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Defence Against Infectious Disease

This article follows on from some of the SL syllabus focusing on Human Health and Physiology. Our defence system is also known as our immune system and as mentioned in Topic 6, the immune system protects us from harmful pathogens that cause disease. Can you explain the basics of antibody production? Hopefully yes if youve read topic 6, but can you describe what this has to do with immunity and vaccination? Do you know how antibodies can be used as bullets or the mechanism behind blood clotting? What can you say about the MMR/autism controversy and a failed clinical trial? Read on to find out...

Antibody production
When a pathogen enters the body, it is recognised due to the presence of an antigen attached to it. The antigen is what triggers an immune response that eventually leads to the production of antibody that will lead to the destruction of that pathogen (antibody that is specific for that antigen). The immune response is achieved by a fascinating yet complex series of reaction as outlined in topic 6.3

Examiner Tip
Before going any further it would be a good idea to check out the SL material on antibody production. You should be able to explain the above diagram; if you cant, go back to Topic 6.3 and make sure that you understand the process of antibody production. http://www.youtube.com/watch?feature=player_embedded&v=37zJFVsKlKQ In addition to the details you learnt at SL, you must know the following:

The last part of the production of antibody (step 6 in the diagram above) is the change in B cells to memory cells. This is important because it is the memory cells that act as the basis for immunity. This will be discussed in greater detail below.

The process of antibody production is governed by challenge and response. Challenge and response is the way that the body responds to a threat. When the immune system recognises a pathogen, the pathogens antigen challenges the immune mechanisms. In turn, the immune system begins a reaction, which primarily involves the production of antibody to destroy that pathogen and its antigen. Antibody is produced via clonal selection. Clonal selection refers to the specific part of antibody production, where only one B cell is activated by an activated helper T cell. This B cell then proliferates and creates many clones of itself. In this way, many identical B cells have been created that will produce the same antibody, that is effective against the same antigen. In other words, clonal selection is the way that a large amount of one antibody is produced.

Important
Challenge and response is the theory underlying the production of antibody; antigen challenges the immune response and it responds by producing antibody. Clonal selection is how a specific antigen causes one type of B cell to be activated and then replicate many times via mitosis. This ensures that the correct antibody is produced in vast quantities.

Monoclonal antibodies
The antibody that is produced in a normal immune response is described as being polyclonal antibody. Polyclonal, as the name suggests, means that several clones of a B cell have made this antibody. In contrast to this, monoclonal antibodies are produced by only one clone of a B cell. This is a very arbitrary difference and is only really seen in the production of monoclonal antibody as outlined below. A natural response always produced polyclonal antibodies; monoclonal antibodies can only be produced artificially.

Important
Monoclonal antibody is antibody that is produced by only one plasma B cell. The following technique is used to make large quantities of monoclonal antibody:

1. An animal (often a rat or mouse) is inoculated with a form of a pathogen. This means that at least the antigen of that pathogen is injected into the animal. The antigen used will determine the antibody that will be produced. For example, Hepatitis B vaccine contains Hepatitis B Virus Surface Antigen (HBsAg) rather than the whole pathogen, i.e. the whole virus. 2. The animal then has an immune response that results in the production of B cells producing the desired antibody. One of these B cells is extracted from the animal. 3. A tumour cell, which has the capacity to grow and divide endlessly is fused with this B cell via placing the two cells in close proximity and running an electric current through them. The result of this combination is a hybridoma cell that is able to divide endlessly and produce the desired antibody. 4. This hybridoma cell is then allowed to divide until there is a large number of cells and then the antibody that they produce is extracted and purified.

Be Aware
Do not confuse monoclonal and polyclonal antibodies. In normal immune reactions there are polyclonal antibodies as several different B cells can be activated. It is only artificially that monoclonal antibodies are produced.

Important
The production of monoclonal antibodies requires an animal to be exposed to an antigen. Following inoculation, one of the animals cells is removed and fused with a tumour cell to form a hybridoma that will produce large quantities of the correct antibody. Once purified, monoclonal antibody has many uses, particularly in medicine, for example in the treatment and diagnosis of many diseases.

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Monoclonal antibodies are being used more and more in the treatment of cancer. In short, a specific type of monoclonal antibody is produced. This antibody will look for, recognise and then bind to cancer cells. The trick is that attached to the monoclonal antibody is a variety of substances that are used to destroy the cancer cells. In some instances the antibody has a flag attached to it that attracts the bodys immune system and causes the cancer cell to be destroyed, as with Rituxan in non-Hodgkin lymphoma. In other cases, the attached molecule can act to directly stop further production of cancer cells such as the effects of Herceptin against HER2/neu. Check out the following link to see a comprehensive overview of this topic:

Pregnancy tests

Monoclonal antibodies are also frequently used as diagnostic tools; they are used to check whether an individual has a certain disease or condition. One specific example of this is with pregnancy testing: A pregnancy test stick is dipped into the womans urine and stick will recognise a specific molecule that is only produced in pregnancy called human chorionic gonadotrophin (hCG). If hCG is present it will bind to monoclonal anti-hCG antibodies that are present on the pregnancy test stick to form a hCG-anti-hCG antibody complex. The hCG-anti-hCG antibody complex then moves down the stick towards the reaction strip. The binding of the hCG-anti-hCG antibody complex with another type of antibody that recognises the complex causes a reaction with a dye present in the reaction strip. As such a colour change is seen. There is also a control strip on the stick that will react if the test has been carried out properly. In this strip, there are different antibodies that recognise the anti-hCG antibodies, even if there is no hCG attached to it and causes a colour change. This strip will always have a colour change unless the test is broken so it acts as confirmation of the test. A pregnant woman will have hCG in her urine, so this will trigger the reaction strip and the confirmation strip to change colour. A woman who is not pregnant will have no hCG so there will be no binding of hCG to the antihCG antibodies. As such, there will be no binding of the hCG-anti-hCG antibody complexes to the antibodies in

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the reaction strip (no colour change), but there will still be binding of the anti-hCG antibodies to the antibodies in the confirmation strip (colour change). This is explained in detail, with a good animation, in the following link:

Important
Monoclonal antibodies are used in the diagnosis and treatment of many medical conditions, as well as in pregnancy testing.

Examiner Tip
Dont worry if youre not comfortable with the exact details of the uses of monoclonal antibodies; as long as you can briefly outline their applications in medical treatment and pregnancy testing you should be fine in the exam!

