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A teenage girl has sought medical care because of feelings of chronic fatigue. Upon examination, it appears that her radial pulse is rapid and weak - symptoms that would signify irregularities within the circulatory system. She is then subjected to an echo cardiogram and coronary angiograph which reveal that she is suffering from a condition termed ventricular septal defect, which is exacerbated by another anomaly - mitral stenosis, as well as sinus tachycardia. Her blood samples prove to be ailed with a negative ratio of LDL to HDL in her plasma cholesterol. It remains unclear however, how the symptoms have exacerbated each other, the chronic fatigue, or are otherwise related. It is found that the circulatory system has been manipulated in such a way that the defects within the heart are intensifying the lack of nutrients being supplied to the bodily cells, as well as impairing the girls ability to breathe and complete rapid respiration. Her high cholesterol levels are found to have no medical links to the heart conditions, however could in future evolve into the more perilous condition of atherosclerosis.
Correct Circulatory Physiology
In humans, the heart is a two-sided, four-chambered pump made almost entirely of muscle. Every blood vessel of the body is connected in some way to the heart, and in this manner, nutrient loaded and deficient blood is circulated at the required rate all around the body (Klabunde, 2011).
After its circulation, the nutrient deficient blood is pumped by powerful veins back to the right atrium of the heart. At this point, the atria are in a state of diastole, and blood can culminate inside the right atrium. From there, the blood flows passively through the tricuspid valve and into the right ventricle, where a contraction occurs and the blood is pumped through the pulmonary artery and into the lungs where it is oxygenated. The blood is pumped then into the pulmonary vein which returns it to the left atrium of the heart (now in diastole, as the ventricles are in systole). The blood flows passively through the mitral valve into the left ventricle, from which it is pumped to all the necessary blood vessels by various arteries (Johnson, 2009).
IMG. 1.0 - The heart
An important aspect of the heart is the muscly wall separating the two ventricles: the septum. The septum is extremely vital as it segregates the nutrient rich blood from that which is nutrient deficient. As such, it creates a circumstance where it is impossible for the two types of blood to coexist. If the septum were to be defective or non-existent, a situation would arise where differentiation between which blood was to be oxygenated would not be possible, thus ruining the effectiveness of the system and allowing for nutrient deficiency in bodily cells (Medicine.net, 2012).
IMG. 1.2 - Ventricular Septum: Cross-section view
Within the first month of a foetus' growth inside its mother's womb, there is no sign of either an interatrial septum or an interventricular septum (Robert H. Anderson, 2002). Throughout the second month and onwards, the interatrial septum develops over a series of stages, as do the ventricles. The ventricles are initially built with a small opening in-between called the intra-ventricular foramen. During foetal development, the foramen is gradually closed, and the large cavity is divided by the primary septum inferius, later termed the interventricular septum (Medicine & Health, 2008). However, in some humans, the intra-ventricular foramen is never fully repaired by the interventricular septum, leaving a large cavity between the two ventricles. This condition is termed ventricular septal defect, and affects approximately three out of every one thousand children born (Children's Heart Centre, 2012).
The information provided in the case study states that the girl has been diagnosed with Ventricular Septal Defect (VSD). When a heart is afflicted with VSD, it allows the nutrient rich and oxygen deficient blood to synthesise through the hole(s) in the ventricular wall. In this manner, a certain percentage of the blood is useless to the cells when it circulates around the body once again. When the cells are deprived of the essential nutrients, they do not have the necessary energy required to function properly; thus, VSD is the probable basis of the girl's chronic fatigue. Though, the percentage of nutrient rich to nutrient lacking blood can be worsened by another illness diagnosed: mitral stenosis.
The mitral valve is located between the left atrium and left ventricle. The valve has two cusps through which it allows blood to flow into the left ventricle when the left atrium is in systole. When the left ventricle contracts, the valve remains closed and the blood cannot re-enter the left atrium and so must flow through the aortic valve into the aorta and out into the body (British Heart Foundation, 2012). The valve's functions are possible due to thin strands of tissue called chordae. Through these chordae, the cusps are anchored to the inside wall of the ventricle, preventing them from turning inside out. Through rheumatic heart disease, calcification, congenital heart diseases and complex heart deformities the valve or chordae can become scarred which then prevents the valve from operating correctly - leading to mitral stenosis, and occasionally, mitral regurgitation (British Heart Foundation, 2012).
