2. A2 Biology

3. INDEX PAGE THE ENDOCRINE GLAND THE EXOCRINE GLAND HORMONES AND TARGET TISSUE 1 ST AND 2 ND MESSENGER (ADRENALINE AND cAMP) FUNCTION OF THE ADRENAL GLANDS HISTOLOGY OF THE PANCREAS BLOOD GLUCOSE REGULATION CONTROL OF INSULIN SECRETION TYPE 1 AND TYPE 2 DIABETES MELLITUS INSULIN FROM GM BACTERIA IN STEM CELLS AND TREATMENT HORMONAL AND NERVOUS MECHANISMS INVOLVED IN HEART RATE

4. HORMONES AND GLANDS HEINEMANN BIOLOGY 1.1.10, 1.1.11, 1.1.12 START -- THE ENDOCRINE GLAND

5. HORMONES AND SIGNALLING The endocrine system is the bodily communication system into which substances such as hormones are directly secreted. Using blood vessels as pathways to target cells, the endocrine system is useful when the body needs to transport messages over long distances, targeting specific cells in bulk. It is worth noting that for obvious reasons the endocrine system is not as fast as the neuronal system, but not all parts of the body are directly connected to a nerve and a nervous response may not always be appropriate, so endocrine glands come into play here. The glands themselves are ductless (unlike exocrine glands) and secrete straight into capillaries. Exocrine glands secrete their product (non-hormonal) into a small duct, not a blood vessel, that will carry it to somewhere else. The messengers of the endocrine system (hormones) exist in two forms; steroid hormones and protein/peptide hormones. Protein hormones are amino acids and their derivatives and are insoluble in the phospholipid bilayer and so do not enter the cell. Steroidal hormones are able to pass into the cell and have a direct effect on the DNA of said cell. In order for hormones to carry out their function, they must communicate with a cell or group of cells (tissue) so that a response may take place. For this to happen, the target cell must possess the cell surface receptor complementary in shape to the hormone. In this fashion, a hormone will bind to the receptor site and cause a change within that cell. As all hormones are different, a large amount can be released into the endocrine system and still only target a few cells; there is a large element of specificity.

6. ENDOCRINE SYSTEM

7. ADRENALINE AND THE ADRENAL GLANDS As a hormone of amino acid derivative, adrenaline is unable to enter it’s target cell and so must cause a change by binding to a cell surface receptor. The specific receptor is on the outside of the plasma membrane and is associated with an enzyme on the inner surface membrane called Adenyl Cyclase. When adrenaline binds to it’s complementary receptor we say it is acting as the first messenger, activating the associated AC enzyme and causing it to convert ATP to cAMP (cyclic AMP). This cAMP molecule is said to be the second messenger, as it then goes on inside the cell to cause other responses by activating enzyme action. ADRENALINE (FIRST MESSENGER) APPROACHES RECEPTOR SITE ADRENALINE BINDS, ACTIVATING ADENYL CYCLASE ADRENALINE-RECEPTOR COMPLEXFIRST MESSENGER APPROACHESATP ----------------------------> cAMP SECONDARY MESSENGER PROCESS INITIATED INSIDE CELL IN OUT IN OUT IN OUT

8. ADRENALINE AND THE ADRENAL GLANDS The adrenal glands are located anterior to/just above the kidneys and have a medulla and a cortex region that control two main different processes. The medulla is found at the centre of the gland and is responsible for the production and release of the hormone adrenaline in response to pain and shock. Most cells have adrenaline receptors as it’s main function is to prepare the body for activity. Specifics of this purpose are listed below... - relax smooth muscle in the bronchioles - cause pupil dilation - cause general vasoconstriction to increase blood pressure - increase stroke volume and heart rate - decrease activity in the gut - increase mental awareness - stimulate conversion of glycogen to glucose - cause body hair to erect The adrenal cortex produces steroid hormones from cholesterol, which have a variety of roles within the body. The mineralocorticoids (like aldosterone) help control the concentration of sodium and potassium in the blood, whilst the glucocorticoids (like cortisol) help to control the metabolism of carbohydrates and proteins in the liver.

9. HISTOLOGY OF THE PANCREAS Oddly, the pancreas is an organ that has both an exocrine and an endocrine function. It is located underneath the stomach and is responsible for the production and secretion of bile, as well as the monitoring of blood glucose concentrations. The exocrine function of the organ is thus; cells gathered in small groups around tubules secrete digestive enzymes into the tubules, which themselves join up to form the pancreatic duct. The fluid travels in this duct and contains a mixture of amylase, trypsinogen, lipase and sodium hydrocarbonate. The latter is alkaline and helps to neutralise the contents of the stomach so that enzymes may work. The endocrine function of the pancreas is to monitor glucose concentrations via cells in the Islets of Langerhans, that produce insulin or glucagon appropriately. Alpha cells in the Islets are responsible for the production of glucagon (detect too much glucose) and the beta cells are responsible for the production of insulin (detects too little glucose), both of which are secreted directly into the bloodstream via the Islet’s copious blood supply.

