Lesson 12 Flashcards
What is hypertension, how does our body control blood pressure?
hypertension is linked to blood pressure which **is a vital physiological parameter reflecting the pressure of the liquid component within our bodies, considering blood and other fluids. Approximately 70% of a 70 kg individual’s body comprises fluids, distributed into intracellular and extracellular compartments. The latter includes interstitial and intravascular fluids, with intravascular fluids representing a modest fraction. These fluid volumes are meticulously regulated, as tissue perfusion, crucial for ensuring adequate blood supply to all tissues, profoundly influences organ functions, for instance kidney function, which is dependent on pressure.
to control this parameter our body has pressure sensors, vital for maintaining homeostasis, operating in low-pressure systems within atrial and pulmonary vasculature. These sensors respond to wall stress variations, triggering compensatory mechanisms. Baroreceptors in the aortic arch and carotid artery, crucial pressure sensors, relay signals to the parasympathetic system, leading to decreased heart rate, or activate the sympathetic system, inducing vasoconstriction. also, the juxtaglomerular apparatus in the kidney plays an important role.
In instances of altered arterial pressure, compensatory systems come into play.
- decreased arterial pressure prompts increased sympathetic activity and renal involvement, culminating in enhanced sympathetic activity releasing noradrenaline. This, in turn, stimulates alpha1 and beta1 receptors, resulting in vasoconstriction, increased cardiac output, and elevated arterial pressure. Simultaneously, the kidneys respond by reducing renal blood flow, triggering renin release, and initiating the renin-angiotensin-aldosterone system (RAAS), promoting sodium and water reabsorption to bolster intravascular volume and elevate pressure. This happens thrugh the juxtaglomerular apparatus, This apparatus, formed by cells found in the nephrons of the kidney, plays a crucial role in regulating blood pressure. In response to decreased arterial pressure, reduced renal blood flow, or increased sympathetic activity, the juxtaglomerular cells release an enzyme called renin into the bloodstream. Renin acts on a plasma protein called angiotensinogen, converting it into angiotensin I. Angiotensin I, in turn, undergoes further conversion to angiotensin II by the action of angiotensin-converting enzyme (ACE), primarily located in the lungs. Angiotensin II is a potent vasoconstrictor, meaning it induces the narrowing of blood vessels, thereby increasing peripheral resistance. Angiotensin II also stimulates the release of the hormone aldosterone from the adrenal glands. Aldosterone acts on the renal tubules, specifically the distal tubules and collecting ducts, promoting the reabsorption of sodium and water. This increased reabsorption elevates intravascular volume, contributing to an overall rise in arterial pressure. The juxtaglomerular cells themselves possess a significant number of beta1 receptors. Activation of these beta1 receptors, often initiated by factors like reduced stretch of the vascular wall or sympathetic stimulation, triggers the release of renin. This forms a feedback loop, reinforcing the release of renin and further amplifying the production of angiotensin II.
- when we have an increased arterial pressure, when there is an increase in arterial pressure, both the juxtaglomerular apparatus (JGA) in the kidneys and the baroreceptors in the cardiovascular system respond to help lower the pressure back to normal levels. Here’s how these mechanisms work, when the JGA senses an increase in arterial pressure it reduces the release of renin, and with less renin being released, there is a reduced conversion of angiotensinogen to angiotensin I and subsequently to angiotensin II. Therefore, by releasing less renin, the JGA helps to lower blood pressure. Increased arterial pressure can lead to constriction of the afferent arterioles of the glomeruli, reducing blood flow into the glomeruli and thereby decreasing the glomerular filtration rate, which can help reduce blood pressure. When baroreceptors detect an increase in blood pressure, they send signals to the brain. The brain responds by increasing parasympathetic nervous system activity and reducing sympathetic nervous system activity. The activation of the parasympathetic nervous system causes a reduction in heart rate (negative chronotropy) and the force of heart contractions (negative inotropy), leading to a decrease in cardiac output. Simultaneously, the reduction in sympathetic activity causes vasodilation, which lowers the resistance in the blood vessels, making it easier for blood to flow and reducing blood pressure.
When can we say that we are suffering from hypertension? What are the symptoms? What are the two main types? And how is it determined?