Immunity
Our immune system is made up of different types of cells including phagocytes (macrophages), B cells, Helper T-cells, memory cells, and plasma cells. Immunity is the term used to describe when our immune system has already met a certain disease or pathogen before and thus is able to respond to it more effectively. Humans gain natural and active immunity by catching a disease and recovering from it. It is important that you know the different classifications of immunity, outlined below.

Important
Immunity is the way in which the body is able to more effectively to respond to a pathogen having encountered it once before. There are two types of immunity: active immunity and passive immunity. Active immunity involves the body being forced to produce antibodies because it has been exposed to a pathogen followed by the normal immune response of T helper cells, B cells and plasma cells. Specifically, it is the final stage in the production of antibody that leads to immunity.

Adaptive immunity

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After the activated B cell has been stimulated to proliferate and form many plasma cells (clones), these clones produce antibody and destroy the antigen/pathogen. Once the disease has been combated, a few of the plasma cells become memory cells. Memory cells are dormant cells, until they are once again stimulated by their specific antigen. Upon stimulation they revert to plasma cells and are able to produce the necessary antibody immediately and in greater quantities than normally. This is because they do not have to go through the process of being selected by the helper T-cells before taking action. In this way, the immune response is generated before the pathogen has time to actually cause disease and there is thus immunity to that pathogen! In contrast to this, there is passive immunity, which is where an individual acquires antibody without producing any itself. In passive immunity there is no challenge and response in the individual because the antibodies are made externally and then transferred across. The main ways in antibody can be transferred are via the placenta, via the breast milk (as a substance known as colostrum) and via direct injection of antibodies. Once these antibodies have been transferred into the individuals they act in exactly the same way as naturally produced antibodies.

Important
Active immunity is immunity due to the production of antibodies by the organism itself after the bodys defence mechanisms have been stimulated by antigens.

Important
Passive immunity is immunity due to the acquisition of antibodies from another organism in which active immunity has been stimulated, including via the placenta, colostrum, or by injection of antibodies.

Examiner Tip
During the first six months after birth, a baby is relatively well-protected from infectious diseases thanks to the fact that it carries the same antibodies as its mother, transferred through the placenta. After this, the baby must rely on its own immune defence system which is much weaker. It is thus not a coincidence that many national vaccination programmes against for example tetanus and diphtheria start at such an early age as 3 months.

Vaccination

Vaccinations are used to induce immunity artificially. A vaccine contains either dead, weakened (attenuated) or subunit forms of the pathogen. After the pathogen/antigen has entered the body, it is recognised by phagocytes/macrophages and a normal immune response occurs. This leads to antibodies being produced to

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destroy the pathogen/antigen and importantly leads to the production of plasma cells and then memory cells. This initial response to a pathogen/antigen is known as the primary immune response. Memory cells are vital to immunity as they are re-activated when the pathogen/antigen is encountered for real. They facilitate the production of large amounts of antibody quickly and this means that the pathogen is destroyed before it has chance to cause disease. As the pathogen is no longer able to cause the disease, that individual is said to be immune to that pathogen or have immunity to that disease. The re-activation of memory cells and production of antibody is known as the secondary immune response. Most vaccines are administered by injection, with some need to be ingested (swallowed). Often a booster shot may be needed years after the first vaccination to complete the immunisation process. This is the case for example with tetanus. Immunity lasts for life or for a very long period (decades).

Important
Vaccination is an artificial way of providing long lasting immunity to a pathogen/disease, usually via injection or ingestion of that pathogen.

Important
Vaccination involves the introduction of an attenuated pathogen into an individual so that an immune response is triggered; because the pathogen has been weakened, it is easier for the immune response to destroy it. Once the pathogen has been cleared, plasma B cells become memory cells capable of mounting a strong immune response very quickly.

The benefits and dangers of vaccination

Vaccination is a great health policy that is designed to prevent disease. There are numerous advantages to vaccination that cover more than just the immediate healthcare implications. However, vaccination is not without risk (even though these risks are very small) so there are both advantages and disadvantages as follows:

Benefits

Complete elimination of disease Prevention of epidemics/pandemics Prevention of effects/symptoms of disease Reduction in healthcare costs

Important
The benefits of vaccination include prevention of, elimination of and reduced spread of a disease, as well as reduced cost of treating diseases.

Dangers

Possible toxic effects of mercury (a part of most vaccines)

Possible overload of the immune system Past concerns over links to autism (although now found to be unfounded concerns)

Important
The dangers of vaccination include health concerns over parts of vaccines and the immune system being overwhelmed. The concerns of a possible link to autism were particularly with the MMR (mumps, measles and rubella) vaccine in the UK in the early 1990s. The following link outlines how a team of doctors made a huge mistake in one study that led thousands of British children not receiving the MMR vaccine.

Process of blood clotting

The constituents of blood were described in Topic 6, where it was stated that blood consists of red cells, white cells, platelets, and plasma. In the process of clotting, it is platelets (or thrombocytes) that play a pivotal role.

The start point for clotting is when a cell is damaged and the classic example of this is a break to the skin such as a cut/gash. When cells are damaged or die, there is a large amount of clotting factor released from platelets and it is this release of clotting factor that initiates the clotting cascade. The clotting cascade is a series of interconnected reactions that lead to the formation of a scab. The first reaction is the conversion of pro-thrombin into thrombin and it is this reaction that is directly caused by the presence of clotting factors.

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The next reaction is the conversion of fibrinogen to fibrin. Fibrinogen is a soluble protein, however fibrin is an insoluble protein that is found as a series of strands. These strands are adherent and form a sticky mesh that traps parts of blood in it. In particular, red blood cells and platelets become stuck in the fibrin mesh and form the initial blood clot.

The process of blood clotting is very important. Without it a small cut could lead to organisms bleeding to death. Also, the formation of scabs acts as a barrier to prevent microorganisms from entering the body, which helps prevent infection and illness. Whilst clotting is very useful, excess clotting can be very dangerous. The clotting cascade, with its interlinked reactions is designed to prevent from blood clotting unnecessarily.

Important
Blood clotting involves the activation of pro-thrombin via tissue factor, which causes fibrinogen to become insoluble fibrin and form a mesh that is the initial blood clot.

Important
Clotting prevents excess blood loss and pathogens entering the body. As clotting occurs as a reaction cascade, it cannot easily be stimulated so it is unlikely to occur unnecessarily, which can lead to various health problems.

