Coronary Artery Disease

The heart pumps bloodthroughout the body and this requires a thick muscular wall. This prevents oxygen from diffusing into the cardiac tissue and provides the need for coronary arteries. These arteries run along the outside of the heart and supply oxygen to the cardiac tissue. These arteries can become blocked which causes coronary artery disease. The main components of blood are RBC, WBC and cholesterol. As the cholesterol is making its way through the coronary artery it sees damage in the artery wall and decides to invade these areas of damage. The WBC react to this and attempt to follow the cholesterol into these damaged parts of the artery wall. This is the start of the inflammatory process - atherosclerosis which results in hardening of the blood vessel. The WBC attempt and fail to remove the cholesterol causing a mass build up of cholesterol and WBC in a damaged artery creating a fatty plaque that begins to occlude the blood vessel and prevent blood from flowing through the coronary artery and providing oxygen to the cardiac tissue. It takes ~10years for this to happen and cause symptoms. 

At rest enough blood can pass by a fatty plaque within a coronary artery. This allows the heart to function as normal without any adverse effects. Any strain on the heart e.g. exercise that causes an increase in heart rate from rest and all of a sudden there isnt enough blood getting to the cardiac tissue. This means the muscle will become hypoxic and can no longer carry out its function effectively. This produces the symptom angina pectoris. This is a reproducible symptom so if you stop asking your heart to provide more blood to the body to compensate for the increase in exercise, less oxygen is needed by the heart as its doing less work and the angina pectoris goes away. Hence, the term stable. 

Stress upon the fatty plaque formed of cholesterol and WBC can be caused by hypertension for example or spontaneously. The covering on top of the plaque can rupture and expose all the necrotic matter inside the plaque. This matter is incredible thrombogenic and attracts blood. The platelets in the blood and clotting factors are going to attach to the ruptured plaque material. A blood clot then forms on this plaque. This plaque could start flapping about inside the blood vessel depending on how it is attached to the plaque. This could occasionally cause full occlusion of the blood vessel or be absolutely fine depending on which orientation the thrombus is. This causes completely random hypoxia even at rest. 

The thrombus that has formed on the ruptured plaque, can become so big that it completely occludes the blood vessel. This can be called thrombosis. Embolisation can also occur where the thrombus breaks off from the ruptured plaque and block off a smaller blood vessel further down in the coronary artery. Both these events causes a heart atteck. This completely occludes the artery its occluding and kills the heart muscle that artery supplies. If the heart muscle is left without oxygen for longer than ~20 minutes the heart muscle cannot be saved. 

Framingham Heart Study showed there were risk factors for CAD. The FHS described 2 categories of risk factors: modifiable and non-modifiable. 

Non-modifiable: age (men over 45 and women over 55 are at higher risk due to chronic plaque build up. Gender (men have a less healthy cholesterol profile than women possibly due to estrogen levels or due to the interesting study conducted into wome listening more to their doctors when recommended lifestyle changes). Family history. ethnicity (people of African decent have higher rates of hypertension a risk factor in CAD.

Modifiable: Higher LDL blood cholesterol levels (forms the plaques in the blood vessels); high triglycerides, free fatty acids increase key enzymes that increase plaque formation; Hypertension is a risk factor for CAD as all the stress caused by the increased pressure of blood flowing through the heart can cause damage to the coronary vessels; Smoking damages blood vessels, biggest risk factor, the toxins in ciggarettes damge the blood vessel walls directly anywhere in the body. Diabetes excess glucose in blood causes damage to blood vessels by binding to the blood vessels through glycosylation and makes them hard. Lifestyle/obesity increase excersize and improve glucose and cholesterol and fat in blood, lower blood pressure. Cocaine and amphetamine use can also cause acute coronary syndromes e.g. unstable angina and heart attacks. cocaine causes vasospasms, the closing off of arteries and imitates a plaque.

It is the main contributor to CAD. It causes the build up of fatty plaques in the coronary arteries. A healthy artery has a clear path for blood to flow through. An atherosclerotic artery has a build up of cholesterol that obstructs the blood flow through the artery. The blood vessel wall has 3 layers. The inner sigle cell endothelial layer - a barrier to protect the other layers of the blood vessel wall. It also secretes anti-thrombotic proteins onto its surface. There has to be an irritant present that predisposes the atherosclerosis - too many lipids, cigarette smoke toxins, hypertension. These irritants will cause damage to the endothelium of the blood vessel. The LDL cholesterol will collect under the damaged endothelium creating a fatty streak. The cholesterol deposits become oxidised alerting the immune system and summoning monocytes to the area. The monocytes become macrophages and attack the cholesterol deposits in the fatty streak through phagocytosis. This does not work and the macrophage dies within the fatty streak, full of cholesterol and become foam cells. Dead WBC release signalling miolecules that alert other immune cells to the area to help. This build up of cholesterol and foam cells continues and bulges into the blood vessel. The smooth muscle layer (middle) of the blood vessel take notics=e and begin to migrate into the fatty streak to prevent it from attracting thrombi so they produce a fibrous cap composed of collagen and elastin. The signals released from the foam cells cause the SMC to release calcium into the plaque making the arteries really hard and occluded. If this plaque ruptures it exposes highly thrombogenic material to the blood and results in the formation of a blood clot - artery occlusion and the MI (possibly fatal)

