Your Uncle not the same as last time who has been taking clopidogrel for a number of years approaches you, a dental student, to explain something to him. After two weeks of weariness and fever, his doctor recently diagnosed Infective Endocarditus by blood cultures. An echocardiogram indicated a bicuspid aortic valve, and listening to the chest using a stethoscope the doctor could also detect a slight murmur. His doctor had asked him whether he had had any dental treatment recently. He admitted that he had not seen a dentist for a number of years and a cursory investigation revealed dental caries and inflammation of the gums. His reason for avoiding the dentist was because of bleeding in the mouth following visits.
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Your Uncle was quizzical about a number of things and has asked for your advice. He wants to know what information the echocardiogram and stethoscope can reveal. Further, he wants to understand the connection between oral health and an individual’s general medical condition. Specifically, what oral bacteria are present, what roles do they play in oral biology, how they could cause systemic problems, and what sort of strategies could be employed to prevent infection.
Working in your groups, generate a list of leaning outcomes for this topic and return an individual copy by 23rd November by email to email@example.com.
These learning outcomes will be assessed, and intended learning outcomes returned to assist you with your report.
Individually write a 2000 word manuscript in a scientific manner addressing the learning outcomes by 7th January (2013) and upload via QMplus. Please note that with QMplus the time ‘cut-off’ is 23:55.
1. To identify the connection between clopidogrel and excessive bleeding gums.
2. To describe normal and abnormal heart valve formations.
3. To understand and describe the information that echocardiograms and stethoscope can provide regarding heart function.
4. To explain how oral derived bacterial flora can colonise heart valves.
5. To explain why the heart valves are susceptible to bacterial colonisation.
6. To describe when prophylactic antibiotics should be prescribed prior to oral treatments.
Bacteraemia is a condition that is caused when bacteria enters the blood stream. When large amount of bacteria are present in the blood it can cause infections such as meningitis, pericarditis and endocarditus. Individuals with heart valve disorders, prosthetic joints, chronic diseases or weakened immune system are at increased risk of developing infections during Bacteraemia. Dental induced Bacteraemia is caused by minor injury from tooth brushing or from dental procedures. In the above problem based learning scenario we have been presented with ‘our uncle’ who has been taking Clopidogrel for a number of years and has now been diagnosed with Infective Endocarditis by blood cultures. Below I will expand on the proposed learning outcomes.
 FIG.1Identify the connection between Clopidogrel and excessive bleeding gums.
Clopidogrel is an oral antiplatelet drug which reduces the risk of blood clots forming. It works by preventing Adenosine diphosphate (ADP), which causes platelets aggregation, from binding to its P2Y12 receptors on platelets and stops activation of the glycoprotein GPIIb/IIIa complex. This prevention reduces the likelihood of clots forming.  Source:Harvey, R; Champe, P “Lippincott illustrated reviews: Pharmacology”, 4th edition. LWW: 2009.
Blood clots can be very dangerous as they can cause blockages of blood vessels reducing the blood supply to an organ. A reduction in blood flow to the brain or heart can cause a stroke or heart attack. This explains Clopidogrel’s biggest use in patients who have had a recent heart attack or stroke; it helps to stop a reoccurrence. 
Taking Clopidogrel therefore can cause excessive bleeding gums. If a blood vessel ruptures when brushing the teeth, through dental treatment or even by eating the gums will carry on bleeding for longer than usual because of the lack of platelet aggregation. http://birthnow.com/wp-content/uploads/2012/05/Clopidogrel.gif
Describe normal and abnormal heart valve formations.
A healthy human heart consists of four chambers; two upper atria and two lower ventricles and four valves; two semilunar and two atrioventricular valves. The aortic and pulmonic valves are both semilunar valves and found in the arteries leaving the heart. The tricuspid and mitral valves are the atrioventricular valves and are found between the atria and ventricles. 
Valves are made up of cusps which basically act as flaps or leaflets that are responsible for the one way flow of blood going into and out of a ventricle. Each valve has three leaflets, except the mitral valve, which only has two.
