Cardiovascular Disorders: Atherosclerosis

Cardiovascular Disorders

Atherosclerosis

• Definition: Fibrous fatty lesions (plaques) that form in large and medium-sized arteries, reducing blood flow and causing ischemia to supplied organs/tissues
• Principally a disease of the tunica intima of arteries
• Results in:
  • Increased wall thickness and decreased elasticity
  • Reduced vessel radius and flow rate
  • Ischemia to supplied organs/tissues

Etiology of Atherosclerosis

• Related to endothelial cell damage
• Causes:
  • Hyperlipidemia
  • Cigarette smoke
  • Diabetes
  • Immune mechanisms
  • Turbulent blood flow
• Results in:
  • Increased endothelial permeability to plasma protein and lipids
  • Migration of monocytes and other leukocytes into sub-endothelial layers
  • Macrophages differentiate to lipid-filled foam cells
  • Growth of plaque lesions

Coronary Artery Disease (CAD)

• Cause of ischemic heart disease
• Third leading cause of death in industrialized West
• Nearly all elderly have some coronary impairment
• Essential for healthcare professionals to understand pathophysiology

Ischemic Heart Disease (IHD)

• Disease characterized by ischemia (reduced blood supply) of the heart muscle
• Usually due to coronary artery disease (atherosclerosis of the coronary arteries)
• Coronary arteries:
  • Left (main) and right
  • Originate from the aorta
  • Main arteries on the surface, deeper branches penetrate the muscle
  • Right coronary artery supplies mostly the right ventricle and posterior regions of the heart
  • Left coronary artery supplies mostly the left ventricle and interventricular septum

Myocardial Blood Flow

• In strenuous exercise, coronary blood flow increases 3-4 times
• Nervous control of myocardial blood flow operates by two mechanisms:
  • Autonomic control: parasympathetic via vagus nerve and sympathetic nervous systems
  • Local autoregulatory control: nitric oxide and adenosine
• Myocardial blood flow is highest during diastole

Angina Pectoris

• Stable angina:
  • Chest pain caused by transient myocardial ischemia
  • Not severe enough to cause necrosis
  • Brought on by physical exertion or emotional stress
  • Myocardial blood flow cannot respond to increased demand due to narrowing of one or more coronary arteries by atherosclerotic plaque
• Unstable angina:
  • The surface of a plaque experiences small disruptions, leading to the development of small thromboses
  • Causes periods of occlusion
  • Requires immediate hospitalization for rest, observation, and treatment

Acute Coronary Syndrome (ACS)

• Represents a spectrum of ischemic heart diseases, ranging from unstable angina to myocardial infarction
• Pain persists longer than 20 minutes
• May have a previous history of unstable angina as a risk factor
• Symptoms not relieved by short-acting vasodilators

Myocardial Infarction (MI)

• Immediate result of complete coronary occlusion
• Blood flow ceases in vessels beyond occlusion except for small amount of collateral flow
• Produces acute ischemia in the myocardium supplied and varying degrees of ischemic injury and necrosis
• Two important classifications:
  • STEMI (ST segment elevation on ECG)
  • Non-STEMI (sometimes thrombus disintegrates before complete tissue necrosis)

Diagnostic Features of MI

• Serum cardiac biomarkers (e.g., troponin T)
• ECG changes (STEMI vs. non-STEMI)

Management of Acute Coronary Syndrome

• Immediate care:
  • Nitroglycerin (GTN)
  • Bed rest
  • Pain relief (morphine)
  • 12-lead ECG and ECG monitoring
  • Oxygen therapy
  • Beta blockers (slow HR, lengthen diastole)
  • Anticoagulant therapy (e.g., aspirin, platelet inhibitors)

Causes of Death in Myocardial Infarction

• Decreased cardiac output
• Fibrillation of the heart
• Rupture of the heart

Electrocardiogram (ECG)

• Electrical conduction within a normal heart
• Normal ECG:
  • P wave: Atria depolarize
  • QRS complex: Ventricles depolarize
  • T wave: Ventricles recover from depolarization (repolarize)

Disorders of the Heart

• Pericarditis:
  • Acute inflammation of the pericardium
  • Pain, fever, and various causes
  • Treated by relieving symptoms and anti-inflammatory drugs
• Cardiomyopathy:
  • Diverse group of diseases that primarily affect the myocardium
  • Many cases are idiopathic, some genetic, some acquired (e.g., result of inflammation)### Cardiomyopathies
• Dilated cardiomyopathy:
  • Increased ventricular volume, causing impairment of systolic function
  • Causes: 1/3 inherited, infections, chemotherapy, or idiopathic
  • Typical clinical manifestations: dyspnea, orthopnea, reduced exercise capacity
  • Common cause of heart failure and transplantation
• Hypertrophic cardiomyopathy:
  • Thickening of septum, decreasing left ventricular size and obstructing blood outflow
  • One of the most common types of cardiomyopathies, inherited
  • Mostly asymptomatic, but symptoms can include angina, dyspnea, reduced exercise capacity