What you should know

Challenge and response is the theory underlying the production of antibody; antigen challenges the immune response and it responds by producing antibody. Clonal selection is how a specific antigen causes one type of B cell to be activated and then replicate many times via mitosis. This ensures that the correct antibody is produced in vast quantities. Monoclonal antibody is antibody that is produced by only one plasma B cell. Monoclonal antibodies are used in the diagnosis and treatment of many medical conditions, as well as in pregnancy testing. Immunity is the way in which the body is able to more effectively to respond to a pathogen having encountered it once before. Active immunity is immunity due to the production of antibodies by the organism itself after the bodys defence mechanisms have been stimulated by antigens. Passive immunity is immunity due to the acquisition of antibodies from another organism in which active immunity has been stimulated, including via the placenta, colostrum, or by injection of antibodies. Vaccination is an artificial way of providing long lasting immunity to a pathogen/disease, usually via injection or ingestion of that pathogen.

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Vaccination involves the introduction of an attenuated pathogen into an individual so that an immune response is triggered; because the pathogen has been weakened, it is easier for the immune response to destroy it. Once the pathogen has been cleared, plasma B cells become memory cells capable of mounting a strong immune response very quickly. The benefits of vaccination include prevention of, elimination of and reduced spread of a disease, as well as reduced cost of treating diseases. The dangers of vaccination include health concerns over parts of vaccines and the immune system being overwhelmed. Blood clotting involves the activation of pro-thrombin via tissue factor, which causes fibrinogen to become insoluble fibrin and form a mesh that is the initial blood clot. Blood clotting involves the activation of pro-thrombin via tissue factor, which causes fibrinogen to become insoluble fibrin and form a mesh that is the initial blood clot. Clotting prevents excess blood loss and pathogens entering the body. As clotting occurs as a reaction cascade, it cannot easily be stimulated so it is unlikely to occur unnecessarily, which can lead to various health problems.

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Muscles and Movement

In Topic 6 the nervous system was introduced, explaining how signals from the central nervous system are sent to effector structures such as muscles in order to bring about movement. In this article, the specific details of how muscles contract is examined and you will see the details of this complex process. Did you know that ATP is needed to form myosin actin cross-bridges? Can you explain the cross-bridge cycle?

Structures required for movement

The Body
Animals have a complex arrangement of systems and structures that enable them to move. It is the interaction of the muscular and skeletal systems that allows movement, but there are other important structures that are required.

Bones
Bone is the main support of the body of an animal. In humans, we have 206 bones and these provide a framework for our bodies, as well as acting as protection for internal organs, such as the skull around the brain and the ribs around the lungs. Specifically, bones act as a rigid platform that muscles can be anchored to.

Important
Bones are the basic support structures of the human body, which act to support the rest of the body and protect internal organs.

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Muscles
Muscles are the driving force behind movement. It is the contraction and relaxation of muscle groups (described as antagonistic pairs) that physically move and reposition limbs as well as giving structural support to the rest of the body. For example, the muscles in the back enable us to remain upright and not slump forward. Importantly, it is muscles that contract to bring about the movement of joints.

Important
Muscles facilitate the movement of limbs and work in antagonistic pairs.

Ligaments
Ligaments are strong filament-like structures that hold joints together. Ligaments play a crucial role in holding two bones together in a way that means they have both strength and a range of movements. Without ligaments, there would be no concept of joints as bones would all be fused together!

Important
Ligaments are the structures that hold joints together; they link one bone to another.

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Tendons
Tendons are similar to ligaments as they are again strong filament-like structures, but their function is to attach muscles to bones. It is this attachment that allows muscles to create forces by contracting; muscles pull against the resistance of the bone they are attached to and thus move the joint/limb/structure.

Important
Tendons attach muscles to bones so that muscle contraction causes movement.

Nerves
Nerves are also filament-like structures, but they are very delicate and much more like fine thread than strong rope. Their role is the innervation of muscles, which means transmitting nerve impulses from the brain and spinal cord (CNS) to that muscle or group of muscle. In other words, it is nerves that convey the message to move to muscles so that they can contract and then bring about movement.

Important
Nerves are the structures that allow the CNS to control muscles and cause contraction.

The elbow joint

http://www.youtube.com/watch?feature=player_embedded&v=mPdhHMDueiY

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You need to appreciate the general roles of the structures required for movement (as above), but you must also have a specific understanding of the structures of the elbow joint. You may also be asked to draw a diagram of the human elbow and should include the following parts with their correct functions:

Comparing the movement of different joints

The hip joint and knee joint carry out different movements. Both are referred to as synovial joints, meaning that they are formed from bone and ligaments, but they differ in their range and type of movements.

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The Hip Joint

The hip joint is said to be a ball and socket joint and it is capable of moving in all directions. It can flex, extend, abduct, adduct and rotations. In other words it can move forwards, backwards, from side to side and can turn inwards and outwards.

Important
The hip joint is a ball and socket joint, which can move in all directions/planes.

The Knee Joint

The knee joint is not as flexible as it is a hinge joint that can only move in one plane; it can only flex and extend, so it can only bend backwards and then straighten.

Important
The knee joint is a hinge joint, which can only move in one plane/direction.

Examiner Tip

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When thinking about the differences between ball and socket joints and hinge joints, try to relate them to every day structures. Ball and socket joints are like a joystick, whereas hinge joints are like the spine on a book. Check out this link to see the knee moving under MRI.

Muscles, myofibrils and sarcomeres

Muscles are made up of many smaller components structures. One large muscle contains many smaller muscle fibres. Each muscle fibres is self contained by its own sarcolemma (a specific type of cell membrane) and contains several myofibrils that consist of repeating units called sarcomeres. Sarcoplasmic reticulum (a specific type of endoplasmic reticulum) surrounds the myofibrils, and mitochondria are situated between the myofibrils.

The sarcomeres that make up myofibrils have dark and light bands formed from two types of protein called actin and myosin. The dark bands of myofibrils are where actin and myosin overlap, whereas the light bands are where there is only actin or myosin (no overlap). The overlap of action and myosin leads to the formation of cross-bridges and it is there cross-bridges that produce the contraction of muscle. At either end of a sarcomere, there are structures called Z lines. It is these lines that anchor the actin and myosin filaments in place. You should be able to label a diagram of a sarcomere with the structures includes below:
Actin filaments (thin) Myosin filaments (thick) Light and dark bands Z lines

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Important
A muscle is made up of many muscle fibres, each of which is composed of myofibrils that contain thousands of individual sarcomeres. A sarcomere consists of interlinked actin and myosin filaments.

