Liver

Question 1

What is the relative position of the liver in the body?

Answer 1

In the abdomen and partially protected by the rib-cage.

Sits right below the diaphragm.

Covers a large region of the upper abdomen.

Question 2

How many liver lobes are there?

Answer 2

FOUR: 
Right lobe (the biggest); left lobe; caudate lobe (posterior and medial); and the quadrate lobe (posterior-medio-inferiorly).

Question 3

What is the purpose of the ligaments of the liver? Particular example?

Answer 3

Ligaments attach the liver to surrounding structures.

Falciform ligament – connects liver to the diaphragm.

Question 4

Where does the gall bladder lie in relation to the liver?

Answer 4

Gallbladder is posterior and pokes out the bottom slightly. It is found across half the length of the right lobe.

Question 5

Where vasculature is associated with the liver? (x3)

Answer 5

Blood is delivered by the hepatic portal vein and the hepatic artery.

Hepatic vein leads to the IVC.

Question 6

How many functional units are there in the liver? What is meant by this?

Answer 6

Liver can be split into 8 functionally separate units. Functionally separate because each contains own blood supply and venous drainage, and bile duct.
So, you can remove one segments with no upstream consequences.

Question 7

What are the three branches of the hepatic vein?

Answer 7

Hepatic vein splits into middle, left and right.

Question 8

What is the proportion of the CO that goes to the liver?

Answer 8

25% of cardiac output goes to the blood.

Question 9

What proportion of blood comes from the hepatic artery and hepatic portal vein?

Answer 9

80% comes from hepatic portal vein from the gut.

Question 10

Purpose of the blood delivered to the liver by (i) hepatic portal vein; (ii) hepatic artery?

Answer 10

HEPATIC PORTAL VEIN: takes catabolic products of digestion directly from gut. Liver is the first organ that blood from the gut perfuses through, before blood enters the systemic circulation.

HEPATIC ARTERY: increases oxygenation of incoming blood, and delivers nutrient rich blood to the liver.

Question 11

What are the morphological divisions of the liver?

Answer 11

HEXAGONAL LOBULES. On outside, there is the hepatic portal vein and artery which mixes into a sinusoid, which passes through the lobule and into a central vein.

Bile duct also found on the outside – the bile canals have contents that move in the opposite direction = outwards.

The grouping of one hepatic portal vein, artery and bile duct is called the PORTAL TRIAD. Arranged at each CORNER of the hexagon.

Question 12

What are the cell types of the liver? (x5) Relative proportion?

Answer 12

HEPATOCYTES: 80%; Endothelial cells (lining blood vessels and sinusoids); cholangiocytes (aka bile duct epithelial cells – lining biliary structures); Kupffer cells; hepatic stellate cells.

Question 13

What are the cell types of the liver? (x5) Relative proportion?

Answer 13

HEPATOCYTES: 80%; Endothelial cells (lining blood vessels and sinusoids); cholangiocytes (aka bile duct epithelial cells – lining biliary structures); Kupffer cells; hepatic stellate cells.

Question 14

What are the positions of each liver cell type in the liver?

Answer 14

Look at photo. The space between the endothelium and hepatocytes is called space of disse. Quiescent = non-active.

Question 15

What do Kupffer cells and hepatic stellate cells look like histologically? (x2)

Answer 15

Flattened cells. Dense cell nuclei.

Question 16

What do hepatocytes look like histologically? (x2)

Answer 16

Large cells, with pale and rounded nuclei.

Question 17

How are hepatocytes arranged in each liver lobule?

Answer 17

Hepatocytes are arranged in sheets (cords) around the central vein.

Question 18

What is an acinus?

Answer 18

These are the FUNCTIONAL unit of the liver. As oppose to lobules which are morphological functional units.
Zone 1 – closest to portal triad (PERIPORTAL).
Zone 2 – intermediate to zone 1 and 3 (TRANSITION ZONE).
Zone 3 – closest to hepatic vein (PERICENTRAL).
Each zone describes proximity to the blood supply.

Question 19

Which of the zones of the acinus is most susceptible to (i) ischaemia; (ii) viral hepatitis and haemachromatosis?

Answer 19

Zone 1 receives most oxygenated blood, so least susceptible to ischaemia, but making it most susceptible to viral hepatitis or hemosiderin deposition in haemachromatosis (overload of iron in body).
Zone 3 is more susceptible to ischaemia.

Question 20

What metabolic processes are the hepatocytes in each of the acini zones associated with? (x3 and x3)

Answer 20

Zone 1 is involved in gluconeogenesis, oxidation of fatty acids, and cholesterol synthesis.
Zone 3 is involved glycolysis, lipogenesis and drug detoxification.

Question 21

What is bile produced from? (x2)

Answer 21

Bile is produced by hepatocytes, from breakdown products of RBCs, cholesterol breakdown products, and more.

Question 22

What are the functions of hepatic stellate cells? (x2)

Answer 22

Hepatic stellate cells: Vitamin A storage and production of ECM through a process of fibrogenesis – they turn into this fibro-genic myofibroblast phenotype in pro-inflammatory environments. Fibrogenesis from HSCs is therefore associated with liver cirrhosis – fibrogenesis replaces functional with non-functional tissue.

Question 23

What is the property of sinusoidal endothelial cells that make them suitable for their function?

Answer 23

Sinusoidal endothelial cells: VERY LEAKY, so are fenestrated such that lipids and other large molecules can move to and from hepatocytes.

Question 24

What are the functions of Kupffer cells? (x2)

Answer 24

Kupffer cells: Liver macrophages and phagocytosis (including RBC breakdown which contributes to bile). Also secretes cytokines that promote hepatic stellate cells to proliferate, contract and start fibrogenesis.