Valvular Dysfunction

• Can be congenital or acquired
• Most common acquired cause: rheumatic heart disease (after Streptococcus pyogenes infection)
• Most commonly affects aortic and mitral valves
• Two types of disruptions can occur:
  • Stenosis: narrowing of valve opening, causing turbulent flow and enlargement of emptying chamber
  • Incompetent (regurgitant) valve: permitting backward flow
  • Sounds made by abnormal flow = "murmurs"

Heart Failure (HF)

• Heart is unable to generate an adequate cardiac output (stroke volume x heart rate)
• Stroke volume depends on preload, afterload, and myocardial contractility
• HF may cause inadequate perfusion of tissues or increased pulmonary capillary pressures
• Common causes: coronary artery disease, valvular disease, and cardiomyopathies
• Most common reason for hospital admission in people over 65 years old

Risk Factors for Heart Failure

• Ischemic heart disease
• Older age
• Hypertension
• Diabetes mellitus type 2
• Lack of exercise
• Smoking
• Obesity

Terms Affecting Stroke Volume

• Preload:
  • Volume of blood in the ventricle at the end of diastole
  • Determined by amount of blood entering ventricle during diastole, blood left in ventricle after systole, and Frank-Starling law of the heart
• Afterload:
  • Resistance to ejection of blood from the left ventricle
  • Peripheral vascular resistance is usually a good indicator of afterload
• Inotropy (contractility):
  • Contractility of muscle
  • Ability of actin and myosin to interact and shorten against a load
  • Increases cardiac output, independent of preload and afterload

Systolic and Diastolic Heart Failure

• Systolic heart failure:
  • Myocardial contractility is impaired, leading to decreased ejection fraction
  • Causes: decreased contractility, volume overload, or pressure overload
  • More blood remains in the ventricle after contraction, leading to pulmonary or peripheral edema
• Diastolic heart failure:
  • Decreased diastolic relaxation, leading to decreased cardiac output
  • Causes: conditions that decrease expansion of the ventricle, increase wall thickness, or delay diastolic relaxation

Left and Right Heart Failure

• Left heart failure (LHF):
  • Decreased cardiac output to systemic circulation
  • Can be systolic, diastolic, or both
  • Decreased cardiac output to systemic circulation leads to increased pulmonary venous pressure
  • Most common causes: hypertension, acute MI, cardiomyopathy
• Right heart failure (RHF):
  • Inability of right ventricle to move deoxygenated blood from systemic circulation into pulmonary circulation
  • Pressure rises in systemic venous circulation, leading to peripheral edema
  • Causes: left heart failure, cor pulmonale, or right heart issues

Compensatory Mechanisms in Heart Failure

• Sympathetic nervous system activation:
  • Increases blood pressure and cardiac output
  • However, increases heart rate and contractility, putting more strain on the heart
• Renin-angiotensin-aldosterone system (RAAS) activation:
  • Vasoconstriction increases afterload, and increased blood volume increases preload, both of which put more strain on the heart
• Hypertrophy:
  • Varying degrees of ventricular wall thickening or thinning, leading to increased ischemia or dilation and impairment of contraction

Circulatory Failure: Shock

• Acute failure of the circulatory system to supply the body with an adequate blood supply, resulting in cellular hypoxia
• Many causes and clinical manifestations
• Ultimately leads to organ failure and death unless corrected

Types of Shock

• Cardiogenic shock:

  • Decreased cardiac output due to decreased contractility, increased preload, and/or increased afterload
  • Decrease in blood pressure causes compensation: increase in epinephrine release and RAAS system

• Hypovolemic shock:

  • Not enough blood volume
  • Causes: significant loss of whole blood, plasma, or interstitial fluid
  • Begins to develop when intravascular volume has decreased by about 20%

• Distributive shock:

  • Result of massive vasodilation
  • Blood volume has not changed, but the amount of space containing the blood has increased
  • Three shock states share this mechanism: neurogenic, anaphylactic, and septic

• Obstructive shock:

  • Results from mechanical obstruction of blood flow through the central circulation (great veins, heart, or lungs)
  • Elevated right heart pressure occurs
  • Significant decrease in cardiac output
  • Often classified under cardiogenic shock### Primary Hypertension

• Most cases (95%) are due to a combination of genetics and environmental factors.

• Factors that can lead to primary hypertension include family history, age, gender, race, high dietary sodium intake, insulin resistance, cigarette smoking, and obesity.

• Determined by several BP measurements at different times and tests to exclude secondary hypertension, including complete blood count (CBC), urinalysis, blood chemistry, ECG, and assessing target-organ damage.

Pathophysiology of Hypertension

• Increased blood pressure is due to an increase in circulating blood volume, increased peripheral resistance, or both.
• Interaction of several factors, including:
  • Sympathetic nervous system, which increases heart rate and vasoconstriction.
  • Overactivity of the renin-angiotensin-aldosterone system (RAAS), which increases vasoconstriction and blood volume and pressure by retaining sodium and water in the kidneys.
  • Chronic inflammation, which results in smooth muscle contraction.