Hypertension is **characterized by blood pressure levels at or exceeding 140/90 mmHg. It poses significant health risks, especially in the elderly. While aging may slightly elevate normal blood pressure ranges, sustained high levels are indicative of hypertension. This condition is associated with an elevated risk of cardiovascular disorders, including strokes, myocardial infarction, heart failure, renal insufficiency, and aortic dissecting aneurysms, collectively contributing to coronary artery disease (CAD).
Often asymptomatic, hypertension is also called “the silent killer.” Absence of noticeable symptoms makes it dangerous, as individuals may remain unaware until severe cardiovascular complications arise. The hypertensive heart exhibits increased contractile force and thicker ventricular walls, posing additional challenges. Regular blood pressure monitoring is a crucial preventive measure.
Hypertension can be divided in two main types:
- Essential hypertension, accounting for 90-95% of cases, lacks a discernible cause and is likely multifactorial, involving factors like alcohol consumption, obesity, salt intake, and smoking.
- Secondary hypertension results from identifiable mechanisms, such as overproduction of aldosterone, oral contraceptive use, renal vascular diseases, or intrinsic renal issues.
Understanding hypertension’s complexity is fundamental for effective management, emphasizing lifestyle modifications and targeted interventions based on etiology. Regular blood pressure assessments are important for the prevention and control of this cardiovascular concern.
Arterial blood pressure is determined by peripheral resistance and cardiac output. Any alteration in vasomotor tone or cardiac output can lead to hypertension. Cardiac output, in turn, is influenced by heart rate and stroke volume. The parasympathetic nervous system decreases the heart rate, while the sympathetic system increases it. Stroke volume depends on the contractility of the left ventricle and preload. Contractility is controlled by the sympathetic nervous system (inotropic effect), while preload is influenced by venous tone, intravascular volume, and sympathetic and parasympathetic effects. Venus tone, affecting preload, is increased by the parasympathetic system and intravascular volume, influenced by drinking and sodium/water retention, regulated by the sympathetic nervous system through beta1 receptors, aldosterone, and antidiuretic hormone/natriuretic peptides.
Systemic vascular resistance is regulated by direct innervation from the sympathetic nervous system (alpha-1 receptors) and various regulators like catecholamines and angiotensin II. Local regulators, including NO, prostacyclin, endothelin, angiotensin, and adenosine, play a role in controlling vascular resistance.
So, hypertension can result from various mechanisms related to cardiac function, vascular resistance, volume retention, or neuroendocrine dysfunction. A rational pharmacologic approach
to the treatment of both primary and secondary hypertension requires an understanding of the physiology of normal blood pressure regulation and the mechanisms that could be responsible for hypertension in individual patients. So basically we treat it with personalized medicine.
What types of hypertension do you know
There are many types of hypertension:
- Pump-Based Hypertension: we have a persistent blood pressure elevation due to an increase in cardiac output, termed pump-based hypertension, it can result from excessive sympathoadrenal activity or increased sensitivity to neurohumoral regulators. This is often observed in younger patients with essential hypertension.
- Vascular Resistance-Based Hypertension: Common in the elderly, this type results from damage to the endothelium, abnormal responsiveness to sympathetic stimulation, and dysregulation of ion channels. It may present as a predominant elevation in systolic blood pressure.
- Volume-Based Hypertension: Excessive sodium and water retention by the kidneys, caused by renal parenchymal disease or renovascular disease, lead to volume-based hypertension. Renal parenchymal disease reduces functional nephron mass, while renovascular disease results from conditions like atherosclerosis or fibromuscular dysplasia.
- Neuroendocrine Dysfunction-Related Hypertension: Secondary hypertension can occur due to neuroendocrine dysfunction, involving abnormal regulation of sympathetic tone, stress responses, and hormonal production. Examples include excessive catecholamine secretion (pheochromocytoma), aldosterone production (primary aldosteronism), and thyroid hormone production (hyperthyroidism). Surgical intervention is often the primary solution for pheochromocytoma.
Hypertension is a clinical challenge, as it can remain asymptomatic for years, leading to significant organ damage. Effective treatment necessitates identifying asymptomatic patients, and lifestyle modifications are the first-line approach due to the potential inconvenience of antihypertensive drugs. Lifestyle changes include weight reduction, limiting salt intake, increasing daily exercise, moderating alcohol consumption, quitting smoking, and incorporating more fruits and vegetables.
Speak about diuretics
Various drugs are available for hypertension treatment. The general approach aims to decrease arterial blood pressure by reducing peripheral resistance and/or cardiac output. Drugs can act on smooth muscles, interfere with the renin-angiotensin-aldosterone system (RAAS), and modulate the sympathetic nervous system.