Muscle contraction
The process of muscle contraction ultimately involves the shortening of the sarcomere. In order for muscles to contract in the first place they need energy in the form of ATP, but the actual mechanism of muscle contraction involves the formation of cross-bridges between the actin and myosin filaments. 1. As an action potential arrives at the muscle (from a motor neuron) it causes the release of Ca2+ from the sarcoplasmic reticulum. 2. Calcium allows the actin and myosin fibres to join together as it acts to expose a binding site on actin that myosin heads can attach to. This is the formation of actin-myosin cross-bridges. 3. ATP then binds to the cross bridges, which allows the myosin heads to alter their shape and prepares the two filaments for movement. 4. ATP is hydrolysed to ADP and phosphate and this releases energy that is used to shorten the sarcomere (move actin closer to the centre). 5. A new ATP then binds and causes the cross-bridge to break and the myosin head to reset to its original position so that it can form a new cross-bridge.

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6. This is referred to the cross-bridge cycle of attaching, sliding, detaching and resetting and it is how muscle contracts.

Important
Muscle contraction occurs as a cycle. When an action potential reaches a muscle, calcium ions are released, which leads to the binding of myosin heads onto actin filaments. With the addition and hydrolysis of ATP, myosin pulls actin towards the centre of the sarcomere and contraction occurs as the sarcomere shortens.

What you should know

Bones are the basic support structures of the human body, which act to support the rest of the body and protect internal organs. Muscles facilitate the movement of limbs and work in antagonistic pairs. Ligaments are the structures that hold joints together; they link one bone to another. Tendons attach muscles to bones so that muscle contraction causes movement. Nerves are the structures that allow the CNS to control muscles and cause contraction. The hip joint is a ball and socket joint, which can move in all directions/planes. The knee joint is a hinge joint, which can only move in one plane/direction. A muscle is made up of many muscle fibres, each of which is composed of myofibrils that contain thousands of individual sarcomeres. A sarcomere consists of interlinked actin and myosin filaments. Muscle contraction occurs as a cycle. When an action potential reaches a muscle, calcium ions are released, which leads to the binding of myosin heads onto actin filaments. With the addition and hydrolysis of ATP, myosin pulls actin towards the centre of the sarcomere and contraction occurs as the sarcomere shortens.

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The Kidney
Humans have two kidneys located just under the ribs at the back of the abdomen. The kidneys are responsible for excretion, which is the way in which the body can remove any waste products or toxic metabolites. In particular, excretion removes the waste products of many of the chemical reactions that naturally occur inside the body (metabolic reactions).Are you able to explain the mechanisms involved in excretion? Do you know why glucose is found in the urine of patients with poorly controlled diabetes? Or why drinking too much coffee or coke makes you need the toilet? Read on for the answers...
Excretion occurs in the form of the kidney producing urine and filtering the blood to determine which substances and how much of each substance the body wants to keep or get rid of. Excretion involves two processes known as ultrafiltration and selective reabsorption. The kidney also has various homeostatic functions such as regulating the water concentration of the body, which is called osmoregulation.

Important

The kidneys play vital roles in excretion and water balance. Excretion is the removal from the body of the waste products of metabolic pathways. Excretion consists of ultrafiltration followed by selective reabsorption.

Diagram of the structure of the human kidney

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You need to be able to draw the macrostructure of a kidney for the exams. When drawing the human kidney, make sure to include the following:

Cortex (outer edge of the kidney) Medulla (middle of the kidney, shown with pyramids) Pelvis on the concave side of the kidney Ureter shown connected to the pelvis on the concave side Renal artery and vein shown originating from the concave side

Diagram of a nephron
In addition to the macrostructure of the kidney, you must also be able to draw the microstructure of the kidney (including all of the following structures). Each kidney is made up of hundreds of thousands of nephrons and it is the nephron that you need to be able to draw. A nephron is the functional unit of the kidney and each of its structures has specific functions that are important in its role of excretion.

Branches of renal artery Glomerulus Bowman's capsule Proximal convoluted tubule (PCT) Loop of Henl (ascending and descending limbs) Distal convoluted tubule (DCT)

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Collecting duct

Ultrafiltration
Ultrafiltration is the first step in the process of excretion. In order for ultrafiltration to occur, the kidney needs to have direct access to the blood, so the blood supply for the kidney is a very good one via the renal artery. Once the renal artery has entered the kidney, it splits into thousands of smaller branches that are called arterioles. Each nephron has its own arteriole and every arteriole is divided into two parts; the afferent and efferent arteriole. The afferent arteriole branches many times to form the glomerulus, which is a complex system of blood vessels and it is here that ultrafiltration actively occurs. The efferent arteriole comes back off the glomerulus and leads to the renal vein. Think of the afferent and efferent arterioles as being on either side of the glomerulus; afferent enters the glomerulus and efferent exits the glomerulus.

As blood passes through the glomerulus, it is under very high pressure for two reasons. Firstly, it is because the afferent arteriole has a larger diameter than the efferent arteriole, so blood is squeezed into the efferent arteriole. Secondly, the diameter of the branches of the glomerulus is very small so blood is being forced through a narrow space. Due to high pressure, a lot of the substances that are contained in blood are forced out of the blood and into the Bowmans capsule. However, there are elements of control over what is filtered.

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The wall of the glomerulus is formed by what are described as fenestrated capillaries. Fenestrated capillaries have spaces or pores, which can act as filters. In this instance, the fenestrations act to prevent large molecules (such as proteins) from leaving the blood plasma. The basement membrane of the Bowmans capsule also contributes to filtration of substances because it is made up of podocytes. Podocytes are a type of specialised cells that have foot-like projections that moderate what is transported across the capsule. As such, only small molecules are able to pass from the blood into the Bowmans capsule.

Examiner Tip
To remember which arteriole is afferent and efferent think about how the Efferent arterioleExits the glomerulus.

Important
Ultrafiltration occurs in the glomerulus of each nephron; it is the movement of small substances from the blood into the Bowmans capsule. Ultrafiltration occurs due to the high pressure of blood in the glomerulus (because of the difference in size of afferent and efferent arterioles), the fenestrated nature of capillaries and the podocytes of the Bowmans capsule.

