Excretion (continued)

Acetate combines with Coenzyme A to form acetyl CoA which then enters the Krebs cycle. Oxidised NAD is needed to oxidise fatty acids. Too much alcohol means insufficient oxidised NAD so fatty acids accumulate in hepatocytes. This is called fatty liver and it severely reduces the ability of hepatocytes to carry out their functions. This can also lead to alcohol-related hepatitis (inflammation) and cirrhosis (hardening) The liver breaks down other products of the metabolism such as hydrogen peroxide. It breaks down hormones, preventing them having an effect for too long. The liver also detoxifies certain drugs. The concentration of amino acids, hormones and glucose all build up in the blood if the liver is damaged.

Location of the kidneys

Longitudinal section of the kidney

Each kidney is made up of one million tiny tubules called nephrons. Each nephron starts in the cortex with a knot of capillaries called the glomerulus. Ultrafiltration takes place in the glomerulus. The glomerulus is surrounded by a cup-shaped structure called the Bowmans capsule which collects the filtered substances. There are two main stages of urine formation ultrafiltration and selective reabsorption.

Ultrafiltration
Ultrafiltration requires no ATP and is a passive process. When all substances with a smaller molecular mass than plasma proteins are removed from the blood and the glomerular filtrate is formed. The glomerulus is supplied with blood from the afferent arteriole. The efferent arteriole takes blood away from the glomerulus and is narrower than the afferent arteriole. This narrowing causes very high pressure in the glomerulus. The hydrostatic pressure of the blood forces water and solutes out of the capillaries and through the basement membrane into the Bowmans capsule. There are three layers between the blood and the lumen of the Bowmans capsule. First is the endothelium of the capillaries has small pores between cells through which water and solutes can pass. Secondly, the basement membrane determines what gets out of the blood and what doesnt. It consists of a mesh of collagen fibres and glycoproteins. The basement membrane is the filtration surfaces and allows small enough substances to be filtered out of the blood. Most proteins and all the blood cells are too large to pass through them. Lastly, the epithelial cells of the Bowmans capsule are called podocytes and are highly specialised. The podocytes have long, finger-like extensions of the cytoplasm called pedicels which wrap around the capillaries. The filtrate passes through the narrow slit-pores between the pedicels and into the Bowmans capsule. The substances filtered out of the blood are water, amino acids, glucose, ions and urea. The substances that remain in the blood are proteins, blood cells (red blood cells in particular) The filtrate passes through pores on the endothelium of the capillaries, through pores in the basement membrane and then between the pedicels of the podocytes The plasma proteins in the blood create an osmotic pressure (low water potential) which prevents all of the water leaving the blood because some will immediately diffuse back in down the water potential gradient.

Selective Reabsorption
Ultrafiltration is non-selective but reabsorption involves some selection. Reabsorption can be passive or active depending on the substance. The Proximal Convoluted Tubule (PCT) is in the cortex and is surrounded by capillaries. About 90% of the filtrate is reabsorbed here. Most of the water is reabsorbed into the blood by osmosis. Most of the salts are reabsorbed by active transport. All of the glucose and the amino acids are reabsorbed by a special kind of facilitated diffusion. (sodium co-transport) The epithelial cells in the lining of the PCT are adapted for reabsorption: They are cuboidal. The cell surface membrane on the filtrate side is highly folded into microvilli to increase the surface are for reabsorption. It contains co-transporter proteins which transport sodium ions (with glucose) and amino acids into the cell by facilitated diffusion. The opposite membrane on the capillary side is also highly folded to increase its surface area and contains sodium-potassium pumps. The cytoplasm contains many mitochondria to produce ATP for active transport. The cells have tight junctions which force substances to enter the cell through the cell surface membrane. This allows reabsorption to be selective.

How reabsorption takes place 1. Sodium-potassium pumps actively transport sodium ions from the epithelial cells lining tubule.

2. Sodium ions diffuse down their concentration gradient from the filtrate into the epithelial cells by facilitated diffusion. At the same time the same carrier protein cotransports glucose or amino acids. 3. Sodium ions, glucose and amino acids then diffuse down their concentration gradients out of the opposite side of the cell into the blood. 4. The water potential of the filtrate rises as that of the capillaries falls so water is reabsorbed by osmosis, down the water potential gradient into the blood.