It’s observed that the body’s compensatory responses can limit the efficacy of antihypertensive drugs, leading to the need for dose adjustments or combining multiple agents for long-term blood pressure control. Physicians often face challenges in achieving optimal efficacy without compromising safety.
Diuretics are compounds that reduce blood volume by increasing renal excretion of Na+ and H2O, leading to increased urine flow. They not only cause volume depletion but also induce vasodilation, contributing to their antihypertensive effect. Most of the absorption at the level of the kidney happens in the proximal tubule, where we have 100% of reabsorption, while diuretics work on distal tube and the loop of Henle so they do not have a super strong effect. Over the course of 24 hours, the kidneys filter ~180 L of fluid. To increase or decrease body fluid volume, the kidneys must increase or decrease renal Na+ reabsorption from the large daily volume of glomerular filtrate. Pharmacologic inhibition of ion reabsorption leads to the reduction of the osmotic driving force that favours water reabsorption in the water-permeable segments of the nephron.
The diuretics which work on the proximal tubule are only used to treat the edema but not hypertension. hypertension drugs instead, work on the medullary thick ascending limb of loop of Henle, the distal convoluted tubule, and the collecting duct.
Thiazide diuretics, composed of thiazide, target sodium reabsorption in the distal convoluted tubule. They are commonly prescribed orally and are active for an extended period, making them suitable for once-daily administration. They are often preferred for patients with volume-based hypertension. Thiazide diuretics act on the distal convoluted tubule by blocking the sodium-chloride cotransport, resulting in increased calcium entry into cells through TRPV5 channels. This leads to vasodilation and complements the initial decrease in intravascular volume, contributing to sustained blood pressure reduction. Administering diuretics to asymptomatic patients may be challenging due to the increased frequency of urination, albeit not classified as a side effect. Thiazides are effective in treating volume-based hypertension but necessitate careful consideration of compensatory responses and potential side effects. Thiazides influence both cardiac output and systemic vascular resistance and hence are first-line agents to treat volume based hypertension.
Loop Diuretics, although infrequently prescribed for moderate hypertension due to their relatively short duration of action (4–6 hours), are highly effective against edema. Their antihypertensive efficacy is often modest, primarily because of compensatory responses involving neurohumoral regulators of intravascular volume and systemic vascular resistance. These diuretics act by blocking sodium cotransporters, particularly those responsible for transporting sodium, chloride, and potassium. By inhibiting these transporters, loop diuretics decrease sodium reabsorption and increase sodium excretion. However, their short duration of action necessitates more frequent administration, and compensatory effects limit their efficacy in controlling intravascular volume. Loop diuretics find specific applications in diseases such as malignant hypertension or hypertension in patients with kidney diseases, in these cases they are preferred to thiazide diuretics. Their main side effect is their upstream action in the nephron, leading to increased potassium secretion and proton secretion, resulting in metabolic alkalosis. When used in conjunction with thiazides, loop diuretics, acting at more proximal sites, increase the sodium load presented to the collecting duct’s principal cells. This stimulation results in increased secretion of potassium and protons, predisposing to hypokalemia and metabolic alkalosis.
Potassium-Sparing Diuretics are drugs acting on the final part of the nephron. These drugs act directly on the distal convoluted tubules and collecting ducts of the nephron by blocking the sodium channels through which sodium is reabsorbed. When sodium reabsorption is inhibited, less potassium is secreted or lost. This results in increased sodium and water excretion and reduced potassium excretion. They do not significantly increase potassium elimination, making them less efficient compared to others. However, their combination with loop diuretics or thiazides reduces the risk of hypokalemia. These diuretics block the epithelial sodium channel, reducing sodium absorption and consequently decreasing potassium excretion. Combining potassium-sparing diuretics with other diuretics results in a synergistic therapeutic effect. However, caution must be exercised, and patients should avoid potassium supplements to prevent hyperkalemia.
An exception is spironolactone, an aldosterone receptor antagonist that is especially effective in the treatment of secondary hypertension caused by hyperaldosteronism. This antagonist prevents the expression of sodium-potassium ATPase and ENaC, leading to reduced sodium and water reabsorption.
In general, diuretics should be used cautiously in patients with renal insufficiency, and their use requires careful monitoring to prevent adverse effects on electrolyte balance.