Selective Reabsorption
Selective reabsorption follows on from ultrafiltration and it is how the kidney determines how much of a substance is moved back into the blood and how much is allowed to pass into urine and be excreted. Once substances have been ultrafiltered into the Bowmans capsule, they are said to be in the glomerular filtrate and it is the job of the proximal convoluted tubule (PCT) to reabsorb these substances if need be. Selective reabsorption is so called because the PCT can actively select what and how much it wants to reabsorb. For example, very little urea is selectively reabsorbed, but all glucose should be (see more on this below). In the PCT, there is a layer of microvilli that is similar to the microvilli found in the small intestine of the digestive tract. These microvilli act to increase the surface area of the PCT and thus increase the area over which selective reabsorption can occur. Glucose, amino acids and various sodium/potassium salts are actively transported out of the glomerular filtrate and into the surrounding blood of the efferent arteriole. In addition to active transport, there is also osmosis. Osmosis occurs because of the movement of glucose/amino acids/salts into the blood of the efferent arteriole. As such, the blood has a high concentration and water is able to across via osmosis.

Be Aware
Do not get confused about where the blood vessels surrounding each nephron come from. The efferent arteriole that leaves the glomerulus/Bowmans capsule does not go directly to the renal vein. It follows the path of the nephron, wrapping around various tubules and ducts.

Important
Selective reabsorption occurs in the proximal convoluted tubule (PCT) of the nephron; it is the re-uptake of specific substance found in the glomerular filtrate.

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Selective reabsorption involves active transport of certain substances such as glucose and amino acids and the osmosis of water. The PCT has microvilli that increase its surface area so increase the area over which reabsorption can occur.

Blood, glomerular filtrate and urine

Due to the processes of ultrafiltration and selective reabsorption, there are differences in the concentration of proteins, glucose and urea between blood plasma, glomerular filtrate and urine. The differences are outline in the chart below:

Protein is found solely in the blood, as it is too large to travel through the fenestrated capillaries of the glomerulus or in between the podocytes of the basement membrane of the Bowmans capsule. Glucose is found in roughly equal concentrations in the blood and glomerular filtrate, as it is almost entirely ultrafiltered. However, no glucose is meant to be found in urine because it is an important substance used in a huge number of metabolic processes. As such, glucose should be completely reabsorbed by the PCT of the nephron.

Important
Protein should not be found in either the glomerular filtrate or urine. Glucose should be found in the glomerular filtrate, but not urine. Urea should be found in both the glomerular filtrate and in urine where it will be at a higher concentration.

Glycosuria and diabetes

Glycosuria is the medical terms for the presence of glucose in urine. Glucose is not normally found in the urine since as it is actively transported back into the blood in selective reabsorption. However, glucose is sometimes found in the in the urine of people with untreated or poorly controlled diabetes.

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Diabetes is a condition in which there is a deficiency of insulin and consequently a rise is the concentration of glucose in the blood (as insulin acts to lower blood glucose). When there is a raised blood glucose concentration, the transporters in the proximal convoluted tubule for glucose can become overwhelmed and struggle to cope. As such, some glucose will not be reabsorbed and will pass into urine. It is important to note that the appearance of glucose in the urine of diabetic patients is not due to the failure of the kidney; the transporters in the PCT are perfectly functional, but they cannot handle the amount of glucose in the glomerular filtrate.

Important
Glycosuria is glucose in the urine and indicates diabetes; this occurs because blood glucose is elevated in diabetes, and thus glucose transporters in the PCT cannot handle the amount of glucose in the glomerular filtrate and some passes into the urine.

Examiner Tip
Before other diagnostic tools were developed, doctors used to taste the urine to determine whether the patient had diabetes. Because of the glycosuria, the urine produced by diabetes patients has a sweet taste.

Osmoregulation
Osmoregulation is the regulation of the concentration of water within an individual and it is another of the important functions of the kidney. Water balance is controlled by the collecting ducts and the Loop of Henl, with the hormone Anti-diuretic hormone (ADH) playing an important role in this process.

Collecting ducts and ADH

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The main site of the control of water regulation is the collecting duct. When the body senses that there has been a decrease in the amount/concentration of water in the body (actually, an increase in blood concentration of sodium chloride) it acts by releasing anti-diuretic hormone (ADH). ADH is also known as Vasopressin and is released when there is a stimulus registered by osmoreceptors in the hypothalamus. The two main stimuli for osmoreceptors are high blood plasma concentration of sodium chloride and reduced blood pressure. When ADH is released by the pituitary gland (part of the brain) there is a huge increase in the permeability of the collecting ducts as ADH creates pores for water to move out of the collecting ducts and back into the blood. Simply put, if ADH is present, water is able to leave the collecting duct and there will be less water moving into urine, so less water is lost from the body. In addition to anti-diuretics, there are also diuretics, which make you urinate more as they prevent the formation of water channels. One such natural diuretic is caffeine, which is found in coffee and cola amongst other substances. This link discusses this in further detail.

Loop of Henl

The Loop of Henl controls water balance by altering the amount of water that can be reabsorbed via the collecting ducts. The role of the loop of Henl is to create an osmotic gradient within the medulla of the kidney (the area surrounding each nephron) and it does this by reabsorbing water and ions.

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In the descending limb of the Loop of Henl, water moves into the medulla, which increases the concentration of the glomerular filtrate. As the medulla is now less concentrated than the glomerular filtrate, sodium and potassium ions diffuse into the medulla. This shift of sodium and potassium means there is now an osmotic gradient between the medulla and the fluid in the collecting ducts, which draws water out of the collecting ducts and into the medulla via osmosis. Water is then reabsorbed from the medulla by the efferent arteriole and this cycle begins again. It is important that water in the medulla is regularly reabsorbed by the body via the efferent arteriole. This regular reabsorption means that when the glomerular filtrate first reaches the descending limb, it is less concentrated than the medulla and so water will move into the medulla and the Loop of Henl cycle can begin. Osmoregulation occurs in a cyclic fashion because: 1. The descending limb of the Loop of Henl is permeable to water and impermeable to salts, so water can move into the medulla, but sodium/potassium cannot. 2. The ascending limb of the Loop of Henl is impermeable to water and permeable to salts, so sodium/potassium can move into the medulla, but water cannot.

Important
Osmoregulation is the control of the water balance of the blood, tissue or cytoplasm of a living organism. Osmoregulation is largely down to the effects of ADH on the collecting ducts and the action of the Loop of

Henl.