Mitral stenosis is a condition in which the scarred chordae prevent the mitral valve from opening fully, presenting a narrowed or 'stenosed' valve for blood flow. This consequently restricts the blood flow from the left atrium to ventricle, thus reducing the amount of oxygenated blood available to be pumped to the body. Mitral stenosis can lead to a myriad of issues that can be chronic and severe, including: blood coughing, shortness of breath (pulmonary edema), angina pectoris (chest pains), and fatigue.
"When the heart is not able to pump blood to the body efficiently, it can back up into the veins that take blood through the lungs to the left side of the heart. As the pressure in these blood vessels increases, fluid is pushed into the air spaces (alveoli) in the lungs. This fluid reduces normal oxygen movement through the lungs. This and the increased pressure can lead to shortness of breath." (A.D.A.M. Medical Encyclopedia, 2012).
Pulmonary edema (shortness of breath) tends to occur primarily in exercise, but can progress to affecting rest if the stenosis develops. Shortness of breath occurs due to the congestion and culmination of blood and fluids in the air sacs of the lungs. This is possible through a build-up of blood in the left atrium, which then progresses back through the pulmonary vein and into the lungs. This blood is then susceptible to being drawn up during coughing fits. Angina is generally provoked by muscle contractions or spasms in next to empty arteries due to oxygen deficiency.
Due to the aforementioned heart conditions, it appears reasonable that the girl's heart would have to contract at a greater rate to account for the extremely low levels of oxygenated blood being pumped around the body due to VSD and mitral stenosis. The general term for an irregular heartbeat is arrhythmia; however, a specifically fast heartbeat is denoted by the term tachycardia, or sinus tachycardia - also a condition that the girl is diagnosed with (Health Study, 2011). This is a feasible explanation for the girl's rapid yet weak radial pulse.
Overview of Lipoproteins
HDL and LDL are frequently discussed as the two types of cholesterol in the body. In reality, the two aren't cholesterol molecules of any kind, but rather cholesterol transporter particles - units that transport cholesterol molecules around the body to areas where they are needed, or to be converted into waste product. Their structural composition based differences helping them to direct their way to the right cells (Hendrickson, 2011).
"There are two "types" of cholesterol but only one cholesterol molecule. The body needs cholesterol to maintain normal cellular function, which is why it has mechanisms for taking it up from the digestive tract. Too much cholesterol, however, increases the risk of heart disease. For this reason, the body also has cholesterol transporters that can help rid the body of excess cholesterol" - Dr. Lauralee Sherwood, "Human Physiology."
LDL acronymically stands for low density lipoprotein. Lipoproteins are biochemical assemblies containing both proteins and lipids (bound to the proteins, where the proteins serve to emulsify the lipids), which allow fats to move through the interstitial and intracellular fluids inside and outside cells (Hendrickson, 2011). Produced in the liver, the low density lipoproteins carry cholesterol to the body's cells for uptake. "Structurally, it consists of a core of cholesteryl esters, which are modified cholesterol molecules, as well as some triglycerides, which are fats" - Dr. Reginald Garrett and Dr. Charles Grisham, "Biochemistry". This body is enclosed by a phospholipid membrane, like a common cell (Hendrickson, 2011).
IMG 2.0 - Structure of HDL and LDL
Conversely, HDL stands for high density lipoprotein, another cholesterol transporter. This molecule carries excess cholesterol, as well as other lipids from the bodily cells and returns them to the liver for excretion. This method helps to ensure that excess cholesterol is not allowed to culminate in the bloodstream. Structurally, the composition of a HDL molecule is relatively similar to the LDL molecule, with a few discrepancies. Like LDL it is composed of a cholesterol-containing core, which is surrounded by a cell membrane of phospholipids. However, the density of the core is much higher due to a greater proportion of proteins to the much less dense lipids, as can be seen in figure 2.0 (Hendrickson, 2011).
