Chapter 17: Energy for biological processes

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17.1 Energy cycles

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15.2 Thermoregulation in ectotherms

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15.3 Thermoregulation in endotherms

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15.4 Excretion, homeostasis, and the liver

The liver has a crucial role in metabolism of proteins and the storage and detoxification of hormones and ingested or absorbed poisons (ke alcohol). The most important aspects of protein metabolism in the liver are deamination and transamination of amino acids, removal of ammonia from the body by producing urea, and synthesis of non-essential amino acids.Its other roles in metabolism include the regulation of glycogen storage, decomposition of red blood cells and the production of hormones. Estimates of the livers total number of functions vary, but textbooks generally cite it being around 500. Lobules are collection of hepatocytes (liver cells).

Histology of the liver

The liver is connected to the rest of the body through four transporting vessels:

Hepatic artery: supplies the liver with oxygenated blood from the heart

Hepatic vein: carries deoxygenated blood away from the liver

Hepatic portal vein: brings blood rich in products of digestion from the dodenum (first part of the small instestine) and ingested harmful substances can be removed or broken down straight away.

Bile duct: takes bile that is produced by the liver to the gall bladder to be stored.

Branches of the bile duct, hepatic artery and hepatic portal vein form the portal track/triad.

The liver is a reddish brown organ that makes up about 5% of the total body mass making it the largest internal organ of the body. It lies just below the diaphragm and is made up of several lobes. The liver is very fast growing and damaged areas generally regenerate very quickly.

The liver has a very rich blood supply, oxygenated blood is supplied to the liver by the hepatic artery and removed from the liver and returned to the heart in the hepatic vein. The liver is also supplied with blood by a second vessel, the hepatic portal vein. This carries blood loaded with the products of digestion straight from the intestines to the liver and this is the starting point for many metabolic activities of the liver. Up to 75% of the blood flowing through the liver comes via the hepatic portal vein.

The structure of the liver

The liver carries out many different complex functions but the cells are surprisingly simple and uniform in appearance. Hepatocytes (liver cells) have large nuclei. prominent Golgi apparatus, and lots of mitochondria. indicating that they are metabolically active cells (Figure I). They divide and replicate - even if around 65% of the liver is lost, it will regenerate in a matter of months.

Excretion in mammals

The main metabolic waste products in mammals are:

Carbon dioxide: one or the waste products of cellular respiration which is excreted from the lungs.

Bile pigments: formed from the breakdown of haemoglobin from old red blood cells in the liver. They are excreted in the bile from the liver into the small intestine via the gall bladder and bile duct. They colour the faeces.

Nitrogenous waste products (urea): formed from the breakdown of excess amino acids by the liver. All mammals produce urea as their nitrogenous waste. Fish produce ammonia while birds and insects produce uric acid. Urea is excreted by the kidneys in the urine.

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15.5 The structure and function of the mammalian kidney

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15.6 The kidney and osmoregulation

https://www.abpischools.org.uk/topic/homeostasis-kidneys/6

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15.7 Urine and diagnosis

Urine and pregnancy testing

The human embryo implants in the uterus, around six days after conception. The site of the developing placenta then begins to produce a chemical called human chorionic gonadotrophin (hCG). Some of this hormone is found in the blood and the urine of the mother. Until the 1960s, the most reliable available pregnancy test was to inject the urine from a pregnant woman into an African clawed toad (Xenopus laevis). If she was pregnant, the hCG triggered egg production in the wad within 8-12 hours of the injection. It could not be used until the woman was several weeks pregnant.

Modern pregnancy tests still test for hCG in the urine, but they rely on monoclonal antibodies. Some are so sensitive that pregnancy can be detected within hours of implantation.

Making monoclonal antibodies

Monoclonal antibodies are antibodies from a single clone of cells that are produced to target particular cells or chemicals in the body.

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 done of millions

of 'living factories' making the desired antibody. These monoclonal antibodies are collected, purified and used in a variety of ways.

These are the main stages in a pregnancy test:

the wick is soaked in the first urine passed in the morning- this will have the highest levels of hCG.

The test contains mobile monoclonal antibodies that have very 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 a hCG/antibody complex (complete with coloured bead).

The urine carries on along the test structure until it reaches a window.

Here there are immobilised monoclonal antibodies arranged in a line or a pattern such as a positive (+) sign that only bind to the hCG/antibody complex. if the woman is pregnant, a coloured line or pattern appears in the first window.