 FIG.3Strong fibrous cords called chordae tendineae also known as heart strings are attached to the papillary muscles found on the floor of the ventricles and they act as anchors to stop the valves from inverting back into the atria. When the valve closes the papillary muscles contract and tenses the chordae tendineae to ensure the one way flow of blood. The valves are also supported and surrounded by a fibrous skeleton called annuli that also acts as another anchor. http://www.tokresource.org/tok_classes/biobiobio/biomenu/transport_system/heart-valves.jpg
 FIG.4Blood flows from the right and left atria into the ventricles through the open tricuspid and mitral valves respectively. When the ventricles are full, the tricuspid and mitral valves shut. The ventricles now begin to contract and the pulmonic and aortic valves are forced open and blood is pumped out. Blood from the right ventricle passes through the open pulmonic valve into the pulmonary artery and carries deoxygenated blood to the lungs while blood from the left ventricle is oxygenated and travels through the open aortic valve into the aorta and goes to the rest of the body. This happens in a cycle, between heartbeats the ventricles will then relax, the semilunar valves will close and the atrioventricular valves will open and allow blood from the body and lungs to enter the heart. http://mitral-valve-repair.com/wp-content/uploads/2011/01/heart-valves_heart-chambers.jpg
Heart valves can however malfunction in several ways. Abnormal heart valve formations fall into two main groups; Regurgitation and Stenosis. Regurgitation of the valves is when they fail to close properly which causes the backward leakage of blood, this is often happens as a result of coronary heart disease, rheumatic heart disease or because or bacterial and viral infections including infective endocarditus. 
Mitral regurgitation is the most common heart valve disorder being found in 20% of adults over the age of 55. 
The backward leakage of blood causes an increase in atrial pressure and the wall of the left atrium will thicken by hypertrophy and possibly dilate. The pulmonary venous pressure will also rise which produces pulmonary oedema (fluid accumulation in the air spaces).It also reduces the blood supply to the rest of the so the left ventricle will also become thicker and the heart rate will increase to try and maintain normal cardiac output. Symptoms include shortness of breath, chest pains, dizziness and the pulse becomes faster.  
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Stenosis of the heart valves occurs when the valve is narrowed and obstructs the forward flow of blood, it is usually a result of a congenital defect which has caused the valve to become inflamed or calcified.
 FIG.5 Aortic Stenosis Aortic valve Stenosis is one of the most common valve disorders, when the valve doesn’t open correctly there is reduced blood flow from the left ventricle into the aorta. In severe cases the walls of the left ventricle will become thicker as it has to work harder to maintain cardiac output into the aorta. Symptoms include dizziness, chest pain and an irregular heart beat. If the condition worsens it can lead to heart failure and more uncommonly to endocarditus.http://www.heart-valve-surgery.com/Images/aortic-stenosispicture-275.jpg
Aortic Stenosis develops over time because or turbulent blood flow through a usually bicuspid aortic valve. Calcific valvular disease is an inflammatory process and the biggest cause of the disorder, calcification of the valve makes it very stiff and makes it difficult for the valve to open easily. Again as with regurgitation rheumatic fever and endocarditis are also causes of Stenosis.  
Valve deformations are more common in the left side of the heart but they do also occur in the right hand side. Stenosis and regurgitation can affect all four valves and not only the two mentioned above.  Other abnormal valve formations are congenital heart valve diseases which are those present at birth when the aortic or pulmonary valves don’t form properly.
Understand and describe the information that echocardiograms and stethoscope can provide regarding heart function.
Echocardiography is a non-invasive technique used to assess cardiac structure and function by the use of ultrasound. Echoes are used to listen for congestion in the lungs, irregular heartbeats and murmurs. 
There are several types of echocardiograms; transthoracic (TTE) are the most common. A device called a probe or transducer is placed on the chest and high frequency sound waves are used to produce sounds and images of the heart. It picks up echoes of sound waves and transmits them as electrical impulses which are then converted to 2D or 3D moving pictures on the screen. A Doppler echocardiogram shows the movement of blood. If a clear picture cannot be formed a small amount of liquid can be injected via IV to give a better picture. 
Echocardiograms show details of the chambers including size, volume and thickness of the walls which helps to identify certain disorders including hypertension, the pumping function can also be reviewed and this can show conditions such as cardiomyopathy. Echoes also help with diagnosis of heart valve disorders including those mentioned above. It identifies the basic structures of the valve including thickness and movement and shows any abnormalities such as calcification and scaring. The Doppler will show any leakage through the heart valves and if there is a restriction in blood flow.