What you should know

The kidneys play vital roles in excretion and water balance. Excretion is the removal from the body of the waste products of metabolic pathways. Excretion consists of ultrafiltration followed by selective reabsorption. Ultrafiltration occurs in the glomerulus of each nephron; it is the movement of small substances from the blood into the Bowmans capsule. Ultrafiltration occurs due to the high pressure of blood in the glomerulus (because of the difference in size of afferent and efferent arterioles), the fenestrated nature of capillaries and the podocytes of the Bowmans capsule. Selective reabsorption occurs in the proximal convoluted tubule (PCT) of the nephron; it is the re-uptake of specific substance found in the glomerular filtrate. Selective reabsorption involves active transport of certain substances such as glucose and amino acids and the osmosis of water. The PCT has microvilli that increase its surface area so increase the area over which reabsorption can occur.

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Protein should not be found in either the glomerular filtrate or urine. Glucose should be found in the glomerular filtrate, but not urine. Urea should be found in both the glomerular filtrate and in urine where it will be at a higher concentration. Glycosuria is glucose in the urine and indicates diabetes; this occurs because blood glucose is elevated in diabetes, and thus glucose transporters in the PCT cannot handle the amount of glucose in the glomerular filtrate and some passes into the urine. Osmoregulation is the control of the water balance of the blood, tissue or cytoplasm of a living organism. Osmoregulation is largely down to the effects of ADH on the collecting ducts and the action of the Loop of Henl.

The Reproductive Systems

In topic 6, the reproductive system was introduced. Here we will zoom in on the structure of the reproductive systems in males and females and have a closer look at the function of structures that are important in order for reproduction to occur. Furthermore you will learn about the process of birth and how fertilisation can take place outside of the body (IVF).

Testis

You must be able to recognise certain structures when looking at a light micrograph of testis tissue including:

Interstitial cells (Leydig cells) Germinal epithelium cells Developing spermatozoa Sertoli cells

Examiner Tip

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For more information and to gain some understanding of what a light micrograph looks like,watch this video, but remember that this goes into more detail than you need to know.

Spermatogenesis
http://www.youtube.com/watch?feature=player_embedded&v=MBe8DD_7r30 Spermatogenesis is the male form of gametogenesis (the formation of gametes); it is the production of spermatozoa, also known as sperm, and it takes place in the seminiferous tubules of the testes. There are several stages in spermatogenesis: 1. Spermatogenesis begins with a single spermatogonium. Spermatogonia are diploid cells (2n) so they have a full amount of genetic material. Cell division by mitosis takes place so that there are many spermatogonia. 2. The spermatogonia then grow (there is the cell growth) and form larger cells that are called primary spermatocytes. 3. Primary spermatocytes then divide by meiosis. The first half of meiosis (meiosis I) results in the production of a haploid cell (n), which is called a secondary spermatocyte. The second division of meiosis occurs (meiosis II) and the secondary spermatocytes become known as spermatids. 4. Spermatids are then matured in the Sertoli cells of the testis and undergo differentiation to form mature spermatozoa (sperm).

Important

Spermatogenesis is the formation of gametes, specifically the formation of sperm cells.

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Spermatogenesis occurs in the testes; initially in seminiferous tubules and then later in Sertoli cells. Spermatogenesis involves mitosis, cell growth, meiosis and then differentiation.

Hormones in spermatogenesis
One role of Luteinising Hormone and Follicle Stimulating Hormone is in the regulation of the menstrual cycle and in particular the preparation of the ovaries for the release of an egg. As such, it is no surprise that these two hormone two hormones also play an important role in spermatogenesis. Testosterone, the male sex hormone, is also required for the production of mature and functional sperm.

LH is released from the anterior pituitary gland and stimulates the secretion of testosterone by the interstitial cells, which are also known as Leydig cells. FSH is also released from the anterior pituitary gland and triggers meiosis I to start; FSH causes the reduction division of meiosis that turns primary spermatocytes into secondary spermatocytes. Testosterone is produced in the testes and has a similar effect to FSH in that it prompts the second division of meiosis and thus prompts the development of secondary spermatocytes into spermatids. Testosterone also generally helps with the maturation of sperm (from primary spermatocyte onwards).

Important
LH stimulates the secretion of testosterone. FSH stimulates meiosis I. Testosterone stimulates meiosis II.

The production of semen

When males ejaculate, they do not produce sperm alone; the fluid produced is known as semen and is a mixture of sperm and various useful substances. Upon ejaculation, sperm exit the testicle and pass through the epididymis, the seminal vesicle and then the prostate gland before being propelled along and then out of the urethra. The substances that make up semen are produced by the seminal vesicle and prostate. Whilst the epididymis does not directly produce a component of semen, it plays a vital role in the development of sperm. The image to the right shows a semen sample, with four sperm in it (stained dark purple).

Important

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Semen consists of sperm and various fluids, which are required for sperm to survive the hostile conditions of the female reproductive system and reach the ovum. The epididymis is attached to the bottom of the testicle and it responsible for the concentration of sperm, which it does by removing unnecessary testicle fluid. It is also where sperm learn how to swim, a vital process in order for sperm to be functional. The seminal vesicle produces various nutrients that will allow the sperm to survive as they travel towards an egg. In particular, fructose is made as this can be used in cellular respiration to provide the sperm with energy. Mucus is also added, which acts to protect the sperm. The prostate gland releases a fluid that is alkaline, which is crucial as this alkaline fluid neutralises the acids produced by the vagina. There is also the addition of several useful minerals that will nourish the sperm.

Important
The epididymis is where sperm mature and learn how to swim. The seminal vesicle produces fructose and mucus. The prostate gland produces alkaline fluids containing useful minerals.

Diagram of ovary

In the same way that you might be asked to analyse an image of testis tissue, you must also be familiar with and able to label a diagram of an ovary with the following structures:

Germinal epithelium Primary follicles The mature follicle(Graafian follicle) Secondary oocyte

You could include the following for the sake of completeness:

Primary oocyte Corpus luteum

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Corpus albicans Outer layer of germ cells medulla Stroma Region where blood vessels enter and leave

Examiner Tip
For more information and to gain some understanding of what a light micrograph looks like,watch this video, but remember that this goes into more detail than you need to know.

