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Renin-Angiotensin-Aldosterone System

  1. Systemic hypertension means high blood pressure in the systematic arteries - the arteries that transfer blood from the heart to other tissues in the body (apart from the lungs). It is commonly known as High Blood Pressure. It is caused due to the constriction of arterioles. Due to this constriction, the peripheral resistance to blood flow increases thereby increasing the workload of the heart and raising the arterial pressure. Systemic hypertension is a risk factor for cardiovascular diseases.

Renin-Angiotensin-Aldosterone System (RAAS) is a hormonal mechanism that controls if the body is hemodynamically stable by keeping a check on the blood pressure, sodium-potassium balance and fluid volume. Due to this, a problem in any molecule that has the RAAS present in it contributes to the development of hypertension. The RAAS and the Sympathetic Nervous System together share responsibility for the development of hypertension in states of insulin resistance. Aldosterone is responsible for increasing the blood pressure by performing actions such as sodium retention and plasma volume expansion.

When the sodium levels are low and potassium levels high, the kidney releases an enzyme named renin. Renin changes the angiotensinogen to angiotensin I and this is changed into angiotensin II by another enzyme. Angiotensin II causes blood vessels to constrict, increasing blood pressure. It then causes the release of aldosterone in the adrenal glands which causes sodium retention in the renal tubules. Angiotensin II and aldosterone work together to raise the blood pressure and sodium levels, maintaining a balance in sodium, potassium and fluid levels. If the RAAS system becomes overactive, it will result in consistently high blood pressure. 

  1. Hypertension is often called the "silent killer". High blood pressure can damage the body for years without showing symptoms outwardly. The prolonged impact of hypertension can range from poor quality of life to heart failure. Hypertension damages the arteries, making them narrower and reducing elasticity. When fat tries to travel through narrow arteries, it is unable to, causing blockages. This limits blood flow throughout the body. When blood is not able to flow freely to the heart, it can result in chest pain (angina), arrhythmia or even something as serious as a heart attack. The strain on the heart over time due to inadequate blood flow and high blood pressure causes the heart to work less efficiently. The muscles in the heart become weaker, thus overwhelming the heart, causing it to fail. The pressure that the heart must work against to eject blood is known as the afterload. It is proportional to the arterial pressure.

Hypertrophy involves the abnormal thickening of the heart muscles due to stress on the heart. It tends to affect the left ventricle more as it is larger and does more of the pumping work. High blood pressure increases the left ventricular afterload and vascular resistance. Chronic pressure results in the mechanism of ventricular hypertrophy. The purpose of this mechanism is to preserve cardiac output and delay cardiac failure. Over time, the left ventricle decompensates causing diastolic dysfunction. When this happens, the left ventricle loses its ability to relax normally, resulting in the inability of the heart to fill normally with blood.

  1. Oedema, in medical terms, means a fluid build-up in the body. The retention of fluid causes the affected tissues to become swollen. Swelling can occur in a specific part of the body or in general on the whole body. In Harold's case, the swelling exists in his lower limbs and lungs. Oedema is a common result of high blood pressure and heart failure. Since Harold is diagnosed with both, it is not uncommon for him to show signs of oedema as well.

The left ventricle of the heart is larger than the right. It is therefore responsible for the bulk of the pumping. If there occurs a failure on the left side of the heart, the left ventricle has to work harder so that it can produce the same amount of blood as before. When the left ventricle fails, there is a pressure that builds up in the veins that causes fluid to leak into the tissues. This results in congested heart failure and pulmonary oedema. Due to this, one may feel lightheaded, shortness of breath and weakness. The left-sided heart failure can be systolic or diastolic.

Right-sided heart failure occurs often as an aftermath of left-sided failure. But it can also occur if the right ventricle gets negatively affected in the event of a heart attack. Failure of the left ventricle forces backs the fluid pressure through the lungs damaging the right side. The loss of functioning on the right side causes blood to go back up the veins. This causes various parts of the body such as ankles and legs, to swell up. In worse cases, the swelling spreads to the knees and ultimately to the liver and intestines.