Echoes of mitral regurgitation will show a dilated left atrium and left ventricle and echoes of aortic Stenosis will show the thickened calcified leaflets.
In cases of suspected endocarditis a transesophageal echo can be used instead to show high-quality images of the heart and its valves. It is slightly more invasive and a long tube is passed down the oesophagus. 
A stethoscope is a non invasive diagnostic instrument used to listen to or auscultate a patient’s heart, lungs, pulse and abdomen. It can also be used to help check blood pressure by listening to blood flow restoration when the sphygmomanometer cuff is removed. The diaphragm is placed on the patient’s chest where it picks up vibrations and amplifies them as sounds to the earpieces going via a hollow tube. http://upload.wikimedia.org/wikipedia/commons/3/3c/Stethoscope_(PSF).png
A healthy heart produces a double beat or ‘lub dub’ with little other sound when the semi lunar valves open and close. A stethoscope helps detect a heart murmur which makes a whooshing sound after the heart beat, this can indicate serious other problems such as infective endocarditis. 
 FIG.6 S Mutans adhering to surface of mitral valve Explain how oral derived bacterial flora can colonise heart valves & Explain why the heart valves are susceptible to bacterial colonisation.
Streptococcus mutans are a type of bacteria found in dental plaque of the oral cavity that is largely responsible for causing tooth decay and cavities via the process of demineralisation. However on occasion after dental treatment or from brushing the teeth if blood is exposed it can enter the blood stream and cause bacteraemia. Diseased Aortic Valve
Endocarditis typically develops on surfaces of the heart, which have become rough and sticky after sustaining endothelial damage after being subject to turbulent blood flow. (In bicuspid valves blood flow is more turbulent and this creates a high pressure which makes the surface of the valve rough and more susceptible to bacterial colonisation). 
Platelets and fibrin attach to the endochardium surface and form a platform which the bacteria can attach to; ‘vegetation’ is now formed. This vegetation can damage the heart valves and affect how they open and close, or breakaway and cause complications in other areas of the body. The aortic and mitral valves of the left side of the heart are the most common to be affected. S mutants are thought to be responsible for 50% of all bacterial endocarditus cases. Staphylococci found on the skin can also cause it. 
The risk of developing endocarditis is increased in a person who has already got artificial heart valves, general heart valve conditions, congenital birth defects, rheumatic fever and those with a lowered immune system.
The problem with when bacteria colonises heart valves is that the valves don’t have a designated blood supply to them so white blood cells are unable to fight the infection that is forming there.  Full-size image (41 K)
 FIG.7 Transthoracic echocardiogram (a) and apical four-chamber view (b) demonstrating a well circumscribed vegetation measuring 2 Ã- 1 cm, confined to the posterior mitral valve leaflet and impinging on the left atrium.
Describe when prophylactic antibiotics should be prescribed prior to oral treatments.
The term prophylactic antibiotics refer to when antibiotics are given prior to an event as a preventative measure to infection. ‘Where rheumatic fever is still common, control and prevention will prevent rheumatic heart disease and associated endocarditis.’ Previously people with heart valve conditions and artificial valves were thought to be at high risk of developing endocarditus when receiving dental treatment and other surgical operations so a treatment of antibiotics, usually penicillin were given prior to the procedure in question. Today however this practice is questioned as there were no placebo trials conducted. The large scale use of penicillin as a preventative measure comes with risks such as anaphylactic shock so now as recommended by the National Institute for Health and Clinical Excellence (NICE) it is mainly only offered to those patients who have an infection beforehand and those with artificial valves.
In conclusion to this PBL I now understand that the presence of bacteria in the blood can have serious consequences all over the body and not just at the site of entry. In answer to ‘my uncles’ question about preventing infection it would be worth noting that meticulous oral and skin hygiene is significant in preventing such infections like endocarditis. With regards to oral hygiene a dentist should be seen at least every 6 months so any issues that may be present can be resolved before they develop further. Brushing twice a day, flossing and keeping ones toothbrush clean are always that can prevent bacteraemia.
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