Questions on the liver: detoxification, deamination and the making of urea

Question 1

In a hepatocyte, the ammonia from deamination enters the ornithine cycle. In a mitochondrion, ammonia and bicarbonate, derived from carbon dioxide, combine and join ornithine to form citrulline. In the cytoplasm, citrulline gains a second nitrogen from the amino acid aspartate and becomes arginine, and the arginine is then hydrolysed to urea and ornithine. Describe what happens to an amino acid that the body does not need, from deamination to the urea leaving the body, and explain, using this information, why the liver needs only a small amount of ornithine however much urea it makes.

Accepted Answer

B1 deamination in a hepatocyte removes the amino group as ammonia, and the rest of the molecule is respired or converted to carbohydrate or fat B1 ammonia is very soluble and highly toxic, so it is converted at once into urea, which is far less toxic B1 the urea diffuses into the blood and is carried to the kidneys, where it is filtered out of the blood and excreted in urine B1 the ornithine used at the first step is released again when arginine is hydrolysed, so it is regenerated at every turn of the cycle B1 each ornithine molecule is therefore used over and over, so a small, fixed amount can convert any quantity of ammonia into urea

Question 2

Describe the structure of a liver lobule, and describe the direction in which blood and bile each travel through it.

Accepted Answer

B1 a lobule is a roughly hexagonal block of hepatocytes with a central vein running down its axis B1 at each corner sit branches of the hepatic artery and of the hepatic portal vein, together with a bile ductule B1 blood from both vessels flows inwards from the corners along wide leaky capillaries called sinusoids, mixing as it goes, and drains into the central vein B1 bile is secreted by the hepatocytes into bile canaliculi running between them and travels outwards to the ductules at the corners, so blood and bile move in opposite directions

Question 3

Explain how the liver deals with the alcohol in a drink, and explain why heavy drinking over many years leads to fat accumulating in the liver.

Accepted Answer

B1 ethanol is oxidised by ethanol dehydrogenase to ethanal B1 ethanal is oxidised by ethanal dehydrogenase to ethanoate, which is converted to acetyl coenzyme A and fed into respiration B1 both steps pass hydrogen to NAD, so reduced NAD accumulates in the hepatocytes B1 a cell with plenty of reduced NAD synthesises fatty acids rather than oxidising them, so fat builds up in the hepatocytes, and sustained damage leads on to cirrhosis as scar tissue replaces the cells

Question 4

Describe the role of Kupffer cells in the liver, and describe what happens to the haem group of an old red blood cell that they break down.

Accepted Answer

B1 Kupffer cells are macrophages fixed in place along the sinusoids of the liver B1 they engulf bacteria arriving from the gut in the blood, and they break down worn-out red blood cells B1 the haem group from those red blood cells is converted into bile pigments B1 the bile pigments leave the liver in the bile, pass into the gut and colour the faeces, which is why faeces contain some body-derived material as well as undigested food

Question 5

Explain why a drug taken as a tablet by mouth may reach the rest of the body at a much lower concentration than the same dose given by injection.

Accepted Answer

B1 a swallowed drug is absorbed from the gut into the blood of the hepatic portal vein B1 the hepatic portal vein carries that blood, and everything dissolved in it, directly to the liver before it reaches any other tissue B1 hepatocytes detoxify a wide range of substances using enzymes such as those of the cytochrome P450 group, so a significant fraction of the drug can be broken down on this first pass through the liver B1 an injected drug enters the general circulation directly and is diluted throughout the whole blood volume before any of it reaches the liver, so a much higher fraction of the same dose reaches the rest of the body intact

Question 6

A patient with cirrhosis is prescribed a drug that is normally broken down entirely by enzymes in the smooth endoplasmic reticulum of hepatocytes. Suggest why their doctor prescribes a lower dose than usual, and suggest what would happen if the normal dose were given repeatedly.

Accepted Answer

B1 in cirrhosis, many working hepatocytes have been replaced by fibrous scar tissue, so there is less of the enzyme available to detoxify the drug B1 the same dose is therefore broken down more slowly than in a person with a healthy liver B1 a lower dose is prescribed so that the concentration of active drug reaching the blood stays within a safe range despite the slower removal B1 if the normal dose were given repeatedly, the drug would not be cleared between doses, so its concentration in the blood would keep rising with each dose and could reach a toxic level even though each individual dose was the standard one

Question 7

Birds and reptiles convert nitrogenous waste into uric acid rather than into urea. Uric acid is almost insoluble in water and comes out of solution as a solid, whereas urea is very soluble. A bird's egg exchanges gases through its shell but takes in no liquid water after it is laid, and waste made by the embryo stays inside the shell until hatching. Explain why uric acid is a more suitable excretory product than urea for an animal that develops inside a shelled egg.