The urine continues up through the test to a second window.

Here 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 simply indicates thai 1he Lest is working

Urine and anabolic steroids

Some athletes have tried to cheat in competitions by using anabolic steroids. Anabolic steroids are drugs that mimic the action of the male sex hormone testosterone and they stimulate the growth of muscles. They are,sz however, excreted in the urine. By testing the urine using gas chromatography and mass spectrometry, scientists can show that an individual has been using these drugs. which are banned in all sports. The urine sample is vaporised with a known solvent and passed along a wbe. The lining of the tube absorbs the gases and is analysed to give a chromatogram that can be read to show the presence of the drugs.

Urine and drug testing

Urine is tested for tlhc presence of many different drugs, inducting alcohol. Because drugs or metabolites - the breakdown products of drugs- are filtered through the kidneys and stored in the bladder, iL is possible to find drug traces in the mine some time after a drug has been used.

If someone is suspected of having taken an illegal drug, they may be asked to provide a urine sample and this will be divided into two. The first sample may be tested by an immunoassay, using monoclonal antibodies to bind to the drug or its breakdown product. If this shows positive, the second sample may be run through a gas chromatograph/ mass spectrometer to confirm the presence of the drug.

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15.8 Kidney failiure

There are a number of reasons why the kidneys may fail. They include kidney infections, where the structure of the podocytes and the tubules themselves may be damaged or destroyed; raised blood pressure that can damage the structure of the epithelial cells and basement membrane of the Bowman's capsule; and genetic conditions such as polycystic kidney disease where the healthy kidney tissue is replaced by fluid-filled cysts or damaged by pressure from cysts.

lf the kidneys are infected or affected by high blood pressure this may cause:

Protein in the urine- if the basement membrane or podocytes of the Bowman's capsule are damaged, they no longer aa as filters and large plasma proteins can pass into the filtrate and are passed out in the urine.

Blood in the urine- another symptom that the filtering process is no longer working.

If the kidneys fail completely, the concentrations of urea and mineral ions build up in the body. The effects include:

Loss of electrolyte balance- if the kidneys fail, the body cannot excrete excess sodium, potassium, and chloride ions. This causes osmotic imbalances in the tissues and eventual death.

Build-up of toxic urea in the blood - if the kidneys fail the body cannot get rid of urea and it can poison the cells.

High blood pressure - the kidneys play an important role in controlling the blood pressure by maintaining the water balance of the blood. If the kidneys fail, the blood pressure increases

and this can cause a range of health problems including heart problems and strokes.

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 the production of a hormone called erythropoietin that stimulates the formation of red blood cells. When the kidneys fail it can reduce the production of red blood cells causing tiredness and lethargy.

Measuring glomerular filtration rate

Kidney problems almost always affect the rate at which blood is filtered in the Bowman's car sules of the nephrons. The glomerular filtration rate (GFR) is widely used as a measure to indicate kidney disease. The rate of filtration is not measured directly- a simple

blood test measures the level of creatinine in the blood. Creatinine is a breakdown product of muscles and it is used to give an estimated glomerular filtration rate (eGFR). The units arc cm 3/ min. If the levels of creatinine in the blood go up. it is a signal that the kidneys arc not working properly. Certain factors need to be taken into account in the calculations to work out GFR. For example, GFR decreases steadily with age even if you arc healthy, and men usually have more muscle mass and therefore more creatinine than women.

Hemodialysis and peritoneal dialysis are not perfect. They do some of the work of the kidney, but it is not as good as a real kidney. So people who need dialysis are not as healthy. They must take medicines. For example, in kidney failure, the kidneys do not make any erythropoetin. Doctors have to give people erythropoetin so they make enough red blood cells.

Haemodialysis

This involves the use of a dialysis machine. It is usually carried out in hospital although sometimes patients will have a machine in their own home. Blood leaves the patient's body from an artery and flows into the dialysis machine, where it flows between partially permeable dialysis membranes. These membranes mimic the basement membrane of the Bowman's capsule. On the other side of the membranes is the dialysis fluid. During dialysis it is vital that patients lose the excess urea and mineral ions that have built up in the blood. It is equally important that they do not lose useful substances such as glucose and some mineral ions.