  1. Candesartan belongs to a class of drugs known as Angiotensin Receptor Blockers or ARBs. Candesartan can also be used to treat heart failure. It also helps with strokes and kidney problems. Since candesartan is an angiotensin receptor blocker, its main function is to block the effect of angiotensin II. As mentioned earlier, angiotensin II causes the blood vessels to constrict, which causes the blood vessels to become narrow. As a result, it is difficult for the blood to flow freely. It also causes salt and water retention in the body, thereby further increasing the blood pressure. By blocking the effect of angiotensin II, candesartan allows the blood vessels to relax. As a consequence, the pressure within the blood vessels is reduced. This makes it smoother for the heart to pump blood to the body without overwhelming it.

Candesartan is a nonpeptide selective blocker. It is a prodrug which has been tested as effective in the treatment of heart failure. Candesartan is characterised by a strong binder affinity to the angiotensin II type 1 receptor. ARBs are commonly used for treating hypertension and to limit further damage from a heart attack. Candesartan lowers cardiovascular as well as overall mortality, heart failure hospitalization among patients with systolic dysfunction. It also helps angiotensin II return to pre-treatment levels.

  1. Hydrochlorothiazide comes under a class of drugs known as diuretics, which also means "water pills". Diuretics work by causing the kidneys to get rid of unwanted water and salt from the body, in the form of urine.

Since Harold is diagnosed with heart failure due to hypertension as well as oedema, he had been prescribed with diuretics as it is effective in the treatment of all of the above-mentioned conditions. Using diuretics to treat heart failure is common, as it relieves the congestive symptoms. A class of diuretics called Loop Diuretics causes decreased sodium and chloride reabsorption. It helps the kidneys release sodium through urination. Sodium takes away the water from the blood, hence decreasing the amount flowing through the arteries, thereby decreasing the blood pressure. Loop diuretics also stimulate the synthesis of prostaglandins which causes dilation of the renal artery and vein. This helps with some of the cardiac-related consequences, like the reduction of pulmonary pressure. Diuretics ease the swelling and congestion of lungs, lower blood pressure, reduce chances of heart attack and the reduction of sodium levels in the body helps with the problem of oedema.

It is evident from Harold's diagnosis that water retention is a major concern for him. Smoking from an extremely young age has taken a severe toll on his body. Cigarette smoking causes inflammation throughout the body, which increases swelling as the inflammatory response within the skin tissues causes the further build-up of lymph fluid. This ultimately leads to chronic swelling. Thus, hydrochlorothiazide being prescribed to Harold is justified as he needs diuretics to help with his oedema and issues related to hypertension and heart failure. 

References for Harold’s Diagnosis

Casu, G., & Merella, P. (2015). Diuretic Therapy in Heart Failure – Current Approaches. European Cardiology Review, 10(1), 42. https://doi.org/10.15420/ecr.2015.10.01.42

Heran, B. S., Musini, V. M., Bassett, K., Taylor, R. S., & Wright, J. M. (2012). Angiotensin receptor blockers for heart failure. Cochrane Database of Systematic Reviews. https://doi.org/10.1002/14651858.cd003040.pub2

Oh, G. C., & Cho, H.-J. (2020). Blood pressure and heart failure. Clinical Hypertension, 26(1), 1. https://doi.org/10.1186/s40885-019-0132-x

Ripley, T. L., Chonlahan, J. S., & Germany, R. E. (2006). Candesartan in heart failure. Clinical Interventions in Aging, 1(4), 357–366. https://doi.org/10.2147/ciia.2006.1.4.357

Other Sources:

Ercolano, A. (2019, October 24). Cigarettes and Chronic Swelling: Smoking’s effects on lymphedema. The Lymphie Life. https://thelymphielife.com/2019/01/28/cigarettes-and-chronic-swelling-smokings-effects-on-lymphedema/#:%7E:text=Increased%20inflammation.,further%20buildup%20of%20lymph%20fluid.

Heart Failure Types and Left-Sided Heart Failure | Abbott Cardiovascular. (2020). Abbott. https://www.cardiovascular.abbott/us/en/patients/conditions/heart-failure-symptoms-causes-diagnosis/heart-failure-types.html

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