IMG 2.1- LDL Build up in an Artery
Health Concerns Associated with a High LDL/HDL Ratio
The case study makes mention of the girl having a high LDL to HDL ratio. Unfortunately, the ratio in her plasma cholesterol favours the low density lipoproteins- commonly termed the "bad" lipoprotein. High percentage of LDL is generally due to three main reasons: physical inactivity, poor dieting and alcoholism, and inherited diseases (Santander, 2009). As abovementioned, LDL are used to transport cholesterol and other lipids to bodily cells and HDL are used to remove these cholesterols from the body. As the girl has a lower number of HDL to LDL, it can be presumed that there are plaque and cholesterol build-ups occurring in her chief blood vessels as there are a limited number of HDL to remove such congestion, as can be seen in figure 2.3.
IMG 2.3 - A blood vessel with cholesterol build-up developing atherosclerosis
Congestions of plaque and cholesterol in the bloodstream cause the vessels to be at risk of developing such illnesses such as atherosclerosis and cardiovascular disease, which can lead to such complications as coronary artery disease, kidney disease, mesenteric artery ischemia, peripheral artery disease, renal artery stenosis, strokes, and abdominal aortic aneurysms (A.D.A.M. Medical Encyclopedia, 2011), of which over 25% of Americans suffer from. Atherosclerosis is most common, and is the leading cause of death in the country (Life Extension, 2012).
Atherosclerosis refers to two simultaneous problems in the arterial walls: the first being the thickening, narrowing, and stiffening of arteries, and the second - endothelial dysfunction (Fogoros, 2011). Stiffening of the arterial wall occurs when cholesterol and other substances build-up along the wall, forming hard structures called plaques, which can cause blood clots and blockages in addition to preventing the contraction and dilation of the artery (A.D.A.M. Medical Encyclopedia, 2011). The plaque can also work adversely to weaken the artery, leading to aneurysms and ruptures. Plaque also causes the necrosis of the underlying cells by starving them of nutrients and oxygen, which often leads to heart attacks or strokes.
IMG 2.4 - Damaged endothelium as a result of atherosclerosis
The outermost cells which are in contact with the plaque layer are named endothelium. In normal vascular function, these cells work to prevent blood clotting whilst acting as a selective barrier between the vessel lumen and surrounding tissue, as well as assisting in the control of blood pressure through vasoconstriction and vasodilation. When atherosclerosis occurs, it inadvertently prevents the endothelium from completing these jobs, thus causing endothelial dysfunction (Stem Cells Research, 2012).
Probable Causes of High LDL Ratio
A well-known condition known to increase the levels of low density lipoproteins is the inherited disease familial hypercholesterolemia. The condition is present at birth (passed down autosomal dominantly), and is exhibited through a raised number of LDL molecules in comparison to HDL molecules (eMedicine.net, 2012). The defect itself makes it almost impossible for the body to remove the low density lipoprotein cholesterol transporters from the blood. This is possible through an autosomal dominant mutation of the LDL receptors in chromosome 19. As the condition is present from birth, often victims suffer from angina, heart attacks and strokes at young ages, and often, patients do not live longer than 30 years (eMedicine.net, 2012).
Links between Symptoms
As previously mentioned, a high LDL content level can be caused or affected by lack of exercise, or general inactiveness. It is also found that the girl is suffering from ventricular septal defect and mitral stenosis, suffers from a weak pulse, and may also have developed pulmonary edema. It can then be further concluded and assumed that the girl may find it difficult to perform physically exerting tasks where heavy respiration is required, firstly owing to her inability to intake oxygen at an increased rate, and secondly due to her incapability of circulating the ingested oxygen through the body. As such, exercise may have been neglected throughout her life, and an increase in LDL has been intensified as a result.
Depending on what type of VSD the girl is ailing of, and how severe the case is, the girl is applicable for surgery to rectify her heart oddities. The surgeries often require open heart operation, however can be achieved using a catheter (a thin tube that is entered through the groin), and involve a patching procedure that repairs or plugs the hole in the septum (Mayo Clinic, 2012). Mitral stenosis is also corrected through open heart surgery by a procedure in which the mitral valve is completely replaced (Cleveland Clinic, 2012).