Question 25

What are the major functions of the liver? (x4)

Answer 25

Digestion, biosynthesis, energy metabolism, degradation and detoxification.

Question 26

How does liver act as a glucose store? Significance of this store?

Answer 26

Liver stores enough glycogen for 24 hours – provides a source of glucose for the body – used as the first store of glucose, before other sources like fat. Once glycogen supply in liver is exhausted, you tend to ‘hit the wall’ – because body has to switch to more complex, less efficient, slower sources of glucose like fat.

Question 27

How is the liver involved in energy-production in muscle cells when oxygen is in short supply? Name of cycle?

Answer 27

During muscle contraction, ATP is constantly being produced from aerobic respiration. If muscular activity continues, the availability of oxygen for use at the end of the electron transport chain becomes the limiting factor and TCA cycle and oxidative phosphorylation both stop. Pyruvate ACCUMULATES because glycolysis continues in anaerobic conditions. Pyruvate is converted into glucose in the liver, so that ATP can still be produced in the muscle cells from glycolysis. HOW DOES THIS HAPPEN? Pyruvate is converted into lactate in the muscle. Lactate is sent to the liver and converted back into pyruvate using lactate dehydrogenase. Gluconeogeneisis creates glucose from pyruvate in the liver using 6 ATP. Glucose is then sent off back to the muscle to produce ATP from glycolysis while oxygen is still the limiting factor.

Question 28

How is the liver involved in protein synthesis? Where do the substrates come from? (x2)

Answer 28

Come from diet or muscle breakdown – delivers amino acids. SYNTHESIS OF PROTEINS: Liver takes the amino acids and produces lots of essential proteins – REMEMBER, liver produces a lot of proteins for the blood e.g. plasma proteins, clotting factors, lipoproteins.

Question 29

What is the mechanism by which the liver is involved in transamination? Using alanine as an example.

Answer 29

TRANSAMINATION: not all amino acids come from the diet e.g. alanine from diet enters liver, and amino group is transferred to keto acid to produce a different amino acid e.g. alpha-ketoglutarate and alanine --\> glutamate and pyruvate. This process is reversible.

Question 30

What keto-acids are involved in transamination in the liver, and give examples of the amino acids they can produce? What determines the amino acid produced?

Answer 30

Different keto acids can be converted into different amino acids depending on the transaminase enzyme (vital or production of non-essential amino acids). 1. alpha-keto glutarate --\> glutamate, proline. 2. pyruvate --\> alanine. 3. oxaloacetate --\> aspartate.

Question 31

What is the cycle called that does deamination? What is deamination?

Answer 31

DEAMINATION: in the glucose-alanine cycle. This is used to produce energy from amino acids by removing the amino group, and feeding the carbon structure remaining into the metabolism cycle e.g. alanine to pyruvate.

Question 32

What are the problems of deamination and how are they overcome? (x2 problems)

Answer 32

Conversion requires energy, and to remove nitrogen as urea requires energy. SOLUTION: transfer problem to the liver in the glucose-alanine cycle.

Question 33

Example of deamination in the liver?

Answer 33

Glutamate and pyruvate (from glycolysis) can be used to produce alanine. Alanine goes to liver + alpha-ketoglutarate --\> back into pyruvate and glutamate. * Glutamate + 4ATP --\> urea which goes into blood for excretion. * Pyruvate + 6ATP --\> glucose, which can be used in glycolysis back in the muscle cell or other tissues.

Question 34

When does the liver revert to fat storage?

Answer 34

When glycogen stores in liver is full, excess glucose and amino acids are stored as fat in the LIVER and ADIPOSE TISSUE.

Question 35

How is the liver involved in energy production from fat catabolism? (x2 mechanisms)

Answer 35

1. When energy is needed, triglycerides are turned into fatty acids in the adipose tissue cells. Fatty acids are converted into Acetyl CoA in to the liver by B-oxidation. This is fed into the TCA cycle which produces energy IN THE LIVER. 2. IN ADDITION, liver can produce ketones – another source of energy. Fatty acids converted into Acetyl CoA. Two of these combine to form acetoacetate rather than feeding into TCA cycle. This travels into the blood to tissue, where they breakdown the ketones to liberate the Acetyl CoA for their own TCA cycle.

Question 36

How is the liver involved in lipoprotein synthesis?

Answer 36

LIPOPROTEIN SYNTHESIS: glucose moves into liver and converted into PYRUVATE and GLYCEROL. * Pyruvate converts into Acetyl CoA by the link reaction which --\> FATTY ACIDS AND CHOLESTEROL. * FATTY ACIDS and GLYCEROL --\> tri-acyl glycerol (triglyceride). * Phospholipids and apoproteins combine with triglycerides and cholesterol to form LIPOPROTEINS.

Question 37

What are the three main types of lipoprotein? Functions of each and how are they produced?

Answer 37

VLDL PRODUCED BY LIVER: has very high fatty acid content; delivered to adipose tissue for store. HDL PRODUCED BY LIVER: has lower fatty acid content, and are termed ‘empty’; HDL picks up excess cholesterol in the blood and delivers this to the liver for breakdown and metabolism. LDL IS NOT PRODUCED FROM THE LIVER. It is PRODUCED FROM VLDL: transports CHOLESTEROL to tissues.

Question 38

What is the function of liver in relation to vitamins?

Answer 38

VITAMIN STORAGE: liver stores all fat-soluble vitamins, as well as iron for blood cell production, and copper.

Question 39

How does the liver detoxify toxic compound in the blood? (x2)

Answer 39

DETOXIFICATION: If a toxic compound enters the liver, it uses P450 enzymes and (i) tries to make the molecule more hydrophilic so that it can be more easily excreted in the urine; (ii) liver adds water-soluble side chain to make the toxic molecule less reactive and less likely to leave the blood until it gets to the kidney for urination.