Deconstructed Cardiology Gaurang_MD

Adopted from UKY website







Cardiac amyloidosis occurs when an abnormal protein — called amyloid — builds up in the heart tissue. This buildup makes it difficult for your heart to relax completely in between heart beats, making the heart stiff. This stops blood from getting into the heart. There is a “traffic-jam” of blood waiting to enter the heart all across the body, causing congestion. The congestion causes “leakage of fluid” from the blood into the tissues- manifesting as fluid in lungs, legs, various internal organs and elsewhere. The common symptoms are shortness of breath, swelling in legs, lethargy and loss of appetite. This is a progressive disease and an increasingly recognized cause of heart failure.







Figure 1: Normal heart chamber squeezing and relaxing







Read further to understand this in detail.







Normal heart:







Heart is supposed to relax completely in-between heart beats. This allows the blood to enter the heart chambers, like a balloon blowing up with air (figure 1).







The relaxation of the heart is an equally important requirement to keep the blood moving forward in the continuous circuit around the body.























The circuit around the heart:







This has been explained in details elsewhere







In brief, the blood goes around the body as shown in figure 2. Here, the left and right chambers are the chambers of the heart.







Figure 2: The journey of blood around the body















The issue with cardiac amyloidosis:







The essential problem is deposition of abnormal and sticky proteins (amyloid) in various organs which interfere with the function of that organ. When the deposition occurs in the heart, this is called cardiac amyloidosis.















Two main types of cardiac amyloidosis:







There are two main types of cardiac amyloidosis:







* Transthyretin amyloidosis (ATTR amyloidosis): This type results from mutated deposits of transthyretin, a protein made by the liver. The two subtypes of ATTR are:* Wild-type amyloidosis: Usually affects people in their 60s or older* Hereditary amyloidosis: Runs in families and typically affects people in their 40s or older















* Light chain amyloidosis (AL amyloidosis): This type of amyloidosis is associated with blood cancers like multiple myeloma. It is not a type of cancer, but it is treated with chemotherapy.







The type of amyloid protein deposited in the above two types of cardiac amyloidosis is completely different and formed by different mechanisms, however the essential problem is the same- abnormal protein deposition.







AL amyloidosis







In AL amyloidosis, excessive abnormal antibodies are being formed by abnormal antibody-forming cells. The antibody forming factory has malfunctioned and starts manufacturing multiple batches of unusable antibodies. These antibodies belong to the same mould and are being manufactured in large quantities (figure 3).







Figure 3: Excessive antibodies formed from the same mould in AL amyloidosis







Antibodies are made of heavy chains and light chains (figure 4)







Figure 4: Antibody

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All opinions expressed here are those of the author and not of the employer. Information provided here is for medical education only. It is not intended as and does not substitute for medical advice. The discussion is not all-inclusive or exhaustive and individual patient findings may vary. Please review the disclaimer.

Figure 1: Coronavirus







The first cases of the novel 2019 coronavirus (COVID-19) was reported in Wuhan, China in December 2019 1 and since has rapidly spread worldwide. In its essence, the virus is a non-living strand of protein called RNA enclosed in a fatty acid envelope.







It appears spherical under an electron microscope and has certain particles on its surface which appear like a crown or ‘corona’ (figure 1). Coronavirus can affect the heart in several ways, many of which are still unknown, but the end result is direct injury, heart failure or death.















Why did COVID-19 become such a big deal?







The novel coronavirus has a totally new configuration. Human race has never been exposed to anything like it before, so the entire world population lacks any sort of immunity to this. It seems, every human is susceptible to be infected.







In other words, humans lack antibodies against COVID-19. Antibodies are like special task forces, specialized to disable only one type of foreign cell or protein. These form in the body after an infection or vaccination and prevent future infections with the same organism. Just like the governments around the world are racing to make a vaccine, the human body has its own ‘vaccine lab’ called the plasma cells. Unfortunately, the plasma cells need time while they work on making antibodies. In the meantime, the body sends out its reserve forces against the virus. These soldier cells are not specialized to kill COVID virus and they use any possible means – machine guns, hand grenade, assault tanks against the virus, while the plasma cells can work on making antibodies. In most cases, this is enough to keep the virus suppressed while the antibodies are made. Once the antibodies are ready, the virus is destroyed and the patient recovers after suffering mild symptoms.