Carrier protein

Sodium- potassium pump

The Loop of Henle

The Loop of Henle acts as a counter current multiplier. This means the fluid in each limb runs in opposite directions and that increases the conc of the urine. The counter current multiplier allows us to produce urine that is more conc than the blood. This helps to conserve water. The longer the Loop of Henle the more conc the urine will be. Animals living in an arid climate have a longer Loop of Henle e.g. camels and the kangaroo rat. Animals living in a freshwater climate have a shorter Loop of Henle e.g. beaver. The descending limb is permeable to water but the ascending limb is not, especially in the upper part. 1. Sodium and chloride ions are actively transported out of the upper part of the ascending limb.

2. A high salt conc builds up in the tissues of the medulla leading to a low water potential. 3. Water is drawn out of the descending limb (which is permeable to water) by osmosis down the water potential gradient but it passes immediately into the capillaries as the plasma proteins create a low water potential in the blood. 4. As the filtrate passes down the descending limb it becomes more and more conc. The longer the limb, the more water moves out, so the more conc the fluid will be. 5. As the filtrate moves up the ascending limb it becomes less conc as ions diffuse out of the lower part and are then actively pumped out of the upper part. 6. Water is drawn out of the filtrate in the collecting duct by the low water potential (high solute conc) in the medulla. 7. The urine becomes more and more conc.

Medulla

Urine is hypertonic

Filtrate becomes more and more conc Hypertonic: conc of filtrate is more than the blood. as water moves out. 4 Hypotonic: concisof filtrate is less than the blood. Filtrate hypotonic.

In the Distal Convoluted Tubule (DCT) sodium ions are actively pumped out and potassium ions pumped in

Osmoregulation
Osmoregulation is the maintaining of bloody fluids at the correct concentrations by controlling water and solute concentrations and is an example of negative feedback. The body can gain water by drinking water, eating food and respiring fats (metabolic water) The body can lose water through sweat, urine, breathing and egestion. Osmoregulation involves a hormone called ADH. ADH is produced by the pituitary gland. Osmoreceptors in the hypothalamus detect changes in the water potential of the blood. If the water potential falls (high conc of ions) there is a need to conserve as much water as possible so as little as possible must be lost in the urine. The fall in water potential is detected by the osmoreceptors. They respond by stimulating neurosecretory cells to release ADH. ADH flows down the axons of the neurosecretory cells to the terminal bulbs (synaptic knob) in the posterior pituitary gland from which it is secreted into the blood. ADH travels in the plasma to the kidney where it acts on its target cell membranes in the walls of the collecting duct. The target cells have receptors which are complementary in shape to the ADH. ADH causes aquaporins (groups of protein molecules) to insert themselves into the cell surface membrane of the cells lining the collecting duct. It acts as a channel for water to pass through. This allows more water to leave the filtrate and pass out of the collecting duct to be reabsorbed into the bloodstream. This results in a small quantity of concentrated urine. It is important that ADH is quickly broken down so it does not have a permanent effect on the walls of the collecting duct. When a large quantity of water is drunk: The increase in the water potential of the blood is detected by osmoreceptors in the hypothalamus. They respond by secreting less ADH. Less ADH flows down the axons. Aquaporins move back into the cytoplasm. The collecting duct walls become less permeable. More water is left in the collecting duct. Large quantities of dilute urine are produced.

Kidney failure
Kidney failure is a condition in which the kidneys stop working properly. Acute kidney failure may happen suddenly in the space of a few days. Chronic kidney failure may develop slowly over many years. The most common causes of kidney failure are diabetes, a kidney infection and heart failure. Other possible causes of kidney failure are inflammation of the glomerulus, a blood infection or problems after a surgery.

