2015 Organ Replacement ANSBRO, SEAN P Organ Replacement Sean Ansbro Dear Rod Keller Attached to this letter is the research that has been observed and collected in regards to the liver and those who receive liver transplants, those include transplants that involve organically grown organs created in a lab from the cells of the patient and organs that have been created artificially from inorganic compounds or components, these include purely mechanical components or components and polymers that have been created to simulate the effects of organic material. I am thankful for you allowing permission for me to look into this subject. Sincerely, Sean Ansbro, Abstract The research contained in this report pertains to the medical field, more precisely the science of biological rejection of major organs at the cell level. This is caused by the body’s immune system, the one that receives that organ, finding the sugars on the cells of the organ lacking the correct structures to be determined as part of the whole self. This “other” sugar causes the correct response as the body kills the outside cells causing the organs functionality to decline and is usually coupled with flu like symptoms and in some extreme cases, internal hemorrhaging. The scope of this research to find alternatives to using organs gained though donations that are better compatible to the receiver of the organ, to work around the issue of rejection mechanical and lab grown organs are becoming a real possibility and primitive mechanical structures are being used in the medical field at labs and hospitals as a way to replace certain functions in the organ and body iv Table of Contents Introduction Sub-part 1 – Overview………………………………………………………………….....1 Sub-part 2 – Inform about subject………………………………………………………...2 Part 1 Sub-part 1 – Introduction………………………………………………………………….2 Sub-part 2 – Bile and Digestion…………………………………………………………...3 Sub-part 3 – Metabolism…………………………………………………………………..4 Sub-part 4 – Detoxification………………………………………………………………..5 Part 2 Sub-part 1 – Rejection of Organ…………………………………………………………..6 Sub-part 2 – the Criteria…………………………………………………………………...6 Sub-part 3 – Grown Organ………………………………………………………………...7 Sub-part 4 – Synesthetic Organ…………………………………………………………...7 Sub-part 5 – Considerations and Recommendation……………………………………….8 Part 3 Sub-part 1- Replacement issues…………………………………………………………...8 Sub-part 2 – Pros and cons……………………………………………………………….10 References………………………………………………………………………………..12 1 Sean Ansbro Report Writing May 5, 2015 Research Report (Draft 1) Introduction Sub-part 1 – Overview The failing of the human body are quite obvious to anyone who has seen the human body age over a short period of time, things that seemed to be at their peak of functionality fail and unlike a machine, these parts have major difficulties when being replaced. These issues usually fall under certain things such as rejection, infection, incompetence, and disagreeable lifestyles that continue to harm the replaced part. The primary premise for the paper is to outline the effects of transplants on the human body using artificial non-organic created organs, and the effects of organically grown organs in a lab that are grown from the cells of the patient who will receive the transplant. The effects on the body can and will vary from the type of 2 implant/replacement and if the patient’s body rejects the organ in the short term or the long term. What will be looked at is the cost of both implants and the time to create/grow the organ, along with the time the organ can and will remain functional. Sub-part 2 – Inform about subject Part one will discuss what the organ that will be replaced does in a healthy patient, along with this, the issue that will be touched upon later in the paper will be introduced. The organ that will be used as the example is the liver, which is a key organ in the human body. Part two will go into detail about how each replacement works. The pros and cons of each will be discussed, though even if one comes out to be better than the other, both will be used to explain how transplants work and the dangers and survivability of such operation. Part three will use previously stated data to answer how an artificial liver will react to an older male, 50 to 70 years old with a lifestyle that has been straining on his liver. Part 1 Sub-part 1 – Introduction The liver’s processes can be broken down into sub topics dealing with substances at the chemical level, these topics will include the digestion part or bile, the effects and role it plays in metabolism, and how it removes toxins from the body and how it works is key to understanding how to replace this vital organ with an artificial mechanism. The process that will be described is the basic functions that it plays in detoxification, hormone production, synthesis, and glycogen regulation. Located above the stomach in the abdominal cavity, rest the liver. This key organ 3 preforms processes that keeps are bodies alive with Digestion and detoxification. I shall explain the processes it carries out as one observing the processes and when I am done. One reading will have a better understanding as to how the organ functions. Sub-part 2 – Bile and Digestion Nutrients are absorbed into the lymph system from the small intestine and Non-lipids are sent to the liver directly. Lipids are sent though a lymphatic canals and deposited into the circulatory system just before the heart. The lipids then travel though the heart and the circulatory system before reaching the liver, any damage that would be done by these chemicals and lipids may have a chance to be done to the heart and body before reaching the liver and kidneys. Bile is injected into the small intestine from the liver via a drainage canal. This is a major aid in the digestion of lipids and acts as a filter to attempt to stop large amounts of fats entering the blood stream due to the ineffective way of treatment. Bile in a solution that contains water, electrolytes and other organic molecules usually in varying amounts due to the individual. (Bile acids, cholesterol, phospholipids and bilirubin). This organic solution is stored, processed, and then later concentrated in the gallbladder. In the gall bladder, bile is concentrated due to the action of water being absorbed by the surrounding tissue in the act of osmosis, the removal of water leaves virtually all organic compounds in the solution. Bile works to aid digestion by Emulsifying lipids Emulsifying is the act of suspending one solution of lesser amounts in another solutions, these solutions will normally separate due to the denser fluid being pulled towards gravity, though any force applied will cause them to become mixed again. 