In some cases though, the initial response is not enough and the organs (lungs, heart etc.) get caught in this cross-fire between the virus and the soldiers. The result is an overwhelming inflammatory response called a cytokine storm. Cytokines are a byproduct of the war raging inside the infected body. In low levels cytokines help to destroy the virus and only result in mild symptoms like fever. They activate soldier cells all over the body and recruit them to the affected area, like recruiting the military to calm riots inside the country. Cytokines have other favorable functions as well.







However, when the virus levels rise, the war rages on, cytokines build up. Soldier cells all over the body get activated and infiltrate the organs. If the organs are already weak from an underlying disease or old age, they can fail.







Symptoms:







The common symptoms include fever (89% hospitalized patients), cough (68% patients), pain in the throat, headache, tiredness 2. In severe cases it can totally flood the lungs with fluid (pulmonary edema), severely affecting its function. Lungs are like sponge which allow free passage of air, but when soaked in water, no air can pass through. This is called severe acute respiratory distress syndrome or SARS.







For an update on the likely symptoms, refer to the CDC website.







Effect on the heart:







As mentioned above, heart can sustain collateral damage from the cytokines in some cases. There have also been reports of the virus directly injuring heart cells.







Just like the lungs, heart muscle can also get flooded with fluid (myocardial edema) 3 and soldier cells infiltrate the heart. These soldier cells that have been activated by the cytokines are like grenades with pins removed.

Heart attack usually results from a sudden blockage in the arteries supplying the heart.







There are three main blood vessels or arteries which supply the heart. Left anterior descending artery, called the ‘widow-maker’ is the largest and supplies the front of the heart. The other two arteries – left circumflex and the right coronary arteries, surround the heart in the middle and supply the left, right and back sides of the heart (figure 1).







Figure 1: Blood supply to the heart







Cholesterol plaques are formed by certain cells in the blood called macrophages ingesting (or eating) fat globules. This is one of the way body gets rid of excess fat through scavenging. Some arteries are especially prone to have these cells ‘settle’ in the walls of the arteries, heart arteries being one of them. Over time these cells may die and release the fat to the vicinity creating a cholesterol filled plaque (figure 2). This could be an ongoing process which may slowly obstruct the flow downstream. This is like a 4-lane highway progressively becoming 2-lane and finally a single lane highway due to construction.







Figure 2: Deconstructed cholesterol plaque within the walls of the artery







On occasions the plaque may rupture and expose its innards to the blood. The exposed plaque acts as a magnet for platelets and other clotting agents and starts forming a clot. This can result in a sudden and sometimes complete obstruction of the artery. This may happen within a few minutes and results in a heart attack. This is like a 4-lane highway getting totally blocked by a sudden car pile-up. The heart muscles dependent on the artery for nutrition and oxygen supply are suddenly starved (figure 3).







Figure 3: Heart attack zone







A plaque is prone to rupture in presence of risk factors such as smoking or untreated high blood pressure. Read about the other risk factors and treatment.







Symptoms: 







Chest pain, shortness of breath, funny-feeling fast heart rate and/or dizziness are the most common symptoms. Chest pain is classically described as dull aching pressure like discomfort, going down the left arm. This textbook description of chest pain however happens in a minority. The pain could be sharp, shooting, stabbing or may have some other unusual characteristics. Some other types of pain, such as abdominal pain, could also signal a heart attack but so could multiple other things. This is where the difficult dilemma comes in, since all the characteristics of pain described above could also be caused by number of other things, some completely unrelated to the heart.







What is done during a heart attack?







An early visit to the closest emergency room is very important because in heart attack the heart muscle starts dying if the blood supply does not start soon. Heart attack may create a certain pattern on the ECG which can be recognized by a healthcare professional. The most common way of opening the obstruction is through ballooning the obstruction with or without stent placement. Alternatively a clot buster may be administered if the procedure is unavailable at the hospital. A good discussion with your physician is emphasized.

Salt in the diet can have some profound effect on the blood pressure. Read on to understand this in detail.







Refer to the section on blood pressure to understand how blood pressure works and how it is measured. Briefly, blood pressure is represented as two numbers. The higher number represents the spike in blood pressure when the heart pumps blood into the arteries with each heart-beat. Like a wave traveling forward and this is felt as a pulse. The lower number represents the pressure within the arteries in between the heart-beat.  







Blood is made of multiple components, and it behaves like saline water. The concentration of salinity in the blood is maintained at the same level by kidneys. Any dilution and the kidneys make more urine and any increase in salinity and the kidneys start retaining water. This overlies the basis of the effect of excessive salt in diet. 