Oogenesis
Oogenesis is the production of an ovum, also known as an egg, and occurs in the ovaries. It is the female form of gametogenesis and has many similarities to spermatogenesis. 1. An individual oogonium divides by mitosis (cell division) to form many oogonia. 2. Each oogonium then develops and grows within an individual follicle of the ovaries. Developed oogonia are called primary oocytes. 3. Primary oocytes are diploid and divide via the reduction division of meiosis I to form two haploid nuclei as the pairs of homologous chromosomes are separated. However, the division of the primaryoocyte is not equal. More cytoplasm goes to one half of the chromosomes to form the secondary oocytes. The other set of chromosomes is left with very little cytoplasm and is called the first polar body, which will degenerate and breakdown. 4. Secondary oocytes then undergo the second division of meiosis to form a mature ovum. Again, there is an unequal distribution of cytoplasm with the ovum taking most of it leaving a small structure called the second polar body, which will degenerate as the first polar body did.

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{definitionbox_start} Oogenesis is the formation of gametes, specifically the formation of ova. Oogenesisoccurs within the follicles of the ovaries. Oogenesis involves mitosis, cell growth, and then meiosis. {definitionbox_end} The timing of oogenesis is not as simple as spermatogenesis. In spermatogenesis one process follows the other without interruption, but in oogenesis there are two pauses: Firstly, primary oocytes begin meiosis I, but stop in metaphase, which is described as arrested development. Anaphase does not occur until a female reaches puberty, at which stage the primary oocyte is finally able to divide to form the secondary oocyte and first polar body. The secondary oocyte then begins meiosis II, but is also stopped in metaphase. It is not until a sperm has penetrated the outer layer of an egg that the secondary oocyte progresses through meiosis II to produce the mature ovum and second polar body.

Another difference between oogenesis and spermatogenesis is the timing of the two. Spermatogenesis does not occur at all until a boy reaches puberty. After puberty has begun, the production of sperm will continue throughout virtually all of the mans life. On the other hand, the production of ova begins in a female foetus, which means it occurs even before that female has been born. It is also important to note that by the time a female is born she is not able to increase the number of eggs that she has i.e. the number of oocytes a woman has at birth is the maximum number she will ever have and this number decreases with every menstrual cycle.

Important

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Oogenesis has various pauses in it; oogenesis pauses in metaphase I until puberty and then again in metaphase II until a sperm has penetrated the Zona Pellucida of the egg cell.

What you should know

Spermatogenesis is the formation of gametes, specifically the formation of sperm cells. Spermatogenesis occurs in the testes; initially in seminiferous tubules and then later in Sertoli cells. Spermatogenesis involves mitosis, cell growth, meiosis and then differentiation. LH stimulates the secretion of testosterone. FSH stimulates meiosis I. Testosterone stimulates meiosis II. Semen consists of sperm and various fluids, which are required for sperm to survive the hostile conditions of the female reproductive system and reach the ovum. The epididymis is where sperm mature and learn how to swim. The seminal vesicle produces fructose and mucus. The prostate gland produces alkaline fluids containing useful minerals. Oogenesis is the formation of gametes, specifically the formation of ova. Oogenesisoccurs within the follicles of the ovaries. Oogenesis involves mitosis, cell growth, and then meiosis. Oogenesis has various pauses in it; oogenesis pauses in metaphase I until puberty and then again in metaphase II until a sperm has penetrated the Zona Pellucida of the egg cell.

Reproduction
This article is a HL extension of the SL reproduction topics. In particular, this article focuses on how reproduction occurs and takes you from gamete to zygote; sperm and egg to baby. Can you explain the acrosome reaction? Are you able to describe the function of the umbilical cord? Do you know what processes control birth? The answers are below...

Spermatogenesis compared to oogenesis

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In the previous article the processes of spermatogenesis and oogenesis were outlined. You need to be able to outline both processes and a common way of examining this is to ask you to compare the two. Drawing a table such as the one below clearly shows the differences between the two processes. Notice how there are many more differences than similarities:

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Mature sperm and egg

The process of fertilisation is the joining of the two gametes; the sperm and the egg. In order to understand this process, you must be aware of the structure of each of the gametes. You might be asked to draw a diagram of each in the exam and if you are able to draw a diagram of the gametes your understanding of the processes involved in fertilisation should improve! Include the following structures for the sperm and egg respectively:

Acrosome Plasma membrane Haploid nucleus Centriole

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Mitochondria

Note the ratios of size between head, mid piece and tail.

Important
Fertilisation is the joining of two haploid nuclei (sperm and egg) to form a diploid nucleus (zygote).

Haploid nucleus Cytoplasm (must show large volume relative to nucleus four to one ratio of diameter at a minimum) First polar body (needs to be drawn on the outside of the cell) Plasma membrane Cortical granules (need to be drawn in vicinity of plasma membrane) Zona Pellucida

The process of fertilization

Fertilisation is the way in which two haploid nuclei fuse to form a diploid nucleus. It is how a sperm and an egg create a zygote and it is the basis of sexual reproduction! Fertilisation occurs as a series of steps, with several specific reactions that you need to be familiar with:

Step 1
Firstly, there is the acrosome reaction. As the sperm reaches the ovum in the uterus it attaches to glycoproteins in the Zona Pellucida. This attachment leads to an influx of calcium ions into the sperm, which in turn, causes

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the release of the enzymes contained with the acrosome vesicle. Enzymes are released, which digests a part of the Zona Pellucida to allow the sperm entry.

Step 2

The sperm head burrows into the egg membrane through the hole created via the acrosome reaction. Once the head of the sperm has passed inside the eggs plasma membrane, the secondary oocyte then recommences meiosis and there is the production of the ovum and the second polar body. The image to the right shows an electron micrograph of the process of the acrosome reaction. A is the initial contact of the sperm and egg. B is a close up showing how glycoproteins of the Zona Pellucida interact with the sperm. C and D show the sperm head moving further inside the egg,

Step 3
Lastly, there is the cortical reaction, which involves the exocytosis of the enzymes contained in the cortical granules. As these enzymes react with the glycoproteins of the Zona Pellucida, they cause a series of crosslinks to be formed. These cross-links create an impenetrable barrier as the Zona Pellucida thickens and prevents other sperm from entering.