4 Bile breaks down lipid chunks into smaller particles. The reason for smaller particles is to increase surface area to make it easier to digest by lipases (enzymes that causes hydrolysis of lipids). Also Bile aids in the transportation of toxins in water environments by being able to emulsify lipid molecules. This is key for certain vitamins to be absorbed by fats. Sub-part 3 – Metabolism The liver preforms the process of gluconeogenesis to create glucose to be used by the body. To perform this function the liver requires access to non-carbohydrate substrates. The process occurs more specifically in the mitochondria of the cells. In the cells the molecules undergo a reaction that starts with the use of an ATP and uses pyruvate. Oxaloacetate is produced then reduced to malate using a NADH and is removed from the mitochondria. Malate is oxidized and made into Oxaloacetate. Oxaloacetate undergoes decarboxylation and then undergoes phosphorylation to create phosphoenolpyruvate. Water is used to remove one phosphate creating Glucose-6-phosphate. Lastly Glucose-6-phosphate is hydrolyzed to make Glucose. The product is moved to the Endoplasmic Reticulum’s membrane. Sub-part 4 - Detoxification Enzyme break down is one of the two ways for the liver to detoxify the body. The enzymes work along with oxygen to destroy and process the outside toxins that have entered the body. Enzymes transfer the toxins that are lipid soluble to water soluble compounds. This is considered phase one of detoxification and this prepares the toxins for stage 2. After being converted to water soluble forms certain short comings of phase 1 come to light. Phase 1 fails to make the toxin water soluble enough to complete the whole pathway. And 2, some toxins are 5 now more destructive due to the change. Phase 2 deals with these issues by decreasing the toxicity and increasing the solubility. Stage 3 deals with transportation of the now water soluble toxin. Proteins are used to remove and transport the toxin though and out of the body, these are called ABC transporters and they require chemical energy (ATP) to function. Though these cells can harbor cancer cells during chemotherapy. The second way is for the liver to use semi-destroyed toxins and combine with sulfur or amino-acids that can be removed though bile or urine. Part 2 Sub-part 1 – Rejection of Organ Rejection in the medical field rejection can mean death for the patient who was rejected, this can be blood, organ, or marrow transplants that fail to be accepted by the human body. When the body rejects outside elements that have invaded its domain, whether due to a medical professional, artist, or due to an unforeseen accident, it can cause more harm than good when it tries to deal with and remove the outside substance or object. The effects of rejection can be easily observed when blood is administered to from one to another and the type is incompatible to the receiver. This results in the body’s immune system attacking the unknown blood. Some basic symptoms for blood rejection include, body pain, bloody urine, dizziness, and flushed skin. 6 While long term effects include anemia, lung failure, and kidney failure. These effects are amplified when an organ is placed into another person. The problem when artificial organs and home grown organs are used is the body rejection. What I will describe is the effects of internal metal rejection and organ rejection. Also I will include what happens when an organ is accepted to a degree and how the immune system can be suppressed and tricked to allow artificial organs can be used and whether home grown parts or built organs are the better choice. Sub-part 2 – the Criteria The criteria that will be looked at is the price for the receiver, time for production of the organ, current technology, will it be rejected by the body, lifespan of the replacement, and efficiency of the organ. This requirements for the organ will be looked at. This report is meant to create an educated prediction of the technology that will be present in the next five to ten year, using current scientific research as a bases for the prediction. Sub-part 3 – Grown Organ Let’s start with the homegrown organs or what they are better known as, lab grown organs. The major benefit of tissues and organs grown in a lab is that the starting cells for it are usually taken from the patient who will receive the product. This dramatically reduces the chance of the organ or tissue being rejected by the body to the point of being zero. This means that the person in need of the organ will not have to spend their entire life or sections of their life on an immunosuppressant so the body won’t reject the organ. Although in less severe cases, the method to create organs and tissue can be used to repair, not replace, damaged organs. The cons are that the organ must be grown from a base amount of cells and may be weaker for a time then an adult organ. Though with certain recent creations and innovations, such as the 3-D printer, 7 which the base idea has been modified to use a cellular matrix instead of plastic in some place of the world. The major drawback now is the cost to produce complex organs. While arteries and hallow transport ways in the body are possible today, whole organ growing is still in the experimental stages of devolvement. Sub-part 4 – Synesthetic Organ The second option is to forego the organic component of organ replacements and supplement the damaged or operational organ or tissue with a mechanical replacement. Similar to laboratory growth of organs, mechanical organs have a range of verities that