Cardiovascular I Hypertension PDF

**Cardiovascular I** **Hypertension** [Classification of Blood Pressure] -- -- -- -- -- -- -- -- **Pathophysiology** **Sympathetic Nervous System:** This is part of the autonomic nervous system, which controls involuntary bodily functions, lik...

**Cardiovascular I** **Hypertension** [Classification of Blood Pressure] -- -- -- -- -- -- -- -- **Pathophysiology** **Sympathetic Nervous System:** This is part of the autonomic nervous system, which controls involuntary bodily functions, like heart rate and breathing. When activated, it releases hormones like: - **Norepinephrine & Epinephrine:** These trigger the \"fight or flight\" response, increasing heart rate and constricting blood vessels. - **Alpha-1 Adrenergic Receptors:** Found on blood vessels, they cause vasoconstriction (narrowing of the blood vessels) when activated. - **Beta-1 Adrenergic Receptors:** Found on the heart muscle, they increase heart rate and the strength of the heart\'s contraction.  - **Increased SV:** This means the heart pushes out more blood with each beat, increasing blood pressure. **Other Hormones:** In addition to the sympathetic nervous system, there are other hormones that contribute to blood pressure regulation: - **Antidiuretic hormone:** Makes the kidneys reabsorb more water, leading to an increase in blood volume (BV), which then increases blood pressure. - **Thyroid hormone & Cortisol:** These hormones can increase the body\'s responsiveness to catecholamines (like norepinephrine and epinephrine), making those hormones have a stronger effect on blood pressure overall. **Renin-angiotensin-aldosterone system (RAAS)** The Renin-Angiotensin-Aldosterone System (RAAS) is a complex hormonal system that plays a major role in regulating blood pressure and fluid balance in the body.  Here\'s a simple explanation of how it works: 1. **Low Blood Pressure:** When blood pressure drops, the kidneys release renin.  2. **Renin\'s Action:** Renin converts angiotensinogen (a protein in the blood) into angiotensin I.  3. **Angiotensin I to Angiotensin II:** An enzyme called ACE (angiotensin-converting enzyme) converts angiotensin I into angiotensin II. 4. **Effect of Angiotensin II:** Angiotensin II is a powerful vasoconstrictor (it narrows blood vessels) and stimulates the release of aldosterone from the adrenal glands. 5. **Aldosterone\'s Action:** Aldosterone causes the kidneys to retain sodium and water, leading to increased blood volume and pressure. Overall, the RAAS system helps maintain blood pressure by increasing blood volume and constricting blood vessels when blood pressure drops. RAAS.jpg A**ngiotensin II:** A potent vasoconstrictor, it narrows blood vessels, increasing resistance to blood flow and therefore increasing blood pressure. **Aldosterone:** Causes the kidneys to retain sodium and water, increasing blood volume and ultimately increasing blood pressure. **Proposed mechanism for the development of hypertension** - **Increased Sympathetic Nervous System Activity:** - This means the \"fight or flight\" response is more easily triggered, leading to increased release of catecholamines (like norepinephrine and epinephrine).  - These hormones cause vasoconstriction (narrowing of blood vessels) and increase heart rate, leading to higher blood pressure. - It can also cause an increase in the reactivity of these receptors, making them more sensitive to stimulation and leading to an even stronger response. - **Over-Expression of the RAAS:** - The RAAS system being overly active results in more vasoconstriction and increased sodium and water retention. - Both of these factors directly contribute to higher blood pressure. - **Mutations in Genes Affecting Renal Tubules:** - These mutations can disrupt the normal process of sodium reabsorption in the kidneys. - This leads to more sodium being retained in the body, which increases blood volume and contributes to higher blood pressure. - **Decreased Production of Vasodilators:** - Vasodilators are substances that help relax blood vessels, lowering blood pressure.  - A deficiency in these vasodilators can contribute to increased blood vessel constriction, which is a key factor in hypertension. **\ ** **Hemodynamic Changes/Consequences** These refer to changes in blood flow dynamics, particularly how blood pressure and resistance affect the heart and blood vessels. **Increase in SVR with normal CO:** - SVR refers to systemic vascular resistance - basically how much resistance blood faces as it travels through the body. This increases due to vasoconstriction caused by hypertension.  - CO refers to cardiac output - the volume of blood pumped by the heart per minute. This might remain normal initially, but it will eventually be affected by the increased SVR. **Increased left ventricular afterload:** - The heart\'s left ventricle needs to work harder to pump blood against the increased resistance in the blood vessels (SVR). This increased workload is referred to as afterload. - Over time, this increased afterload can weaken the left ventricle. **Turbulence of blood causes shear stresses on vascular endothelium:** - The increased pressure and resistance in blood vessels due to hypertension also cause increased turbulence (rough flow) of blood.  - This turbulent flow creates friction (shear stress) against the lining of the blood vessels (endothelium), which can damage it over time. **\ ** **Vascular Remodeling:**  This refers to structural changes within the blood vessels due to the constant stress of high blood pressure.  **Increased levels of angiotensin II:** This hormone contributes to vascular remodeling by causing: - **Hypertrophy:** The smooth muscle cells in the blood vessel walls thicken, leading to a narrowing of the lumen (the inside space of the vessel). - **Hyperplasia:** The number of smooth muscle cells increases within the blood vessel walls, further narrowing the lumen. - **Reorganization:** The smooth muscle cells in the blood vessels start to form thicker bands, further hindering blood flow. **Degenerative changes in the arterial wall:** - These changes can include weakening of the arterial wall, making it more prone to damage and rupture. **Risk factors** - **Genetic predisposition/family history:** This is a significant factor in hypertension development, potentially contributing to 30-40% of cases. This means if a person\'s family has a history of high blood pressure, they may be more likely to develop it themselves. - **Black Race:** Individuals of Black race have a higher incidence of hypertension, likely due to a combination of genetics and social determinants of health, such as access to healthcare and socioeconomic status. - **Older Age:** As people age, their arteries become less flexible (reduced arterial compliance), and they are more likely to develop health conditions that contribute to secondary hypertension (hypertension that is a symptom of another medical condition). - **Dietary Factors:** - **High sodium:** Too much sodium in the diet can increase blood volume, leading to higher blood pressure.  - **Low potassium, magnesium, or calcium:** These minerals are important for blood vessel function, and low levels can contribute to high blood pressure. - **Tobacco Use:** Smoking damages blood vessels, causing vasoconstriction (narrowing) and contributing to atherosclerosis (plaque buildup in the arteries) - all of which lead to high blood pressure. - **Alcohol:** Excessive alcohol consumption increases blood pressure, particularly in Black men, even at low-moderate levels. - **Obesity:** Adipose cells (fat cells) release leptin, a hormone that stimulates the sympathetic nervous system, leading to increased sodium reabsorption by the kidneys and contributing to high blood pressure. **Clinical Consequences of Uncontrolled Hypertension** **Atherosclerosis** This is a chronic disease where plaque builds up inside the arteries. The plaque is made of cholesterol, fat, and other substances. - **Abnormal thickening and hardening of the arterial wall:** This is the key characteristic of atherosclerosis. The buildup of plaque makes the arterial wall thicker and less flexible, which can restrict blood flow.  - **Examples:** - **Coronary artery disease leading to myocardial ischemia/infarction:** - This occurs when atherosclerosis affects the coronary arteries, which supply blood to the heart muscle.  - The narrowed arteries reduce blood flow, leading to myocardial ischemia (lack of oxygen to the heart muscle), which could lead to a heart attack, also known as myocardial infarction. - **Peripheral artery disease:** - Atherosclerosis affects arteries in the limbs, reducing blood flow and leading to pain, cramping, numbness, and tingling. - **Cerebrovascular ischemia/ischemic stroke:** - This occurs when atherosclerosis affects arteries in the brain, which reduces blood flow to the brain and can cause a stroke. **Heart Failure** - The constant strain of the heart pumping against high blood pressure can lead to left ventricular failure, particularly of a diastolic nature (the heart has trouble relaxing and filling with blood). **Chronic Kidney Disease** - High blood pressure can damage the blood vessels in the kidneys, leading to a gradual decline in kidney function. **Aneurysm** - High blood pressure weakens the walls of blood vessels, making them more prone to bulging or ballooning out, which is what an aneurysm is.  - **Examples:** - **Cerebral aneurysm:** Aneurysm in the brain arteries can burst, causing a hemorrhagic stroke. - **Aortic aneurysm:** Aneurysms in the aorta (the main artery from the heart) can cause a rupture that can be fatal. **Ocular Changes** - High blood pressure can damage the tiny blood vessels in the retina (the back of the eye), potentially causing vision loss. **Metabolic Syndrome** - This is a cluster of conditions including high blood pressure, high blood sugar, high cholesterol, and abdominal obesity.  - Increased levels of angiotensin and epinephrine, which are often elevated in hypertension, can contribute to the development of insulin resistance, which is a key factor in metabolic syndrome **Dyslipidemia** This is a general term for having a high concentration of fat-like substances (lipids) in the blood.  - **Lipids:** These are fats, and they are essential for many bodily functions, but high levels can be harmful. - **Types of Lipids:** - **Triglycerides**: These are the most common type of fat found in the blood. They are made up of glycerol and fatty acids. The liver can create triglycerides, and they are found in many foods (oils and fats, both saturated and unsaturated). - **Cholesterol**: This is a type of fat that serves as a building block for cell membranes and is used to create important hormones. **Types of Lipoproteins**: These are particles that carry lipids through the bloodstream. - **Chylomicrons:** They carry fats absorbed from your food (dietary lipids) from the small intestine to other parts of your body for storage or energy use. - **Very Low-Density Lipoproteins (VLDL):** These are made by your liver and transport fats (primarily triglycerides) from the liver to your tissues for energy. - **Intermediate-Density Lipoproteins (IDL):** These are created when VLDL is partially broken down. They contain some triglycerides and some cholesterol. - **Low-Density Lipoproteins (LDL):** Often called \"bad\" cholesterol, these carry cholesterol throughout the bloodstream. Though cholesterol is necessary, high levels of LDL can lead to plaque buildup in your arteries (atherosclerosis), which is a major risk factor for heart disease. - **High-Density Lipoproteins (HDL):** Often called \"good\" cholesterol, these pick up excess cholesterol from your tissues and transport it to your liver. The liver then removes the cholesterol from your body. High levels of HDL are considered protective against heart disease. **Risk Factors** - **Genetic Predisposition (Familial Dyslipidemia):** This means some people are genetically more likely to have high cholesterol or other lipid problems. There are at least six known gene mutations that can contribute to dyslipidemia. - **Dietary Factors:** - **High Cholesterol (Red Meat, Full Fat Dairy Products):** Diets high in these items can raise cholesterol levels. - **Saturated Fats (Animal Products):** These raise LDL (\"bad\") cholesterol. - **Trans Fats (Margarine, Commercial Baked Goods):** These are a type of unsaturated fat that has been linked to higher LDL and lower HDL (\"good\") cholesterol levels. - **Obesity (BMI \> 30):** When a person is obese, they have more visceral adipose tissue (fat around the organs). This tissue releases signals that can: - Promote insulin resistance: This makes it harder for the body to use sugar for energy, which can lead to higher blood sugar levels. - Increase LDL and VLDL: This means more \"bad\" cholesterol is circulating in the blood. - **Lack of Exercise:** Regular exercise can raise HDL (\"good\") cholesterol, which helps remove excess cholesterol from the bloodstream.  - **Hyperinsulinemia/Diabetes Mellitus:** People with diabetes often have high insulin levels (hyperinsulinemia), which can raise LDL and lower HDL cholesterol levels. This can be further aggravated by **hyperglycemia** (high blood sugar), which itself can lead to a higher LDL level. [\ ] [Physiology of LDL Production and Metabolism] - **Significance:** The section highlights the importance of understanding how LDL is made and broken down because it\'s crucial for: - Developing medications that lower LDL levels (lipid-lowering medications) - Understanding the process by which LDL builds up in arteries and causes atherosclerosis, which can lead to heart disease (pathophysiology of atherosclerosis). - **First Step of Cholesterol Production:** The production of LDL starts with the enzyme **HMG-CoA reductase**. This enzyme initiates a complex series of steps that ultimately create cholesterol, a necessary component of cell membranes and hormones. - **Complex Synthesis:** The entire process involves approximately 36 steps, each catalyzed by a different enzyme.  - **VLDL Formation:** Within liver cells (hepatocytes), cholesterol combines with other lipids and a protein called apolipoprotein to form **very low-density lipoproteins (VLDL)**. - **VLDL to LDL Conversion:** VLDL is released into the bloodstream and gradually breaks down, losing triglycerides and becoming denser. It eventually gets converted into **intermediate-density lipoproteins (IDL)** and then **LDL**.  - **LDL Uptake:** Cells in the tissues and the liver can absorb LDL to obtain cholesterol they need. But to take in LDL, a cell must have (or create) **LDL receptors** on its surface. These receptors are like docking stations that bind to LDL particles and allow them to enter the cell. **Laboratory Evaluation** It lists specific tests performed to measure lipid levels, which are crucial for understanding your risk for heart disease:  - **Elevated LDL-C and/or VLDL:** Indicates higher than normal levels of \"bad\" cholesterol, which can contribute to plaque buildup in arteries. - **Low HDL-C:** Suggests lower than normal levels of \"good\" cholesterol, which helps remove cholesterol from the bloodstream. - **Elevated Cholesterol:** This is an overall measure of total cholesterol in the blood.  - **Elevated Triglycerides:** Triglycerides are another kind of fat in the blood, and high levels can also be detrimental. - **Considerations:** These are important guidelines for ensuring reliable results from these laboratory tests.  - **Fasting:** The individual should fast for at least 12 hours before the blood test, meaning only water is allowed. - **No Alcohol:** Alcohol intake should be avoided for at least 24 hours before the test, as it can affect lipid levels. **Atherosclerosis** It\'s a buildup of plaque inside the arteries, which makes the artery walls thicker and harder (hence the \"thickening and hardening\") and less flexible. - **Causes:** The section points to two main causes of atherosclerosis: - **Endothelial Injury:** Damage to the lining of the blood vessels (the endothelium) can trigger the inflammatory process that leads to plaque buildup. - **Dyslipidemia:** This refers to abnormal levels of fats and cholesterol in the blood. High levels of \"bad\" cholesterol (LDL) promote plaque formation, while low levels of \"good\" cholesterol (HDL) reduce the body\'s ability to clear out cholesterol. [Risk Factors for Endothelial Injury ] These factors can damage the delicate lining of the blood vessels, contributing to the development of atherosclerosis. - **Hypertension:** High blood pressure puts stress on the blood vessel walls, leading to damage and inflammation. - **Tobacco Use:** Chemicals in tobacco smoke directly damage the endothelium, promoting inflammation and increasing the risk of atherosclerosis. - **Diabetes Mellitus:** Diabetes can lead to high blood sugar levels, which can cause damage to blood vessels over time. - **Infection:** Certain infections can trigger inflammation in the blood vessels, leading to damage. - **Autoimmune Diseases/Immune Reactions:** These conditions involve the immune system attacking the body's own tissues, including blood vessels. - **Hyperhomocysteinemia:** This condition involves high levels of an amino acid called homocysteine in the blood, which can damage blood vessels. [\ ] **[Pathophysiology]**  **[Laboratory Evaluation]** This refers to specific blood tests done to measure lipid levels and markers for inflammation.  **Evidence of Dyslipidemia** - **Total Cholesterol:** Healthy levels are generally less than 200 mg/dL. This is an overall measure of all cholesterol in your blood. - **Triglycerides:** Healthy levels are less than 150 mg/dL. These are a type of fat found in your blood. - **Lipoproteins:** These are particles that carry fats in your blood.  - **HDL:** High levels are desirable (\"good\" cholesterol) because they help remove cholesterol from the body. Levels greater than 40 mg/dL are healthy. - **LDL:** Low levels are desirable (\"bad\" cholesterol) because high levels contribute to artery blockage. Levels less than 130 mg/dL are generally considered good, especially for those at low risk of heart disease. **Evidence of Atherosclerosis** - **Elevated High Sensitivity C-Reactive Protein (hs-CRP):** This protein is a marker of inflammation in the body. Higher hs-CRP levels can indicate inflammation in the blood vessels, a key factor in atherosclerosis.  - **Considerations:** - **hs-CRP can be used to guide lipid-lowering therapy:** Doctors can use hs-CRP levels to decide if a patient needs medication to lower cholesterol levels and prevent atherosclerosis. - **hs-CRP is a general indication of inflammation:** Elevated hs-CRP levels can reflect inflammation in any part of the body, not just the blood vessels. - **Other:** This section mentions a common test used for diabetes: - **Fasting glucose/HbA1c:** These tests are used to evaluate blood sugar control. They are not directly related to dyslipidemia or atherosclerosis but are often part of a comprehensive assessment of heart health