Important
Fertilisation involves the acrosome reaction, penetration of the egg cell membrane by the sperm and the cortical reaction.

http://www.youtube.com/watch?feature=player_embedded&v =MBe8DD_7r30 Embryonic development

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Once fertilisation has been completed i.e. once the two nuclei of the sperm and ovum have fused, the result is described as a zygote. Fertilisation usually occurs in the fallopian tube and by the time the zygote has floated down to the uterus, it will have begun to divide via mitosis. The first mitotic division usually occurs approximately twenty four hours after fertilisation and mitosis will then continue throughout the rest of the pregnancy. The diagram to the right shows the basics of early embryonic development and where it occurs in relation to the female reproduction system. With every mitotic division the zygote grows in size and a progressively larger ball of cells is created. The zygote becomes two cells, then four, then eight and so on and eventually forms a structure called the blastocyst. Approximately six days following fertilisation the blastocyst will consist of around thirty two cells and will have reached the uterus. The blastocyst is a hollow ball of cells, which consists of a collection of cells called the inner cell mass that will form the actual foetus and then cells that surround the inner cell mass called chorionic villi, which will form the placenta. Chorionic villi burrow into the endometrium (the lining of the uterus) in the process of implantation, which allows the blastocyst to attach firmly to the uterus.

Important
Fertilisation usually occurs in one of the fallopian tubes. After fertilisation, the zygote repeatedly divides via mitosis until it reaches a point where it has enough cells to form a blastocyst. The blastocyst consists of an external chorion and an internal inner cell mass. The chorion of the blastocyst is the part of the zygote that actively implants into the lining of the uterus, the endometrium.

The role of hCG in early pregnancy

hCG (human chorionic gonadotrophin) is a vital hormone for the development of a pregnancy. It is secreted by the placenta (formed once a blastocyst has implanted into the endometrium) and stimulates the ovaries. In particular, hCG targets the corpus luteum and turns into a structure called the corpus luteum of pregnancy, which releases large amounts of oestrogen and progesterone.

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Oestrogen and progesterone have two important actions. Firstly, they maintain the endometrium so that the placenta has access to a good blood supply, which is required for the blastocyst to develop properly. Secondly, oestrogen and progesterone have negative feedback effects of FSH and LH so pregnancy will lead to the prevention of another menstrual cycle and the release of another egg. hCG can be detected in both the mothers blood and urine and withhelp of monoclonal antibodies, hCG levels can be detected in urine and this is the basis of the standard pregnancy test.

Important
hCG causes the corpus luteum to develop and produce enough oestrogen and progesterone to maintain the endometrium and inhibit the menstrual cycle.

The placenta
The placenta is the structure that links mother and foetus; it is the route by which all substances enter and exit the baby. It is quite literally the foetus life line and has important roles in pregnancy. As is often the case in biology the placenta has specific adaptations that allow it to carry out its functions more effectively. Running between mother and baby is the umbilical cord, which is attached to the placenta (mother) and directly to the foetus. The umbilical cord has two umbilical arteries and one umbilical vein. The umbilical vein is the structure that brings oxygenated blood and other important nutrients to the foetus and strangely, it is the umbilical arteries that transports deoxygenate blood away from the foetus (arteries normally carry oxygenated blood). Importantly, the placenta is the point at which maternal and foetal blood come into close contact. Blood from the two cannot mix as they may be different types of blood and mixing would lead to considerable problems and likely termination of the pregnancy. Instead, maternal blood flows very close to foetal cells so that there can be the vital exchange of materials between mother and baby.

Important
The placenta (umbilical cord) is the link between mother and baby that allows for the exchange of nutrients and important substances such as oxygen. In addition to supporting the foetus with everything that it needs in terms of oxygen and nutrients, the placenta also plays a role in hormone release and the more general maintenance of pregnancy. After around 40 days, the ovaries and the corpus luteum no longer play an important role in the maintenance of pregnancy. After roughly 6 weeks it is the placenta that produces progesterone and oestrogen to maintain the endometrium and prevent menstruation/ovulation (via FSH and LH negative feedback).

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Important
The placenta takes over the production of oestrogen and progesterone approximately 40 days after fertilisation. An important part of the placenta is the amniotic sac, which is a derivation of cells of the external most part of the placenta (the chorion). The amniotic sac protects the foetus and also produces amniotic fluid, which also protects the foetus. Amniotic fluid and its surrounding sac act to cushion the foetus within the uterus.

The image to the right shows a foetus at eight weeks, with the amniotic sac surrounding it.

Important
The amniotic sac contains amniotic fluid, which protects the foetus.

Birth
The process of birth has an incredibly complex control mechanism involving dozens of different enzymes and stimulants with aspect of both negative feedback and positive feedback. Thankfully, you do not need to know the full detail of birth, only the shortened version that is summarised below: 1. The process of birth (labour) begins when progesterone levels fall. 2. The hormone oxytocin is then secreted, which causes the the uterus to contract. As well as the endometrium of the uterus, there is also the myometrium, which is the muscular part of the uterus that actively contracts. 3. Oxytocin acts in a positive feedback loop, which means that oxytocin stimulates the process of more oxytocin and so forth. As such, the concentration of oxytocin rapidly increases accompanied by stronger, more powerful contractions.

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4. Before the baby is able to leave the uterus, it has to push through the opening of the uterus, which is the cervix. The cervix is a disc-like structure that relaxes and widens once oxytocin has reached a certain concentration and it is this dilation of the cervix that means labour is almost complete. 5. Once the cervix has dilated, the baby pushes through the cervix and out of the vagina (the birth canal) and the umbilical cord is cut. At this stage, the baby begins to breathe for itself. Contractions continue after the baby has been born so that the placenta is removed from the uterus too.

Important
Labour is triggered by a fall in progesterone levels, which causes the release of oxytocin. In turn, Oxytocin causes contractions in the myometrium of the uterus leading to the birth of the baby.

What you should know

Fertilisation is the joining of two haploid nuclei (sperm and egg) to form a diploid nucleus (zygote). Fertilisation involves the acrosome reaction, penetration of the egg cell membrane by the sperm and the cortical reaction. Fertilisation usually occurs in one of the fallopian tubes. After fertilisation, the zygote repeatedly divides via mitosis until it reaches a point where it has enough cells to form a blastocyst. The blastocyst consists of an external chorion and an internal inner cell mass. The chorion of the blastocyst is the part of the zygote that actively implants into the lining of the uterus, the endometrium. hCG causes the corpus luteum to develop and produce enough oestrogen and progesterone to maintain the endometrium and inhibit the menstrual cycle. The placenta (umbilical cord) is the link between mother and baby that allows for the exchange of nutrients and important substances such as oxygen. The placenta takes over the production of oestrogen and progesterone approximately 40 days after fertilisation. The amniotic sac contains amniotic fluid, which protects the foetus. Labour is triggered by a fall in progesterone levels, which causes the release of oxytocin. In turn, Oxytocin causes contractions in the myometrium of the uterus leading to the birth of the baby.