15.4-15.8 Excretion, liver and kidney

Question 1

What are some reasons that kidneys fail?

Answer 1

-Kidney infections; structure of the podocytes and tubules themselves may be damaged or destroyed.
- High blood pressure; damage structures of epithelial cells and basement membrane of Bowman’s capsule
- genetic conditions e.g. polycystic kidney disease where the healthy kidney tissue is replaced by fluid filled cysts, or damaged by the pressure from the cysts.

Question 2

What happens if the kidneys are infected or affected by high blood pressure?

Answer 2

• Protein in the urine; basement membrane or podocytes of the Bowman’s capsule are damaged, they can no longer act as filters and large plasma proteins can pass into the filtrate and are passed out as urine
• Blood in the urine; another symptom that the filtering process is no longer working.

Question 3

What happens when the kidneys completely fail?

Answer 3

• Loss of electrolyte balance- body can’t excrete excess Na, K and Cl ions. Causes osmotic imbalances in tissues and eventual death
• Build up of toxic urea in the blood; if the kidneys fail, the body can’t get rid of urea and it can poison cells.
• High BP; kidneys help control BP by maintaining water balance of the blood.
• Weakened bones as the calcium/ phosphorus balance in the blood is lost
• Pain and stiffness in joints as abnormal proteins build up in the blood
• Anaemia; the kidneys are involved in production of erythropoietin that stimulates the formation of RBCs. This means that failure can reduce production of RBCs causing tiredness and lethargy.

Question 4

How is GFR measured?

Answer 4

The rate isn’t measured directly, a blood test is used to measure the level of creatinine in the blood. Creatinine is a breakdown product of muscles and it is used to give an estimated GFR. If the levels of creatinine go up, kidneys aren’t working properly.

Question 5

How is haemodialysis carried out?

Answer 5

Blood leaves the patients body from an artery and flows into the dialysis machine where it flows between a partially permeable dialysis membrane. These membranes mimic the basement membrane of the Bowman’s capsule. On the other side of the membranes is the dialysis fluid. During dialysis urea and excess mineral ions are removed, however they can’t lose useful substances like glucose and some mineral ions. This is controlled by monitoring of dialysis fluid. It contains normal plasma levels of glucose to ensure there is no net movement of glucose out of the blood. Whole process of dialysis relies on diffusion down a conc. gradient.

Question 6

What is peritoneal dialysis?

Answer 6

Its dialysis done inside the body. It makes use of the natural dialysis membranes formed by the lining of the abdomen, the peritoneum.
- Usually done at home and patient can carry on normal life whilst it is happening.
- The dialysis fluid is introduced into the body using a catheter. It is left for several hours for dialysis to take place across the peritoneal membranes, so that urea and excess mineral ions pass out of the blood capillaries, into the tissue fluid, and out across the peritoneal membrane into the dialysis fluid.
- The fluid is them drained off and discarded, leaving the blood balanced again and excess urea and excess minerals are removed.

Question 7

What is the main problem with treating kidney failure with a transplant?

Answer 7

The risk of rejection.
- The antigens on the donor organ differ from the antigens on the cells of the recipient and the immune system is likely to recognise this. This can result in rejection and the destruction of the new kidney.

Question 8

How can the risks of kidney transplants be reduced?

Answer 8

• The match between antigens of the donor and the recipient are made as close as possible.
• The recipient is given drugs to supress their immune response for the rest of their lives. Helps prevent rejection. However they prevent the patient from responding effectively to infectious diseases.

Question 9

What are the pros and cons of dialysis vs kidney transplant?

Answer 9

Dialysis is much more readily available than donor organs so it is there whenever kidneys fail. It enables patients to lead a relatively normal life. However, patients have to monitor their diet carefully and need regular sessions on the machine. Long term dialysis is much more expensive than a transplant and can eventually cause dame to the body.
If a patient receives a kidney transplant, they are free from the restrictions that come with regular dialysis session and dietary monitoring. This is generally the ideal scenario for patients waiting for a transplant.
There is a shortage of kidneys. Many people don’t sign up to be a donor and there are less road accidents that are fatal.

Question 10

What are the ways that blood enters and leaves the liver?

