OCR UNIT F214 EXCRETION (3)

Specification:

1. Explain, using water potential terminology, the control of the water content of blood, with reference to the roles of the kidney, osmoreceptors in the hypothalamus and the posterior pituitary gland

2. Outline the problems that arise from kidney failure and discuss the use of renal dialysis and transplants for the treatment of kidney failure

3. Describe how urine samples can be used to test for pregnancy and detect misuse of anabolic steroids

The Loop of Henle

The wall of the Loop of Henle is one cell thick. The thinner and thicker regions of the Loop reflect the differences in the diameter of the lumen of the tubule, in different regions

Different Permeabilities of the Ascending and Descending Limbs to Water and Sodium and Chloride Ions

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MOLECULE or ION DESCENDING LIMB ASCENDING LIMB

Water Permeable Impermeable

Sodium ions Slightly permeable Permeable

Chloride ions Slightly permeable Permeable

Location of the Loops of Henle in the medulla

Remember that each nephron has a Loop of Henle and that each Loop of Henle is located in the medulla region of the kidney

If the kidney has approximately one million nephrons, there are approximately one million Loops of Henle located in the medulla

As shown in the diagram on page 1, the Loops of Henle are very close to the collecting ducts in the medulla

The medulla is a tissue consisting of cells bathed in tissue fluid

The vasa recta is the network of capillaries that lie adjacent to each Loop of Henle. These vasa recta capillaries are also U shaped and lie parallel to the limbs of the Loops of Henle

Processes occurring between the Loops of Henle and the Medulla

1. Descending Limb

The filtrate entering the top of the descending limb from the proximal convoluted tubule is isotonic to the blood plasma (same water potentials)

As the filtrate trickles down the descending limb, water leaves the filtrate, by osmosis, from a higher water potential (in the filtrate) to a lower water potential (in the medulla). The cell surface membranes of the cells making up the wall of the descending limb are permeable to water, since they have protein channels called aquaporins

The cell surface membranes of the cells of the descending limb wall are slightly permeable to Na+ and Cl- ions. This means that Na+ and Cl- ions slowly diffuse down a diffusion gradient, from the medulla (higher ion concentration) into the filtrate in the descending limb (lower ion concentration)

The net effect of water leaving the filtrate and ions diffusing into the filtrate is that the filtrate becomes more concentrated in terms of solute, as the filtrate moves down the descending limb. The filtrate

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becomes hypertonic to blood plasma (higher solute concentration/lower water potential)

2. Ascending Limb

The cell surface membranes of the cells making up the ascending limb wall are permeable to ions

In the lower, thinner region of the ascending limb, Na+ and Cl- ions diffuse out of the filtrate into the medulla, down a diffusion gradient, by facilitated diffusion

In the upper, thicker region of the ascending limb, Na+ and Cl- ions are actively pumped out of the filtrate into the medulla. This process requires ATP

The Loops of Henle make the medulla tissue very salty in terms of Na+ and Cl- ions. The tissue fluid surrounding the cells, therefore, has a very low water potential

Since the cell surface membranes of the cells forming the ascending limb wall are impermeable to water (no aquaporins), water cannot follow the ions from the filtrate into the medulla

By the time the filtrate has moved to the top of the ascending limb, the filtrate is hypotonic to blood plasma (the filtrate has a lower solute concentration)

Role of the Loop of Henle

The Loops of Henle make the medulla water potential much lower, by increasing the salt concentration in the medulla tissue

This means that the water potential of the medulla tissue surrounding the collecting ducts is lower than the filtrate flowing through the collecting ducts

The lower water potential of the medulla means that more water can be re-absorbed from the filtrate in the collecting ducts, by osmosis, if necessary

For terrestrial mammals, having Loops of Henle is very important for water conservation in the body. The urine produced is hypertonic to blood plasma and the water that is re-absorbed into the salty medulla, enters the vasa recta blood capillaries and is retained in the body

Examination tip: if you are asked to describe the role of the loop of Henle in an examination question, it might be useful to describe how the loop creates a lower water potential in the medulla ie describe the processes occurring in the ascending limb

Counter current Multiplier3

The descending limb and ascending limb arrangement of the Loop of Henle is called a hairpin countercurrent multiplier system

The two limbs are close together and the fluid flow in the two limbs is in opposite directions (countercurrent flow)

The changes that occur in the filtrate concentration as it moves down the descending limb and then up the ascending limb result in a lower water potential the medulla

The longer the Loop of Henle, the greater the countercurrent multiplier effect

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Osmoregulation

Definitions:

Osmoregulation is the control of the water potential of blood plasma and tissue fluid within narrow limits. Osmoregulation involves a negative feedback mechanism

This negative feedback control is where changes in blood plasma water potential are detected, resulting in a sequence of events that correct this change and return the plasma water potential to its normal value

Organs involved in Osmoregulation:

The hypothalamus (part of the forebrain) that detects changes in blood plasma water potential and produces antidiuretic hormone (ADH)

The posterior pituitary gland that stores and secretes ADH

The kidney, in particular the collecting ducts that respond to ADH concentration in blood plasma

Sequence of Events if Blood Plasma Water Potential Decreases

Blood plasma water potential would decrease during exercise as more water is lost from the body during increased sweating and increased ventilation

Exposing the body to hot conditions would also result in increased sweating

Decreased blood plasma water potential is detected by osmoreceptors in the hypothalamus. It is suggested that these osmoreceptors lose water if blood plasma water potential decreases below normal and shrink

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The hypothalamus also contains the thirst centre and initiates the feeling of thirst and the desire to drink

The shrinkage of osmoreceptors stimulates neurosecretory cells in the hypothalamus

These neurosecretory cells are specialised neurones that produce ADH in their cell bodies. They transport ADH down their axons to their terminal bulbs, located in the posterior pituitary gland. ADH is stored in these terminal bulbs

When the neurosecretory cells in the hypothalamus are stimulated, they transmit impulses down their axons to their terminal bulbs in the posterior pituitary gland

The posterior pituitary gland then secretes more ADH into the blood plasma

The ADH acts on the cells of the collecting duct walls (its target cells). Cells of the distal convoluted tubule are also target cells

ADH binds to ADH receptors on the cell surface membranes of the target cells in the collecting ducts. This can be seen in the diagram below. The ADH receptors are located on the basal and lateral plasma membranes of the target cells

ADH stimulates a sequence of enzyme controlled reactions in the target cells eg phosphorylase enzyme is activated

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The outcome is that more ADH causes the insertion of more aquaporins (water permeable channels) into the luminal cell surface membranes. This is also shown in the diagram below. There are different types of aquaporins but the one that responds to ADH is aquaporin 2. Note that the vesicles with aquaporins are guided to the luminal membrane by the cytoskeleton

The collecting duct cells become more permeable to water so that more water is re-absorbed, by osmosis, from the collecting duct filtrate into the medulla, and then into the blood plasma

The blood plasma water potential then increases, returning to a normal level

The urine becomes more concentrated and lower in volume

ADH is slowly broken down (half life of 20 mins) to reduce the stimulation of the collecting ducts

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Aquaporin Structure

What type of molecule is T? ……………………………………………………………………………………………..

Why can water molecules pass through this channel and pass less easily through the phospholipid bilayer?

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……………………………………………………………………………………………… Why can’t sodium ions pass through the aquaporin?

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Flow Diagram Showing the Sequence of Events if Blood Plasma Water Potential Decreases below the Normal Level

Sequence of Events if Blood Plasma Water Potential Increases

Blood plasma water increases if excess fluid is taken into the body

The increased blood plasma water potential is detected by the osmoreceptors in the hypothalamus

There is less/no stimulation of neurosecretory cells in the hypothalamus and less/no ADH is secreted from the posterior pituitary gland into blood plasma

Less/no ADH binds to ADH receptors on the collecting duct cell membranes. In the absence of ADH, aquaporins are taken back into the cytoplasm by endocytosis at the luminal plasma membrane

The collecting duct cells become less permeable/impermeable to water and less/no water is re-absorbed into the medulla and then into blood plasma

Blood plasma water potential returns to a normal level

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Urine volume increases and its solute concentration decreases

Re-absorption of Urea from the Collecting Duct

As the filtrate is moving down the collecting duct, more water is re-absorbed and the urea concentration in the filtrate increases

This creates a steep diffusion gradient for urea and therefore some urea is re-absorbed from the filtrate (in the collecting duct) into the medulla, by diffusion, down a diffusion gradient.

Although one role of the kidney is the excretion of urea from the body, this re-absorption of urea into the medulla is a helpful feature for its osmoregulation role

As the urea concentration in the medulla increases, the medulla water potential is lowered and this helps in the re-absorption of water, from the collecting duct, as part of the osmoregulatory function of the kidney

What is ADH and how is it removed from the body?

What type of molecule is ADH? ………………………………………………………

What are the monomers called? ……………………………………………………..

What is the name of the bond between the monomers? ………………………….

ADH needs to be removed from the body after it has completed its role of returning blood plasma water potential to a normal level. Why is its removal important?