For reducing LDL levels, a doctor may prescribe statins and other drugs which reduce LDL production by over 70% (Payne, 2009). A new dietary plan, consisting of foods lacking high cholesterol levels is recommended also. "A varied diet that emphasizes plants, fish, legumes, whole grains, and fruits shows significantly powerful results at lowering problematic cholesterol" - Christopher Gardner, Stanford University. Studies show that regular aerobic exercise for a period of about 12 weeks can modestly increase beneficial HDL cholesterol-between 5 and 10 percent, and more for some people (Payne, 2009). Though not scientifically proven, theory states that endurance exercise lowers triglyceride levels and that lower triglyceride concentrations in the blood are attributed to increases in skeletal muscle and adipose tissue lipoprotein lipase activity resulting from aerobic training (Dr. Len Kravitz, 1993).
30 minutes of exercise a day and good dieting will produce less drastic results than drug ingestion, but are an accepted technique for lowering LDL levels (Payne, 2009). Less likely to work is Omega 3 - fatty acids supplements that claim to have an effect on LDL levels. Though these cannot be disproven, they have are not an official 'fix' either (Payne, 2009). Proper dieting will also help the girl ingest foods that keep her blood glucose levels higher for longer, which may reduce her feelings of chronic fatigue.
To cure Familial hypercholesterolemia a liver transplant is rarely required; however some cases are so severe that it is the recommended procedure. More often, patients are first taken through a procedure called extracorporeal apheresis. Lipoprotein apheresis is considered for patients who, in spite of the maximum amount of drug treatment and a cholesterol reducing diet, still have a high level of LDL (NHS Foundation Trust, 2012). The procedure involves placing two cannulae (needles) into a blood vessel. Blood is taken from the body and the LDL content is removed from it. This is accomplished by using a specialised adsorber column. The treated blood is then returned to the blood stream. This treatment can lower LDL content in the bloodstream by 50-65% (NHS Foundation Trust, 2012).
Past, Present and Future Concerns for Sufferers
The first surgery on the heart was performed by a Norwegian surgeon, Axel Cappelen on the 4th of September 1895 (US National Library of Medicine, 2012). Before this historical day, and for many years after, open heart surgery was a shady and unsafe medical procedure. People with congenital heart defects and diseases had no way of repairing such illnesses. As a result, many lived in suffering, and countless more died. In 1925, Henry Souttar successfully operated on a young woman with mitral stenosis; however he did not have the knowledge needed to repair the valve and the woman died several years later (US National Library of Medicine 2012, 1965).
Since then, the development of cardiac surgery and related techniques has reduced the mortality rates of these surgeries to a relatively low percentage. For instance, congenital heart defect repairs are currently estimated to have 2% to 5% mortality rate (Care Quality Commission, UK, 2009). One of the only major concerns still associated with cardiac surgery is the incidence of neurological damage: for example, strokes still occur in 2-3% of all people undergoing cardiac surgery (Care Quality Commission, UK, 2009).
One of the major hopes for the future of heart surgery is to be able to grow a completely new heart from stem cells. Researchers at the University of Minnesota have discovered that the cultivation is possible; however no fully-functioning and beating heart has yet been grown (White, 2011). The revolutionary idea would aid in circumventing ethical issues related to donating organs, and transplanting; however it may raise ethical issues of its own. Many people are concerned that humans should not attempt the growth as it is viewed as an attempt to "play God". Relatedly, a team of researchers at the University of Miami have proven that damaged heart tissue can be repaired by inserting the patient's own stem cells directly into the heart. The Miami scientists have already recorded a substantial reduction in scar tissue and a noteworthy enhancement in heart function (White, 2011).
By exploring the anatomical structure of the circulatory and respiratory systems, it has become apparent that the girl's chronic fatigue is probably caused by VSD, mitral stenosis, diet, and possibly pulmonary edema, which has prevented her from exercising, resulting in the accumulation of low density lipoproteins in her bloodstream. This could lead to the further issues of atherosclerosis, strokes, heart attacks, arterial aneurysms, and blood haemorrhages; though with proper treatment her LDL levels can be effectively reduced. However, surgery may have to be completed on the girl's heart as the two defects exacerbate each other in a dangerous manner.