the implication of the 3 zone model?

Answer 9

Due to zone 1 having early exposure, this is where liver damage from toxins can be seen. However, if there is ischaemic damage where liver is not being perfused with enough oxygen, zone 3 is where you would see the damage.

Question 10

What are the features and function of the sinusoidal endothelial cell?

Answer 10

No basement membrane
Fenestrated (discontinuous endothelium)
Allow lipids & large molecule movement to and from hepatocytes

Question 11

What is the function of the Kupffer cell?

Answer 11

Sinusoidal macrophage cells
Attached to endothelial cells and carry out phagocystosis - eliminate & detoxify substances arriving in liver from portal circulation

Question 12

What is the function of the hepatic stellate cell?

Answer 12

Exist in dormant state and store vit A in liver cytosolic droplets
Activated (fibroblasts) in response to liver damage
Proliferate, chemotactic & deposit collagen in ECM
These are the cells which cause damage in patients who have liver cirrhosis.

Question 13

What is the function of the hepatocyte?

Answer 13

Are 80% of liver mass
Cubical
Involved in synthesis e.g. albumin, clotting factors & bile salts
Drug metabolism
Receive nutrients & building blocks from sinusoids

Question 14

What is the function of the cholangiocyte?

Answer 14

Secrete HCO3- & H2O into bile. When the canaliculus develops into a proper bile duct, has these cells lining it.

Question 15

Summarise the functions of hepatocytes

Answer 15

Metabolic & catabolic functions:synthesis & utilization of carbohydrates, lipids and proteins.

Secretory& excretory functions:synthesis &secretion of proteins, bile and waste products.

Detoxification & immunological functions:breakdown of ingested pathogens & processing of drugs

Question 16

What is glycolysis and where does it take place?

Answer 16

anaerobic conversion of glucose to lactate happens in RBCs, renal medulla & skeletal muscle
aerobic oxidation of glucose happens in CNS, heart, skeletal muscle, most organs

Question 17

What is gluconeogenesis and where does it take place?

Answer 17

Production of glucose from non-sugar molecules.
Amino acids (glutamine) in liver & renal cortex.
Lactate (from anaerobic glycolysis in RBCs & muscles)
Glycerol (from lipolysis)

Question 18

Describe carbohydrate metabolism of hepatocytes

Answer 18

Glycolysis takes place in muscles during aerobic respiration or increased energy states like exercise. However, oxygen soon becomes a limiting factor and when this happens, TCA cycle is inhibited causing pyruvate to accumulate. However, glycolysis continues even under anaerobic conditions so end up getting a build up of lactate. Hence, lactate transported to liver. Cori Cycle refers to the metabolic pathway in which lactate produced by the anaerobic glycolysis muscles moves into the liver and is converted back to pyruvate by pyruvate dehydrogenase, then back to glucose and finally shuttled back to muscles for glycolysis.

Question 19

Describe protein synthesis in hepatocytes

Answer 19

In fed state, amino acids come from diet while in the fasted state, from the breakdown of muscle. In the liver, these are then converted to proteins which are important to determine synthetic liver function, making plasma proteins like clotting factors and lipoproteins.

Question 20

Describe synthesis of non-essential amino acids in the liver

Answer 20

Different keto-acids can be converted into multiple amino acids depending on the transaminase enzyme (vital for production of non-essential amino acids).
alpha-keto glutarate → e.g. glutamate, proline, arginine
Pyruvate → e.g. alanine, valine, leucine
Oxaloacetate → e.g. aspartate, methionine, lysine

Question 21

Why is glucose-alanine cycle needed?

Answer 21

Muscle can potentially utilise amino acids to produce glucose for energy but convertion of pyruvate to glucose requires energy and removing nitrogen as urea requires energy. Hence, muscle transfers the problem to the liver.

Question 22

What is the glucose-alanine cycle?

Answer 22

Glutamate produced from amino acid breakdown and pyruvate from glycolysis react to undergo a transamination reaction, forming alpha-keto glutarate and alanine. Alanine is the principal amino acid released from muscles during starvation – important for hepatic gluconeogenesis. When muscles degrade amino acids for energy needs, resulting nitrogen is transaminated to pyruvate which forms the alanine. This alanine then shuttled across the liver where nitrogen eventually enters urea cycle and the pyruvate is used to make glucose.