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How would ADH be removed from the body?

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Recognising Questions on Osmoregulation

You may feel that you understand osmoregulation but have difficulty identifying questions that require its explanations.

This identification skill will improve as questions are practised.

If a question asks for an explanation of why urine concentration/volume is variable from day to day or throughout the day, the explanation will involve osmoregulation.

Be careful about involving the Loop of Henle too much. This part of the nephron is involved in osmoregulation only because it creates the very low water potential in the medulla and hence a steep water potential gradient for water re-absorption from the collecting duct.

If a question asks for an explanation of how a salty meal leads to reduced urine excretion, your answer should not involve the Loop of Henle. It should tell the story of the salt in the meal being absorbed into the blood lowering the blood plasma water potential. This blood plasma φ lowering is detected by the osmoreceptors in the hypothalamus and so on.

Think carefully about which part of the osmoregulation story is required in your answer. If asked to describe the role of the kidney in osmoregulation, you should include detail of the effects of ADH on the collecting ducts and their re-absorption of water. A description of the role of the Loops of Henle would be relevant here too. Including the roles of the hypothalamus and posterior pituitary gland would not be so relevant.

Adaptations of Mammals Living in Dry Habitats to Water Conservation

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The kangaroo rat is an example of a mammal well adapted to living in desert conditions. It is found in North American deserts.

It produces a very small volume of highly concentrated urine daily (4 times more concentrated than human urine).

Its kidney adaptations are:

1. It has longer Loops of Henle in a deeper medulla tissue

2. All Loops of Henle are long

3. These Loops of Henle create a very low water potential in the medulla so that more water can be re-absorbed from the collecting ducts, by osmosis

4. The collecting duct cells are more permeable to water because their plasma membranes are more sensitive to ADH and incorporate more aquaporins into the luminal plasma membranes

The kangaroo rat also makes use of metabolic water when feeding. It eats seeds that contain lipid as energy storage molecules. When these molecules are aerobically respired, a lot of ‘metabolic’ water is produced. Lipid is a better source of metabolic water than carbohydrate (I gram of lipid produces almost twice as much metabolic water compared with 1 gram of carbohydrate).

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Testing Urine Samples

Pregnancy Testing

A human embryo implanted in the uterus lining secretes a small hormone called human chorionic gonadotrophin (hCG). Because it is small, this hormone is filtered out of the blood plasma by the kidneys (into the Bowmans capsule) and is found in the urine within 6 days of conception.

The presence of hCG in the urine is the basis of the pregnancy test.

The test kits contain monoclonal antibodies specific to hCG antigen.

A small volume of urine is pipetted onto the test strip section labelled ‘sample’

At the sample position, hCG molecules (antigen) bind to the mobile monoclonal antibodies. The antigen and antibody have complementary shapes

The antibody-hCG complex moves up the strip with the urine, until it binds to a band of immobilised antibodies at the ‘test’ point on the strip. The immobilised antibody is attached to a pink or blue dye that is visible at the ‘test’ position and has a complementary shape to the antibody-hCG complex

The mobile antibody from the ‘sample’ position will move with the urine, up the test strip even if it hasn’t bound to hCG antigen. This mobile antibody will bind to the immobilised antibody at the ‘control’ position on the strip forming a pink/blue line

There is always one coloured line as a control. If the urine contains hCG, there will be two coloured lines on the test strip and this shows a positive pregnancy test.

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Anabolic Steroid Testing

Athletes are tested regularly to check that they have not been taking anabolic steroids to build up muscle mass (anabolic steroids stimulate protein synthesis).

Anabolic steroids are banned by all major sporting bodies.

Urine samples are tested using gas chromatography or mass spectrometry.

These steroids have a half life of 16 hours so it is important to take urine samples close to the event

Should Steroids be permitted for use in Sports?

Possible reasons ‘against’:

It gives a person an unfair advantage and is a form of cheating

There are health risks and dangerous side effects such as depression, aggression, liver damage, heart attack, infertility, development of male features in females or female features in males

Conveys distrust of ‘outstanding performances’

Athletes should be role models for younger people

Possible reasons ‘for’:

Can train for longer without tiring

Can build up muscle mass

Can recover from injury faster

There is a great deal of pressure to keep up with rival competitors

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Kidney Failure

Main Reasons for Kidney Failure

1. Diabetes mellitus (both type I and type II)

2. Hypertension

3. Infection

Consequences of complete kidney failure

The kidneys cannot filter the blood, therefore:

Blood will contain higher concentrations of urea, ions and water

Blood pressure will increase and swelling in tissues (oedema) occurs as tissue fluid builds up

This will lead to death if untreated.