The loss of these is prevented by careful control of the dialysis fluid. It contains normal plasma levels of glucose to ensure there is no net movement of glucose out of the blood. The dialysis fluid also contains normal plasma levels of mineral ions, so any excess mineral ions in the blood move out by diffusion down a concentration gradient into the dialysis fluid, thus restoring the correct electrolyte balance of the blood. The dialysis fluid contains no urea meaning there is a very steep concentration gradient from the blood to the fluid, and as a result, much of the urea leaves the blood. The blood and the dialysis fluid flow in opposite directions to maintain a countercurrent exchange system and maximise the exchange that takes place.

The whole process of dialysis depends on diffusion clown concentration gradients- there is no active transport. Dialysis takes about eight hours and has to be repeated regularly. Patients with kidney failure who rely on haemodialysis have to remain attached to a dialysis machine several times a week for many hours. They also need to manage their diets carefully, eating relatively lillie protein and salt and monitoring their fluid intake to keep their blood chemistry as stable as possible. The only time they can cat and drink what they like is at the beginning of the dialysis process.

Peritoneal dialysis

Peritoneal dialysis is done inside the body- it makes use of the natural dialysis membranes formed by the lining of the abdomen, that is. the peritoneum. It is usually done at home and the patient can carry on with their normal life while it takes place. Before treatment starts, a cut (incision) is made near your belly button and a thin tube called a catheter is inserted through the incision and into the space inside your abdomen (the peritoneal cavity). This is left in place permanently. The dialysis fluid is introduced into the abdomen 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 nuid, and out across the peritoneal membrane into the dialysis fluid. The fluid is then drained off and discarded, leaving the blood balanced aga in and the urea and excess minerals removed.

Complications may include infections within the abdomen, hernias, high blood sugar, bleeding in the abdomen, and blockage of the catheter. Use is not possible in those with significant prior abdominal surgery or inflammatory bowel disease. It requires some degree of technical skill to be done properly.

Kidney transplants

Long-term dialysis has some serious side effects. The best solution for the patient is a kidney transplant, where a single healthy kidney from a donor is placed within the body. The blood vessels arc joined and the ureter of the new kidney is inserted imo the bladder. If the transplant is successful the kidney will function normally for many years.

The main problem with transplanted organs is 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. There are a number of ways of reducing the risk of rejection. The match between the antigens of the donor and the recipient is made as close as possible. For example, a donor kidney can be used with a 'tissue type' very similar to the recipient (from people with the same blood group).

The recipient is given drugs to suppress their immune response (immunosuppressant drugs) for the rest of their lives. This helps to prevent the rejection of their new organ. immunosuppressant drugs are improving all the time and the need for a really close tissue match is becoming less important. The disadvantage of taking immunosuppressant drugs is that they prevent the patients from responding effectively to infectious diseases. They have to take great care if they become ill in any way. However. most people feel this is a small price to pay for a new, functioning kidney.

Transplanted organs don't last forever with the average transplanted kidney functioning for around 9- 10 years, although some have continued working for around 50 years. Once the organ starts to fail the patient has to rerum to dialysis and wait until another suitable kidney is found.

Transplants Vs dialysis

Dialysis is much more readily available than donor organs, so it is there whenever kidneys fail. It enables the paticm 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 damage to the body.

If a patient receives a kidney transplant they are free from the restrictions which come with regular dialysis sessions and dietary monitoring. This is generally the ideal scenario for patients waiting for a transplant. The main source of donor kidneys is from people who die suddenly, often from road accidents, strokes, and heart attacks. In the UK, organs can be taken from people if they carry an organ donor card or arc on the online donor register. Alternatively, a relative of someone who has died suddenly can give their consent.

Unfortunately for people needing a transplant, there is a shortage of donor kidneys. Many people do not register as donors. In addition, as cars become safer, fewer people die suddenly in traffic accidents. Whilst good. this means there arc fewer potential donors. At any one time there arc thousands of people undergoing kidney dialysis. Most will not have the opportunity to have a kidney transplant. In 2013-14, 3257 people in the UK had kidney transplants. However, there were still around 6000 people on dialysis waiting for a kidney. There arc increasing numbers of live donor transplants. where a family member of someone with a tissue match donates a kidney. In 2013-14. 2143 people received kidneys from donors who had died, and 1114 were from living donors. In 2011, scientists grew functioning embryonic kidney tissue from stem cells. Going forward, the hope is that whole new kidneys can be grown perhaps even without the antigens which trigger the immune reaction so that patients don't need to take immunosuppressant drugs.