Accepted Answer

B1 the embryo cannot obtain more water to dilute its waste, so any soluble waste stays in the limited water inside the egg B1 urea would accumulate in solution and its concentration would keep rising as development continued, until it reached toxic levels B1 a rising concentration of dissolved urea would lower the water potential of the fluid around the embryo, so water would leave the embryo's cells by osmosis B1 uric acid leaves solution as a solid, so it adds almost nothing to the solute concentration: it neither poisons the embryo nor lowers the water potential, and it uses very little of the egg's water

Question 8

Compare the excretion of carbon dioxide with the excretion of urea, referring to where each waste is produced, the organ where each is processed for removal, and the organ where each actually leaves the body.

Accepted Answer

B1 carbon dioxide is produced by respiration in essentially every living cell, whereas urea is produced specifically in the liver, from the deamination of surplus amino acids B1 carbon dioxide needs no processing before excretion, being carried in the blood mostly as hydrogencarbonate ions, whereas the more toxic ammonia from deamination is processed in the liver into far safer urea first B1 carbon dioxide leaves the body at the lungs, across the alveolar epithelium, whereas urea leaves the body at the kidney, filtered out at the renal capsule and concentrated in the urine B1 both are true excretory products under the same definition, since both are waste products of the body's own metabolism, even though one requires a dedicated chemical conversion by an organ before it can be safely excreted and the other does not

Question 9

Name the two blood vessels that carry blood into the liver and the vessel that carries blood away from it, stating what the blood in each of the incoming vessels contains.

Accepted Answer

B1 the hepatic artery, carrying oxygenated blood from the aorta B1 the hepatic portal vein, carrying deoxygenated blood from the gut that is rich in absorbed food and in anything else taken in with a meal B1 the hepatic vein, which carries blood away to the inferior vena cava

Question 10

A freshwater fish excretes its nitrogenous waste as ammonia, while a mammal spends ATP converting the same ammonia into urea. Explain why the mammal does so.

Accepted Answer

B1 ammonia is extremely soluble and very toxic, particularly to nervous tissue, so only a very low concentration can be tolerated in the blood B1 excreting it would therefore require a large volume of water, which a fish surrounded by water can lose freely but a land mammal cannot replace B1 urea is far less toxic and still soluble, so it can be carried in the blood at a much higher concentration and concentrated further in the urine, and the ATP spent on the ornithine cycle makes that saving possible

Question 11

A patient with advanced liver damage has a blood urea concentration below the normal range and a blood ammonia concentration above it. Suggest an explanation for both measurements, and suggest why the urea reading could give a misleading impression of how well the kidneys are working.

Accepted Answer

B1 urea is made in the liver, so with fewer working hepatocytes there are fewer ornithine cycles running and less urea is produced B1 deamination continues and ammonia also arrives from gut bacteria along the hepatic portal vein, but too little of the cycle remains to convert it, so ammonia accumulates B1 blood urea is usually read as a measure of kidney excretion on the assumption that production is steady; here production has fallen, so a low value says nothing reassuring about the kidneys

Question 12

Hepatocytes contain unusually large amounts of the enzyme catalase. Explain what this enzyme does, and explain why a liver cell needs so much of it.

Accepted Answer

B1 catalase catalyses the decomposition of hydrogen peroxide into water and oxygen B1 hydrogen peroxide is toxic and is produced continuously as a by-product of the many metabolic reactions, including detoxification reactions, taking place in a hepatocyte B1 because hepatocytes carry out so much metabolism, they generate hydrogen peroxide faster than most cells, so they need a correspondingly large amount of catalase to break it down before it can damage the cell

Question 13

An athlete eats a very high-protein diet for several weeks to build muscle, far more protein than their body needs. Suggest what happens to the extra amino acids, and suggest why their blood urea concentration is likely to be higher than average as a result.

Accepted Answer

B1 the surplus amino acids cannot be stored, since there is no store for amino acids as glycogen stores glucose, so they are deaminated in the liver: the amino group leaves as ammonia and the keto acid remaining is respired or converted to glucose or fat B1 the ammonia produced enters the ornithine cycle and is converted into urea, so more surplus protein being deaminated means more urea being produced per day than in someone eating a normal amount of protein B1 because the extra urea is made continuously while the high-protein diet continues, and the kidney takes time to filter and excrete each batch, the athlete's blood urea settles at a higher steady level than someone eating less protein, even with normally functioning kidneys

Question 14

State what is meant by excretion, and state why the passing out of faeces is not an example of it.

Accepted Answer

B1 excretion is the removal from the body of the waste products of metabolism, such as carbon dioxide and urea B1 faeces consist of undigested food, bacteria and dead gut lining, which are not products of the body's own metabolism, so passing them out is egestion

Question 15

State where carbon dioxide is excreted from the body, and state what happens to blood pH if carbon dioxide is allowed to accumulate.

Accepted Answer

B1 carbon dioxide is excreted at the alveoli of the lungs B1 excess carbon dioxide forms carbonic acid in the blood, so the blood pH falls