Answer 10

Enters;
- Hepatic artery
- Hepatic portal vein- carries blood containing products of digestion straight from the intestines to the liver, it is the starting point for many metabolic activities in the liver

Leaves;
- Hepatic vein.

Question 11

What are the key features of hepatocytes (liver cells)?

Answer 11

Have a large nuclei, prominent Golgi apparatus and lots of mitochondria as they are metabolically active cells. They secrete bile from the breakdown of the blood into spaces called canaliculi.

Question 12

What are sinusoids and why are they important?

Answer 12

The blood from the hepatic artery and the hepatic portal vein is mixed up in spaces called sinusoids which are surrounded by hepatocytes. This increases the oxygen content of the blood from the hepatic portal vein, supplying the hepatocytes with enough oxygen for thein needs.
Sinusoids contain Kupffer cells which act as the macrophages of the liver, ingesting foreign particles and helping to protect against disease.

Question 13

What are the main functions of the liver?

Answer 13

Carbohydrate metabolism
Deamination of excess amino acids
Detoxification

Question 14

How does the liver metabolise carbohydrates?

Answer 14

Hepatocytes are closely involved in the homeostasis of control of glucose levels in the blood by their interaction with insulin and glucagon.
Blood glucose levels rise, insulin levels rise and stimulate hepatocytes to convert glucose to glycogen.
Blood glucose levels fall, glucagon triggers hepatocytes to convert the glycogen back into glucose.

Question 15

What is transamination and what is the importance of this?

Answer 15

Its the conversion from one amino acid into another.
Its important as the diet doesn’t always contain the required amino acids, but transamination can overcome the problems that this might cause.

Question 16

What is deamination and why is it important?

Answer 16

It is the removal of an amine group from a molecule. The body cant store either proteins or amino acids. Any excess protein would be excreted and therefore wasted if it weren’t for hepatocytes.

Question 17

Explain the process of deamination.

Answer 17

Hepatocytes deaminate the amino acids, removing the amino group, and converting it into ammonia which is very toxic, and then into urea.
Urea is toxic in high concentrations but not in concentrations normally found in the blood. Urea is excreted by the kidneys.
The remainder of the amino acid can then be fed into cellular respiration or converted into lipids for storage.

Question 18

What is the ornithine cycle?

Answer 18

The ammonia produced in the deamination of proteins is converted into urea in a set of enzyme-controlled reactions- the ornithine cycle. NH3 is combined with ornithine, using CO2 and producing water and citruline. Citruline is the combined with more ammonia to produce arginine and water. Arginine is then combined with water to produce urea and more ornithine.

Question 19

How do hepatocytes break down hydrogen peroxide?

Answer 19

Hydrogen peroxide is a by-product of various metabolic pathways in the body. Hepatocytes contain the enzyme catalase which splits the hydrogen peroxide into water and oxygen.

Question 20

How does the liver detoxify ethanol?

Answer 20

Hepatocytes contain the enzyme alcohol dehydrogenase that breaks down the ethanol into ethanal. Ethanal is then converted to ethanoate which may be used to build up fatty acids or used in cellular respiration.

Question 21

What is the structure of the kidney?

Answer 21

• The cortex is the dark outer layer. This is where the filtering of the blood takes place and it has a very dense capillary network carrying the blood from the renal artery to the nephrons.
• The medulla is lighter in colour than the cortex. It contains the tubules of the nephrons that form the pyramids of the kidney and the collecting ducts.
• The pelvis of the kidney is the central chamber where urine collects before passing out down the ureter.

Question 22

What are the main structures within a nephron?

Answer 22

• Bowman’s capsule
• Proximal convoluted tubule
• Loop of Henle
• Distal convoluted tubule
• Collecting duct.

Question 23

What is the proximal convoluted tubule?

Answer 23

Its the first coiled region of the tubule after the Bowman’s capsule, it is found in the cortex of the kidney. It is where many of the substances needed by the body are reabsorbed into the blood.

Question 24

What is the loop of henle?

Answer 24

Its a very long tubule that creates a region with a very high solute concentration in the tissue fluid deep in the kidney medulla. The descending loop runs down from the cortex through the medulla to a hairpin bend at the bottom of the loop. The ascending limb travels back up through the medulla to the cortex.

Question 25

What is the distal convoluted tubule?