Salt

in diet has many effects on the body, one of which is to increase the

salinity of blood. The kidneys respond to this by increasing the water

retention to dilute the salinity. The kidneys aim to keep the salinity

of blood at constant levels all the time. Water retention increases the

volume of blood. More blood in the arteries results in more blood

pressure. This is like opening the tap wider while watering the plants

using a hose. More water in the pipe increases the pressure and the

water jets out. 







Refer to the effects of high blood pressure in the other section. In brief, excessive blood pressure increases the up-hill task for the heart. The heart has to push the blood into an already high-pressure system (figure 1).







Figure 1: As the blood pressure increases, the uphill task on the heart increases.







If the heart pump is weak, then it is unable to handle the excessive weight it must push against and the blood moves slower through the system. When this happens, kidneys do not get adequate blood supply and the kidneys perceive this as though the body does not have enough blood (figure 2).







Figure 2: Weak heart pump is unable to pump enough blood to kidneys which perceive the body as ‘dry’.







The kidneys are ‘fooled’ into thinking that the body has lost blood since not much is coming to it. This is an adaptation from the ages when humans would hunt for prey or be hunted. Loss of blood was a common reason for death. The kidneys respond by retaining water to maintain the blood volume. This was helpful when the actual cause was loss of blood, however, in heart failure this can worsen the pressure on the heart. All of this is a never-ending cycle which keeps worsening and results in a hospital admission. This is the basis of worsening heart failure and is explained elsewhere. 







Excessive salt also puts an undue pressure on the kidneys which are entrusted with the role to maintain the salinity of blood. If the kidneys are weak, salt does not get filtered out as fast as it needs to be. This results in salt retention and with it water retention, again increasing the blood pressure as mentioned above.





























All opinions expressed here are those of the author and not of the employer. Information provided here is for medical education only. It is not intended as and does not substitute for medical advice.







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As per the new ACC/AHA guidelines, blood pressure >130/80 is high blood pressure or hypertension. Emphasis is given to multiple readings obtained on multiple occasions rather than a single reading. This is because various factors can influence a single blood pressure reading including prior activity, smoking, caffeine intake, cuff size, stress etc.







Refer to the section on blood pressure to understand how blood pressure works and how it is measured. Briefly, blood pressure is represented as two numbers. The higher number represents the spike in blood pressure when the heart pumps blood into the arteries with each heart-beat. Like a wave travelling forward and this is felt as a pulse. The lower number represents the pressure within the arteries in between the heart-beat.  Read about the effect of salt on blood pressure.







Why do we have blood pressure? 







Blood pressure is required to push the blood to various organs. Like a garden hose, without continuous water pressure applied by the tap, water will not flow and come out of the other end. Too low water pressure and the water flow dries out. Too high pressure and the water jets out too fast and may even rupture the pipe at the weak segments. 







What effects does high blood pressure or hypertension have? 







On the artery: 







Too much pressure in the arteries is a constant stress on the artery wall. High pressure causes changes in the artery, making them firm. This is like a garden hose replaced with a lead pipe, inflexible and non-expandable. This increases the resistance to blood flow and further increases the pressure (figure 1).







Figure 1: High pressure causes arteries to become thick, inflexible and in-expansible.







Constant stress and injury to the wall can also accelerate cholesterol plaque formation. 







On the heart: 







The heart has to work against the high pressure to pump the blood forward. This is like a small car, with a trailer attached at the back, trying to climb a steep slope. Higher the pressure, steeper the slope. (figure 2). More uncontrolled the blood pressure or hypertension, more the effort required by the heart.







Figure 2: As the blood pressure increases, the uphill task on the heart increases.







The

heart responds initially by becoming thicker and beefed up (like arm

muscles after lifting heavy weights). Like adding more horsepower to the

car going up the hill. Shouldn’t this be favorable? Actually, no.  







Firstly, the heart is now consuming more energy and if the blood supply is not good, then this can cause the heart to fail. Like the car running out of gas midway through the climb. Secondly, the thick heart does not expand fully to accept the incoming blood (figure 3).







Figure 3: Thickened heart does not relax fully to accept the blood. This causes backup of pressure in the entire system.







More pressure is needed to push the blood into the heart. This is the difference between filling air in a balloon compared to filling air in a car tire. The pressure in the entire blood system goes up: the arteries, the veins, the lungs, various organs etc. Excessive pressure causes fluid to leak out from the blood vessels,