Most commonly happens due to atherosclerotic plaques in the coronary arteries. If the artery is blocked, there is no oxygen supply to the downstream heart muscle and that section of the heart becomes hypoxic and possibly dies. The muscle cells of the heart are called cardiomyocytes that are connected for efficient function of the heart. A plaque within the coronary artery has build up and through increased blood flow, ruptured and formed a thrombus. The artery downstream is not going to get much blood, starving the cardiomyocytes of oxygen. These cardiomyocytes send pain signal to the brain. The clot continues to grow and blocks off more of the artery. The pain increases. This may cause pain to radiate into the arms from your chest (referred pain) or even to the jaw. The hypoxic condition of the cardiomyocytes comprises the way the heart should beat. In response adrenaline is released to correct the uncoordinated beating. This causes and increase in heart rate but has no affect on the thrombus that is still growing. There is no oxygen reaching the cardiomyocytes now and they have had to reduce the rate of contraction of the heart because they have no energy. The rest of the heart compensates for this by beating faster everywhere else. The dying cardiomyocytes start to degrade and their membranes rupture. There is no way to remove toxic byproducts from the area as there is no bloodflow so these begin to build up inside the cardiomyocytes. The cardiomyocytes start to leak cardiac specific troponins. The heart is now weaker and causing more effects in the body e.g. breathing difficulty due to fluid in lungs (backflow), dizziness due to lack of blood in brain. The cardiomyocytes will begin to burst and die around 15-18 mins after the onset of a MI. After 20 mins, 500 cardiomyocytes die/sec. These are irreplacable. MI can be full-thickness (transmural) if it kills the full muscle section of the heart or partial thickness (subendocardial). 

Time is muscle. 2 out of 3 makes an MI probable and 3/3 makes it definite according to WHO guidelines.

History - determine length and breadth of symptoms (under 20 mins?). Chest pain (crushing, radiating, central chest), shortness of breath (backflow of blood in lungs), nausea & vomitting (ANS), dizziness (pumping ability compromised - no blood to brain), sweating. Mena and woman experience both. Women seem to get nausea, vomitting, dizziness more often in studies than men. Diabetics - nerve damage to heart pain nerves so may not feel pain at all. 

ECG - compare a normal ECG trace to the patient with suspected MI. This can tell us what type of MI they have had and the location of the MI. P wave is atrial contraction, QRS represents ventricular contraction and atrial relaxation, T wave represents ventricular relaxation. Elevation of the S and T waves (STEMI) is a full-thickness infarct. Depression of the S and T waves (N-STEMI) is a partial thickness infarct. 

Blood work- Looking for cradiac markers. Proteins released from ruptured cardiomyocytes e.g. troponins, myoglobin, creatine kinase MB (CKMB). Myoglobin is unspecific and rarely tested for. CKMB is more specific and is sometimes tested for. Troponins T and I are specifically found in cardiomyocytes and are always tested for as there presence in the blood signifies cardiomyocyte damage exclusively. 

Unstable angina and N-STEMis are treated the same, it is different for STEMis. An ECG is taken immediately and continuously to monitor for arrythmias and to decide which kind of MI has occured. Oxygen could be given if there O2 levels were low in the blood. Morphine could be given to reduce pain and anxiety thus reducing heart demand. Aspirin to reduce the thrombus development possibly causing the MI (most important intervention for reduciing mortality). This all happpens immediately for all acute coronary syndromes.

Next is reperfusion to remove the thrombus and encourage blood back into the deprived area. STEMI- ECG establishes STEMI and they present within 2 hours of onset, an intervention to breakdown the thrombus is given (thrombolysis) to restablish blood flow and reduce heart damage. This only works for STEMIs as it is a different type of clot in other ACS.