Clinical Manifestations of Hypertension

• Early stages have no symptoms or signs, other than elevated blood pressure (also known as a "silent disease").
• Some people may never develop signs, symptoms, or complications, while others may become severely ill and die.
• Clinical manifestations become evident when damage to other organs/systems occurs, and are specific to the affected organ/system, including:
  • Coronary heart disease
  • Kidney disease
  • CNS dysfunction (stroke, dementia)
  • Impaired vision

Treatment of Hypertension

• Includes lifestyle modification:
  • Exercise
  • Weight loss
  • Stop smoking and alcohol use
• Medications:
  • Diuretics and other anti-hypertensives, e.g., ACE inhibitors

Hypertension during Pregnancy

• Can be classified as:
  • Pre-existing: present before pregnancy or appears before 20 weeks of pregnancy
  • Gestational: occurs at or after 20 weeks of pregnancy
• Possibly due to a decrease in placental blood flow, leading to release of toxic compounds that cause changes in blood vessel walls throughout the body.

Preeclampsia

• Diagnosed if a woman presents with:
  • Hypertension (either gestational or pre-existing)
  • Proteinuria
  • Adverse conditions, e.g., persistent or new headache, visual disturbances, persistent abdominal pain, elevated liver enzymes, etc.
• Can lead to eclampsia, which is the occurrence of convulsions and possible coma, due to development of blood clots in cerebral vessels.
• Decrease in placental blood flow in gestational hypertension also affects the fetus, frequently resulting in infants who are small for gestational age and requiring early delivery.

Diseases of the Arteries

• Orthostatic (Postural) Hypotension:
  • Specific decrease in blood pressure within 3 minutes of moving to a standing position, causing dizziness, fainting
  • More frequently observed in the elderly
  • Normal mechanisms to maintain BP when standing up do not function, e.g., due to use of certain medications (e.g., antihypertensives), ageing, dehydration
• Aneurysm:
  • Local outpouching of vessel or heart chamber wall, usually in the abdominal aorta
  • Most commonly caused by atherosclerosis and hypertension
  • Manifestations depend upon where the aneurysm is, and involve the production of pressure on local structures
• Thrombus:
  • Caused by any condition that promotes activation of coagulation (surgery, infection, low BP, inflammation, etc.)
  • Can occlude the artery/vein or break off to form an embolus
• Embolism:
  • Obstruction of a vessel by an embolus (air bubble, fat, dislodged thrombus, clump of cells)
  • No matter how tiny, it will eventually lodge in a vessel
  • Arterial emboli arise from the left heart and are associated with thrombi that occur after heart trauma (e.g., heart attack)
  • Pulmonary emboli arise from the venous side (e.g., DVT or in the right heart)

Diseases of the Veins

• Varicose Veins:

  • Definition: Veins in which blood has pooled, producing distended, tortuous, and palpable vessels
  • Why do they occur in the legs?:
    • There are no valves in the inferior vena cava or the common iliac veins, making the veins in the legs responsible for supporting the blood in these vessels
    • If pressure increases in the abdomen (pregnancy, repeated heavy lifting) this increases the strain on these valves
    • Standing for long periods of time also puts extra strain on these valves, as the leg muscles are not being used to pump blood back to the heart

• Development of Varicose Veins:

  • If a valve in a vein is damaged, a section of the vein is subjected to the pressure of a larger volume of blood under the influence of gravity
  • The vein swells and edema develops in the surrounding tissue
  • This can damage the remaining upstream valves in the vein, making them unable to maintain normal venous pressure

• Risk factors for Varicose Veins:

  • Standing long periods, crossing legs at the knee, age, female gender, family history, obesity, pregnancy, deep venous thrombosis, and previous leg injury

• Treatment for Varicose Veins:

  • Wearing compression stockings, physical exercise, surgical ligation, vein stripping

• Possible complication of Varicose Veins:

  • Chronic Venous Insufficiency (CVI), which is inadequate venous return over a long period of time, impairing blood flow to the area, especially in obese individuals.

• Deep Venous Thrombosis (DVT):

  • Development of a thrombus in a deep vein, occurring primarily in the lower extremity
  • Risk factors include:
    • Venous stasis, due to immobility, allowing pooling of clotting factors (e.g., after hip fracture, joint replacement, spinal cord injury)
    • Impaired cardiac function (e.g., acute myocardial infarction, congestive heart failure)
    • Venous endothelial damage (e.g., intravenous drug use/groin injection)
    • Hypercoagulable states (e.g., inherited disorders, pregnancy)
  • Development of DVT:
    • Clotting factors and platelets accumulate (often near a valve) and form a thrombus
    • Inflammation around the thrombus promotes further platelet aggregation and the thrombus grows
    • Because the vein is deep in the leg, it is usually asymptomatic (may get edema if vessel is obstructed significantly)