Kidney failure can lead to rapid death because there is a build-up of toxic waste products e.g. urea and there is an imbalance of ions and water in the blood In haemodialysis blood from the patients vein is passed through very small tubes made from a partially permeable membrane. Dialysis fluid flows along the other side of the membrane and has the water potential and conc of ions that the patients blood should have if there kidney were working properly. As their blood flows through the tubes, water, ions and glucose are able to diffuse freely through the membrane. Allowing the conc of each in the patients blood to become the same as the dialysis fluid. Blood cells, plasma proteins and antibodies are too large to pass through the membrane. Peritoneum is a layer of tissue lining the abdominal cavity. The cavity contains fluid which bathes the internal organs. In peritoneal dialysis a catheter is inserted into the cavity and dialysis fluid is passed through it, filling the cavity. It is left there for some time, allowing exchange between the fluid and the blood. The substances that will diffuse from the patients blood into the dialysis fluid are sodium ions, potassium ions, magnesium ions and urea. The fluid is then drained off. I takes about 30-45 mins for the fluid to be introduced to the abdomen, take up waste and then be drained. The dialysis fluid must contain glucose because of it did not then the glucose molecules inside the patients blood plasma would diffuse out of their blood. This would prevent them from respiring and making ATP. In most cases patients can walk around with the fluid inside them, though they do need to have fluid introduced and removed several times each day. The risk of infection for a kidney transplant is minimised by giving the patient immunosuppressant drugs which they have to take every day for the rest of their lives. The drugs suppress the effects of the immune system, so some patients are kept in isolation.

Advantages of haemodialysis More efficient than peritoneal dialysis at removing unwanted substances from the blood.

While connected to the machine the patient can indulge in food that he or she cannot usually eat e.g. foods high in sugar like chocolate

Disadvantages of haemodialysis It takes several hours and the patient has to be connected to a dialysis machine. This means that they cannot be mobile or carry on working while on dialysis Dialysis machine very expensive and in short supply. Treatment done intermittently so patient has to take great care over what they eat to avoid a large build-up of urea or other toxic substances.

Advantages of peritoneal dialysis Patient free from being connected to an immovable machine. Continuous process so no swings in blood

Disadvantages of peritoneal dialysis Has to be done more times than haemodialysis.

volume or content. This means they will feel well and eat a normal diet High risk of infection as pathogens can get in through the catheter. The bag can be uncomfortable. Not as efficient as haemodialysis in removing toxins from the blood.

Advantages of a kidney transplant Diet is less limited. Freedom from the dialysis machine. They will start to feel physically better. And have a better quality of life. They will no longer see themselves as chronically ill.

Disadvantages of a kidney transplant

There is a need for immunosuppressant drugs for the life of the kidney. There is a need for major surgery under a general anaesthetic Risks during the surgery e.g. infection or bleeding and damage to the surrounding organs Side effects from the anti-rejection drugs can cause fluid retention and high blood pressure. Immunosuppressant drugs increase susceptibility to infections There are ethical problems with poor people selling their kidneys for monetary gain. Kidney transplant is not a permanent solution.

Testing urine samples

Any molecules of a small molecular mass will be filtered out of the blood in the kidney. If they are not useful to the body they will not be reabsorbed so they will remain in the filtrate and will appear in the urine. Urine can therefore be used to detect pregnancy and also for the presence of illegal drugs such as anabolic steroids.

Pregnancy testing Pregnancy test use monoclonal antibodies to test for the hormone chronic gonadotrophin (hCG). hCH is a small glycoprotein secreted by the embryo following implantation. It can be detected in the urine as early as 6 days after conception. The testing sticks have three antibodies in them. 1. At the base of the strip is an antibody bound to a colour marker e.g. blue. This antibody-blue complex will bind to any hCG that is in the urine. 2. In the middle of the stick (in the Patient Test Result region) is an immobilised antibody that will bind to antibody-blue-hCG complexes that diffuses up the stick.

3. Near the top (in the Procedural Control region) is another antibody that will bind to any antibody-blue complexes that have not combined with hCG.

Patient Test Result region

Procedural Control region

The purpose of the control region is to make sure that the testing stick works and to show a person that they are not pregnant.

Anabolic Steroids They stimulate anabolic reactions in cell, particularly protein synthesis, resulting in the buildup of more cells in the muscle These are banned for non-medical use because they have dangerous side effects and give an unfair advantage to competitors. Anabolic steroids remain in the blood for some time and, since they are small molecules they are filtered out of the blood and reabsorbed They are detected by gas chromatography and mass spectrometry.