10. GLUCOREGULATION The concentration of glucose in the blood is carefully regulated and monitored by the alpha and beta cells in the Islets of Langerhans. Deviations from the normal levels of 90mg per 100cm³ are detected by these cells, which release hormones according to the direction in which levels have travelled. If the concentration is too high, then this is detected by alpha cells, which secrete the hormone glucagon. If the concentration drops, then beta cells secrete insulin to bring levels up again. After secretion from the beta cells, insulin travels in the blood until it reaches its target cells; hepatocytes, muscle cells and some other cells. The hormone will bind with specific (complementary) receptors on the cell surface and cause the associated adenyl cyclase to become activated, converting ATP to cAMP. Through this insulin causes; more glucose channels to be placed in the cell membrane, more glucose to enter the cell, glucose to be converted to glycogen (glycogenesis), more glucose converted to fats and also more glucose to be used in respiration. Conversely, glucagon targets only hepatocytes where it binds to a specific receptor and causes glycogen stores to be converted to glucose (glycogenolysis), fats and amino acids to be converted to glucose (gluconeogensis) and also causes more fatty acids to be used in respiration. INSULIN CAUSES BLOOD GLUCOSE LEVELS TO FALL, GLUCAGON CAUSES BLOOD GLUCOSE LEVELS TO RISE

11. CONTROL OF INSULIN SECRETION K+ ATP CA2+ K+ POTASSIUM ION CHANNELS IN THE CEELL MEMBRANE ALLOW K+ TO FLOW OUT HIGH GLUCOSE CONCENTRATIONS CAUSES GLUCOSE TO ENTER THE CELL GLUCOSE IS METABOLISED TO PRODUCE ATP ATP CAUSES POTASSIUM CHANNELS TO CLOSE, AND THEREFORE A CONENTRATION GRADIENT TO BUILD UP, SO THE CELL BECOMES LESS NEGATIVE THAN IT’S ENVRIONMENT CHANGE IN POTENTIAL DIFFERENCE ACROSS THE MEMBRANE CAUSES VOLTAGE GATED CA2+ CHANNELS TO OPEN CALCIUM IONS IN THE CELL CAUSE INSULIN IN VESICLES TO BE RELEASED BY EXOCYTOSIS ß CELL 1 2 3 4 5 6 K+

12. DIABETES MELLITUS The control of blood glucose concentration is a simple negative feedback mechanism that helps keep the concentration near where it needs to be (bearing in mind it will always fluctuate due to meals, exercise etc). Hypoglycaemia is where blood glucose levels get too high, hypoglycaemia is where they drop too low, both can happen in diabetes mellitus. Type 1 diabetes results from the inability of the beta cells to secrete insulin and can also include cell receptors for insulin not working as they should. It is thought that the body attacks the beta cells as part of an autoimmune response but it can also result from a viral infection. It usually begins during childhood and is treated via insulin injections administered according to information given by monitoring apparatus. Type 2 diabetes is the type in which have reduced responsiveness to insulin, probably due to a decreased susceptibility of the insulin receptors on the liver and other target tissues. This type of the disease can be brought on by obesity, Afro- Caribbean heritage, high sugar (particularly refined) diet and a history of it in the family. It is treated by careful monitoring of the diet and following strict eating guidelines. Insulin injections can supplement this treatment, as well as drugs that slow down the absorption of glucose from the digestive system. Insulin used in the treatment of diabetes used to come from the pancreas of pigs, but nowadays we use GM bacteria. These bacteria have had the gene for human insulin inserted into their DNA so that they produce the hormone. This is advantageous over the previous method, as; it is more ethical, there is less chance of rejection due to an immune response, there is less chance of infection and developing a tolerance, it’s cheaper, more adaptable to demand and the end product is an exact replica of human insulin, so it’s faster and more effective than animal insulin.

13. CONTROLLING HUMAN HEART RATE The heart pumps blood around the body so that cells may receive glucose, nutrients and oxygen, whilst becoming free from potentially metabolic-inhibiting waste products like carbon dioxide and urea. As requirements vary according to activity, the rate at which fresh nutrients and oxygen are supplied and wastes removed will need to change so that cells may function correctly. When cells need more oxygen and glucose, the heart rate increases, it’s strength of contractions increase and the stroke volume also increases. As a myogenic muscle, the heart controls it’s own contractions thanks to it’s SAN and AVN. The SAN initiates a wave of excitation across the aortic walls, which stimulates contraction and then is picked up by the AVN. This node then re-sends the excitation down the Purkyne tissue between ventricles to the apex, where it travels back up over ventricular walls and stimulates contraction. The SAN is supplied by nerves from the medulla oblongata of the brain, which do not initiate the excitation, but can effect the frequency of contractions. The accelerator nerve is used to increase the frequency; the vagus nerve to decrease it. Adrenaline in the blood can also affect the muscle directly.

14. CONTROLLING HUMAN HEART RATE DETECTORRESPONDING TOCOURSE OF ACTION Stretch receptors in musclesMovement in the muscles i.e. during exercise Causes the heart to prepare for the possibility of increased oxygen demand by increasing contraction frequency via the accelerator nerve. Chemoreceptors in aorta, carotid arteries and the brain Fluctuations in the blood pH levels, caused by an increase or decrease in the amount of CO2 in the blood, which can react with water in the plasma to for carbonic acid Causes impulses to be sent from the receptors to the cardiovascular centre in the brain, where the frequency of contractions increases via the accelerator nerve, or decreases via the vagus nerve (appropriately). HeartAdrenaline in the bloodPrepare the body for activity by increasing heart rate Stretch receptors in walls of carotid sinus (a swelling in the carotid artery) Fluctuations in blood pressure i.e. during or after exercise Causes impulses to be sent to the cardiovascular centre where the heart rate is changed accordingly

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