Answer 25

Its where the fine-tuning of the water balance of the body takes place. The permeability of the walls to water varies in response to the levels of the ADH in the blood. Further regulation of the ion balance and the pH of the blood also takes place in this tubule.

Question 26

What is the collecting duct? What happens here?

Answer 26

The urine passes down the collecting duct through the medulla to the pelvis. More fine-tuning of the water balance takes place, the walls of this tubule are also sensitive to ADH.

Question 27

Explain the process of ultrafiltration.

Answer 27

The glomerulus is supplied with blood by a relatively wide afferent arteriole from the renal artery. The blood leaves through a narrower efferent arteriole and as a result, there is a high pressure in the capillaries of the glomerulus. This forces the blood out through the capillary wall- it acts like a sieve.
- The fluid then passes through the basement membrane. It is made up of a network of collagen fibres and other proteins that make up a second sieve. Most plasma contents can pass through the basement membrane but the blood cells and many proteins are retained in the capillary due to their size.

Question 28

What role do podocytes play in ultrafiltration?

Answer 28

They have extensions called pedicels that wrap around the capillaries, forming slits that make sure any cell, platelets or large plasma proteins that have manages to get through the epithelial cells and the basement membrane don’t get through into the tubule itself.
The filtrate which enters the capsule contains glucose, salt, urea and many other substances in the same concs that they were in the blood plasma.

Question 29

What role does the proximal convoluted tubule play in reabsorption?

Answer 29

• All the glucose, amino acids, vitamins and hormones are moved from the filtrate back into the blood by active transport. About 80% of the NaCl and water is reabsorbed as well- the sodium ions are moved by active transport while the Cl ions and water follow passively down conc. gradients.
• It is covered in microvilli, greatly increasing the SA over which substances can be reabsorbed
• They have many mitochondria to provide the ATP needed in active transport systems.
• The filtrate reaching the loop of Henle at the end of the proximal convoluted tubule is isotonic with the tissue fluid surrounding the tubule and isotonic with the blood.

Question 30

What role does the descending limb of the loop of Henle play in reabsorption?

Answer 30

• It leads from the PCT. This is the region where water moves ot of the filtrate down a conc gradient. The upper part is impermeable to water but the lower part of the descending limb is, and runs down into the medulla.
• The conc of sodium and chloride ions in the tissue fluid of the medulla gets higher moving through from the cortex to the pyramids, as a result of the activity of the ascending limb of the loop of Henle.
• The filtrate entering the descending limb is isotonic with the blood. As it travels down the limb, water passes out of the loop into the tissue fluid by osmosis. It then moves down a conc gradient into the blood of the surrounding capillaries.
• It isn’t permeable to Na and Cl ions, so no active transport takes place. The fluid that reaches the hairpin is very concentrated and hypertonic to the blood in the capillaries.

Question 31

What is the role of the ascending loop of Henle in reabsorption?

Answer 31

• First section is very permeable to sodium and chloride ions and they move out of the concentrated solution by diffusion down a conc gradient.
• In the second section, Na and Cl ions are actively pumped out into the medulla tissue fluid against a conc gradient. It is impermeable to water, sow water cannot follow the chloride and sodium ions down an conc gradient. It means that the ascending limb becomes increasingly dilute, while the tissue fluid of the medulla develops a very high conc of ions essential for the kidney to produce urine that is more conc than the blood.

Question 32

What is the role of the distal convoluted tubule in reabsorption?

Answer 32

• The cells lining the DCT have many mitochondria so they are adapted to carry out active transport.
• If the body lacks salt, sodium ions will be actively transported out of the DCT with chloride ions following down an electrochemical gradient.
• Water can also leave, concentrating the urine, if the walls of the tubule are permeable in response to ADH.
• It also plays a role in balancing the pH of the blood.

Question 33

What is the role of the collecting duct in reabsorption?

Answer 33

• It passes down through the conc tissue fluid of the renal medulla. This is the main site where the conc and volume of the urine produced is determined. Water moves out of the collecting duct by diffusion as it passes through the renal medulla.
• As a result, the urine becomes more concentrated. The level of sodium ions in the surrounding fluid increases through the medulla from the cortex to the pelvis. This means water can be removed from the collecting duct all the way along it’s length, producing a very hypertonic urine when the body needs to conserve water.
• The permeability of the collecting duct to water is controlled by the level of ADH.