Treatment of Kidney Failure

Two main treatments: Renal dialysis and kidney transplant

Renal Dialysis

The most common treatment for kidney failure that relies on passive diffusion

Excess water, salts and urea are removed from the blood by passing the blood over a partially permeable dialysis membrane, that separates the blood from a dialysis fluid

The dialysis fluid contains the correct concentrations of salts, water and other molecules in blood plasma, such as glucose and amino acids. Any substances in excess in the blood plasma diffuse down their diffusion gradients into the dialysis fluid.

Any substances that are too low in blood plasma, diffuse from the dialysis fluid, down their diffusion gradients, into the blood plasma

Dialysis fluid and blood flow in opposite directions so that there is a diffusion/concentration gradient maintained along the whole length of the dialyser (see diagram on page 16)

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Two Types of Dialysis

1. Haemodialysis

Haemodialysis is usually carried out in a hospital three times a week for several hours per session. Some patients carry it out at home with their own dialyser.

Blood is taken from a vein in the lower arm. This vein is surgically connected to an artery in the lower arm forming an arteriovenous shunt (see diagrams above and on page 17). Arterial blood flows into the vein that has the needle and tube inserted, to ensure a high blood flow rate into the dialysis machine.

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The blood is passed into a machine through tubes of dialysis membrane. The tubes are surrounded by the dialysis fluid.

Heparin (anticoagulant) is added to the blood just after it enters the machine. The dose given will prevent blood clots forming whilst the blood is flowing in the dialysis machine.

It is not necessary to add any more heparin before the blood returns to the body, because the blood re-entering the body must be allowed to clot normally after treatment.

Air bubbles are removed from the blood before it returns to the body, to prevent air bubbles blocking blood vessels.

Blood is returned to the body into the same vein, from which blood was removed.

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2. Peritoneal Dialysis Dialysis fluid is inserted into the abdominal cavity, via a permanent abdominal tube.

Urea and other molecules in excess diffuse from the blood across the peritoneum (lining of the abdomen) into the dialysis fluid which is removed/replaced after a certain length of time

This dialysis is usually performed daily at home or work. The patient can walk around during this dialysis

Kidney Transplants

The old kidneys are not removed unless they are diseased or cancerous

Kidney transplantation is major surgery

The new kidney is implanted into the lower abdomen and attached to the blood vessels and to the bladder

Kidney transplantation is the best life-extending treatment for kidney failure but there are risks as detailed below and on page 19

Why the donor kidney tissues must be closely matched to the recipient’s tissues

The donated kidney tissues will be recognised as non-self by the recipient because the antigens (such as glycoproteins) on the donor cells will be different

This will result in tissue and organ rejection by the recipient’s immune system

It is always necessary to treat the recipient with Immuno-suppressant drugs. These drugs reduce the chance of rejection but increase the chance of infection by pathogens since the immune response is far less effective

The size of the donor organ must also be closely matched to the recipient. A small child, for example, would need to receive another child’s small donor kidney

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Advantages and Disadvantages of Kidney Transplantation

ADVANTAGES DISADVANTAGES

No need for time consuming dialysis Need to take immunosuppressant drugs for life of the kidney

Diet is less limited Need major surgery under general anaesthetic

Feeling better physically Risks of surgery – include infection, bleeding and damage to surrounding organs

Better quality of life since no time spent on regular kidney dialysis – can travel

Frequent check ups for signs of kidney rejection

Psychologically better since don’t perceive oneself as chronically ill

Side effects of drug treatment- fluid retention and high blood pressure.

Immuno-suppressants increase susceptibility to infections

Kidney Donors

1. Kidneys can be removed from dead people provided the next to kin agree to the removal for transplant purposes

2. People can choose to carry donor cards with their consent to their kidney donation, in case of their fatality in an accident

3. People can choose to donate a kidney to a close relative where there is a close tissue match. It is possible for the donor to have a normal healthy life with only one kidney

4. People can choose to donate a kidney to an organ bank. The donor receives no payment and donates one kidney because they are kind and totally unselfish, allowing a sick person with kidney failure the opportunity of living a relatively normal life

5. Illegal kidney transplants do occur and there is a growing trade in human organs. Poor people and children below the legal age for consent sell their organs so that their families can benefit from the money they raise. Unfortunately, agents and some medical groups exploit these poor people and children by selling the kidneys on to rich people for a much higher price than they paid

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Is it ethical for live donors to be used as a source of kidneys for transplantation?

Include the following:

Donor advantages

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Donor disadvantages

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Recipient issues

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