These patients will also be given medication for life to reduce mortality associated with having had a heart attack. B-blockers to restore the oxygen supply and demand balance, making the heart beat slower and with a reduced force to reduce oxygen demand. Nitrates are vasodilators that improve blood flow by dilating vessels. Anti-coagulants to prevent the development of blood clots e.g. heparin or warfarin as well as aspirin. These slow down the growth of the clot that caused the MI and any further clots that might occur. Statins to reduce blood cholesterol levels and therefore decrease the rate of atherosclerotic plaque build up. ACE inhibitors to reduce blood pressure and have been shown to reduce the structural changes in the heart after MI 

Reserved for STEMIs or last resort for N-STEMIs or is they have high risk factors for coronary vessel disease. Firstly, a coronary angiogram is performed (Xray of blood vessels) using contrast dye. This checks the health and blockages/narrwing of the coronary arteries. Procedures are determined by the extent of damage to the coronary arteries. 

Percutaneous coronary intervention (PCI). A catheter is thresded through an artery e.g. femoral up to the coronary vessels. Depending on how basd the blockage or damage is, they perform and angioplasty. This is where they blow a balloon up that is on the end of the catheter and re-opens the blocked vessel pushing al the atherosclerotic black aside and returning blood flow through the vessel. If this is not enough a stent will also be inserted, a metal mesh cylinder, that is left in the vessel to hold it open. 

Coronary Bypass Grafts - open heart surgery. Done on patients with severe coronary artery disease - significant plaques in atleast 3 vessels (triple vessel disease). This compromises the blood supply to huge areas of heart muscle. Blood vessels from elsewhere in the body and use them to bypass the blockage. Vessels are usually the internal mammory artery, radial artery and the great saphenous vein. This re-routes the blood around the plaque that has caused the blockage and restores the blood flow after it.   

A thrombus develops upstream of some cardiomyocytes and persists for over 20 mins. The cardiomyocytes affectd will struggle in a hypoxic environment for about 4 hours and then start to ruture and enzymes start to denature the cardiomyocytes structural proteins. The remannts of these dead cardiomyocyte proteins remains for several days after they have broken down - called coagulative necrosis. 

Neutrophils invade after ~12-24 hours. They start tidying away the netrotic material and call for reinforcments to help them. Neutrophils break down the cardiomyocytes further.

1-3 days later, the reinforcements arrive. More neutrophils to degrade the cardiomyocytes.

4-7 days later. The neutrophils begin to die. The macrophages show up and begin clearing away the necrotic material - dead cardiomyocytes and neutrophils through phagocytosis. This is the most dangerous period for rupturing of the myocardium of the the heart. 

7-10 days later. the nectrotic material is still being cleared. However, small blood vessels start to grow into the area and provide the working cells with oxygen and nutrients to repair the damaged heart. Fibroblasts begin to lay down type III collagen as a new structure for the missing cardiomyocytes. This collagen and vessel network is called granulation tissue. 

30-50 days later. the granulation tissue will be replaced by type I collagen which is much stronger, also called scar tissue. not as strong as heart tissue or contractile. Predisposes to weak contractions and maybe heart failure later on. 

Psychological impact lasts for months afterward on the patient and relatives. Going from no medication to lots. Depression and anxiety. 

Decreased contractility - damage to heart muscle so it cant contract very well. Cannot effectively pump blood out of the left ventricle to the body resulting in hypotension. There is not enough blood in the coronary arteries that is required. This causes ischaemia in other parts of the heart not just the infarcted area causing probems with maintaining cardiac output - cardiogenic shock. This predisposes thrombus formation on the inner wall of the heart chamber as the blood is no longer moving. This can break away and cause an infarct in another part of the body (embolism) and lead to a stroke for example.  

Electrical instability - the ions that move back and forth across the heart muscle cell membrane to maintain the heart rate get disrupted. This can cause arrythmias. The 2 major pacemakers are in the right atrium. the sinoatrial node and the atrioventricular node. Having an MI in the atrium could potentially knock out the biggest regulators of contractility in the heart. 

Tissue necrosis - cardiomyocyte death. There is an inflammatory response. This can cause inflammation around the heart itself. The heart sits in a fibrous cover called the pericardium. If the outside of the heart is inflamed, it can irritate the pericardium resulting in percarditis. Necrosis of the septum separating the left and right ventricle resulting in the mixing of oxygenated and dexoygenated blood, resulting in hypoxaemia. This would also cause damage to the arteries in the lungs. The new high pressure blood would be pushed into the lungs which is a low pressure environment. Weakened heart walls due to necrosis could cause the heart to rupture and blood to poool in the pericardium surrounding the heart. This would stress the heart and effect beating - cardiac tamponade. Commonly, papilliary muscles will be necrosed and although the valves dividing the artium and ventricles to invert into the atria as the chordae tendinae is no longer being held in place by the papilliary muscle at the base of the ventricle. This is called a leaky valve as blood can now travel back into the left atria instead of the aorta with a leaky mitral valve for example. 

All these complications  can lead to congestive heart failure as the heart cannot keep up with demand.