are even used today. One of the mechanical additions that can be added to those whose heart is weak or has an odd rhythm is the pacemaker. What this does is supplement the organic pacemaker that already exist in the heart. In addition to this external machines already exist that replace and supplement internal organ function. One machine function is to perform liver and kidney dialysis. Some mechanical organs look similar to the grown ones and some or grown, though the difference is one uses cells and the other uses a polymer mesh in they’re place. Using organic polymer instead of the inelegant metal that is used today is a way the false organs can be used without the risk being rejected by the patient’s immune system. Sub-part 5 – Considerations and Recommendation Looking at both methods of organ replacement, the cost for both, if similar methods are used, are the same. Though the amount of time they can be used varies considerably. The organ grown from semi-organic polymers are designed to be degradable, while the organic, cellular organ is designed to be lifelong. Or, as long as the organ doesn’t undergo the same damage the 8 obsolete one did. This may mean a change of lifestyle for some. Both can be produced mostly in the same location and time requirements for their production don’t vary by that much. Considering the breakdown of the polymer required, the cellular grown organ seems to be better than the organic polymer organ. Since both have the same restraints and benefits almost, the choice of the organ should be up to the medical staff and what is at hand for production or what can be created quicker. Part 3 Sub-part 1- Replacement issues This section will contain info relating to post surgery problems that arise in patients who receive liver transplants. Post-surgery symptoms can include infection can occur in the area were surgery occurred and even areas far connected to the operated area. The strain even mild surgeries place upon the body can increase cortisol levels and cause the immune system to overreact due to the damage and because more harm, this can lead to a weakening of the body’s immune system. Localized infection can occur at the site of operation due to outside agents that sometimes enter though the opened cavity, these can cause more severe problems that will require antibiotics or surgery to clean away the infection. Blood infection can occur when localized infections enter and spreads though out the circulatory system, this is intensely problematic as the infection can be transported to other important organs and cause damage, though both the brain and heart are mostly what is worried 9 about. As well as having the infection damaging other organs the body’s immune system may attack the infection and cause more damage than good. The primary concern is rejection, even if all that can be done is done to allow the body to assimilate the organ, it still may reject it due to slight differences in the sugars on the cell’s surfaces. Drugs that are administered during surgery may have an adverse effect on the patient, including neurological damage and farther organ damage. In the case of cancer removal, the cancer may grow more rapidly if nay cells are left behind in the local area, this is due to the weakened immune system of the body after and during surgery. High blood pressure and increased levels of cholesterol may occur after surgery. When the body is stressed, mentally and/or physically, cortisol is released into the body’s systems along with the previously stated symptoms, it can also suppress the immune system. Diabetes can occur after a surgery due to poor blood flow to the liver and kidneys. During surgery most doctors focus on maintaining function in the heart and the brain, other organs usually are not taken care of as much as needed, one is the kidney, who quickly dies and loses function do to poor blood flow to it and the local area of the body. More obvious symptoms that can show that something a faulty can occur after surgery. These can include Jaundice, the yellow pigmentation of the body’s tissue due to a failing and faulty liver, due to an increase of bilirubin in the system that has been deposited in the tissue of the skin, and in the sclera of the eye. Fever will be promenade in those who reject the organ, this is due to the body’s immune system activating and attempting to kill of the foreign cell or organ that has invaded the body, also Nausea can happen, which is a basic symptom of immune reaction. The reaction the body will have to the chosen organ that will be placed into it will vary depending on the type and how it 10 was made. External mechanical livers offer a fix for liver failure, yet these do have their flaws. The patient will need constant medical care as the machine needs maintenance and cleaning. Sub-part 2 – Pros and cons The patient will have to be bed stuck for long periods of time if the machine used is meant to replace the liver, not support it. Internal organs that are created using a plastic polymer mesh and cover offer benefits that the large external variants can’t. Patients can carry one a relatively normal life as if the organ they received was from a donor without fear of it rejecting them later in life. A con of polymer organs is that they may require more surgery to be replaced again as the polymer may break down over time. The best option for organ transplants may be lab grown organs that use the cells of the patient to grow it, in this sense that patient is the donor. Benefits of this is that there is near zero chance of the body rejecting the organ. The organ also will not break down like a polymer organ. This is not accounting for the aging of the liver though a normal life. 11 References (n.d.). Retrieved June 1, 2015, from http://www.ed.ac.uk/news/2014/livingorgan-250814 (n.d.). Retrieved June 3, 2015, from http://www.bbc.com/news/health-28887087 An organ shortage is killing people. Are lab-grown organs the answer? (2014, November 20). Retrieved June 1, 2015, from http://www.vox.com/2014/11/20/7252365/lab-grownorgans Artificial Organs. (n.d.). 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