Question 34

Explain the mechanism of ADH action.

Answer 34

• Released from the pituitary gland and carried in the blood.
• It can’t cross the membrane of the tubule cells- it binds to the receptors on the cell membrane and triggers the formation of cAMP. The cAMP causes a cascade of events;
• Vesicles in the cell lining of the collecting duct fuse with the cell surface membranes on the side of the cell in contact with the tissue fluid of the medulla.
• The membranes of these vesicles contain protein-based water channels (aquaporins) and when they are inserted into the cell surface membrane, they make it permeable to water.
  This provides a route for water to move out of the tubule cells into the tissue fluid of the medulla and the blood capillaries by osmosis.

Question 35

What happens when ADH levels fall?

Answer 35

Levels of cAMP fall, then the water channels are removed from the tubule cell membranes and enclosed in vesicles again. The collecting duct becomes impermeable to water once more. This results in the production of large amounts of dilute urine and maintains the water potential of the blood and tissue fluid.

Question 36

Explain the negative feedback control mechanism that takes place when water is in short supply.

Answer 36

The concentration of inorganic ions in the blood rises and the water potential of the blood and tissue fluid becomes more negative. This is detected by the osmoreceptors in the hypothalamus. They send nerve impulses to the posterior pituitary which in turn releases stored ADH into the blood. The ADH is picked up by receptors in the cells of the collecting duct and increases the permeability of the tubules to water. Water leaves the filtrate in the tubules and it passes into the blood in the surrounding capillary network.

Question 37

Explain the negative feedback control mechanism that takes place when water is in excess supply.

Answer 37

When large amounts of liquid are taken in, the blood becomes more dilute and its water potential becomes less negative. The change is detected by the osmoreceptors of the hypothalamus. Nerve impulses to the posterior pituitary are reduced or stopped and so the release of ADH is inhibited. Very little reabsorption of water can take place because the walls of the collecting duct remain impermeable to water. In this way, the conc of blood is maintained.

Question 38

How are monoclonal antibodies made for pregnancy testing?

Answer 38

• A mouse is injected with hCG so it makes the appropriate antibody.
• The B-cells that make the required antibody are then removed from the spleen of the mouse, and fused with a myeloma, a type of cancer cell which divides very rapidly. This new fused cell is known as a hybridoma.
• Each hybridoma reproduces rapidly, resulting in a clone of millions of ‘living factories’ making the desired antibody. These monoclonal antibodies are collected, purified and used in a variety of ways.

Question 39

What are the main stages in how a pregnancy test works?

Answer 39

1. The wick is soaked with urine first passed in the morning, it will have the highest levels of hCG.
2. Test contains mobile monoclonal antibodies that have small coloured beads attached to them. They will only bind to hCG. If the woman is pregnant, the hCG in her urine binds to the mobile monoclonal antibodies and forms an hCG-antibody complex.
   - urine carries along test structure.
   - Reaches immobilised monoclonal antibodies arranged in a line or pattern that only bind to the hCG-antibody complex. If the woman is pregnant, a coloured line appears in the first window.
   - After, there is usually a line of immobilised monoclonal antibodies that bind only to the mobile antibodies regardless of whether they are bound to hCG or not. This coloured line forms regardless of whether the woman is pregnant. It indicates the test is working.

Question 40

How are the tests for anabolic steroids carried out?

Answer 40

By testing the urine using gas chromatography and mass spec, scientists can show that an individual has been using drugs. The urine sample is vaporised with a known solvent and passes along a tube. The lining of the tube absorbs the gases and is analysed to give a chromatogram that can be read to show the presence of drugs.

Question 41

How can urine be used to test for drugs other than anabolic steroids?

Answer 41

Urine is tested for the presence of many different drugs, including alcohol. Because drugs or metabolites are filtered through the kidney and stored in the bladder, it is possible to find drug traces in the urine some time after the drug has been used.
The sample is split into 2, one tested by an immunoassay, using monoclonal antibodies to bind to the drug or its breakdown product. If it shows as positive, the second sample may be run through a gas chromatogram/ mass spec to confirm the presence of the drug.